buprenorphine and Opioid-Related-Disorders

The crisis caused by prescribed opioids and their related side effects are a public health problem worldwide. Most of these are prescribed for coping with chronic pain. The coexistence of opioid use disorder (OUD) in patients with chronic pain represents a complex challenge due to the need for managing both pain and OUD. The aim of this systematic review is to evaluate the efficacy of feasible treatments for this population with OUD and comorbid chronic pain for both conditions. A systematic database search has been performed using Cochrane Library, MEDLINE, PsycINFO and ClinicalTrials.gov in compliance with PRISMA guidelines. Eligible articles addressed the outcomes in chronic pain patients with comorbid opioid use disorder after treatment interventions were applied. Of 593 identified articles, nine were eligible for qualitative review (n = 7 pharmacological interventions; n = 2 psychological interventions). Methadone, buprenorphine, cognitive-behavioral and mindfulness showed promising results, but data were inconclusive (<2 RCT with low risk of bias). It is unclear whether the opioid agonist treatment should be maintained or tapered and which drug should be prescribed for the opioid substitution therapy (methadone or buprenorphine/naloxone). Mindfulness and cognitive behavioral therapy have a discrete effect on improving negative affect but not pain. The therapeutic approach might be individualized under a shared decision-making basis.. La crisis causada por los opioides recetados y sus efectos secundarios relacionados son un problema de salud pública en todo el mundo. La mayoría de estos medicamentos se recetan para el afrontamiento del dolor crónico. La coexistencia del trastorno por uso de opioides (TUO) en pacientes con dolor crónico representa un desafío complejo debido a la necesidad de controlar tanto el dolor como el TUO. El objetivo de esta revisión sistemática es evaluar la eficacia de los tratamientos posibles para dicha población con TUO y dolor crónico. Se ha realizado una revisión sistemática usando las bases de datos Cochrane Library, MEDLINE, PsycINFO y ClinicalTrials.gov, conforme a las pautas PRISMA. Los artículos elegibles abordaron los resultados en pacientes con dolor crónico y diagnóstico comórbido de TUO, después de aplicar una intervención. De 593 artículos identificados, nueve eran elegibles para la revisión cualitativa (n = 7 intervenciones farmacológicas; n = 2 intervenciones psicológicas). La metadona, la buprenorfina, la terapia cognitivo-conductual y el mindfulness mostraron resultados prometedores, pero los datos no eran concluyentes (<2 ECA con bajo riesgo de sesgo). No está claro si el tratamiento con agonistas opioides debe mantenerse o disminuirse y qué fármaco debe prescribirse para la terapia de sustitución de opioides (metadona o buprenorfina/naloxona). El mindfulness y la terapia cognitivo-conductual tienen un efecto discreto en la mejora del afecto negativo, pero no del dolor. El enfoque terapéutico podría individualizarse sobre la base de una toma de decisiones conjunta.

Topics: Analgesics, Opioid; Buprenorphine; Chronic Pain; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders

To assess studies examining the prevalence of chronic pain (CP) in patients treated with Opioid Substitution Treatment (OST - buprenorphine or methadone) for Opioid Used Disorder (OUD), we conducted a systematic review and meta-analysis of the literature between the years 2000 and 2020. We searched EMBASE, PsycINFO, Cochrane, and MEDLINE databases and included studies assessing the prevalence of CP in OUD adults treated with OST. The studies were assessed for risk of bias and overall quality and the results were pooled using a random-effects model. Subgroup analyses and meta-regressions were used to identify possible factors associated with CP. Twenty-three studies reported data on the prevalence of CP in patients treated with OST were evaluated. The prevalence obtained was 45.3% (CI95% [38.7; 52.1]). Overall, 78.3% of the studies had a low risk of bias. Subgroup analysis estimates did not vary according to gender, OST, and CP duration. However, it appeared that the clinical settings was associated with a lower CP prevalence when assessed in primary care sites. Our study provided an estimate regarding the prevalence of CP among OST patients. These patients deserve specific attention from health professionals and health authorities. Thus, the real challenge in OST patients is the implementation of a multidisciplinary approach to manage CP. PERSPECTIVE: Our meta-analysis provided an estimate of CP prevalence, reaching almost 50% of OUD patients with OST. Thus, the urgent challenge in OST patients is to pay systematic attention to chronic pain diagnosis, along with the implementation of a multidisciplinary patient-focused approach for an appropriate management of CP. REGISTRATION: PROSPERO (CRD42021284790).

Topics: Adult; Analgesics, Opioid; Buprenorphine; Chronic Pain; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Prevalence

The opioid epidemic continues to be problematic in the United States (US). Medications for opioid use disorder (MOUD) are a commonly used evidence-based approach to treating affected individuals, but little is known about its use in the rural US. We reviewed published literature and summarized access, barriers, and approaches to MOUD delivery in rural areas.. We conducted a search using databases in EBSCOhost, such as Academic Search Complete, Medline, and APA PsycArticles, using. A total of 13 articles met all criteria. Themes from the articles included increase in rural areas with waivered physicians able to prescribe buprenorphine, barriers to physician prescribing, waivered physicians choosing not to prescribe, and inability to assess quality of MOUD practices in rural US settings.. Additional studies of MOUD delivery in rural areas are needed to help explicate themes found in this review. Having a stronger understanding of prescribers operating practices and program roll-out in rural areas may help address some identified barriers and deliver a stronger quality treatment practice for individuals with substance-use disorder.

Topics: Analgesics, Opioid; Buprenorphine; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Physicians; United States

Novel treatments for opioid use disorder (OUD) are needed to address both the ongoing opioid epidemic and long-standing barriers to existing OUD treatments that target the endogenous μ-opioid receptor (MOR) system. The goal of this review is to highlight unique clinical trial design considerations for the study of emerging treatments for OUD that address targets beyond the MOR system. In November 2019, the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership with the US Food and Drug Administration sponsored a meeting to discuss the current evidence regarding potential treatments for OUD, including cannabinoids, psychedelics, sedative-hypnotics, and immunotherapeutics, such as vaccines.. Consensus recommendations are presented regarding the most critical elements of trial design for the evaluation of novel OUD treatments, such as: (1) stage of treatment that will be targeted (eg, seeking treatment, early abstinence/detoxification, long-term recovery); (2) role of treatment (adjunctive with or independent of existing OUD treatments); (3) primary outcomes informed by patient preferences that assess opioid use (including changes in patterns of use), treatment retention, and/or global functioning and quality of life; and (4) adverse events, including the potential for opioid-related relapse or overdose, especially if the patient is not simultaneously taking maintenance MOR agonist or antagonist medications.. Applying the recommendations provided here as well as considering input from people with lived experience in the design phase will accelerate the development, translation, and uptake of effective and safe therapeutics for individuals struggling with OUD.

Topics: Analgesics, Opioid; Buprenorphine; Clinical Trials as Topic; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Quality of Life

More than 20 million people in the United States have a substance use disorder (SUD), increasing their risk for overdose (OD). Patients arriving to emergency departments (EDs) with OD typically require lifesaving interventions, but inconsistencies exist regarding further intervention and discharge instructions. The purpose of the current integrative review was to determine best care practices for patients presenting to EDs with an illicit drug OD. A literature search included the databases PubMed, EBSCO Host, ProQuest Health and Medicine, and Google Scholar. Thirty-five articles outlined interventions for SUD/OD initiated in EDs; most for opioid OD. Best practice intervention components included psychiatric evaluations, SUD screening tools, buprenorphine initiation, naloxone distribution and training, OD prevention education, referrals to medication-assisted treatment, and harm reduction strategies. Barriers to implementation included legislation, insurance/costs, community resource availability, staffing, training, and potential stigma. With myriad approaches, nurses with SUD care experience can advocate for instituting best practices for patients in the ED and upon discharge. [

Topics: Buprenorphine; Drug Overdose; Emergency Service, Hospital; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Substance-Related Disorders; United States

To describe the effectiveness of medications for the treatment of opioid use disorder (OUD) and attention deficit/hyperactivity disorder (ADHD).. Literature search of PubMed, Embase, Web of Science, CINAHL, Medline, PsycINFO, and Google Scholar was performed for studies published from inception to October 25, 2022.. Studies were included if patients were diagnosed with OUD and ADHD and had pharmacotherapy for either condition. Abstracts, commentaries, reviews, case reports, case series, non-English articles, and animal studies were omitted.. This review found 18 studies. Treatment of ADHD was evaluated for impact on ADHD and OUD outcomes, while treatment of OUD was evaluated for OUD-related outcomes. Outcomes assessed included markers for symptom intensity, adherence, and treatment failure. While results were mixed, treatment of ADHD was largely associated with improvements in ADHD severity and retention in OUD treatment programs. ADHD severity was associated with higher rates of illicit substance abuse and worse OUD-related outcomes. It could not be determined which medications for treatment of OUD should be prioritized.. This review summarized key findings from studies that treated ADHD or OUD among dually diagnosed patients and highlighted methodological considerations for future research.. Treatment of ADHD is warranted among patients with OUD and ADHD to improve retention in OUD treatment programs and reduce illicit substance abuse. Pharmacotherapy for the treatment of ADHD or OUD should continue to be determined based on patients' characteristics and the capabilities of the treatment program.

Topics: Analgesics, Opioid; Attention Deficit Disorder with Hyperactivity; Buprenorphine; Humans; Opiate Substitution Treatment; Opioid-Related Disorders

The majority of patients with opioid use disorder do not receive medications for opioid use disorder (MOUD), especially in rural areas. The patient-centered access to healthcare framework posits access as a multidimensional phenomenon impacted by five healthcare system and five patient ability dimensions. Interventions to improve local MOUD treatment outcomes require an understanding of how these dimensions differ across urban and rural communities. This scoping review sought to systematically appraise the literature on MOUD access across urban and rural communities (i.e., rurality) in the US using the patient-centered access framework.. We performed a scoping review of 1) electronic databases, 2) grey literature, and 3) correspondence with content experts (March 2021). We included articles specifying the study sample by rurality and examining at least one dimension of access to MOUD. The analysis and qualitative synthesis of study results examined study characteristics and categorized key findings by access dimensions.. The search produced 3963 unique articles, of which 147 met inclusion criteria. Among included studies, 96% (142/147) examined healthcare system dimensions of access while less than 20% (25/147) examined any of the five dimensions of patient ability. Additionally, 49% (72/147) of studies compared access dimensions by rurality. Across studies, increasing rurality was associated with fewer available MOUD services, but little was known about geographic variation in other critical dimensions of access.. The vast majority of studies examined healthcare system dimensions of MOUD access and few studies made comparisons by rurality or prioritized the patient's perspective, limiting our understanding of how access differs by rurality in the US. As COVID-19 spurs novel changes in MOUD delivery, this inadequate multidimensional understanding of MOUD access may impede the tailoring of interventions to local needs. There is an urgent need for mixed-methods and community-engaged research prioritizing the patient's perspective of MOUD access by rurality.. Open Science Framework (https://osf.io/wk6b9/).

Topics: Buprenorphine; COVID-19; Databases, Factual; Health Services Accessibility; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Rural Population

Craving is a distressing symptom of opioid use disorder (OUD) that can be alleviated with medications for OUD (MOUD). Buprenorphine is an effective MOUD that may suppress craving; however, treatment discontinuation and resumed opioid use is common during the early phases of treatment. More information on the craving response through the high-risk period of initiating buprenorphine may provide meaningful information on how to better target craving, which in turn may enhance outcomes. This systematic review investigated buprenorphine doses and formulations on craving during the induction and maintenance phases of treatment, and for context also compared the craving response to other MOUD (i.e., methadone, extended-release naltrexone [XR-NTX]).. PubMed, PsycInfo, Embase, and Cochrane Central databases were searched for randomized trials of buprenorphine versus placebo, various buprenorphine formulations/doses, or other MOUD that included a measure of opioid craving.. A total of 10 studies were selected for inclusion. Buprenorphine and buprenorphine/naloxone (BUP/NAL) were each associated with lower craving than placebo over time. Craving was greater among those prescribed lower versus higher buprenorphine doses. In comparison to other MOUD, buprenorphine or BUP/NAL was linked to greater craving than methadone in 3 of the 6 studies. BUP/NAL was associated with greater reported craving than XR-NTX.. Craving is reduced over time with buprenorphine and BUP/NAL, although other MOUD may provide greater reductions in craving. Although there is currently considerable variability in the measurement of craving, it may be a valuable concept to address with individuals receiving MOUD, especially early in treatment.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Craving; Delayed-Action Preparations; Humans; Methadone; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Randomized Controlled Trials as Topic

The use and misuse of opioids in pregnancy have been increasing and are a major public health issue. Opioid use in pregnancy and during lactation has been associated with increased maternal and neonatal morbidity and mortality.. This review aims to summarize the existing literature and current recommendations for opioid use while pregnant or lactating.. A PubMed, Cochrane Library, and Google Scholar literature search using the following terms was performed to gather relevant data: "opioids," "opioid maintenance therapy," "opioid use disorder," "suboxone," "buprenorphine," "methadone," "medication for opioid use disorder," "fetal outcomes," "perinatal outcomes," "pregnancy," "lactation," and "neonatal abstinence syndrome.". Available studies on opioid use in pregnancy and during lactation were reviewed and support association with increased odds of maternal death, placental insufficiency, cardiac arrest, preterm birth, neonatal intensive care unit admission, low birth weight, and small for gestational age infants. Studies were also reviewed on pharmacotherapy options in pregnancy and promising prenatal care models.. There is a critical need for research on the effects of opioid use and related pharmacotherapy options in pregnancy. Once the adverse perinatal effects of opioid exposure are identified and well-characterized, patient education, intervention, and antenatal surveillance can be developed to predict and mitigate its impact on maternal and fetal health.

Topics: Analgesics, Opioid; Buprenorphine; Female; Humans; Infant, Newborn; Lactation; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Parturition; Placenta; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth

Topics: Aged; Analgesics, Opioid; Buprenorphine; Drug-Related Side Effects and Adverse Reactions; Humans; Methadone; Naltrexone; Opiate Substitution Treatment; Opioid-Related Disorders

Development and implementation of effective treatments for opioid use disorder (OUD) and prevention of overdose are urgent public health needs. Though existing medications for OUD (MOUD) are effective, barriers to initiation and retention in treatment persist. Therefore, development of novel treatments, especially those may complement existing treatments, is needed.. This review provides an overview of vaccines for substance use disorders (SUD) and mechanisms underlying their function and efficacy. Next, we focus on existing preclinical and clinical trials of SUD vaccines. We focus briefly on related strategies before providing an expert opinion on prior, current, and future work on vaccines for OUD. We included published findings from preclinical and clinical trials found on PubMed and ScienceDirect as well as ongoing or initiated trials listed on ClinicalTrials.gov.. The present opioid overdose and OUD crises necessitate urgent development and implementation of effective treatments, especially those that offer protection from overdose and can serve as adjuvants to existing medications. Promising preclinical trial results paired with careful efforts to develop vaccines that account for prior SUD vaccine shortcomings offer hope for current and future clinical trials of opioid vaccines. Clinical advantages of opioid vaccines appear to outnumber disadvantages, which may result in improved treatment options.

Topics: Analgesics, Opioid; Buprenorphine; Humans; Immunotherapy; Opioid-Related Disorders; Vaccines

Expanding access to medications to treat opioid use disorder (OUD), such as buprenorphine, is an evidence-based response to the mounting drug overdose crisis. However, concerns about buprenorphine diversion persist and contribute to limited access.. To inform decisions about expanding access, a scoping review was conducted on publications describing the scope of, motivations for, and outcomes associated with diverted buprenorphine in the U.S.. In the 57 included studies, definitions for diversion were inconsistent. Most studied use of illicitly-obtained buprenorphine. Across studies, the scope of buprenorphine diversion ranged from 0% to 100%, varying by sample type and recall period. Among samples of people receiving buprenorphine for OUD treatment, diversion peaked at 4.8%. Motivations for using diverted buprenorphine were self-treatment, management of drug use, to get high, and when drug of choice was unavailable. Associated outcomes examined trended toward positive or neutral, including improved attitudes toward and retention in MOUD.. Despite inconsistent definitions of diversion, studies reported a low scope of diversion among people receiving MOUD, with inability to access treatment as a motivating factor for

Topics: Analgesics, Opioid; Buprenorphine; Drug Overdose; Humans; Motivation; Opiate Substitution Treatment; Opioid-Related Disorders; United States

Overdose is a leading cause of pregnancy-associated morbidity and mortality in the United States. As such, all obstetric providers have a responsibility to provide evidence-based care for patients with opioid use disorder to mitigate adverse outcomes associated with substance use during pregnancy.

Topics: Analgesics, Opioid; Buprenorphine; Female; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; United States

Buprenorphine is a partial agonist at the µ-opioid receptor and an antagonist at the delta and kappa opioid receptors. It has high affinity and low intrinsic activity at the µ-opioid receptor. Buprenorphine demonstrates no ceiling effect for clinical analgesia, but demonstrates this for respiratory depression and euphoria. It may provide effective analgesia while producing less adverse effects, making it a promising opioid analgesic. A systematic review and meta-analysis were performed to examine the analgesic efficacy of buprenorphine for patients with chronic noncancer pain.. PubMed, MEDLNE, Embase, and the Cochrane Library were searched up to January 2022. Randomized controlled trials were included if they compared buprenorphine versus placebo or active analgesic in patients with chronic noncancer pain, where pain score was an outcome. Nonrandomized controlled trials, observational studies, qualitative studies, case reports, and commentaries were excluded. Two investigators independently performed the literature search, study selection, and data collection. A random-effects model was used. The primary outcome was the effect of buprenorphine on pain intensity in patients with chronic noncancer pain based on standardized mean difference (SMD) in pain score. Quality of evidence was assessed using the Grade of Recommendations Assessment, Development, and Evaluation (GRADE) approach.. Two separate literature searches were conducted for patients with and without opioid use disorder (OUD). Only one study met the search criteria for those with OUD. Fourteen randomized controlled trials were included for those without OUD. Buprenorphine was associated with reduced pain score (SMD = -0.368, P < .001, I 2 = 89.37%) compared to placebo or active analgesic. Subgroup meta-analyses showed statistically significant differences in favor of buprenorphine versus placebo (SMD = -0.404, P < .001), for chronic low back pain (SMD = -0.383, P < .001), when administered via the transdermal route (SMD = -0.572, P = .001), via the buccal route (SMD = -0.453, P < .001), with length of follow-up lasting <12 weeks (SMD = -0.848, P < .05), and length of follow-up lasting 12 weeks or more (SMD = -0.415, P < .001). There was no significant difference when compared to active analgesic (SMD = 0.045, P > .05). Quality of evidence was low to moderate.. Buprenorphine was associated with a statistically significant and small reduction in pain intensity compared to placebo. Both the transdermal and buccal routes provided pain relief. There was more evidence supporting its use for chronic low back pain.

Topics: Analgesics, Opioid; Buprenorphine; Chronic Pain; Humans; Low Back Pain; Opioid-Related Disorders; Randomized Controlled Trials as Topic; Receptors, Opioid

The opioid overdose and polysubstance use crises have led to the development of low-barrier, transitional substance use disorder (SUD) treatment models, including bridge clinics. Bridge clinics offer immediate access to medications for opioid use disorder (MOUD) and other SUD treatment and are increasingly numerous. However, given relatively recent implementation, the clinical impact of bridge clinics is not well described.. In this narrative review, we describe existing bridge clinic models, services provided, and unique characteristics, highlighting how bridge clinics fill critical gaps in the SUD care continuum. We discuss available evidence for bridge clinic effectiveness in care delivery, including retention in SUD care. We also highlight gaps in available data.. The first era of bridge clinic implementation has yielded diverse models united in the mission to lower barriers to SUD treatment entry, and preliminary data indicate success in patient-centered program design, MOUD initiation, MOUD retention, and SUD care innovation. However, data on effectiveness in linking to long-term care are limited.. Bridge clinics represent a critical innovation, offering on-demand access to MOUD and other services. Evaluating the effectiveness of bridge clinics in linking patients to long-term care settings remains an important research priority; however, available data show promising rates of treatment initiation and retention, potentially the most important metric amidst an increasingly dangerous drug supply.

Topics: Ambulatory Care Facilities; Analgesics, Opioid; Buprenorphine; Child; Continuity of Patient Care; Female; Humans; Infant, Newborn; Opiate Overdose; Opiate Substitution Treatment; Opioid-Related Disorders; Perinatal Care; Pregnancy

Opioid use disorder (OUD) is a chronic disorder in which a person loses control over the use of opioids, develops a compulsive behavior, and defends the use despite knowing the negative consequences. There are numerous treatments for OUD, including buprenorphine. Since it is displacing a full agonist opioid, precipitated withdrawal can occur with standard inductions involving buprenorphine.. Case reports have noted success with a low-dose initiation of buprenorphine, which is different from typical protocols, relatively limited by adverse effects when patients were recently administered full agonists. A cohort investigation studied the use of a transdermal patch as part of the protocol, which was fairly well tolerated. While ongoing research is being conducted on this topic, recent case studies and smaller cohort studies have demonstrated the feasibility of a trial to treat OUD with low-dose initiation of buprenorphine.

Topics: Analgesics, Opioid; Buprenorphine; Chronic Disease; Humans; Opiate Substitution Treatment; Opioid-Related Disorders

The tissue damage and trauma associated with surgery almost always result in acute postoperative pain. The intensity of postoperative pain can range from mild to severe. Naltrexone is suitable for patients who do not wish to be on an agonist treatment such as methadone or buprenorphine. However, naltrexone has been shown to complicate postoperative pain management.. Multiple studies have found that the use of naltrexone can increase the opioid requirement for postoperative pain control. Other modalities exist that can help outside of opioids such as ketamine, lidocaine/bupivacaine, duloxetine, and non-pharmacological management can help manage pain. Multimodal pain regiments should also be employed in patients. In addition to traditional methods for postoperative pain management, other methods of acute pain control exist that can help mitigate opioid dependence and help control pain in patients who use naltrexone for their substance use disorders.

Topics: Acute Pain; Analgesics, Opioid; Buprenorphine; Humans; Methadone; Naltrexone; Opiate Substitution Treatment; Opioid-Related Disorders; Pain, Postoperative

Opioid dependence is associated with substantial health and social burdens, and opioid agonist treatment (OAT) is highly effective in improving multiple outcomes for people who receive this treatment. Methadone and buprenorphine are common medications provided as OAT. We aimed to examine buprenorphine compared with methadone in the treatment of opioid dependence across a wide range of primary and secondary outcomes.. We did a systematic review and meta-analysis in accordance with GATHER and PRISMA guidelines. We searched Embase, MEDLINE, CENTRAL, and PsycINFO from database inception to Aug 1, 2022; clinical trial registries and previous relevant Cochrane reviews were also reviewed. We included all RCTs and observational studies of adults (aged ≥18 years) with opioid dependence comparing treatment with buprenorphine or methadone. Primary outcomes were retention in treatment at 1, 3, 6, 12, and 24 months, treatment adherence (measured through doses taken as prescribed, dosing visits attended, and biological measures), or extra-medical opioid use (measured by urinalysis and self-report). Secondary outcomes were use of benzodiazepines, cannabis, cocaine, amphetamines, and alcohol; withdrawal; craving; criminal activity and engagement with the criminal justice system; overdose; mental and physical health; sleep; pain; global functioning; suicidality and self-harm; and adverse events. Single-arm cohort studies and RCTs that collected data on buprenorphine retention alone were also reviewed. Data on study, participant, and treatment characteristics were extracted. Study authors were contacted to obtain additional data when required. Comparative estimates were pooled with use of random-effects meta-analyses. The proportion of individuals retained in treatment across multiple timepoints was pooled for each drug. This study is registered with PROSPERO (CRD42020205109).. We identified 32 eligible RCTs (N=5808 participants) and 69 observational studies (N=323 340) comparing buprenorphine and methadone, in addition to 51 RCTs (N=11 644) and 124 observational studies (N=700 035) that reported on treatment retention with buprenorphine. Overall, 61 studies were done in western Europe, 162 in North America, 14 in north Africa and the Middle East, 20 in Australasia, five in southeast Asia, seven in south Asia, two in eastern Europe, three in central Europe, one in east Asia, and one in central Asia. 1 040 827 participants were included in these primary studies; however, gender was only reported for 572 111 participants, of whom 377 991 (66·1%) were male and 194 120 (33·9%) were female. Mean age was 37·1 years (SD 6·0). At timepoints beyond 1 month, retention was better for methadone than for buprenorphine: for example, at 6 months, the pooled effect favoured methadone in RCTs (risk ratio 0·76 [95% CI 0·67-0·85]; I·=74·2%; 16 studies, N=3151) and in observational studies (0·77 [0·68-0·86]; I·=98·5%; 21 studies, N=155 111). Retention was generally higher in RCTs than observational studies. There was no evidence suggesting that adherence to treatment differed with buprenorphine compared with methadone. There was some evidence that extra-medical opioid use was lower in those receiving buprenorphine in RCTs that measured this outcome by urinalysis and reported proportion of positive urine samples (over various time frames; standardised mean difference -0·20 [-0·29 to -0·11]; I·=0·0%; three studies, N=841), but no differences were found when using other measures. Some statistically significant differences were found between buprenorphine and methadone among secondary outcomes. There was evidence of reduced cocaine use, cravings, anxiety, and cardiac dysfunction, as well as increased treatment satisfaction among people receiving buprenorphine compared with methadone; and evidence of reduced hospitalisation and alcohol use in people receiving methadone. These differences in secondary outcomes were based on small numbers of studies (maximum five), and were often not consistent across study types or different measures of the same constructs (eg, cocaine use).. Evidence from trials and observational studies suggest that treatment retention is better for methadone than for sublingual buprenorphine. Comparative evidence on other outcomes examined showed few statistically significant differences and was generally based on small numbers of studies. These findings highlight the imperative for interventions to improve retention, consideration of client-centred factors (such as client preference) when selecting between methadone and buprenorphine, and harmonisation of data collection and reporting to strengthen future syntheses.. Australian National Health and Medical Research Council.

Topics: Adolescent; Adult; Analgesics, Opioid; Australia; Buprenorphine; Cocaine; Female; Humans; Male; Methadone; Opioid-Related Disorders

Caring for pregnant women who have a recreational opioid use disorder is a common clinical challenge in modern obstetric care. These are an elusive population who often have multiple social issues that complicate their pregnancy management. Comprehensive and supportive maternal care can motivate these mothers to change her lifestyle. Multidisciplinary non-judgemental approach with appropriate medication and management, can result in good pregnancy outcomes for mother and her baby.

Topics: Analgesics, Opioid; Buprenorphine; Female; Gynecology; Humans; Infant; Methadone; Obstetrics; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnancy Outcome

The Russian invasion of Ukraine in February 2022 caused major disruptions of societal functions, including health care. Patients receiving medications for opioid use disorder (MOUD) depend on receiving daily treatment and face a risk of withdrawal in case of medication supply disruption. MOUD are banned in Russia, making treatment continuation impossible in temporarily occupied areas. In this paper, we review the situation with MOUD delivery in Ukraine during the first year of the Russia-Ukraine war. Legislative changes and mobilization of efforts in the time of crisis ensured treatment continuation for thousands of patients. In areas controlled by Ukraine, most patients were receiving take-home doses for up to 30 days, some experienced temporary dosing reductions. Programs in temporarily occupied regions were shut down likely leading to abrupt withdrawal among many patients. At least 10% of patients have been internally displaced. One year into the war, the number of MOUD patients in governmental clinics of Ukraine increased by 17%, and the data suggest that the coverage of private clinics has also increased. But the risks for program stability remain high as the current medication supply relies on one manufacturing facility. Using lessons learned from the crisis, we provide recommendations for future response to minimize the risks of major adverse outcomes among patients treated for opioid use disorder.

Topics: Analgesics, Opioid; Antisocial Personality Disorder; Buprenorphine; Government; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Russia; Ukraine

Opioid use disorders can be treated with psychosocial interventions which aim to increase quality of life and minimize problems maintaining drug use. In addition, pharmacological treatment with opioid maintenance therapy (OMT) can help minimize morbidity and mortality. The principle for OMT is substituting to another opioid with a more favourable pharmacological profile, primarily buprenorphine or methadone. The first choice is buprenorphine in combination with naloxone. The aim of this review is to summarize current principles for handling patients in OMT.

Topics: Analgesics, Opioid; Buprenorphine; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Quality of Life

Syringe services programs (SSPs) provide a spectrum of health services to people who use drugs, with many providing referral and linkage to substance use disorder (SUD) treatment, and some offering co-located treatment with medications for opioid use disorder (MOUD). The objective of this study was to review the evidence for SSPs as an entry point for SUD treatment with particular attention to co-located (onsite) MOUD.. We performed a scoping review of the literature on SUD treatment for SSP participants. Our initial query in PubMed led to title and abstract screening of 3587 articles, followed by full text review of 173, leading to a final total of 51 relevant articles. Most articles fell into four categories: (1) description of SSP participants' SUD treatment utilization; (2) interventions to link SSP participants to SUD treatment; (3) post-linkage SUD treatment outcomes; (4) onsite MOUD at SSPs.. SSP participation is associated with entering SUD treatment. Barriers to treatment entry for SSP participants include: use of stimulants, lack of health insurance, residing far from treatment programs, lack of available appointments, and work or childcare responsibilities. A small number of clinical trials demonstrate that two interventions (motivational enhancement therapy with financial incentives and strength-based case management) are effective for linking SSP participants to MOUD or any SUD treatment. SSP participants who initiate MOUD reduce their substance use, risk behaviors, and have moderate retention in treatment. An increasing number of SSPs across the United States offer onsite buprenorphine treatment, and a number of single-site studies demonstrate that patients who initiate buprenorphine treatment at SSPs reduce opioid use, risk behaviors, and have similar retention in treatment to patients in office-based treatment programs.. SSPs can successfully refer participants to SUD treatment and deliver onsite buprenorphine treatment. Future studies should explore strategies to optimize the implementation of onsite buprenorphine. Because linkage rates were suboptimal for methadone, offering onsite methadone treatment at SSPs may be an appealing solution, but would require changes in federal regulations. In tandem with continuing to develop onsite treatment capacity, funding should support evidence-based linkage interventions and increasing accessibility, availability, affordability and acceptability of SUD treatment programs.

Topics: Buprenorphine; Case Management; Central Nervous System Stimulants; Humans; Methadone; Motivational Interviewing; Opiate Substitution Treatment; Opioid-Related Disorders

Prior authorization (PA) requirements for buprenorphine are associated with lower provision of the medication for the treatment of opioid use disorder (OUD). While Medicare plans have eliminated PA requirements for buprenorphine, many Medicaid plans continue to require them.. To describe and classify buprenorphine coverage requirements based on thematic analysis of state Medicaid PA forms.. This qualitative study used a thematic analysis of 50 states' Medicaid PA forms for buprenorphine between November 2020 and March 2021. Forms were obtained from the jurisdiction's Medicaid websites and assessed for features suggesting barriers to buprenorphine access. A coding tool was developed based on a review of a sample of forms, including fields for behavioral health treatment recommendations or mandates, drug screening requirements, and dosage limitations.. Outcomes included PA requirements for different buprenorphine formulations. Additionally, PA forms were evaluated for various criteria such as behavioral health, drug screenings, dose-related recommendations or mandates or patient education.. Among the total of 50 US states in the analysis, most states' Medicaid plans required PA for at least 1 formulation of buprenorphine. However, the majority did not require a PA for buprenorphine-naloxone. Four key themes of coverage requirements were identified: restrictive surveillance (eg, requirements for urine drug screenings, random drug screenings, pill counts), behavioral health treatment recommendations or mandates (eg, mandatory counseling or 12-step meeting attendance), interfering with or restricting medical decision-making (eg, maximum daily dosages of 16 mg, requiring additional steps for dosages higher than 16 mg), and patient education (eg, information about adverse effects and interactions with other medications). Eleven states (22%) required urine drug screenings, 6 states (12%) required random urine drug screenings, and 4 states (8%) required pill counts. Fourteen states' forms (28%) recommended therapy, and 7 (14%) required therapy, counseling, or participation in group sessions. Eighteen states (36%) specified dosage maximums; among them, 11 (22%) required additional steps for a daily dosage higher than 16 mg.. In this qualitative study of state Medicaid PA requirements for buprenorphine, themes were identified that included patient surveillance with drug screenings and pill counts, behavioral health treatment recommendations or mandates, patient education, and dosing guidance. These results suggest that state Medicaid plans' buprenorphine PA requirements for OUD are in conflict with existing evidence and may negatively affect states' efforts to address the opioid overdose crisis.

Topics: Aged; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Humans; Medicaid; Medicare; Opioid-Related Disorders; Prior Authorization; United States

Topics: Administration, Sublingual; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Drug-Related Side Effects and Adverse Reactions; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders

Treatment guidelines recommend regular urine drug testing (UDT) for persons initiating buprenorphine for opioid use disorder (OUD). However, little is known about UDT utilization. We describe state variation in UDT utilization and examine demographic, health, and health care utilization factors associated with UDT in Medicaid.. We used Medicaid claims and enrollment data from persons initiating buprenorphine treatment for OUD during 2016-2019 in 9 states (DE, KY, MD, ME, MI, NC, PA, WI, WV). The main outcome was at least 1 UDT within 180 days of buprenorphine initiation, the secondary outcome was at least 3. Logistic regression models included demographics, pre-initiation comorbidities, and health service use. State estimates were pooled using meta-analysis.. The study cohort included 162,437 Medicaid enrollees initiating buprenorphine. The percent receiving ≥1 UDT varied from 62.1% to 89.8% by state. In the pooled analysis, enrollees with pre-initiation UDT had much higher odds of ≥1 UDT after initiation (aOR=3.83, 3.09-4.73); odds were also higher for enrollees with HIV, HCV, and/or HBV infection (aOR=1.25, 1.05-1.48) or who initiated in later years (2018 v 2016: aOR=1.39, 1.03-1.89; 2019 v 2016: aOR=1.67, 1.24-2.25). The odds of having ≥3 UDT were lower with pre-initiation opioid overdose (aOR=0.79, 0.64-0.96) and higher with pre-initiation UDT (aOR=2.63, 2.13-3.25) or OUD care (aOR=1.35, 1.04-1.74). The direction of associations with demographics varied by state.. Rates of UDT increased over time and there was variability among states in UDT rates and demographic predictors of UDT. Pre-initiation conditions, UDT, and OUD care were associated with UDT.

Topics: Buprenorphine; Delivery of Health Care; Humans; Medicaid; Opiate Substitution Treatment; Opioid-Related Disorders; United States

People with opioid use disorder (OUD) are overrepresented in US correctional facilities and experience disproportionately high risk for illicit opioid use and overdose after release. A growing number of correctional facilities offer medication for OUD (MOUD), which is effective in reducing these risks. However, a recent evaluation found that <50% of those prescribed MOUD during incarceration continued MOUD within 30 days after release, demonstrating a need to improve post-release continuity of care. We describe available evidence on contingency management (CM), an intervention wherein patients receive incentives contingent on behavior change, to achieve this goal. A prior systematic review reported strong evidence in support of CM for increasing treatment adherence in MOUD programs, but the trials reviewed did not include incarcerated participants. Research on CM to increase treatment adherence among participants in the criminal justice system is limited with mixed findings. However, in comparison to the trials that supported CM's efficacy in the community, CM trials in the criminal justice system provided smaller rewards with greater delays in the delivery of rewards to patients, which likely contributed to null findings. Indeed, a prior meta-analysis demonstrates a dose-response relationship between the magnitude and immediacy of reward and CM effectiveness. Thus, CM involving larger and more immediately delivered rewards are likely necessary to improve MOUD adherence during the critical period following release from incarceration. Future research on the effectiveness and implementation of CM to improve MOUD retention after release from incarceration is warranted.

Topics: Analgesics, Opioid; Behavior Therapy; Buprenorphine; Drug Overdose; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Prisoners; Treatment Adherence and Compliance

Pharmacotherapeutic options for the treatment of opioid withdrawal are limited by abuse potential, adverse effects, and lack of availability of existing drugs. The results from previous clinical trials on tramadol are contradictory and non-conclusive; hence the present meta-analysis was conducted to evaluate the efficacy and safety of tramadol in the treatment of opioid withdrawal.. Reviewers extracted data from eight relevant clinical trials after a literature search on MEDLINE/PubMed, Cochrane databases, and clinical trial registries. Quality assessment was done using the risk-of-bias assessment tool, and the random-effects model was used to estimate effect size in frequentist and Bayesian approaches. Subgroup analysis, meta-regression, and sensitivity analysis were done as applicable. PRISMA guidelines were followed in reporting findings.. Tramadol significantly reduced opioid withdrawal scale score (SMD: -0.44; 95%CI: -0.76 to -0.13; PI: -1.54 to 0.71; p = 0.006) when all comparators were considered together in the frequentist approach but the reduction was non-significant in Bayesian approach. However, the subgroup analysis revealed no significant difference between tramadol and comparators like placebo (SMD: -1.12; 95%CI: -2.69 to 0.45) buprenorphine (SMD: -0.21; 95%CI: -0.43 to 0.01), clonidine (SMD: -0.26; 95%CI: -0.55 to 0.02) and methadone (SMD: -0.84; 95%CI: -1.78 to 0.10). Meta-regression showed non-significant associations between the SMD in opioid withdrawal score with the duration and dose of tramadol therapy. There were no significant differences in treatment retention at the end of studies between tramadol and comparators. Safety data in the individual studies were inadequate to analyze.. Authors conclude that the efficacy of tramadol in reducing opioid withdrawal symptoms is not significantly different from comparators with low certainty of evidence against placebo, moderate against methadone, whereas with high certainty of evidence against buprenorphine and clonidine.

Topics: Bayes Theorem; Buprenorphine; Clonidine; Humans; Methadone; Narcotics; Opioid-Related Disorders; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome; Tramadol

Collaborative care management (CCM) is an empirically driven model to overcome fractured medical care and improve health outcomes. While CCM has been applied across numerous conditions, it remains underused for chronic pain and opioid use. Our objective was to establish the state of the science for CCM approaches to addressing pain-related outcomes and opioid-related behaviors through a systematic review.. We identified peer-reviewed articles from Cochrane, Embase, PsycINFO, and PubMed databases from January 1, 1995, to October 31, 2022. Abstracts and full-text articles were screened for study inclusion, resulting in 18 studies for the final review. In addition, authors used the Patient-Centered Integrated Behavioral Health Care Principles and Tasks Checklist as a tool for assessing the reported CCM components within and across studies. We conducted this systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement.. Several CCM trials evidenced statistically significant improvements in pain-related outcomes (n = 11), such as pain severity and pain-related activity interference. However, effect sizes varied considerably across studies and some effects were not clinically meaningful. CCM had some success in targeting opioid-related behaviors (n = 4), including reduction in opioid prescription dose. Other opioid-related work focused on CCM to facilitate buprenorphine treatment for opioid use disorder (n = 2), including improved odds of receiving treatment and greater prevalence of abstinence from opioids and alcohol. Uniquely, several interventions used CCM to target mental health as a way to address pain (n = 10). Generally, there was moderate alignment with the CCM model.. CCM shows promise for improving pain-related outcomes, as well as facilitating buprenorphine for opioid use disorder. More robust research is needed to determine which aspects of CCM best support improved outcomes and how to maximize the effectiveness of such interventions.

Topics: Analgesics, Opioid; Buprenorphine; Chronic Pain; Humans; Opioid-Related Disorders; Primary Health Care

Buprenorphine is a safe and effective treatment for opioid use disorder but remains underutilized because a major challenge of conventional buprenorphine initiation (termed

Topics: Buprenorphine; Humans; Opioid-Related Disorders; Physicians; Primary Health Care; Substance Withdrawal Syndrome

Buprenorphine has become an important medication in the context of the ongoing opioid epidemic. However, complex pharmacologic properties and varying government regulations create barriers to its use. This narrative review is intended to facilitate buprenorphine use-including non-traditional initiation methods-by providers ranging from primary care providers to addiction specialists. This article briefly discusses the opioid epidemic and the diagnosis and treatment of opioid use disorder (OUD). We then describe the basic and complex pharmacologic properties of buprenorphine, linking these properties to their clinical implications. We guide readers through the process of initiating buprenorphine in patients using full agonist opioids. As there is no single recommended approach for buprenorphine initiation, we discuss the details, advantages, and disadvantages of the standard, low-dose, bridging-strategy, and naloxone-facilitated initiation techniques. We consider the pharmacology of, and evidence base for, buprenorphine in the treatment of pain, in both OUD and non-OUD patients. Throughout, we address the use of buprenorphine in children and adolescent patients, and we finish with considerations related to the settings of pregnancy and breastfeeding.

Topics: Adolescent; Analgesics, Opioid; Buprenorphine; Child; Female; Humans; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy

The opioid epidemic has resulted in a drastic increase in gestational exposure to opioids. Opioid-dependent pregnant women are typically prescribed medications for opioid use disorders ("MOUD"; e.g., buprenorphine [BUP]) to mitigate the harmful effects of abused opioids. However, the consequences of exposure to synthetic opioids, particularly BUP, during gestation on fetal neurodevelopment and long-term outcomes are poorly understood. Further, despite the known adverse effects of opioids on maternal care, many preclinical and clinical studies investigating the effects of gestational opioid exposure on offspring outcomes fail to report on maternal care behaviors. Considering that offspring outcomes are heavily dependent upon the quality of maternal care, it is important to evaluate the effects of gestational opioid exposure in the context of the mother-infant dyad. This review compares offspring outcomes after prenatal opioid exposure and after reduced maternal care and integrates this information to potentially identify common underlying mechanisms. We explore whether adverse outcomes after gestational BUP exposure are due to direct effects of opioids in utero, deficits in maternal care, or a combination of both factors. Finally, suggestions for improving preclinical models of prenatal opioid exposure are provided to promote more translational studies that can help to improve clinical outcomes for opioid-dependent mothers.

Topics: Analgesics, Opioid; Buprenorphine; Female; Humans; Maternal Behavior; Mothers; Opioid-Related Disorders; Pregnancy

Opioid use disorder is a worldwide societal problem and public health burden. Strategies for treating opioid use disorder can be divided into those that target the opioid receptor system and those that target non-opioid receptor systems, including the dopamine and glutamate receptor systems. Currently, the clinical drugs used to treat opioid use disorder include the opioid receptor agonists methadone and buprenorphine, which are limited by their abuse liability, and the opioid receptor antagonist naltrexone, which is limited by poor compliance. Therefore, the development of effective medications with lower abuse liability and better potential for compliance is urgently needed. Based on recent advances in the understanding of the neurobiological mechanisms underlying opioid use disorder, potential treatment strategies and targets have emerged. This review focuses on the progress made in identifying potential targets and developing medications to treat opioid use disorder, including progress made by our laboratory, and provides insights for future medication development. LINKED ARTICLES: This article is part of a themed issue on Advances in Opioid Pharmacology at the Time of the Opioid Epidemic. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.7/issuetoc.

Topics: Analgesics, Opioid; Buprenorphine; Humans; Methadone; Naltrexone; Opioid-Related Disorders

Topics: Analgesics, Opioid; Buprenorphine; COVID-19 Drug Treatment; Female; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pandemics; Pregnancy; Pregnancy Complications, Infectious; SARS-CoV-2; Systematic Reviews as Topic; Telemedicine; United States

There is mounting evidence that opioid use disorder is experienced differently by people of different genders and race/ethnicity groups. Similarly, in the US access to specific medications for opioid use is limited by gender and race/ethnicity. This study aims to evaluate if gender or race/ethnicity is associated with different rates of treatment retention in the US, for each of three medications used to treat opioid use disorder.. A systematic search was conducted using PubMed, CINHAL, and PsychINFO, databases. All studies that provided a ratio of those retained in treatment at a specified time in terms of gender and/or race/ethnicity and medication were included. Variables were created to assess the effects of time in treatment, recruited sample, required attendance at concurrent psychosocial treatment, and adherence to strict rules of conduct for continuation in treatment on retention. Meta-analytical and meta-regression methods were used to compare studies on the ratio of those who completed a specific time in treatment by race/ethnicity group and by gender.. Nineteen articles that provided the outcome variable of interest were found (11 buprenorphine, six methadone, and two naltrexone). Meta-analyses found that treatment retention was similar for all gender and racial/ethnic groups for all three medications. Meta-regression found that those of the African American group who were recruited into buprenorphine treatment were retained significantly longer than African Americans in buprenorphine treatment who were studied retrospectively. Also, both genders had significantly lower retention in methadone treatment when there was the additional requirement of psychosocial therapy.

Topics: Analgesics, Opioid; Buprenorphine; Ethnicity; Female; Humans; Male; Methadone; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Retrospective Studies; United States

Neonates born to mothers taking opioids during pregnancy are at risk for neonatal opioid withdrawal syndrome (NOWS), for which there is no recognized standard approach to care. Nonpharmacologic treatment is typically used as a first-line approach for management, and pharmacologic treatment is added when clinical signs are not responding to nonpharmacologic measures alone. Although morphine and methadone are the most commonly used pharmacotherapies for NOWS, buprenorphine has emerged as a treatment option based on its pharmacologic profile and results from initial single site clinical trials. The objective of this report is to provide an overview of NOWS including a summary of ongoing work in the field and to review the state of the science, knowledge gaps, and practical considerations specific to the use of buprenorphine for the treatment of NOWS as discussed by a panel of experts during a virtual workshop hosted by the National Institutes of Health.

Topics: Analgesics, Opioid; Buprenorphine; Female; Humans; Infant; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy

Topics: Buprenorphine; COVID-19 Drug Treatment; Humans; Opioid-Related Disorders; Pandemics; Telemedicine

This review synthesizes the literature on the perspectives and experiences of people who use drugs to better understand motivations and behaviors related to the extramedical use and diversion of buprenorphine. Given the particular social construction of buprenorphine against methadone, and the centrality of concerns around extramedical use in delivering opioid agonist therapies, a focus on extramedical buprenorphine use can provide an important lens through which to analyze treatment for opioid use disorder. This review is framed within persistent tensions between potential harm-producing versus harm-reducing effects of extramedical use that have long been described for opioid agonist therapies.. The research team conducted a qualitative meta-synthesis based on a systematic search of eight databases as well as hand searching. The review includes all primary qualitative and mixed-methods studies related to the perspectives and experiences of people who use drugs on extramedical buprenorphine use. The study team carried out three rounds of qualitative coding using NVivo 12, and constructivist grounded theory and the constant comparative method informed the synthesis.. The review includes twenty-one studies. Findings are organized into the following three themes: 1) the experiences of people who use drugs (PWUD) with extramedical use of buprenorphine and their motivations to engage in it (including the desire to self-medicate and achieve "stability", to manage ongoing use of other opioids, and to "get high"); 2) the relationship between extramedical use and formal medical opioid agonist therapy programs; and 3) the established drug economy of extramedical buprenorphine.. The review identified varied and often divergent perspectives and experiences with extramedical buprenorphine use. An examination of the reported "normalizing" effects of extramedical buprenorphine suggests this practice as extending medicalized discipline beyond the clinical environment. Taken together, these findings identify a need to move beyond the tension of harm-reducing versus harm-producing effects toward forms of health care and promotion that focus on the needs, perspectives, and priorities of people who use drugs.

Topics: Analgesics, Opioid; Buprenorphine; Humans; Methadone; Motivation; Opiate Substitution Treatment; Opioid-Related Disorders

The opioid epidemic has resulted in increased opioid-related critical care admissions, presenting challenges in acute pain management. Limited guidance exists in the management of critically ill patients with opioid use disorder (OUD). This narrative review provides the intensive care unit clinician with guidance and treatment options, including nonopioid analgesia, for patients receiving medications for OUD and for patients actively misusing opioids. Verification and continuation of the patient's outpatient medications for OUD regimen, specifically buprenorphine and methadone formulations; assessment of pain and opioid withdrawal; and treatment of acute pain with nonopioid analgesia, nonpharmacologic strategies, and short-acting opioids as needed, are all essential to adequate management of acute pain in patients with OUD. A multidisciplinary approach to treatment and discharge planning in patients with OUD may be beneficial to engage patients with OUD early in their hospital stay to prevent withdrawal, stabilize their OUD, and reduce the risk of unplanned discharge and other associated morbidity.

Topics: Acute Pain; Analgesics, Non-Narcotic; Analgesics, Opioid; Buprenorphine; Critical Care; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pain Management

Opioid use disorder (OUD) is commonly seen in older adults in primary care offices. OUD when left untreated, often leads to overdose deaths, emergency department visits, and hospitalizations due to opioid-related adverse effects, especially respiratory and central nervous system depression. Primary care providers are on the front lines of efforts for its prevention, early detection, and treatment. This includes using the lowest doses of opioids for the shortest possible time for management of pain, routine screening, brief intervention, opioid withdrawal management, prescription of naloxone to prevent overdose death, and treatment with medications and psychosocial interventions for OUD. Referral to addiction treatment centers may be needed in complex cases. This review explores the epidemiology, screening, as well as management of OUD as it pertains to the elderly population.

Topics: Aged; Analgesics, Opioid; Buprenorphine; Humans; Opioid-Related Disorders; Pain; Primary Health Care

Buprenorphine formulations (including buprenorphine/naloxone) are effective treatments of pain and opioid use disorder (OUD). Historically, perioperative management of patients prescribed buprenorphine involved abstinence from buprenorphine sufficient to allow for unrestricted mu-opioid receptor availability to full agonist opioid (FAO) treatment. Evidence is mounting that a multimodal analgesic strategy, including simultaneous administration of buprenorphine and FAO, nonopioid adjuncts such as acetaminophen and nonsteroidal anti-inflammatory drugs, and regional anesthesia, is a safe and effective perioperative strategy for the patient prescribed long-term buprenorphine treatment of OUD. This strategy will likely simplify management and more seamlessly provide continuous buprenorphine treatment of OUD after hospital discharge.

Topics: Acetaminophen; Aged; Analgesics, Non-Narcotic; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Arthroplasty, Replacement, Hip; Buprenorphine; Combined Modality Therapy; Drug Compounding; Female; Humans; Interdisciplinary Communication; Male; Opiate Substitution Treatment; Opioid-Related Disorders; Pain; Pain Management; Pain, Postoperative; Perioperative Care; Receptors, Opioid, mu

This comprehensive review on opioids summarizes the scope of the current opioid epidemic, the diagnosis and treatment of opioid use disorder, and the medical and psychiatric complications of opioid use.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Comorbidity; Disease Management; Drug Overdose; Female; Fentanyl; Harm Reduction; Humans; Male; Mental Disorders; Methadone; Middle Aged; Naltrexone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Practice Guidelines as Topic; Prevalence

The relative neurocognitive effects of the two most common opioid agonist treatments (OAT; buprenorphine and methadone) for opioid use disorder (OUD) are poorly understood. The aim of this systematic review is to examine the neurocognitive effects of OAT (buprenorphine and methadone) and the clinical and sociodemographic characteristics of study samples.. The research team queried PubMed, PsycINFO and Cochrane Reviews for articles (01/1980-01/2020) with terms related to neurocognitive testing in adults (age ≥ 18) prescribed OAT. The team extracted neurocognitive data and grouped them by domain (e.g., executive functioning, learning/memory), and assessed study quality.. The search retrieved 2341 abstracts, the team reviewed 278 full articles, and 32 met inclusion criteria. Of these, 31 were observational designs and one was an experimental design. Healthy controls performed better across neurocognitive domains than OAT-treated persons (buprenorphine or methadone). Compared to those with active OUD, OAT-treated persons had better neurocognition in various domains. However, in seven studies comparing buprenorphine- and methadone-treated persons, buprenorphine was associated with better neurocognition than was methadone, with moderate to large effect sizes in executive functioning, attention/working memory, and learning/memory. Additionally, OAT research underreports clinical characteristics and underrepresents Black and Latinx adults, as well as women.. Findings suggest that compared to active opioid use, both buprenorphine and methadone treatment are associated with better neurocognitive functioning, but buprenorphine is associated with better executive functioning, attention/working memory, and learning/memory. These findings should be interpreted with caution given widespread methodological heterogeneity, and limited representation of ethnoracially diverse adults and women. Rigorous longitudinal comparisons with more diverse, better characterized samples will help to inform treatment and policy recommendations for persons with OUD.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Female; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders

The ongoing overdose crisis continues to adversely affect adolescents and young adults (AYAs) and has led to numerous preventable deaths. Medications for opioid use disorder (MOUD), such as methadone, buprenorphine, and naltrexone, have the potential to reduce opioid use and associated harms; however, there are concerns that AYAs lack access to these potentially life-saving medications.. To systematically review peer-reviewed literature on MOUD access and associated factors to synthesize strategies that can improve MOUD access for AYAs who use opioids.. The MEDLINE, Embase, PsycINFO, CINAHL, Sociological Abstracts, Web of Science, and Global Dissertations & Theses databases were searched from database inception until May 3, 2021. English, French, Russian, or Spanish peer-reviewed studies that evaluated the availability, prescription receipt, or initiation of MOUD were eligible for inclusion.. This systematic review identified 37 cohort (n = 17), cross-sectional (n = 15), and qualitative (n = 5) studies that accounted for 179 785 AYAs (mean [SD] age, 24.4 [3.9] years; 148 779 [85%] were female; 67 771 [84%] were White) and examined access to methadone (30 studies), buprenorphine (26 studies), and naltrexone (10 studies). Findings reinforce concerns that AYAs were less likely to access MOUD and suggest that adolescents were more likely to receive naltrexone or buprenorphine-naloxone, which have a lower potential for abuse, in comparison with young adults. This review also identified other factors that were associated with MOUD access, including criminal justice involvement, residing in the US South, living in a limited-income area, Black race, and Hispanic or Latino ethnicity, suggesting ways in which treatment services may be improved to increase MOUD access and meet the treatment goals of AYAs.. This systematic review found gaps in MOUD access between AYAs and non-AYA populations in addition to differences in MOUD access between adolescents and young adults. Considering that existing clinical guidelines recommend the use of MOUD among AYAs, and in light of the increasing number of opioid toxicity deaths, there is a need to improve MOUD access among AYAs by reducing barriers to MOUD and providing AYAs with a continuum of health and social supports alongside MOUD. Future research into ways to encourage MOUD uptake among AYAs may improve the treatment and health outcomes for this population.

Topics: Adolescent; Adult; Analgesics, Opioid; Buprenorphine; Cross-Sectional Studies; Female; Health Services Accessibility; Humans; Male; Methadone; Naltrexone; Opiate Substitution Treatment; Opioid-Related Disorders; Young Adult

Opioid use disorder is a public health problem and treatment variability, coverage and accessibility poses some challenges. The study's objective is to review the impact of interim opioid agonist treatment (OAT), a short-term approach for patients awaiting standard OAT, in terms of treatment retention, access to standard OAT, quality of life and satisfaction with treatment.. We conducted a systematic review searching MEDLINE, EMBASE, PsycINFO, and CENTRAL up to May 2020. Due to variability between studies and outcome measurements, we did not pool effect estimates and reported a narrative synthesis of findings rating their certainty according to GRADE.. We identified 266 unique records and included five randomized trials with some limitations in risk of bias and one observational study limited by selection bias. The studies assessed similar approaches to interim OAT but were compared to three different control conditions. Four studies reported on treatment retention at 4 months or less with no significant differences between interim OAT and waiting list or standard OAT. Two studies reported treatment retention at 12 months with no differences between interim OAT and standard OAT. Two trials assessed access to standard OAT and showed significant differences between interim OAT and waiting list for standard OAT. We rated the quality of evidence for these outcomes as moderate due to the impact of risk of bias. Data on quality of life or satisfaction with treatment was suboptimal.. Interim OAT is likely more effective than a waiting list for standard OAT in access to treatment, and it is probably as effective as standard OAT regarding treatment retention. PROSPERO registration CRD42018116269.

Topics: Analgesics, Opioid; Buprenorphine; Humans; Methadone; Observational Studies as Topic; Opiate Substitution Treatment; Opioid-Related Disorders; Quality of Life

Rates of at-risk opioid use, opioid use disorder, and opioid overdose remain alarmingly high. There are medications that can be used to treat opioid use disorder, including methadone, buprenorphine, and naltrexone, although access to care remains difficult. This review seeks to provide advanced practice psychiatric nurses (APPNs) with an overview of buprenorphine prescribing, with an emphasis on novel, long-acting delivery systems.. APPNs should be familiar with best practices regarding buprenorphine prescribing. Some patients may benefit from long-acting delivery methods, such as subdermal implants, or subcutaneous injections.. APPNs can reduce barriers to buprenorphine access and should be familiar with best practices related to buprenorphine prescribing.

Topics: Analgesics, Opioid; Buprenorphine; Humans; Methadone; Naltrexone; Opiate Substitution Treatment; Opioid-Related Disorders

Appropriate clinical management of opioid withdrawal is a crucial bridge to long-term treatment for opioid use disorder (OUD), because it is a high-risk time for potential opioid overdose and relapse. We provide a narrative review of evidence-based opioid withdrawal management strategies applicable to a variety of treatment settings and geographies. The goals of opioid withdrawal management include relieving suffering associated with withdrawal, providing appropriate diagnosis and screening, engaging patients in initiation of OUD treatment, and using harm reduction strategies, all guided by a patient-centered approach to care. In addition, we discuss complex cases, relapse prevention strategies, and new developments in opioid withdrawal management.

Topics: Analgesics, Opioid; Buprenorphine; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Secondary Prevention; Substance Withdrawal Syndrome

Opioid use disorder (OUD) is a global public health concern. The standard of care for OUD involves treatment using medications such as buprenorphine, methadone, or naltrexone. No known review exists to assess the contextual factors associated with medication for opioid use disorder (MOUD) in the Arab World. This systematic review serves as an implementation science study to address this research gap and improve the uptake of MOUD in the Arab World.. Systematic searches of Medline, PsycINFO, and EMBASE, and a citation analysis, were used to identify peer-reviewed articles with original data on MOUD in the Arab World. Quality assessment was conducted using the CASP appraisal tools, and main findings were extracted and coded according to the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework.. 652 research articles were identified, and 10 met inclusion criteria for final review. Four studies considered health-systems aspects of MOUD administration, such as cost-effectiveness, the motivations for and impact of national MOUD policies, the types of social, political, and scientific advocacy that led to the adoption of MOUD in Arab countries, and the challenges limiting its wide-scale adoption in the Arab World. Six papers considered MOUD at individual and group patient levels by evaluating patient quality of life, addiction severity, patient satisfaction, and patient perspectives on opioid agonist therapy.. Despite financial and geographic barriers that limit access to MOUD in the Arab World, this review found MOUD to be cost-effective and associated with positive health outcomes for OUD patients in the Arab World. MOUD can be successfully established and scaled to the national level in the Arab context, and strong coalitions of health practitioners can lobby to establish MOUD programs in Arab countries. Still, the relative novelty of MOUD in this context precludes an abundance of research to address its long-term delivery in the Arab World.

Topics: Analgesics, Opioid; Arab World; Buprenorphine; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pharmaceutical Preparations; Quality of Life

Opioid use disorder is a significant global issue and the rate of opioid use in women of childbearing age and pregnant women is on the rise. Whilst the adverse general health, cognitive, and neurodevelopmental outcomes of in utero exposure to opioids have been explored, there is a lack of prospective, controlled, longitudinal research into the ophthalmic outcomes. Existing research suggests that there is an association between prenatal exposure and future risk of abnormalities in visual functioning. This systematic review and meta-analysis analysed studies that measured eye abnormalities in infants or children exposed to opioid maintenance therapy in utero and compared them to non-opioid exposed controls. After considering the clinical findings, limitations of the studies, confounding factors, and quantitative analysis, a causal relationship between in utero opioid exposure and future eye abnormalities could not be confirmed. The implications of the findings and their clinical relevance, in addition to identified gaps for future research are also discussed in this paper.

Topics: Analgesics, Opioid; Buprenorphine; Child; Female; Humans; Infant; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Prenatal Exposure Delayed Effects

The American opioid epidemic has necessitated the search for safe and effective means of treatment for opioid use disorder (OUD). Medication-assisted treatment (MAT) encompasses select medications that are proven effective treatments for OUD. Understanding the mechanisms of action, indications, and implementation of MAT is paramount to increasing its availability to all individuals struggling with opioid addiction.. This review is based on an educational series that aims to educate healthcare providers and ancillary healthcare members on the use of MAT for the treatment of OUD.. The database PubMed was utilized to retrieve articles discussing the implementation of MAT. Boolean operators and Medical Subject Headings (MeSHs) were applied including: MAT and primary care, MAT and telehealth, methadone, buprenorphine, naltrexone, MAT and osteopathic, MAT and group therapy, and MAT and COVID-19.. Three medications have been approved for the treatment of OUD: methadone, naltrexone, and buprenorphine. Identifying ways to better treat and manage OUD and to combat stigmatization are paramount to dismantling barriers that have made treatment less accessible. Studies suggest that primary care providers are well positioned to provide MAT to their patients, particularly in rural settings. However, no study has compared outcomes of different MAT models of care, and more research is required to guide future efforts in expanding the role of MAT in primary care settings.. The coronavirus disease 2019 (COVID-19) pandemic has led to changes in the way MAT care is managed. Patients require a novel point-of-care approach to obtain care. This review will define the components of MAT, consider the impact of MAT in the primary care setting, and identify barriers to effective MAT. Increasing the availability of MAT treatment will allow for greater access to comprehensive treatment and will set the standard for accessibility of novel OUD treatment in the future.

Topics: Buprenorphine; COVID-19; COVID-19 Drug Treatment; Humans; Methadone; Naltrexone; Opiate Substitution Treatment; Opioid-Related Disorders; United States

Buprenorphine possesses many unique attributes that make it a practical agent for adults and adolescents with opioid use disorder (OUD) and/or acute or chronic pain. Sublingual buprenorphine has been the standard of care for treating OUD, but its use in pain management is not as clearly defined. Current practice guidelines recommend a period of mild-to-moderate withdrawal from opioids before transitioning to buprenorphine due to its ability to displace full agonists from the μ-opioid receptor. However, this strategy can lead to negative physical and psychological outcomes for patients. Novel initiation strategies suggest that concomitant administration of small doses of buprenorphine with opioids can avoid the unwanted withdrawal associated with buprenorphine initiation. We aim to systematically review the buprenorphine initiation strategies that have emerged in the last decade. Embase, PubMed, and Cochrane Databases were searched for relevant literature. Studies were included if they were published in the English language and described the transition to buprenorphine from opioids. Data were collected from each study and synthesized using descriptive statistics. This review included 7 observational studies, 1 feasibility study, and 39 case reports/series which included 924 patients. The strategies utilized between the literature included traditional initiation (47.9%), microdosing with various buprenorphine formulations (16%), and miscellaneous methods (36.1%). Traditional initiation and microdosing initiation were compared in the data synthesis and analysis; miscellaneous methods were omitted given the high variability between methods. Overall, 95.6% of patients in the traditional initiation group and 96% of patients in the microdosing group successfully rotated to sublingual buprenorphine. Initiation regimens can vary widely depending on patient-specific factors and buprenorphine formulation. A variety of buprenorphine transition strategies are published in the literature, many of which were effective for patients with OUD, pain, or both.

Topics: Adolescent; Adult; Analgesics, Opioid; Buprenorphine; Chronic Pain; Humans; Observational Studies as Topic; Opioid-Related Disorders; Pain Management

Several pharmacotherapeutic interventions are available for maintenance treatment for opioid-related disorders. However, previous meta-analyses have been limited to pairwise comparisons of these interventions, and their efficacy relative to all others remains unclear. Our objective was to unify findings from different healthcare practices and generate evidence to strengthen clinical treatment protocols for the most widely prescribed medications for opioid-use disorders.. We searched Medline, EMBASE, PsycINFO, CENTRAL, and ClinicalTrials.gov for all relevant randomized controlled trials (RCT) from database inception to February 12, 2022. Primary outcome was treatment retention, and secondary outcome was opioid use measured by urinalysis. We calculated risk ratios (RR) and 95% credible interval (CrI) using Bayesian network meta-analysis (NMA) for available evidence. We assessed the credibility of the NMA using the Confidence in Network Meta-Analysis tool.. Seventy-nine RCTs met the inclusion criteria. Due to heterogeneity in measuring opioid use and reporting format between studies, we conducted NMA only for treatment retention. Methadone was the highest ranked intervention (Surface Under the Cumulative Ranking [SUCRA] = 0.901) in the network with control being the lowest (SUCRA = 0.000). Methadone was superior to buprenorphine for treatment retention (RR = 1.22; 95% CrI = 1.06-1.40) and buprenorphine superior to naltrexone (RR = 1.39; 95% CrI = 1.10-1.80). However, due to a limited number of high-quality trials, confidence in the network estimates of other treatment pairs involving naltrexone and slow-release oral morphine (SROM) remains low.. All treatments had higher retention than the non-pharmacotherapeutic control group. However, additional high-quality RCTs are needed to estimate more accurately the extent of efficacy of naltrexone and SROM relative to other medications. For pharmacotherapies with established efficacy profiles, assessment of their long-term comparative effectiveness may be warranted.. This systematic review has been registered with PROSPERO (https://www.crd.york.ac.uk/prospero) (identifier CRD42021256212).

Topics: Analgesics, Opioid; Buprenorphine; Humans; Methadone; Morphine; Naltrexone; Network Meta-Analysis; Opioid-Related Disorders; Randomized Controlled Trials as Topic

This systematic review synthesizes evidence on both the effects and perspectives of the use of novel long-acting injectable buprenorphine (LAIB) as part of medication-assisted treatment (MAT) and its impact on social determinants of health (SDH), specifically abstinence, accessibility, employment, forensic matters, and gender and social relationships via a framework approach.. The study team searched three databases between January 2010 and June 2020 to identify English-language original research published in peer reviewed journals. This search yielded 9253 papers. A comprehensive search followed by 67 full text publication screenings by two independent reviewers yielded 15 papers meeting inclusion criteria. The study included three randomized control trials, one open label safety study, two case series, and six qualitative papers examining patient perspectives toward the LAIB prior to use. The team assessed the quality of studies via standardized quality assessment tools.. The LAIB was positively associated with improvements in abstinence, accessibility, employment, social relationships, and forensic matters. Limited evidence exists on gender equity within the current literature. The qualitative papers highlighted the importance of patients' preferences and individualization of treatment planning to ensure the success of MAT.. The quality of evidence was rated as medium or high risk of bias, which does limit interpretation of the results. Overall, the LAIB was positively associated with SDH and should be offered as part of MAT in alignment with the recovery model. Future research should evaluate the implementation and longitudinal impacts of LAI buprenorphine compared to treatment as usual (TAU).

Topics: Buprenorphine; Humans; Opioid-Related Disorders; Social Determinants of Health

People with opioid use disorder (OUD) experience lower quality of life (QoL) than the general population, but buprenorphine treatment for OUD could help improve QoL of individuals with OUD. Thus, we conducted a systematic review and meta-analysis of the impact of buprenorphine on QoL among people with OUD.. Seven databases were searched through August 2020. We included English-language studies with pre- and post- QoL assessments internationally. Standardized mean differences were calculated for five domains of QoL measures using a random effects model for correlated effect sizes with robust variance estimation. Meta-regression was used to assess variation in effect sizes based on QoL domain, treatment, and patient factors.. Twenty-one peer-reviewed studies from twelve countries were included. Only three studies included a no-treatment control group and five studies assigned groups using randomization. Improvements between baseline and follow-up were observed across all five domains of QoL measures (overall, physical, psychological, social, and environmental). The certainty of evidence was low for all domains of QoL, and very low for environmental QoL. We did not observe differences in the effect of buprenorphine on QoL by QoL domain, duration, dose, participant characteristics, or adjunctive counseling services.. Buprenorphine treatment likely improves overall, physical, psychological, and social QoL, and may improve environmental QoL, for individuals with OUD. Findings are limited by study quality, including lack of control groups and incomplete reporting. Future studies with more rigorous methods and comprehensive reporting are needed.

Topics: Analgesics, Opioid; Buprenorphine; Cognition; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Quality of Life

Buprenorphine precipitated opioid withdrawal (BPOW) is an uncommon complication of buprenorphine initiation in the emergency department (ED), but it can produce significant discomfort and be distressing to patients. As EDs continue to care for those with opioid use disorder (OUD), clinicians should be aware of how to prevent and treat BPOW.. This narrative review provides an evidence-based update of the epidemiology, prevention strategies, and management of BPOW for the emergency clinician.. BPOW is a rapid worsening of opioid withdrawal symptoms upon initiating buprenorphine. BPOW can be prevented by waiting for the onset of moderate Clinical Opioid Withdrawal Scale (COWS) > 13 opioid withdrawal symptoms and a sufficient amount of time since last full opioid agonist use before buprenorphine administration. Risk factors for BPOW include chronic fentanyl use, methadone use, and concurrent benzodiazepine use. Alternative dosing strategies such as low-dose or "microdosing" and high-dose or "macrodosing" are options for buprenorphine that may impact the development of BPOW. The strategy of treating BPOW with more buprenorphine has a pharmacological basis and has been effective in case reports. Additional management is symptom-based and supportive. Although most cases have a benign course, patients may be significantly less likely to use buprenorphine for OUD in the future or seek care for substance use disorder.. Appropriate initiation of buprenorphine is important to prevent BPOW. Dosing buprenorphine should be based on the patient's patterns of opioid use and response to therapy. Management of BPOW should be symptom-based but include additional buprenorphine and adjunctive medications.

Topics: Analgesics, Opioid; Buprenorphine; Humans; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Substance Withdrawal Syndrome

Suboxone (buprenorphine-naloxone) is an opioid product approved in the US and Canada for the treatment of opioid use disorder. The drug is considered an important response to the opioid overdose epidemic with consistent calls for wider prescribing and deregulation. The history of Suboxone regulation in Canada has not been critically examined. Part of the rationale for doing so stems from the US regulatory experience, with documented irregularities, or what some have called abuses, that support profit-making by Suboxone's manufacturers. This regulatory analysis allows us to determine how opportunities to address health crises through drug innovation are managed at a federal level. We used public drug and patent registries to critically examine Suboxone's Canadian history. First, we investigated Suboxone's entry into the Canadian market to understand how it achieved market exclusivity. Second, we examined Health Canada's risk mitigation process to address extramedical use and diversion to understand the intersection of regulation and brand promotion. Insights from these two analyses were then extended to the recent approval of two related buprenorphine-containing products and their specific pathways to Canadian market exclusivity. We identified inconsistencies in Suboxone's regulatory history that suggest Health Canada's functions of health protection and promotion were compromised in favour of an "innovations" agenda that supports profit-making. Despite six years of market exclusivity in Canada, there was no evidence suggesting Suboxone achieved formal exclusivity (i.e., through patent or data protection). Health Canada's process to address safety concerns of Suboxone were compromised by reliance on the manufacturer to carry out post-market education, allowing the manufacturer to create and market a branded "education" program for its product. Similar inconsistencies have afforded market exclusivity for two related products despite marginal innovation. These analyses reveal a case of permissive regulation, where principles of health protection are compromised by economic imperatives. Such a regulatory approach has the potential to adversely impact public health due to unnecessarily high costs for medicines deemed essential to stem a major health crisis. Alternative pharmaceutical policies are urgently needed to safely and efficiently expand treatment access for opioid use disorder.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Canada; Humans; Opioid-Related Disorders

Illicit opioid use in pregnancy is associated with adverse maternal, neonatal, and childhood outcomes. Opioid substitution is recommended, but whether methadone or buprenorphine is the optimal agent remains unclear.. We searched EMBASE, PubMed, Web of Science, Scopus, Open Gray, CINAHL and the Cochrane Central Registry of Controlled Trials (CENTRAL) from inception to April 2020 for randomized controlled trials (RCTs) and cohort studies comparing methadone and buprenorphine treatment for opioid-using mothers. Included studies assessed maternal and or neonatal outcomes. We used random-effects meta-analyses to estimate summary measures for outcomes and report these separately for RCTs and cohort studies.. Of 408 abstracts screened, 20 papers were included (4 RCTs, 16 cohort, 223 and 7028 participants respectively). All RCTs (4/4) had a high risk of bias and median (IQR) Newcastle Ottawa Scale for cohort studies was 7.5 (6-9). In both RCTs and cohort studies, buprenorphine was associated with; greater offspring birth weight (weighted mean difference [WMD] 343 g (95% CI: 40-645 g) in RCT and 184 g (95% CI: 121-247 g) in cohort studies); body length at birth (WMD 2.28 cm (95% CI: 1.06-3.49 cm) in RCTs and 0.65 cm (95% CI: 0.31-0.98 cm) in cohort studies); and reduced risk of prematurity (risk ratio [RR] 0.41 (95% CI: 0.18-0.93) in RCTs and 0.63 [95% CI: 0.53-0.75] in cohort studies) when compared to methadone. All other clinical outcomes were comparable.. Compared to methadone, buprenorphine was consistently associated with improved birthweight and gestational age, however given potential biases, results should be interpreted with caution.

Topics: Analgesics, Opioid; Buprenorphine; Child; Female; Humans; Infant, Newborn; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy

Opioid use disorder (OUD) has become increasingly prevalent among hospitalized patients in the United States and globally. As its prevalence increases, this provides a valuable opportunity for clinicians in the hospital setting to engage and initiate management and treatment of OUD.. This article aims to provide hospitalists and other clinicians working in the hospital with a narrative review of the management of opioid withdrawal and the initiation of medications for opioid use disorder (MOUD) in the hospital and provide an update on a novel low dose approach to buprenorphine induction (also commonly referred to as the 'microinduction' method).. Authors performed a narrative review of the literature.. Management can initially include treating withdrawal symptoms with opioids as well as with a combination of non-opioid medications such as alpha 2 agonists, benzodiazepines, and/or antiemetics as needed. Besides simply managing withdrawal symptoms, clinicians can further improve the care of patients with OUD through initiating maintenance treatment with MOUD, ideally with opioids used in the initial management of withdrawal. Opioid detoxification is an inferior method of primary treatment and is associated with relapse and poor outcomes. In contrast, treatment with MOUD using methadone or buprenorphine is associated with superior treatment outcomes and reduced relapse compared to detoxification alone. Treatment with MOUD using methadone or buprenorphine can be successfully used in the hospital setting. A novel low dose approach to buprenorphine induction may be useful in minimizing precipitated withdrawals in patients who have recently used or received opioids, which makes this an attractive option in the hospital where patients are frequently on opioids for acutely painful conditions. The hospital setting also provides a valuable opportunity for clinicians to address harm reduction in patients with OUD. Finally, clinicians can improve the long-term outcomes of patients with OUD by ensuring a smooth discharge with adequate and timely follow-up.. Proper management of opioid withdrawal and initiation of MOUD in the hospital can improve outcomes in patients with OUD.

Topics: Analgesics, Opioid; Antiemetics; Benzodiazepines; Buprenorphine; Hospitals; Humans; Methadone; Naltrexone; Opiate Substitution Treatment; Opioid-Related Disorders; Recurrence; Substance Withdrawal Syndrome; United States

Rates of opioid misuse and opioid use disorder have been increasing in recent years. Buprenorphine has emerged as an appealing medication for its use not only as treatment for opioid use disorder, but also as an opioid for chronic pain that has a ceiling effect on risks associated with opioid therapy. As other opioid prescribing decreases, buprenorphine prescribing continues to increase. As a result, it is imperative to understand the safety and efficacy of its use in special populations. This review article will explore the safety and efficacy of buprenorphine when used in subjects with hepatic and renal impairment, the elderly, and pregnant women. While manufacturer labeling for buprenorphine products may caution against their use in these populations, further examination of available data indicates that buprenorphine can be used safely and effectively for both chronic pain and/or opioid use disorder in all four of these populations.

Topics: Aged; Analgesics, Opioid; Buprenorphine; Chronic Pain; Female; Humans; Opioid-Related Disorders; Practice Patterns, Physicians'; Pregnancy

Side effects of medications for opioid use disorder (MOUD) such as weight gain contribute to their stigma. Substantial evidence suggests that women have a more severe side effect profile to MOUD than men, and concerns about weight gain during treatment are prevalent. However, the few studies reporting sex differences in weight gain during treatment show conflicting results and are restricted to methadone. In addition, little is known about possible sex differences in weight gain to buprenorphine, which is the most commonly prescribed MOUD in the United States.. To address these issues, we performed a systematic review and meta-analysis on the few studies reporting longitudinal data on sex differences in body mass index (BMI) gain during methadone treatment (Study 1). In a separate study, we also re-analyzed data from trial CTN-0030 of the National Institute on Drug Abuse Clinical Trial Network (NIDA CTN), which involved a 12-week buprenorphine treatment regimen (Study 2; n = 360; 209 Male, 151 Female).. For Study 1, across all papers reporting longitudinal data (k = 4, n = 362 OUD patients), there were BMI increases that ranged from 2.2 to 5.4 BMI after at least one year of methadone treatment, but there were no significant sex differences in BMI increases (Standardized Mean Difference, Female > Male = 0.352, SE =0.270; 95 % CI = [-0.18 0.88]; p = .193). Study 2 showed no significant differences in weight before and after 12 weeks of buprenorphine treatment nor did it show sex differences in weight change with treatment (β = 2.34, p = .511).. These analyses corroborate evidence of weight gain with methadone treatment but did not observe a sex-based disparity in weight gain with methadone or buprenorphine treatment for OUD.

Topics: Analgesics, Opioid; Buprenorphine; Female; Humans; Male; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Retrospective Studies; Sex Characteristics; United States; Weight Gain

Hospitalizations related to the consequences of opioid use are rising. National guidelines directing in-hospital opioid use disorder (OUD) management do not exist. OUD treatment guidelines intended for other treatment settings could inform in-hospital OUD management.. Evaluate the quality and content of existing guidelines for OUD treatment and management.. OVID MEDLINE, PubMed, Ovid PsychINFO, EBSCOhost CINHAL, ERCI Guidelines Trust, websites of relevant societies and advocacy organizations, and selected international search engines.. Guidelines published between January 2010 to June 2020 addressing OUD treatment, opioid withdrawal management, opioid overdose prevention, and care transitions among adults.. We assessed quality using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument.. Nineteen guidelines met the selection criteria. Most recommendations were based on observational studies or expert consensus. Guidelines recommended the use of nonstigmatizing language among patients with OUD; to assess patients with unhealthy opioid use for OUD using the Diagnostic Statistical Manual of Diseases-5th Edition criteria; use of methadone or buprenorphine to treat OUD and opioid withdrawal; use of multimodal, nonopioid therapy, and when needed, short-acting opioid analgesics in addition to buprenorphine or methadone, for acute pain management; ensuring linkage to ongoing methadone or buprenorphine treatment; referring patients to psychosocial treatment; and ensuring access to naloxone for opioid overdose reversal.. Included guidelines were informed by studies with various levels of rigor and quality. Future research should systematically study buprenorphine and methadone initiation and titration among people using fentanyl and people with pain, especially during hospitalization.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Hospitalization; Humans; Methadone; Opiate Overdose; Opioid-Related Disorders

Buprenorphine induction for treating opioid use disorder is being implemented in emergency care. During this era of high-potency synthetic opioid use, novel and divergent algorithms for buprenorphine induction are emerging to optimize induction experience, facilitating continued treatment. Specifically, in patients with chronic fentanyl or other drug exposures, some clinicians are using alternative buprenorphine induction strategies, such as quickly maximizing buprenorphine agonist effects (eg, macrodosing) or, conversely, giving smaller initial doses and slowing the rate of buprenorphine dosing to avoid antagonist/withdrawal effects (eg, microdosing). However, there is a lack of foundational theory and empirical data to guide clinicians in evaluating such novel induction strategies. We present data from clinical studies of buprenorphine induction and propose a neuropharmacologic working model, which posits that acute clinical success of buprenorphine induction (achieving a positive agonist-to-withdrawal balance) is a nonlinear outcome of the opioid balance at the time of initial buprenorphine dose and mu-opioid-receptor affinity, lipophilicity, and mu-opioid-receptor intrinsic efficacy (the "ALE value") of the prior opioid. We discuss the rationale for administering smaller or larger doses of buprenorphine to optimize the patient induction experience during common clinical situations.

Topics: Algorithms; Analgesics, Opioid; Buprenorphine; Fentanyl; Humans; Opioid-Related Disorders

Medications for opioid use disorder (MOUD), including buprenorphine, represent an evidence-based treatment that supports long-term recovery and reduces risk of overdose death. Patients in crisis from opioid use disorder (OUD) often seek care from emergency departments (ED). The New York Medication for Addiction Treatment and Electronic Referrals (MATTERS) network is designed to support ED-initiated buprenorphine and urgent referrals to long-term care for patients suffering from OUD.. Using the PRECEDE-PROCEED implementation science framework, we provide an overview of the creation of the MATTERS network in Western New York. We also include an explanation of how the network was designed and launched as a response to the opioid epidemic. Finally, we analyzed the program's outputs and outcomes, thus far, as it continues to grow across the state.. The New York MATTERS network was created and implemented in 2019 with a single hospital referring patients with OUD to three local clinics. In the social assessment and situational analysis phase, we describe the opioid epidemic and available resources in the region at the outset of the program. In the epidemiological assessment phase, we quantify the epidemic on the state and regional levels. In the educational and ecological assessment, we review local ED practices and resources. In the administrative and policy assessment and intervention alignment phase, the program's unique framework is reviewed. In the piloting phase, we describe the initial deployment of New York MATTERS. Finally, in the process evaluation phase, we depict the early lessons we learned. By the beginning of 2021, the New York MATTERS network included 35 hospitals that refer to 47 clinics throughout New York State.. The New York MATTERS network provides a structured approach to reduce barriers to ED-initiated buprenorphine and urgent referral to long-term care. An implementation framework provides a structured means of evaluating this best practice model.

Topics: Analgesics, Opioid; Buprenorphine; Emergency Service, Hospital; Humans; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders

Opioid Use Disorder (OUD) is a chronic relapsing disorder that has severe negative impacts on the individual, the family, and the community at large. In 2021, opioids contributed to nearly 70% of all drug overdose deaths in the United States. This number of opioid related deaths coincides with a significant rise in the use of fentanyl, a synthetic opioid that is 150 times more potent than morphine. Furthermore, this overdose trend has spared no demographic and costs the nation an estimated $51.2 billion annually. Thus, it is imperative to better understand the underlying mechanisms of OUD in an effort to identify new treatment targets. Using animal models, studies have shown that rats readily self-administer heroin and increase seeking following exposure to cues for drug, the drug itself, or stress. We have shown that treatment with the glucagon-like peptide-1 receptor (GLP-1R) agonist, liraglutide, can reduce heroin taking and seeking behavior in rats. Therefore, using our rodent model, we established a fentanyl self-administration paradigm to test whether acute treatment with the GLP-1R agonist also can reduce fentanyl seeking in fentanyl experienced rats. The results showed that rats readily self-administered fentanyl (2.5 ug/kg) intravenously, with marked individual differences in drug taking behavior. As with other drugs of abuse tested, rats exhibited high seeking behavior when challenged with a drug-related cue or, after a period of extinction, the drug itself. Here, acute treatment with the GLP-1R agonist, liraglutide (0.3 mg/kg s.c.), was found to attenuate both cue-induced fentanyl seeking and drug-induced reinstatement of fentanyl seeking with the same efficacy as the currently approved partial opioid agonist, buprenorphine. Taken together, these data suggest that a known satiety signal, GLP-1, may serve as an effective non-opioid alternative for the treatment of OUD.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Cues; Fentanyl; Glucagon-Like Peptide-1 Receptor; Heroin; Liraglutide; Opioid-Related Disorders; Rats; Self Administration

The incidence of opioid use disorder (OUD) and overdose deaths is rising yearly within the United States. Many cases are associated with illicitly manufactured fentanyl use. In addition to offering patients medications for OUD (methadone, buprenorphine, and naltrexone), the approach to this epidemic should involve increasing provider awareness and education about substance use disorders, expanding urine toxicology screens to test for fentanyl, and using low-threshold treatment approaches.

Topics: Analgesics, Opioid; Buprenorphine; Fentanyl; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; United States

There are ongoing concerns regarding pharmaceutical opioid-related harms, including overdose and dependence, with an associated increase in treatment demand. People dependent on pharmaceutical opioids appear to differ in important ways from people who use heroin, yet most opioid agonist treatment research has been conducted in people who use heroin.  OBJECTIVES: To assess the effects of maintenance opioid agonist pharmacotherapy for the treatment of pharmaceutical opioid dependence.. We updated our searches of the following databases to January 2022: the Cochrane Drugs and Alcohol Group Specialised Register, CENTRAL, MEDLINE, four other databases, and two trial registers. We checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs).. We included RCTs with adults and adolescents examining maintenance opioid agonist treatments that made the following two comparisons. 1. Full opioid agonists (methadone, morphine, oxycodone, levo-alpha-acetylmethadol (LAAM), or codeine) versus different full opioid agonists or partial opioid agonists (buprenorphine) for maintenance treatment. 2. Full or partial opioid agonist maintenance versus non-opioid agonist treatments (detoxification, opioid antagonist, or psychological treatment without opioid agonist treatment).. We used standard Cochrane methods.. We identified eight RCTs that met inclusion criteria (709 participants). We found four studies that compared methadone and buprenorphine maintenance treatment, and four studies that compared buprenorphine maintenance to either buprenorphine taper (in addition to psychological treatment) or a non-opioid maintenance treatment comparison. We found low-certainty evidence from three studies of a difference between methadone and buprenorphine in favour of methadone on self-reported opioid use at end of treatment (risk ratio (RR) 0.49, 95% confidence interval (CI) 0.28 to 0.86; 165 participants), and low-certainty evidence from four studies finding a difference in favour of methadone for retention in treatment (RR 1.21, 95% CI 1.02 to 1.43; 379 participants). We found low-certainty evidence from three studies showing no difference between methadone and buprenorphine on substance use measured with urine drug screens at end of treatment (RR 0.81, 95% CI 0.57 to 1.17; 206 participants), and moderate-certainty evidence from one study of no difference in days of self-reported opioid use (mean difference 1.41 days, 95% CI 3.37 lower to 0.55 days higher; 129 participants). There was low-certainty evidence from three studies of no difference between methadone and buprenorphine on adverse events (RR 1.13, 95% CI 0.66 to 1.93; 206 participants). We found low-certainty evidence from four studies favouring maintenance buprenorphine treatment over non-opioid treatments in terms of fewer opioid positive urine drug tests at end of treatment (RR 0.66, 95% CI 0.52 to 0.84; 270 participants), and very low-certainty evidence from four studies finding no difference on self-reported opioid use in the past 30 days at end of treatment (RR 0.63, 95% CI 0.39 to 1.01; 276 participants). There was low-certainty evidence from three studies of no difference in the number of days of unsanctioned opioid use (standardised mean difference (SMD) -0.19, 95% CI -0.47 to 0.09; 205 participants). There was moderate-certainty evidence from four studies favouring buprenorphine maintenance over non-opioid treatments on retention in treatment (RR 3.02, 95% CI 1.73 to 5.27; 333 participants). There was moderate-certainty evidence from three studies of no difference in adverse effects between buprenorphine maintenance and non-opioid treatments (RR 0.50, 95% CI 0.07 to 3.48; 252 participants). The main weaknesses in the quality of the data was the use of open-label study designs, and difference in follow-u. There is  very low- to moderate-certainty evidence supporting the use of maintenance agonist pharmacotherapy for pharmaceutical opioid dependence. Methadone or buprenorphine did not differ on some outcomes, although on the outcomes of retention and self-reported substance use some results favoured methadone. Maintenance treatment with buprenorphine appears more effective than non-opioid treatments. Due to the overall very low- to moderate-certainty evidence and small sample sizes, there is the possibility that the further research may change these findings.

Topics: Adolescent; Analgesics, Opioid; Buprenorphine; Heroin; Humans; Methadone; Opioid-Related Disorders; Pharmaceutical Preparations

The United States underwent massive expansion in opioid prescribing from 1990-2010, followed by opioid stewardship initiatives and reduced prescribing. Opioids are no longer considered first-line therapy for most chronic pain conditions and clinicians should first seek alternatives in most circumstances. Patients who have been treated with opioids long-term should be managed differently, sometimes even continued on opioids due to physiologic changes wrought by long-term opioid therapy and documented risks of discontinuation. When providing long-term opioid therapy, clinicians should document opioid stewardship measures, including assessments, consents, medication reconciliation, and offering naloxone, along with the rationale to continue opioid therapy. Clinicians should screen regularly for opioid use disorder and arrange for or directly provide treatment. In particular, buprenorphine can be highly useful for co-morbid pain and opioid use disorder. Addressing other substance use disorders, as well as preventive health related to substance use, should be a priority in patients with opioid use disorder. Patient-centered practices, such as shared decision-making and attending to related facets of a patient's life that influence health outcomes, should be implemented at all points of care.Key messagesAlthough opioids are no longer considered first-line therapy for most chronic pain, management of patients already taking long-term opioid therapy must be individualised.Documentation of opioid stewardship measures can help to organise opioid prescribing and protect clinicians from regulatory scrutiny.Management of resultant opioid use disorder should include provision of medications, most often buprenorphine, and several additional screening and preventive measures.

Topics: Analgesics, Opioid; Buprenorphine; Chronic Pain; Humans; Naloxone; Opioid-Related Disorders; Practice Patterns, Physicians'; Primary Health Care; United States

Novel buprenorphine dosing strategies have emerged with an aim to transition patients from opioid agonists to buprenorphine without prerequisite opioid withdrawal. We applied a configurational approach to a subset of data from our earlier systematic review to answer the following question: when patients received a buprenorphine initiation strategy aimed to eliminate prerequisite withdrawal, what factors consistently distinguished patients that experienced withdrawal during the initiation process from patients that did not?. From the 24 cases identified by our systematic review, we included cases that were treated using buprenorphine microdosing strategies (oral or transdermal), cases with opioid use disorder, and cases that fully transitioned to buprenorphine without continuing the full opioid agonist. Configurational analysis was used to identify combinations of patient and regimen level factors that uniquely distinguished cases experiencing withdrawal during induction.. Fourteen cases were included in our analysis, of which 9 experienced opioid withdrawal symptoms. Three factors were involved in explaining both the presence and absence of withdrawal symptoms: history of heroin use, history of methadone use, and duration of overlap between buprenorphine and the full opioid agonist during induction. For the presence of withdrawal symptoms, the addition of a fourth factor "buprenorphine starting dose" resulted in a model with perfect consistency and coverage; for the absence of withdrawal symptoms, the addition of a fourth factor "induction duration" similarly resulted in a model with perfect consistency and 80% coverage.. Application of configurational methods allowed synthesis of case reports identified through a systematic review.

Topics: Analgesics, Opioid; Buprenorphine; Heroin; Humans; Methadone; Narcotics; Opioid-Related Disorders; Substance Withdrawal Syndrome

Given the ongoing opioid crisis, novel interventions to treat severe opioid use disorder (OUD) are urgently needed. Injectable opioid agonist therapy (iOAT) with diacetylmorphine or hydromorphone is effective for the treatment of severe, treatment-refractory OUD, however barriers to implementation persist. Intravenous buprenorphine for the treatment of OUD (BUP iOAT) has several possible advantages over traditional iOAT, including a safety profile that might enable take-home dosing. We aimed to characterize injecting practices among real-world populations of persons who regularly inject buprenorphine, as well as associated adverse events reported in order to inform a possible future BUP iOAT intervention.. We conducted a systematic review. We searched MEDLINE, EMBASE, and PsycINFO from inception through July 2020 and used backwards citation screening to search for publications reporting on dose, frequency among persons who regularly inject the drug, or adverse events associated with intravenous use of buprenorphine. The review was limited to English language publications and there was no limitation on study type. Study quality and risk of bias was assessed using the Mixed Methods Appraisal Tool. Narrative synthesis was used in reporting the results.. Eighty-eight studies were included in our review. Regular injection of buprenorphine was identified across diverse settings world-wide. Daily dose of oral buprenorphine injected was < 1-12 mg. Frequency of injection was 0-10 times daily. Adverse events could be characterized as known side effects of opioids/buprenorphine or injection-related complications. Most studies were deemed to be of low quality.. Extramedical, intravenous use of buprenorphine, continues to be documented. BUP iOAT may be feasible and results may inform the development of a study to test the efficacy and safety of such an intervention. Future work should also examine acceptability among people with severe OUD in North America. Our review was limited by the quality of included studies.

Topics: Analgesics, Opioid; Buprenorphine; Heroin; Humans; Hydromorphone; Opiate Substitution Treatment; Opioid-Related Disorders

In this issue of Anesthesia & Analgesia, Lim and colleagues offer a scoping review of the available literature encompassing opioid use disorder (OUD) in pregnant patients. As discussed in their review, opioid use and abuse in pregnant patients have increased four-fold in the past decade. As such, these patients can present significant challenges with respect to pain management during labor and delivery. A baseline habituation to opioids can render patients resistant to conventional pain management plans. Those who are additionally prescribed opioid agonist-antagonists or other maintenance medications for OUD such as buprenorphine or methadone have even more complex pharmacologic considerations that make pain management unpredictable. As detailed in their analysis, there is a paucity of literature surrounding optimal management strategies in this population of patients. Reports are increasing over time, however, most publications are of lower tier evidence, with very few randomized trials and systematic reviews to inform practitioners. It becomes plainly evident that this is an area of clinical science that demands greater attention. Specific areas of focus elaborated by the authors include: better characterization of opioid selection and dosing in managing labor analgesia, effectiveness of different regional anesthetic techniques, non-pharmacologic management, and psycho-social support for these patients. The reader is strongly encouraged to review the cited article for an in-depth understanding of the concepts summarized in this infographic.

Topics: Analgesics, Opioid; Anesthetics; Buprenorphine; Female; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy

Opioid use disorder (OUD) is characterized by compulsive opioid seeking and taking, intense drug craving, and intake of opioids despite negative consequences. The prevalence of OUDs has now reached an all-time high, in parallel with peak rates of fatal opioid-related overdoses, where 15 million individuals worldwide meet the criteria for OUD. Further, in 2020, 120,000 opioid-related deaths were reported worldwide with over 75,000 of those deaths occurring within the United States.. In this review, we highlight pharmacotherapies utilized in patients with OUDs, including opioid replacement therapies, and opioid antagonists utilized for opioid overdoses and deterrent of opioid use. We also highlight newer treatments, such as those targeting the neuroimmune system, which are potential new directions for research given the recently established role of opioids in activating neuroinflammatory pathways, as well as over the counter remedies, including kratom, that may mitigate withdrawal.. To effectively treat OUDs, a deeper understanding of the current therapeutics being utilized, their additive effects, and the added involvement of the neuroimmune system are essential. Additionally, a complete understanding of opioid-induced neuronal alterations and therapeutics that target these abnormalities - including the neuroimmune system - is required to develop effective treatments for OUDs.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Humans; Methadone; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; United States

Evidence maps are emerging data visualization of a systematic review. There are no published evidence maps summarizing opioid use disorder (OUD) interventions.. Our aim was to publish an interactive summary of all peer-reviewed interventional and observational trials assessing the treatment of OUD and common clinical outcomes.. PubMed, Embase, PsycInfo, Cochrane Central Register of Clinical Trials, and Web of Science were queried using multiple OUD-related MESH terms, without date limitations, for English-language publications. Inclusions were human subjects, treatment of OUD, OUD patient or community-level outcomes, and systematic reviews of OUD interventions. Exclusions were laboratory studies, reviews, and case reports. Two reviewers independently scanned abstracts for inclusion before coding eligible full-text articles by pre-specified filters: research design, study population, study setting, intervention, outcomes, sample size, study duration, geographical region, and funding sources.. The OUD Evidence Map (https://med.nyu.edu/research/lee-lab/research/opioid-use-disorder-treatment-evidence-map) identified and assessed 12,933 relevant abstracts through 2020. We excluded 9455 abstracts and full text reviewed 2839 manuscripts; 888 were excluded, 1591 were included in the final evidence map. The most studied OUD interventions were methadone (n = 754 studies), buprenorphine (n = 499), and naltrexone (n = 134). The most common outcomes were heroin/opioid use (n = 708), treatment retention (n = 557), and non-opioid drug use (n = 368). Clear gaps included a wider array of opioid agonists for treatment, digital behavioral interventions, studies of OUD treatments in criminal justice settings, and overdose as a clinical outcome.. This OUD Evidence Map highlights the importance of pharmacologic interventions for OUD and reductions in opioid use. Future iterations will update results annually and scan policy-level interventions.

Topics: Analgesics, Opioid; Buprenorphine; Humans; Methadone; Naltrexone; Opiate Substitution Treatment; Opioid-Related Disorders

Follow-up after residential treatment is considered best practice in supporting patients with opioid use disorder (OUD) in their recovery. Yet, little is known about rates of follow-up after discharge. The objective of this analysis was to measure rates of follow-up and use of medications for OUD (MOUD) after residential treatment among Medicaid enrollees in 10 states, and to understand the enrollee and episode characteristics that are associated with both outcomes.. Using a distributed research network to analyze Medicaid claims data, we estimated the likelihood of 4 outcomes occurring within 7 and 30 days post-discharge from residential treatment for OUD using multinomial logit regression: no follow-up or MOUD, follow-up visit only, MOUD only, or both follow-up and MOUD. We used meta-analysis techniques to pool state-specific estimates into global estimates.. We identified 90,639 episodes of residential treatment for OUD for 69,017 enrollees from 2018 to 2019. We found that 62.5% and 46.9% of episodes did not receive any follow-up or MOUD at 7 days and 30 days, respectively. In adjusted analyses, co-occurring mental health conditions, longer lengths of stay, prior receipt of MOUD or behavioral health counseling, and a recent ED visit for OUD were associated with a greater likelihood of receiving follow-up treatment including MOUD after discharge.. Forty-seven percent of residential treatment episodes for Medicaid enrollees are not followed by an outpatient visit or MOUD, and thus are not following best practices.

Topics: Aftercare; Analgesics, Opioid; Buprenorphine; Humans; Medicaid; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Discharge; Residential Treatment; United States

The average length of buprenorphine treatment for opioid use disorder is less than 6 months.. We conducted a systematic review to determine what factors were associated with longer retention in buprenorphine treatment.. We searched Medline, Embase, and Cochrane Database of Systematic Reviews in February 2018. Articles were restricted to randomized controlled trials on human subjects, written in English, which contained ≥ 24 weeks of objective data on retention in buprenorphine treatment.. We assessed whether dose of buprenorphine, treatment setting, or co-administration of behavioral therapy was associated with retention rates.. Over 14,000 articles were identified. Thirteen articles (describing 9 studies) met inclusion criteria. Measures of retention varied widely. Three studies compared doses of buprenorphine between 1 and 8 mg and showed significantly higher rates of retention with higher doses (p values < 0.01). All other studies utilized buprenorphine doses between 8 and 24 mg daily, without comparison. No study found a significant difference in retention between buprenorphine alone and buprenorphine plus behavioral therapy (p values > 0.05). Initiating buprenorphine while hospitalized or within criminal justice settings prior to outpatient treatment programs was significantly associated with retention in buprenorphine treatment (p values < 0.01 respectively).. Setting of treatment initiation and a higher buprenorphine dose are associated with improved long-term treatment retention. More objective data on buprenorphine treatment programs are needed, including a standardized approach to defining retention in buprenorphine treatment programs.. This review was registered with PROSPERO (#CRD42019120336) in March 2019.

Topics: Behavior, Addictive; Buprenorphine; Humans; Opiate Substitution Treatment; Opioid-Related Disorders

People with opioid use disorder (OUD) are disproportionately burdened by HIV. The United States' Centers for Disease Control and Prevention (CDC) has issued guidelines for pre-exposure prophylaxis (PrEP) indication. We know little about PrEP for people receiving medication for OUD. The objective of this study is to report PrEP indication, awareness, and uptake in patients engaged in outpatient OUD treatment with buprenorphine.. Adult patients (n = 137) receiving buprenorphine for OUD at an outpatient substance use disorder treatment clinic completed a cross-sectional survey between July and September 2019. The study determined PrEP indication by 2017 CDC criteria. PrEP awareness and uptake were self-reported. The study assessed statistical differences in PrEP indicators by Pearson's χ. Nearly three-quarters (73.7%, n = 101) of the study sample met CDC criteria for PrEP-indication based on past-year risk behaviors. Ninety-five percent of these participants reported inconsistent condom use, 21.0% engaged in commercial sex, 9.0% shared injection equipment, 8.9% reported a recent bacterial STI, and 4.0% had an HIV+ sexual partner. Of PrEP indicated participants (n = 101), 19 had heard of PrEP prior to the survey, but only 1 participant reported past-year PrEP use.. Among a clinical population of people receiving buprenorphine for OUD, HIV risk behaviors were common, yet PrEP awareness and uptake were low. People engaged in treatment for OUD remain at high risk for HIV and are a priority population for PrEP. In light of the current opioid crisis, more research is needed to guide the integration of comprehensive HIV prevention into outpatient opioid treatment centers.

Topics: Adult; Anti-HIV Agents; Buprenorphine; Cross-Sectional Studies; HIV Infections; Humans; Opioid-Related Disorders; Pre-Exposure Prophylaxis; Sex Work

Sequalae of opioid misuse constitute a public health emergency in the United States. A robust evidence base informs the use of medication for opioid use disorders (MOUD) in adults, with far less research in transition-age youth. This systematic review evaluates the effectiveness of MOUD for transition-age youth (age 16 to 25).. This synthesis was part of a larger systematic review focused on adolescent substance use interventions. The study team conducted literature searches in MEDLINE, the Cochrane CENTRAL Registry of Controlled Trials, EMBASE, PsycINFO, and CINAHL through October 31, 2019. We screened studies, extracted data, and assessed risk of bias using standard methods. The primary and secondary outcomes were the effect of MOUD on opioid abstinence and treatment retention, respectively.. The study team screened a total of 33,272 records and examined 1831 full-text articles. Four randomized trials met criteria for inclusion in the current analysis. All four trials assessed a combination of buprenorphine plus cognitive behavioral therapy versus a comparison condition. Some trials included additional behavioral interventions, and the specific duration/dosage of buprenorphine varied. Risk of bias was moderate for all studies. Studies found that buprenorphine was more effective than clonidine, effectively augmented by memantine, and that longer medication taper durations were more effective than shorter tapers in promoting both abstinence and retention. Notably, we did not identify any studies of methadone or naltrexone, adjunctive behavioral interventions were sparingly described, and treatment durations were far shorter than recommended guidelines in adults.. The literature guiding youth MOUD is limited, and more research should evaluate the effectiveness of options other than buprenorphine, optimal treatment duration, and the benefit of adjunctive behavioral interventions. Subgroup analyses of extant randomized clinical trials could help to extend knowledge of MOUD effectiveness in this age cohort.

Topics: Adolescent; Adult; Analgesics, Opioid; Buprenorphine; Humans; Methadone; Naltrexone; Opioid-Related Disorders; United States; Young Adult

Opioid use disorder and chronic pain are increasingly commonly encountered in medicine and many patients now are prescribed medications (such as buprenorphine) to help treat these conditions. Many radiologists are unfamiliar with how these medications work and how they impact providing procedural sedation during procedures in the radiology department. The focus of this manuscript is to provide radiologists background and guidance on how these medications interact with medications given for procedural sedation and the appropriate management strategy for patients with opioid use disorder and chronic pain who require procedural sedation.

Topics: Buprenorphine; Chronic Pain; Conscious Sedation; Humans; Opioid-Related Disorders; Radiologists

Buprenorphine, approved for treating opioid use disorder (OUD), is not equally efficacious for all patients. Candidate gene studies have shown limited success in identifying genetic moderators of buprenorphine treatment response.. We studied 1616 European-ancestry individuals enrolled in the Million Veteran Program, of whom 1609 had an ICD-9/10 code consistent with OUD, a 180-day buprenorphine treatment exposure, and genome-wide genotype data. We conducted a genome-wide association study (GWAS) of buprenorphine treatment response [defined as having no opioid-positive urine drug screens (UDS) following the first prescription]. We also examined correlates of buprenorphine treatment response in multivariable analyses.. Although no variants reached genome-wide significance, 6 loci were nominally significant (p < 1 × 10. This study had limited statistical power to detect genetic variants associated with a complex human phenotype like buprenorphine treatment response. Meta-analysis of multiple data sets is needed to ensure adequate statistical power for a GWAS of buprenorphine treatment response. The most robust phenotypic predictor of buprenorphine treatment response was intravenous drug use, a proxy for which was HCV infection.

Topics: ADAMTS Proteins; Aged; Analgesics, Opioid; Buprenorphine; Genome-Wide Association Study; Humans; Opiate Substitution Treatment; Opioid-Related Disorders

With the aging population, an increasing number of older adults (> 65 years) will be affected by problematic opioid use and opioid use disorder (OUD), with both illicit and prescription opioids. Problematic opioid use is defined as the use of opioids resulting in social, medical or psychological consequences, whereas OUD is a form of problematic use that meets diagnostic criteria as defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition. Problematic use of opioids by older adults is associated with a number of pertinent adverse effects, including sedation, cognitive impairment, falls, fractures and constipation. Risk factors for problematic opioid use in this population include pain, comorbid medical illnesses, concurrent alcohol use disorder and depression. Treatment of OUD consists of acute detoxification and maintenance therapy. At this time, there have been no randomized controlled trials examining the effectiveness of pharmacological interventions for OUD in this population, with recommendations based on data from younger adults. Despite this, opioid agonist therapy (OAT) is recommended for both stages of treatment in older adults with OUD. Buprenorphine is recommended as a first line agent over methadone in the older adult population, due to a more favourable safety profile and relative accessibility. Use of methadone in this population is complicated by risk of QT interval prolongation and respiratory depression. Available observational data suggests that older adults respond well to OAT and age should not be a barrier to treatment. Further research is required to inform treatment decisions in this population.

Topics: Aged; Analgesics, Opioid; Buprenorphine; Humans; Methadone; Opioid-Related Disorders; Pain

A growing body of research has examined adjunctive interventions supportive of engagement and retention in treatment among patients receiving buprenorphine for opioid use disorder (OUD). We conducted a systematic review of the literature addressing the effect on key outcomes of adjunctive interventions provided alongside standard medical management of buprenorphine in outpatient settings.. We included prospective studies examining adults receiving buprenorphine paired with an adjunctive intervention for the treatment of OUD in an outpatient setting. Data sources included Medline, Cochrane Central Register of Controlled Trials, CINAHL and PsycINFO from inception through January 2020. Two raters independently reviewed full-text articles, abstracted data and appraised risk of bias. Outcomes examined included abstinence, retention in treatment and non-addiction-related health outcomes.. The final review includes 20 manuscripts, 11 randomized control trials (RCTs), three secondary analyses of RCTs and six observational studies. Most studies examined psychosocial interventions (n = 14). Few examined complementary therapies (e.g., yoga; n = 2) or technological interventions (e.g., electronic pill dispensation; n = 3); one study examined an intervention addressing structural barriers to care (patient navigators; n = 1). Low risk of bias RCTs found no evidence that adding psychosocial interventions to buprenorphine treatment improves substance use outcomes.. Research is needed to identify adjunctive interventions with potential to support medication adherence and addiction-related outcomes for patients engaged in buprenorphine treatment. Data from clinical trials suggest that lack of ready access to psychosocial treatments should not discourage clinicians from prescribing buprenorphine.

Topics: Adult; Buprenorphine; Humans; Opioid-Related Disorders; Outpatients

Opioid use disorder is a major public health problem, and opioid replacement therapy with buprenorphine (BPN) is a clinically effective and evidence-based treatment for it. To deter misuse of the tablet through the injecting route, BPN coformulated with naloxone (BNX) in 4:1 ratio is available in many countries. Despite this, significant diversion and injecting use of the BNX combination has been reported from across the world. In this article, the pharmacological properties of BPN and BNX and the evidence for their diversion are reviewed. Also, a critical examination is made of the evidence supporting the role of naloxone in reducing the agonist effects of BPN when used through the injecting route. Based on this evidence, a hypothesis explaining the continued diversion of BNX has been proposed.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Tablets

Medications for opioid use disorder (MOUD) are evidence-based treatments, yet can be controversial among some populations. This study provides a systematic review of prejudice and discrimination toward MOUD, a form of "intervention stigma," or stigma associated with a particular medical treatment.. A systematic search strategy was used in PsychInfo and PubMed to identify studies published between 1998 and 2018. Studies that empirically examined stigma toward MOUD were included if the manuscript was of moderate or high quality. Studies were analyzed using thematic synthesis.. The search yielded 972 studies, of which 28 were included. Most studies utilized qualitative methods to examine intervention stigma toward methadone or buprenorphine, with one including naltrexone. Studies demonstrated that intervention stigma among healthcare providers was influenced by lack of training and abstinent treatment preferences. Providers equated MOUD with illicit substance use and at times refused to care for MOUD patients. Stigma among peer patients seeking treatment was also influenced by abstinent treatment preferences, and among the general public stigma was influenced by lack of MOUD knowledge. Intervention stigma was also driven at the policy level by high regulation of methadone, which fueled diversion and hindered social functioning among patients. Few studies indicated how to reduce intervention stigma toward MOUD.. Intervention stigma affects both provision and perceptions of methadone and buprenorphine, decreasing access and utilization of MOUD. Future research should further develop and test MOUD stigma reduction interventions in a variety of social contexts to improve access to care and reduce patient barriers.

Topics: Analgesics, Opioid; Buprenorphine; Humans; Methadone; Naltrexone; Opiate Substitution Treatment; Opioid-Related Disorders

Treating acute pain among persons with opioid use disorder (OUD) on opioid agonist therapy (OAT) is complex, and the therapeutic benefits of opioids remain unclear when weighted against their abuse potential and respiratory depressant effects.. We conducted a systematic review of experimental pain studies examining opioid-induced analgesia among persons with OUD on OAT. We searched multiple databases from inception to July 30, 2021. Study quality was assessed by previously established validity measures.. Nine studies were identified, with a total of 225 participants, of whom 63% were male, and 37% were female. Six studies included methadone-maintained persons with OUD; four studies included buprenorphine-maintained persons with OUD; and three studies included healthy persons as comparison groups. Either additional doses of OAT or other opioids - morphine, oxycodone, hydromorphone, or remifentanil - were administered. In seven studies, persons with OUD on OAT did not experience analgesia, despite receiving opioid doses up to 20 times greater than those clinically used to treat severe pain among the opioid naïve. Conversely, in two studies, high-potency opioids did produce analgesia, albeit with greater abuse potential. Notably, persons with OUD on OAT remained vulnerable to respiratory depression.. Although persons with OUD on OAT can derive analgesic effects from opioids, high-potency compounds may be required to achieve clinically significant pain relief. Further, persons with OUD on OAT may remain vulnerable to opioid-induced abuse potential and respiratory depression. Together, these finding have clinical, methodological, and mechanistic implications for the treatment of acute pain in the context of OAT.

Topics: Acute Pain; Analgesia; Analgesics, Opioid; Buprenorphine; Female; Humans; Male; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders

Methamphetamine/amphetamine use has sharply increased among people with opioid use disorder (OUD). It is therefore important to understand whether and how use of these substances may impact receipt of, and outcomes associated with, medications for OUD (MOUD). This systematic review identified studies that examined associations between methamphetamine/amphetamine use or use disorder and 3 classes of outcomes: (1) receipt of MOUD, (2) retention in MOUD, and (3) opioid abstinence during MOUD.. We searched 3 databases (PubMed/MEDLINE, PsycINFO, CINAHL Complete) from 1/1/2000 to 7/28/2020 using key words and subject headings, and hand-searched reference lists of included articles. English-language studies of people with documented OUD/opioid use that reported a quantitative association between methamphetamine/amphetamine use or use disorder and an outcome of interest were included. Study data were extracted using a standardized template, and risk of bias was assessed for each study. Screening, inclusion, data extraction and bias assessment were conducted independently by 2 authors. Study characteristics and findings were summarized for each class of outcomes.. Thirty-nine studies met inclusion criteria. Studies generally found that methamphetamine/amphetamine use or use disorder was negatively associated with receiving methadone and buprenorphine; 2 studies suggested positive associations with receiving naltrexone. Studies generally found negative associations with retention; most studies finding no association had small samples, and these studies tended to examine shorter retention timeframes and describe provision of adjunctive services to address substance use. Studies generally found negative associations with opioid abstinence during treatment among patients receiving methadone or sustained-release naltrexone implants, though observed associations may have been confounded by other polysubstance use. Most studies examining opioid abstinence during other types of MOUD treatment had small samples.. Overall, existing research suggests people who use methamphetamine/amphetamines may have lower receipt of MOUD, retention in MOUD, and opioid abstinence during MOUD. Future research should examine how specific policies and treatment models impact MOUD outcomes for these patients, and seek to understand the perspectives of MOUD providers and people who use both opioids and methamphetamine/amphetamines. Efforts to improve MOUD care and overdose prevention strategies are needed for this population.

Topics: Buprenorphine; Humans; Methadone; Methamphetamine; Opiate Substitution Treatment; Opioid-Related Disorders

Patients with opioid use disorder (OUD) display an interindividual variability in their response to medications for opioid use disorder (MOUD). A genetic basis may explain the variability in this response. However, no consensus has been reached regarding which genetic variants significantly contribute to MOUD outcomes.. This systematic review aims to summarize genome-wide significant findings on MOUD outcomes and critically appraise the quality of the studies involved.. Databases searched from inception until August 21st, 2020 include: MEDLINE, Web of Science, EMBASE, CINAHL and Pre-CINAHL, GWAS Catalog and GWAS Central. The included studies had to be GWASs that assessed MOUD in an OUD population. All studies were screened in duplicate. The quality of the included studies was scored and assessed using the Q-Genie tool. Quantitative analysis, as planned in the protocol, was not feasible, so the studies were analyzed qualitatively.. Our search identified 7292 studies. Five studies meeting the eligibility criteria were included. However, only three studies reported results that met our significance threshold of p ≤ 1.0 × 10. The limitations of this study include not being able to synthesize the data in a quantitative way and a conservative eligibility and data collection model.. The results from this systematic review will aid in highlighting significant genetic variants that can be replicated in future OUD pharmacogenetics research to ascertain their role in patient-specific MOUD outcomes. Systematic review registration number CRD42020169121.

Topics: Buprenorphine; Calcium-Calmodulin-Dependent Protein Kinases; Eye Proteins; Genome-Wide Association Study; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Polymorphism, Single Nucleotide

This review describes methods for preclinical evaluation of candidate medications to treat opioid use disorder (OUD). The review is founded on the propositions that (1) drug self-administration procedures provide the most direct method for assessment of medication effectiveness, (2) procedures that assess choice between opioid and nondrug reinforcers are especially useful, and (3) states of opioid dependence and withdrawal profoundly influence both opioid reinforcement and effects of candidate medications. Effects of opioid medications and vaccines on opioid choice in nondependent and opioid-dependent subjects are reviewed. Various nonopioid medications have also been examined, but none yet have been identified that safely and reliably reduce opioid choice. Future research will focus on (1) strategies for increasing safety and/or effectiveness of opioid medications (e.g., G-protein-biased μ-opioid agonists), and (2) continued development of nonopioid medications (e.g., clonidine) that might serve as adjunctive agents to current opioid medications.

Topics: Analgesics, Opioid; Buprenorphine; Choice Behavior; Drug Development; Evidence-Based Medicine; Humans; Methadone; Naltrexone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Receptors, Opioid, mu; Self Administration; Substance Withdrawal Syndrome; Treatment Outcome

Some opioid use disorder (OUD) patients attempt to self-treat using herbal remedies such as kratom. However, kratom use itself can paradoxically cause physical dependence and OUD. Currently, there are no guidelines for treating patients with OUD stemming from kratom use. Our empirically-based hypothesis was that there would be a correlation between the amount of kratom used and the amount of buprenorphine-naloxone required for opioid agonist therapy.. This study includes a systematic review assessing treatment of kratom-dependent patients with buprenorphine-naloxone; a case series of our kratom-dependent patients; calculation of the correlation between the kratom dose and the buprenorphine-naloxone dose required to treat kratom-associated OUD; and our proposed starting doses for using buprenorphine-naloxone to treat kratom OUD.. The OVID MEDLINE (1946-2020) database was searched using the terms "kratom," "buprenorphine," and "case report." This search yielded 3 relevant cases of patients having kratom OUD who were treated with buprenorphine-naloxone with the amounts of all substances reported. Review of the bibliographies, citing articles, and Google Scholar turned up three additional cases, yielding 6 literature cases that were analyzed. We also analyzed 2 patients from our clinic, giving a total of 8 patients included in the Pearson correlation coefficient calculation. We found a strong correlation of 0.84 between these variables, consistent with our hypothesis.. Based on our analysis, patients using <20 g of kratom/d could be initiated on opioid agonist therapy with 4/1 mg-8/2 mg buprenorphine-naloxone/d, while patients using kratom doses >40 g/d could be initiated with 12/3 mg-16/4 mg of buprenorphine-naloxone/day.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Humans; Mitragyna; Naloxone; Narcotic Antagonists; Opioid-Related Disorders

Opioid maintenance treatment with oral methadone or sublingual buprenorphine is the first-line treatment in opioid dependence. Three novel long-acting buprenorphine formulations have been approved or will be available soon: for subcutaneous weekly and monthly application, the depot formulations CAM 2038 (Buvidal

Topics: Buprenorphine; Delayed-Action Preparations; Drug Administration Schedule; Drug Implants; Humans; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders

Micro-induction is a novel buprenorphine induction approach that seeks to avoid withdrawal and minimize precipitated withdrawal, both barriers to standard inductions. We aimed to synthesize evidence on micro-induction effectiveness, and regimens described.. We searched scientific databases and grey literature for studies including adolescents or adults with opioid use disorder who received buprenorphine micro-induction. Study selection, data extraction and quality assessments occurred in duplicate. We narratively synthesized results.. We screened 4,752 citations and included 19 case studies/series and one feasibility study (n = 57 patients; mean age 38 years [SD 12.0]; 57.9% male [33/57]). Studies described 26 regimens; starting and maintenance doses ranged from 0.03 to 1.0 mg, and 8 to 32 mg, respectively. We calculated rate of increase to 8 mg. All patients achieved the desired maintenance dose. Among 54 patients in whom precipitated withdrawal was not reported, mean increases were 1.36 mg/day (SD 0.41). For three patients in whom precipitated withdrawal was specifically reported, mean increase was 1.17 mg/day (SD 0.11). All studies were low quality.. Described regimens are highly variable. Inconsistent reporting, selection bias, and poor quality evidence limit conclusions regarding optimal dosing, and patient characteristics and clinical settings in which micro-induction is likely beneficial.. This systematic review provides the most up-to-date synthesis on buprenorphine micro-induction regimens. Rigorous studies evaluating effectiveness and safety of micro-induction, and patient and clinical factors influencing its success, are needed.

Topics: Adolescent; Adult; Buprenorphine; Female; Humans; Male; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Substance Withdrawal Syndrome

Chronic intrauterine exposure to psychoactive drugs often results in neonatal opioid withdrawal syndrome (NOWS). When nonpharmacologic measures are insufficient in controlling NOWS, morphine, methadone, and buprenorphine are first-line medications commonly used to treat infants with NOWS because of in utero exposure to opioids. Research suggests that buprenorphine may be the leading drug therapy used to treat NOWS when compared with morphine and methadone. Currently, there are no consensus or standardized treatment guidelines for medications prescribed for NOWS. Opioids used to treat NOWS exhibit large interpatient variability in pharmacokinetics (PK) and pharmacodynamic (PD) response in neonates. Organ systems undergo rapid maturation after birth that may alter drug disposition and exposure for any given dose during development. Data regarding the PK and PD of opioids in neonates are sparse. Pharmacometric methods such as physiologically based pharmacokinetic and population pharmacokinetic modeling can be used to explore factors predictive of some of the variability associated with the PK/PD of opioids in newborns. This review discusses the utility of pharmacometric techniques for enhancing precision dosing in infants requiring opioid treatment for NOWS. Applying these approaches may contribute to optimizing the outcome by reducing cumulative drug exposure, mitigating adverse drug effects, and reducing the burden of NOWS in neonates.

Topics: Buprenorphine; Cytochrome P-450 CYP3A; Dose-Response Relationship, Drug; Humans; Infant, Newborn; Methadone; Models, Biological; Morphine; Narcotics; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders

Opioid use disorder is a critical public health problem that continues to broaden in scope, adversely affecting millions of people worldwide. Significant efforts have been made to expand access to medication therapy for opioid use disorder, in particular buprenorphine. As the emergency department is a critical point of access for many patients with opioid use disorder, the initiation of buprenorphine therapy in the emergency department is increasing, and emergency nurses should be familiar with the care of these vulnerable patients. The purpose of this article is to provide a clinical review of opioid use disorder and opioid withdrawal syndrome, medication treatments for opioid use disorder, best clinical practices for ED-initiated buprenorphine therapy, assessment of withdrawal symptoms, discharge considerations, and concerns for special populations. With expanded understanding of opioid use disorder, withdrawal, and available treatments, emergency nurses will be better prepared to deliver and support life-saving treatments for patients and families suffering from this disease. In addition, emergency nurses are well positioned to play an important role in public health advocacy around opioid use disorder, providing critical support for destigmatization and expanded access to safe and efficacious treatments.

Topics: Buprenorphine; Emergency Nursing; Emergency Service, Hospital; Humans; Narcotic Antagonists; Opioid-Related Disorders; Substance Withdrawal Syndrome

Topics: Alcoholism; Body Mass Index; Bone Diseases, Metabolic; Buprenorphine; Female; Heroin; Humans; Male; Methadone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Risk Factors; Sex Factors; Testosterone

Opioid use disorder continues to be a significant problem in the United States and worldwide. Three medications-methadone, buprenorphine, and extended-release injectable naltrexone,- are efficacious for treating opioid use disorder (OUD). However, the utility of these medications is limited, in part due to poor rates of retention in treatment. In addition, minimum recovery milestones and other factors that influence when and whether individuals can safely discontinue medications are unknown. The National Drug Abuse Treatment Clinical Trials Network (CTN) study "Optimizing Retention, Duration, and Discontinuation Strategies for Opioid Use Disorder Pharmacotherapy" (RDD; CTN-0100) will be among the largest clinical trials on treatment of OUD yet conducted, consisting of two phases, the Retention phase, and the Duration-Discontinuation phase. The Retention phase, open to patients initiating treatment, will test different doses and formulations of buprenorphine (standard dose sublingual, high dose sublingual, or extended-release injection), and a digital therapeutic app delivering contingency management and cognitive behavioral counseling on the primary outcome of retention in treatment. The Discontinuation phase, open to patients in stable remission from OUD and choosing to discontinue medication (including participants from the Retention phase or from the population of patients treated at the clinical site, referred by an outside prescriber or self-referred) will study different tapering strategies for buprenorphine (sublingual taper vs taper with injection buprenorphine), and a digital therapeutic app which provides resources to promote recovery, on the primary outcome of relapse-free discontinuation of medication. This paper describes how the RDD trial derives from two decades of research in the CTN. Initial trials (CTN-0001; CTN-0002; CTN-0003) focused on opioid detoxification, showing buprenorphine-naloxone was effective for detoxification, but that acute detoxification did not appear to be an effective treatment strategy. Trials on comparative effectiveness of medications for opioid use disorder (MOUD) (CTN-0027; CTN-0030; and CTN-0051) highlighted the problem of dropout from treatment and few trials defined retention on MOUD as the primary outcome. Long-term follow-up studies on those patient samples demonstrated the importance of long-term continuation of medication for many patients to sustain remission. Overall, these trials highlight the potential

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Humans; Naltrexone; Narcotic Antagonists; Nitrosamines; Opiate Substitution Treatment; Opioid-Related Disorders; United States

Opioid use disorder (OUD) remains a national epidemic with an immense consequence to the United States' healthcare system. Current therapeutic options are limited by adverse effects and limited efficacy.. Recent advances in therapeutic options for OUD have shown promise in the fight against this ongoing health crisis. Modifications to approved medication-assisted treatment (MAT) include office-based methadone maintenance, implantable and monthly injectable buprenorphine, and an extended-release injectable naltrexone. Therapies under investigation include various strategies such as heroin vaccines, gene-targeted therapy, and biased agonism at the G protein-coupled receptor (GPCR), but several pharmacologic, clinical, and practical barriers limit these treatments' market viability. This manuscript provides a comprehensive review of the current literature regarding recent innovations in OUD treatment.

Topics: Analgesics, Opioid; Buprenorphine; Delayed-Action Preparations; Drug Implants; Humans; Injections, Intramuscular; Methadone; Molecular Targeted Therapy; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Receptors, G-Protein-Coupled; Receptors, Opioid, mu; Secologanin Tryptamine Alkaloids; Thiophenes; Urea; Vaccines

Although expanding the availability of buprenorphine-a first-line pharmacotherapy for opioid-use disorder (OUD)-has increased the capacity of healthcare systems to offer treatment, starting this medication is fraught with significant barriers. Standard induction regimens require persons with OUD to taper and discontinue full opioid agonists and experience opioid withdrawal prior to the first dose of buprenorphine. Further, emerging evidence indicates that precipitated withdrawal during induction may impact long-term treatment outcomes. Microinduction is a novel approach that, by harnessing buprenorphine's unique pharmacological profile, may allow circumventing the needed for prolonged opioid tapers, and reduce the risk of precipitated withdrawal-holding promise to enhance treatment access. In this review, we examine the pharmacological basis for microinduction and appraise the evidence of this approach to improve clinical outcomes among persons with OUD. First, we highlight the potential dose-dependent effects of buprenorphine on two key neuroadaptations at the mu-opioid receptor (MOR)-resensitization and upregulation. We then focus on how microinduction may reverse these chronic MOR neuroadaptations, allowing the maintenance of an adequate opioid tone, and thereby potentially circumventing opioid withdrawal. Second, we describe the clinical evidence available, derived from observational reports and open-label studies, examining the potential efficacy of microinduction. Despite significant heterogeneity-exemplified by variable buprenorphine formulations, daily doses, and schedules of administration-these data provide preliminary support for the feasibility of microinduction. Finally, we provide new mechanistic, methodological, and clinical insights to guide future translational research, as well as randomized, placebo-controlled clinical trials in this compelling agenda of pharmacotherapy development.

Topics: Analgesics, Opioid; Buprenorphine; Humans; Narcotic Antagonists; Opioid-Related Disorders; Receptors, Opioid, mu; Substance Withdrawal Syndrome

The novel coronavirus has thrown large sections of our healthcare system into disarray, with providers overburdened by record breaking number of hospitalizations and deaths. The U.S., in particular, has remained the nation with one of the fastest growing case counts in the world. As a consequence, many other critical healthcare needs have not received the necessary resources or consideration. This commentary draws attention to substance use and opioid access during the ongoing crisis, given the potential for breakdowns in treatment access for addiction, the growing concern of mental health comorbidities, and the lack of access for those who require opioids for adequate pain management. Further, the commentary will offer policy and practice recommendations that may be implemented to provide more equitable distribution of care.

Topics: Alcoholism; Analgesics, Opioid; Buprenorphine; COVID-19; Electronic Health Records; Harm Reduction; Health Services Accessibility; Humans; Internet of Things; Opiate Overdose; Opiate Substitution Treatment; Opioid Epidemic; Opioid-Related Disorders; Pain Management; Palliative Care; Practice Guidelines as Topic; Psychosocial Support Systems; Public Policy; SARS-CoV-2; Telemedicine; United States; United States Substance Abuse and Mental Health Services Administration

An increasing number of Americans are turning to kratom for self-management of various pain, anxiety, and mood states and as an opioid substitute. Addiction to this unique botanical develops and carries a high relapse risk and, to date, there are no guidelines on how to maintain long-term abstinence. The aim of this article is to compile all available information on management of "kratom use disorder" (KUD)-as coined here-from the literature, with evidence from the clinical practice of expert addictionologists in an attempt to develop a standard of care consensus.. A systematic literature search was conducted to capture all relevant cases pertaining to maintenance treatment for KUD. Results were supplemented with case reports and scientific posters gleaned from reliable online sources and conference proceedings. Additionally, a survey of members of the American Society of Addiction Medicine (ASAM) was administered to assess the practice patterns of experts who treat patients with KUD in isolation of a comorbid opioid use disorder (OUD).. Based on a literature review, 14 reports exist of long-term management of KUD, half of which do not involve a comorbid OUD. Pharmacological modalities utilized include mostly buprenorphine but also a few cases of naltrexone and methadone, all with favorable outcomes. This is supported by the results of the expert survey, which demonstrated that those who have managed KUD in isolation of a comorbid OUD reported having utilized buprenorphine (89.5%), as well as the other medications for opioid use disorder (MOUD).. This is the first comprehensive review to examine the existing literature referring to management of KUD in combination with a survey of current experts' clinical consensus regarding pharmacological management. Based on this information, it seems reasonable that the indication for MOUD should be extended to cases of moderate to severe KUD.

Topics: Buprenorphine; Humans; Methadone; Mitragyna; Naltrexone; Opioid-Related Disorders; United States

The opioid-related overdose epidemic remains a persistent public health problem in the United States and has been accelerated by the 2019 coronavirus disease pandemic. Existing, evidence-based treatment options for opioid use disorder (OUD) are broadly underutilized, particularly by people experiencing homelessness (PEH). PEH are also more likely to misuse and overdose on opioids. To better understand current gaps and disparities in OUD treatment experienced by PEH and efforts to address them, we synthesized the literature reporting on the intersection of housing status and OUD treatment.. We conducted a scoping review of the literature from the electronic databases MEDLINE, Embase, PsycINFO, and Web of Science Core Collection. We included studies describing treatment-related outcomes specific to PEH and articles assessing OUD treatment interventions tailored to this population. Relevant findings were compiled via thematic analysis and narratively synthesized.. 60 articles met our inclusion criteria, including 43 descriptive and 17 intervention-focused studies. These studies demonstrated that PEH experience more barriers to OUD treatment than their housed counterparts and access inpatient and detoxification treatment more commonly than pharmacotherapy. However, the reviewed literature indicated that PEH have similar outcomes once engaged in pharmacotherapy. Efficacious interventions for PEH were low-barrier and targeted, with housing interventions also demonstrating benefit.. PEH have diminished access to evidence-based OUD treatment, particularly medications, and require targeted approaches to improve engagement and retention. To mitigate the disproportionate opioid-related morbidity and mortality PEH experience, innovative, flexible, and interdisciplinary OUD treatment models are necessary, with housing support playing an important role.

Topics: Buprenorphine; Health Services Accessibility; Health Services Misuse; Humans; Ill-Housed Persons; Methadone; Naltrexone; Opiate Substitution Treatment; Opioid-Related Disorders; United States

To quantify weekly rates of use of buprenorphine for those with employer-based insurance and whether the rate differs based on county-level measures of race, historical fatal drug overdose rate, and COVID-19 case rate.. We used 2020 pharmaceutical claims for 4.8 million adults from a privately insured population to examine changes in the use of buprenorphine to treat opioid use disorder in 2020 during the onset of the COVID-19 pandemic. We quantified variation by examining changes in use rates across counties based on their fatal drug overdose rate in 2018, number of COVID-19 cases per capita, and percent nonwhite.. Weekly use of buprenorphine was relatively stable between the first week of January (0.6 per 10,000 enrollees, 95%CI = 0.2 to 1.1) and the last week of August (0.8 per 10,000 enrollees, 95%CI = 0.4 to 1.3). We did not find evidence of any consistent change in use of buprenorphine by county-level terciles for COVID-19 rate as of August 31, 2020, age-adjusted fatal drug overdose rate, and percent nonwhite. Use was consistently higher for counties in the highest tercile of county age-adjusted fatal drug overdose rate when compared to counties in the lowest tercile of county age-adjusted fatal drug overdose rate.. Our results provide early evidence that new federal- and state-level policies may have steadied the rate of using buprenorphine for those with employer-based insurance during the pandemic.

Topics: Adult; Buprenorphine; COVID-19; Drug Overdose; Humans; Insurance; Opioid-Related Disorders; Pandemics; SARS-CoV-2; United States

The opioid epidemic remains a public health crisis and most people with opioid use disorder (OUD) do not receive effective treatment. The emergency department (ED) can be a critical entry point for treatment. EDs are developing and implementing ED-based efforts to address OUD to improve access to OUD treatment. This study's objective is to identify features of ED-based OUD treatment programs that relate to program implementation, effectiveness, and sustainability.. We obtained data through literature review and semistructured interviews with ED physicians and leaders. The study analyzed these data to develop a framework of key components of ED-based efforts and highlight barriers and facilitators to implementation and program effectiveness.. We identify five key features of ED-based opioid treatment programs that vary across programs and may influence effectiveness and impact: patient identification methods; treatment approaches; program structure; relationship with community partners; and financing and sustainability. Successful implementation of ED-based OUD treatment includes having a champion, a reliable referral network, and systematic tracking and reporting of data for monitoring and feedback.. Going forward, attention to these features may help to improve effectiveness. As researchers conduct studies of ED-based care models, they should assess the impact of variation in key features to improve program effectiveness.

Topics: Analgesics, Opioid; Buprenorphine; Emergency Service, Hospital; Humans; Opioid-Related Disorders; Referral and Consultation

Opioid withdrawal symptoms prior to buprenorphine initiation may be intolerable and as a result, alternative strategies have emerged. We aim to systematically review the efficacy and safety of buprenorphine initiation that aims to omit prerequisite withdrawal.. We conducted a systematic literature search of MEDLINE and CENTRAL from 1996 through April 10, 2020, augmented with searches in Google Scholar and www.clinicaltrials.gov . A study was included if it was in patients with substance use disorder or chronic pain that were taking a full mu opioid agonist and transitioning to buprenorphine without preceding withdrawal, and reported withdrawal during initiation as an outcome. Two investigators independently screened citations and articles for inclusion, collected data using a standardized data collection tool, and assessed study risk of bias.. We included 15 case reports/series, reporting 24 unique cases, in our qualitative synthesis. No controlled studies were identified. Microdosing and bridging with a buprenorphine patch were the most common strategies reported. Transition to buprenorphine with complete cessation of opioid agonists was achieved in 87.5% (n = 21) of cases. Withdrawal during initiation occurred in 58.3% (n = 14) of cases, two of which were at least moderate in severity.. Buprenorphine initiation strategies that omit prerequisite withdrawal have emerged. Low quality evidence from case reports suggests withdrawal during initiation is common but most often mild in severity. There is an unmet need for controlled studies to inform their efficacy and safety compared with traditional strategies, including outcomes during initiation and in the long-term.

Topics: Analgesics, Opioid; Buprenorphine; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Substance Withdrawal Syndrome

Medication for opioid use disorder (MOUD) is associated with substantial reductions in the risk of mortality, and American and Canadian guidelines recommend it as part of the full range of available treatments for youth with opioid use disorder (OUD). We estimated the OUD cascade of care for all adolescents (ages 12-18) and young adults (19-24) with OUD in British Columbia, Canada (BC) in 2018.. Using a provincial-level linkage of six health administrative databases, we classified youth with OUD as adolescents (ages 12-18) or young adults (19-24) to compare with older adults (≥25) and described key factors known to influence engagement in health care. The eight-stage cascade of care included diagnosed with OUD, ever engaged in MOUD, recently in MOUD, currently in MOUD, and retained in MOUD for ≥1 month, ≥3 months, ≥12 months, ≥24 months.. We identified 4048 youth diagnosed with OUD as of September 30, 2018 (6.3% of all people with OUD). Most were young adults, aged 19-24 (n = 3602; 89.0% of all youth), a majority of whom were males (n = 1984; 55.1%). In contrast, adolescents diagnosed with OUD (n = 446; 11.0% of all youth) were mostly females (n = 287; 64.4%). Compared to adolescents, there were more young adults diagnosed with OUD ever engaged in MOUD (71.4% v. 36.5%), currently on MOUD (29.3% v. 16.8%), and retained in care for ≥1 year (8.6% v. 2.0%).. A high proportion of youth aged 12-24 diagnosed with OUD in a health care setting in British Columbia received MOUD yet continued engagement is infrequent, particularly for adolescents. Long-term treatment plans for youth need to consider including MOUD when appropriate as part of tailored, youth-friendly services.

Topics: Adolescent; Aged; Analgesics, Opioid; British Columbia; Buprenorphine; Child; Female; Humans; Male; Opiate Substitution Treatment; Opioid-Related Disorders; United States

Some countries have used opioid agonist medications other than methadone and buprenorphine as a strategy to increase treatment diversity. In Iran and other countries where opium use is common and culturally tolerated, opium tincture (OT) has gained growing popularity and been approved to treat opioid use disorder (OUD). Given the increasing interest in this intervention, we conducted a systematic review of the literature to evaluate the safety and efficacy of OT-assisted treatment for OUD.. We systematically searched international (MEDLINE, Embase, CINAHL, PsychInfo, Google Scholar, and clinicaltrials.gov) and Iranian (Scientific Information Database (SID), Iranmedex, IranDoc, digital library of Iran's Drug Control Headquarters and the Iranian Registry for Clinical Trials) databases on November 04, 2020 without any language or publication date limitations. Two reviewers screened the titles, abstracts, and full-text of the retrieved records to find clinical trials or observational studies that assessed the safety and efficacy of OT-assisted treatment for OUD.. We screened 1301 records and included 21 unique studies on assisted withdrawal (n = 5), maintenance (n = 9), and gradual dose reduction (n = 7) treatment regimens. Most studies included men and people with opium use disorder. We found only six randomized controlled trials (RCT). Our results showed that OT-assisted treatment is associated with comparable outcomes with methadone treatment in both assisted withdrawal and maintenance treatment regimens. We also found promising results for using gradual dose reduction regimen of OT-assisted treatment from observational studies. The overall quality of scientific evidence was low due to the limited number RCT and high risk of bias in the included studies.. The body of evidence supporting the safety and efficacy of OT-assisted treatment in assisted withdrawal, maintenance, and gradual dose reduction regimens is limited but somewhat promising, in particular among people with opium use disorder. Our review calls for higher-quality studies to investigate the comparative efficacy of these treatment methods with standard pharmacotherapies for OUD.

Topics: Buprenorphine; Humans; Male; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Opium

Buprenorphine maintenance treatment (BMT) is widely used in Iran, and its use is growing continuously. We reviewed studies on buprenorphine use, non-prescribed use, use disorder and treatment-seeking for it, buprenorphine-associated poisoning, and mortality in Iran in the current systematic review.. An Iranian database (Scientific Information Database; SID) and three International electronic databases (PubMed, Scopus, and Web of Science) were searched for publications up to August 2020 for the relevant data. Opportunistic methods (Contact with experts and backward citation tracking) were also used for this purpose. Identified records were screened for eligibility criteria, and data of included studies were extracted. For context, the trend of BMT in the country was also examined.. Ten studies were found on the prevalence of non-prescribed buprenorphine use, seven were on the regular use and use disorder, and two studies on buprenorphine poisoning. The last 12-month prevalence of non-prescribed use was lower than 0.5 % in the general population, university, and high school students. The indicator was 2.5 % among persons who use drugs in a 2018 national study. The proportion of buprenorphine poisoning was 4.9 % among all illicit substance poisoning cases admitted to a hospital. The proportion of buprenorphine poisoning cases among all acute pediatric drug poisoning cases increased from 1.2 % to 2.5 % in a 3-year study.. Despite the expansion of BMT in Iran in the last decade, the adverse health consequences associated with buprenorphine are infrequent, when compared to other opioids used in Iran, suggesting the safety of BMT for future expansion.

Topics: Analgesics, Opioid; Buprenorphine; Child; Humans; Iran; Opioid-Related Disorders

Office-Based Opioid Treatment (OBOT) is a delivery model which seeks to make medications for opioid use disorder (MOUD), particularly buprenorphine, widely available in general medical clinics and offices. Despite evidence supporting its effectiveness and cost-effectiveness, uptake of the OBOT model has been relatively slow. One important barrier to faster diffusion of OBOT may be the financial challenges facing clinics that could adopt it.. We review key features and variants of the OBOT model, then discuss different approaches that have been used to fund it, and the findings from previous economic analyses of OBOT's impact on organizational finances. We conclude by discussing the implications of these analyses for the financial sustainability of the OBOT delivery model.. Like other novel services, OBOT poses challenges for providers due to its reliance on services which are 'non-billable' in a fee-for-service environment. A variety of approaches exist for covering the non-billable costs, but which approaches are feasible depends on local payer policies. The scale of the challenges varies with clinic size, organizational affiliations and the policies of the state where the clinic operates. Small clinics in a purely fee-for-service environment may be particularly challenged in pursuing OBOT, given the need to fund a dedicated staff and extra administrative work. The current pandemic may pose both opportunities and challenges for the sustainability of OBOT, with expanded access to telemedicine, but also uncertainty about the durability of the expansion.. The reimbursement environment for OBOT delivery varies widely around the US, and is evolving as Medicare (and possibly other payers) introduce alternative payment approaches. Clinics considering adoption of OBOT are well advised to thoroughly investigate these issues as they make their decision. In addition, payers will need to rethink how they pay for OBOT to make it sustainable.

Topics: Aged; Ambulatory Care Facilities; Analgesics, Opioid; Buprenorphine; Humans; Medicare; Opiate Substitution Treatment; Opioid-Related Disorders; Primary Health Care; United States

Neonatal abstinence syndrome (NAS) due to opioid withdrawal may result in disruption of the mother-infant relationship, sleep-wake abnormalities, feeding difficulties, weight loss, seizures and neurodevelopmental problems.. To assess the effectiveness and safety of using an opioid for treatment of NAS due to withdrawal from opioids in newborn infants.. We ran an updated search on 17 September 2020 in CENTRAL via Cochrane Register of Studies Web and MEDLINE via Ovid. We also searched clinical trials databases, conference proceedings and the reference lists of retrieved articles for eligible trials.. We included randomised controlled trials (RCTs), quasi- and cluster-RCTs which enrolled infants born to mothers with opioid dependence and who were experiencing NAS requiring treatment with an opioid.. Three review authors independently assessed trial eligibility and risk of bias, and independently extracted data. We used the GRADE approach to assess the certainty of evidence.. We included 16 trials (1110 infants) with NAS secondary to maternal opioid use in pregnancy. Seven studies at low risk of bias were included in sensitivity analysis. Opioid versus no treatment / usual care: a single trial (80 infants) of morphine and supportive care versus supportive care alone reported no difference in treatment failure (risk ratio (RR) 1.29, 95% confidence interval (CI) 0.41 to 4.07; very low certainty evidence). No infant had a seizure. The trial did not report mortality, neurodevelopmental disability and adverse events. Morphine increased days hospitalisation (mean difference (MD) 15.00, 95% CI 8.86 to 21.14; very low certainty evidence) and treatment (MD 12.50, 95% CI 7.52 to 17.48; very low certainty evidence), but decreased days to regain birthweight (MD -2.80, 95% CI -5.33 to -0.27) and duration (minutes) of supportive care each day (MD -197.20, 95% CI -274.15 to -120.25). Morphine versus methadone: there was no difference in treatment failure (RR 1.59, 95% CI 0.95 to 2.67; 2 studies, 147 infants; low certainty evidence). Seizures, neonatal or infant mortality and neurodevelopmental disability were not reported. A single study reported no difference in days hospitalisation (MD 1.40, 95% CI -3.08 to 5.88; 116 infants; low certainty evidence), whereas data from two studies found an increase in days treatment (MD 2.71, 95% CI 0.22 to 5.21; 147 infants; low certainty) for infants treated with morphine. A single study reported no difference in breastfeeding, adverse events, or out of home placement. Morphine versus sublingual buprenorphine: there was no difference in treatment failure (RR 0.79, 95% CI 0.36 to 1.74; 3 studies, 113 infants; very low certainty evidence). Neonatal or infant mortality and neurodevelopmental disability were not reported. There was moderate certainty evidence of an increase in days hospitalisation (MD 11.45, 95% CI 5.89 to 17.01; 3 studies, 113 infants), and days treatment (MD 12.79, 95% CI 7.57 to 18.00; 3 studies, 112 infants) for infants treated with morphine. A single adverse event (seizure) was reported in infants exposed to buprenorphine. Morphine versus diluted tincture of opium (DTO): a single study (33 infants) reported no difference in days hospitalisation, days treatment or weight gain (low certainty evidence). Opioid versus clonidine: a single study (31 infants) reported no infant with treatment failure in either group. This study did not report seizures, neonatal or infant mortality and neurodeve. Compared to supportive care alone, the addition of an opioid may increase duration of hospitalisation and treatment, but may reduce days to regain birthweight and the duration of supportive care each day. Use of an opioid may reduce treatment failure compared to phenobarbital, diazepam or chlorpromazine. Use of an opioid may have little or no effect on duration of hospitalisation or treatment compared to use of phenobarbital, diazepam or chlorpromazine. The type of opioid used may have little or no effect on the treatment failure rate. Use of buprenorphine probably reduces duration of hospitalisation and treatment compared to morphine, but there are no data for time to control NAS with buprenorphine, and insufficient evidence to determine safety. There is insufficient evidence to determine the effectiveness and safety of clonidine.

Topics: Buprenorphine; Chlorpromazine; Clonidine; Diazepam; Humans; Hypnotics and Sedatives; Infant, Newborn; Methadone; Morphine; Narcotics; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Opium; Phenobarbital; Randomized Controlled Trials as Topic

Pharmacological treatments for opioid use disorders (OUDs) may have mixed efficacy across diverse groups, i.e., sex/gender, race/ethnicity, and socioeconomic status (SES). The present systematic review aims to examine how diverse groups have been included in U.S. randomized clinical trials examining pharmacological treatments (i.e., methadone, buprenorphine, or naltrexone) for OUDs. PubMed was systematically searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The initial search yielded 567 articles. After exclusion of ineligible articles, 50 remained for the present review. Of the included articles, 14.0% (n = 7) reported both full (i.e., accounting for all participants) sex/gender and race/ethnicity information; only two of those articles also included information about any SES indicators. Moreover, only 22.0% (n = 11) reported full sex/gender information, and 42.0% (n = 21) reported full racial/ethnic information. Furthermore, only 10.0% (n = 5) reported that their lack of subgroup analyses or diverse samples was a limitation to their studies. Particularly underrepresented were American Indian/Alaska Native (AI/AN), Asian, Native Hawaiian/Other Pacific Islander (NH/OPI), and multiracial individuals. These results also varied by medication type; Black individuals were underrepresented in buprenorphine randomized controlled trials (RCTs) but were well represented in RCTs for methadone and/or naltrexone. In conclusion, it is critical that all people receive efficacious pharmacological care for OUDs given the ongoing opioid epidemic. Findings from the present review, however, support that participants from diverse or marginalized backgrounds are underrepresented in treatment trials, despite being at increased risk for disparities related to OUDs. Suggestions for future research are advanced. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Topics: Analgesics, Opioid; Buprenorphine; Humans; Methadone; Naltrexone; Opioid-Related Disorders; United States

There is limited information about trends in the treatment of opioid use disorder (OUD) among Medicaid enrollees.. To examine the use of medications for OUD and potential indicators of quality of care in multiple states.. Exploratory serial cross-sectional study of 1 024 301 Medicaid enrollees in 11 states aged 12 through 64 years (not eligible for Medicare) with International Classification of Diseases, Ninth Revision (ICD-9 or ICD-10) codes for OUD from 2014 through 2018. Each state used generalized estimating equations to estimate associations between enrollee characteristics and outcome measure prevalence, subsequently pooled to generate global estimates using random effects meta-analyses.. Calendar year, demographic characteristics, eligibility groups, and comorbidities.. Use of medications for OUD (buprenorphine, methadone, or naltrexone); potential indicators of good quality (OUD medication continuity for 180 days, behavioral health counseling, urine drug tests); potential indicators of poor quality (prescribing of opioid analgesics and benzodiazepines).. In 2018, 41.7% of Medicaid enrollees with OUD were aged 21 through 34 years, 51.2% were female, 76.1% were non-Hispanic White, 50.7% were eligible through Medicaid expansion, and 50.6% had other substance use disorders. Prevalence of OUD increased in these 11 states from 3.3% (290 628 of 8 737 082) in 2014 to 5.0% (527 983 of 10 585 790) in 2018. The pooled prevalence of enrollees with OUD receiving medication treatment increased from 47.8% in 2014 (range across states, 35.3% to 74.5%) to 57.1% in 2018 (range, 45.7% to 71.7%). The overall prevalence of enrollees receiving 180 days of continuous medications for OUD did not significantly change from the 2014-2015 to 2017-2018 periods (-0.01 prevalence difference, 95% CI, -0.03 to 0.02) with state variability in trend (90% prediction interval, -0.08 to 0.06). Non-Hispanic Black enrollees had lower OUD medication use than White enrollees (prevalence ratio [PR], 0.72; 95% CI, 0.64 to 0.81; P < .001; 90% prediction interval, 0.52 to 1.00). Pregnant women had higher use of OUD medications (PR, 1.18; 95% CI, 1.11-1.25; P < .001; 90% prediction interval, 1.01-1.38) and medication continuity (PR, 1.14; 95% CI, 1.10-1.17, P < .001; 90% prediction interval, 1.06-1.22) than did other eligibility groups.. Among US Medicaid enrollees in 11 states, the prevalence of medication use for treatment of opioid use disorder increased from 2014 through 2018. The pattern in other states requires further research.

Topics: Adolescent; Adult; Analgesics, Opioid; Buprenorphine; Child; Cross-Sectional Studies; Female; Humans; Male; Medicaid; Methadone; Middle Aged; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; United States; Young Adult

Opioid abuse and overdose deaths have reached epidemic proportions in the last couple decades. In response to rational prescribing initiatives, utilization of prescription opioids has decreased; however, the number of deaths due to opioid overdoses continues to rise, largely driven by fentanyl analogues in adulterated heroin. Solutions to the opioid crisis must be multifaceted and address underlying opioid addiction. In recent years, buprenorphine has become a cornerstone in the treatment of opioid use disorder (OUD) and initiation of therapy in the emergency department (ED) has become increasingly common. There have also been calls by many organizations to remove the requirement for additional training and X-waiver to prescribe buprenorphine. In April 2021, the Biden Administration eased prescribing restrictions on the drug. These initiatives are expected to increase ED utilization of the buprenorphine. The purpose of this paper is to provide an updated overview of the role and use of buprenorphine in the ED setting so physicians may adapt to the changing practice environment.. This is a narrative review describing the role of buprenorphine in the ED. A PubMed search was conducted using the keywords "opioid epidemic" "buprenorphine," and "medication assisted therapy", and "emergency department". All the articles that contained information on the opioid epidemic, medication assisted therapy, and the biological effects of buprenorphine, that were also relevant to pain management and the ED, were included in the review.. Multiple studies have pointed to the effective use of buprenorphine as a treatment for OUDs in ED patients and are superior to standard care; however, there are various barriers to its use in the ED setting.. Emergency physicians can influence opioid related morbidity and mortality, by familiarizing themselves with the use of buprenorphine to treat opioid withdrawal and addiction, particularly now that prescribing restrictions have been eased. Further ED research is necessary to assess the optimal use of buprenorphine in this care setting.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Drug and Narcotic Control; Emergency Medicine; Humans; Opiate Substitution Treatment; Opioid-Related Disorders

Buprenorphine is 1 of 3 medications approved by the US Food and Drug Administration for the treatment of opioid use disorder, and practitioners must obtain a federal waiver to prescribe buprenorphine. Until recently, physicians and advanced practice clinicians were required to complete 8 and 24 hours of training, respectively, before applying for this waiver and to provide psychosocial services when prescribing buprenorphine to ≤30 patients. The US Department of Health and Human Services announced in April 2021 that eligible providers would be exempt from the educational requirement for certification, making the waiver more accessible for those intending to prescribe to ≤30 patients. Here, we reviewed the historic background to the exemption and provided practical guidelines to practitioners caring for obstetrical patients with opioid use disorder who are considering applying for the waiver for the first time. Because the educational requirements will no longer be required for X-waiver application, we reviewed fundamental topics and challenging scenarios that are often reviewed in certification courses.

Topics: Buprenorphine; Certification; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Physicians

Although oral opioid agonist therapies (OATs), buprenorphine and methadone, are effective first-line treatments, OAT remains largely underutilized due to low retention rates and wide variation across programs. This rapid review therefore sought to summarize the retention rates reported by randomized controlled trials (RCTs) and controlled observational study designs that compared methadone to buprenorphine (or buprenorphine-naloxone).. We searched four electronic databases (EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials, CINAHL, up to April 2018) for RCTs and controlled observational studies that compared oral fixed-dose methadone to buprenorphine versus methadone (or buprenorphine-naloxone). Data were extracted separately for two different definitions of retention in treatment: (1) length of time retained in the study and (2) presence on the final day of a study. Separate random effects meta-analyses were performed for RCTs and controlled observational studies. Data from controlled observational studies where retention was measured as the length of time retained in the study were not amenable to meta-analysis.. Among 7603 studies reviewed, 10 RCTs and 3 observational studies met inclusion criteria (n = 5065) and compared fixed-dose oral buprenorphine with methadone. Across studies, the average retention rate was highly variable (RCTs: buprenorphine 20.0-82.5% and methadone 30.7-83.8%; observational studies: buprenorphine 20.2-78.3% and methadone 48.3-74.8%). For time period retained in the study, we observed no significant difference in treatment retention for buprenorphine versus methadone in RCTs (standardized mean difference [SMD] =  - 0.07; 95% CI - 0.35-0.21, p = 0.63; quality of evidence: low). For presence on the final study day, we observed no significant difference between buprenorphine and methadone treatment retention in RCTs (risk ratio [RR] = 0.89; 95% CI 0.73-1.08, p = 0.24; quality of evidence: low) and controlled observational studies (RR = 0.75; 95% CI 0.36-1.58, p = 0.45).. Meta-analysis of existing RCTs suggests retention in oral fixed-dose opioid agonist therapy with methadone appears to be generally equal to buprenorphine (or buprenorphine-naloxone), with wide variation across studies. Similarly, a meta-analysis of three controlled observational studies indicated no difference in treatment retention although there was significant heterogeneity among the included studies. The length of follow-up did not appear to affect the retention rate.. PROSPERO CRD42018104452 .

Topics: Analgesics, Opioid; Buprenorphine; Humans; Methadone; Observational Studies as Topic; Opioid-Related Disorders; Randomized Controlled Trials as Topic

The COVID-19 pandemic disrupted healthcare delivery worldwide with likely negative effects on people who use opioids (PWUO). This scoping review of the original research literature describes the impact of the COVID-19 pandemic on healthcare delivery for PWUO and identifies gaps in the literature.. This scoping review of the original research literature maps the available knowledge regarding the impact of the COVID-19 pandemic on healthcare delivery for PWUO. We utilized the methodology developed by the Joanna Briggs Institute for scoping reviews, and content analyses methodology to characterize the current state of the literature.. Of the 14 included studies, administrative database (n = 11), cross-sectional (n = 1) or qualitative (n = 2) studies demonstrated service gaps (n = 7), patient/provider experiences (n = 3), and patient outcomes for PWUO (n = 4). In March 2020, healthcare utilization dropped quickly, sharply increasing only for reasons of opioid overdose by May 2020. Service gaps existed in accessing treatment for new patients during the pandemic due to capacity and infrastructure limits. Physicians reported difficulty referring patients to begin an outpatient opioid treatment program due to increased restrictions in capacity and infrastructure. Patients also reported uncertainty about accessing outpatient treatment, but that telehealth initiation of buprenorphine increased access to treatment from home. Disproportionate increases in overdose rates among African Americans were reported in two studies, with differences by race and gender not examined in most studies. Fatal overdoses increased 60% in African Americans during the pandemic, while fatal overdoses in Non-Hispanic White individuals decreased.. In summary, this beginning evidence demonstrates that despite early reluctance to use the healthcare system, opioid overdose-related use of healthcare increased throughout the pandemic. Service delivery for medications to treat OUD remained at or above pre-pandemic levels, indicating the ability of telehealth to meet demand. Yet, racial disparities that existed pre-pandemic for PWUO are intensifying, and targeted intervention for high-risk groups is warranted to prevent further mortality. As the pandemic progresses, future research must focus on identifying and supporting subgroups of PWUO who are at heightened risk for experiencing negative outcomes and lack of access to care.

Topics: Buprenorphine; COVID-19; Cross-Sectional Studies; Drug Overdose; Emergency Medical Services; Health Services Accessibility; Humans; Methadone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Pandemics; Patient Satisfaction; SARS-CoV-2; Telemedicine

The past two decades have witnessed an epidemic of opioid use disorder (OUD) in the USA, resulting in catastrophic loss of life secondary to opioid overdoses. Medication treatment of opioid use disorder (MOUD) is effective, yet barriers to care continue to result in a large proportion of untreated individuals. Optimal analgesia can be obtained in patients with MOUD within the perioperative period. Anesthesiologists and pain physicians can recommend and consider initiating MOUD in patients with suspected OUD at the point of care; this can serve as a bridge to comprehensive treatment and ultimately save lives.. The Board of Directors of the American Society of Regional Anesthesia and Pain Medicine, American Society of Anesthesiologists, American Academy of Pain Medicine, American Society of Addiction Medicine and American Society of Health System Pharmacists approved the creation of a Multisociety Working Group on Opioid Use Disorder, representing the fields of pain medicine, addiction, and pharmacy health sciences. An extensive literature search was performed by members of the working group. Multiple study types were included and reviewed for quality. A modified Delphi process was used to assess the literature and expert opinion for each topic, with 100% consensus being achieved on the statements and each recommendation. The consensus statements were then graded by the committee members using the United States Preventive Services Task Force grading of evidence guidelines. In addition to the consensus recommendations, a narrative overview of buprenorphine, including pharmacology and legal statutes, was performed.. Two core topics were identified for the development of recommendations with >75% consensus as the goal for consensus; however, the working group achieved 100% consensus on both topics. Specific topics included (1) providing recommendations to aid physicians in the management of patients receiving buprenorphine for MOUD in the perioperative setting and (2) providing recommendations to aid physicians in the initiation of buprenorphine in patients with suspected OUD in the perioperative setting.. To decrease the risk of OUD recurrence, buprenorphine should not be routinely discontinued in the perioperative setting. Buprenorphine can be initiated in untreated patients with OUD and acute pain in the perioperative setting to decrease the risk of opioid recurrence and death from overdose.

Topics: Acute Pain; Analgesics, Opioid; Buprenorphine; Humans; Opioid-Related Disorders; Pain Management; United States

Opioid use disorder (OUD) is a chronic, relapsing condition, often associated with legal, interpersonal, and employment problems. Medications demonstrated to be effective for OUD are methadone (a full opioid agonist), buprenorphine (a partial agonist), and naltrexone (an opioid antagonist). Methadone and buprenorphine act by suppressing opioid withdrawal symptoms and attenuating the effects of other opioids. Naltrexone blocks the effects of opioid agonists. Oral methadone has the strongest evidence for effectiveness. Longer duration of treatment allows restoration of social connections and is associated with better outcomes. Treatments for OUD may be limited by poor adherence to treatment recommendations and by high rates of relapse and increased risk of overdose after leaving treatment. Treatment with methadone and buprenorphine has the additional risk of diversion and misuse of medication. New depot and implant formulations of buprenorphine and naltrexone have been developed to address issues of safety and problems of poor treatment adherence. For people with OUD who do not respond to these treatments, there is accumulating evidence for supervised injectable opioid treatment (prescribing pharmaceutical heroin). Another medication mode of minimizing risk of overdose is take-home naloxone. Naloxone is an opioid antagonist used to reverse opioid overdose, and take-home naloxone programs aim to prevent fatal overdose. All medication-assisted treatment is limited by lack of access and by stigma. In seeking to stem the rising toll from OUD, expanding access to approved treatment such as methadone, for which there remains the best evidence of efficacy, may be the most useful approach.

Topics: Analgesics, Opioid; Buprenorphine; Humans; Methadone; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders

Buprenorphine and methadone are international gold standards for managing opioid use disorders. Although they are efficacious in treating opioid dependence, buprenorphine and methadone present risks, especially during pregnancy, causing neonatal abstinence syndrome and adverse obstetrical outcomes. Buprenorphine and methadone are also abused during pregnancy, and identifying their use is important to limit unprescribed prenatal exposure. Previous studies have suggested that concentrations of buprenorphine, but not methadone markers in unconventional matrices may predict child outcomes, although currently only limited data exist. We reviewed the literature on concentrations of buprenorphine, methadone, and their metabolites in unconventional matrices to improve data interpretation.. A literature search was conducted using scientific databases (PubMed, Scopus, Web of Science, and reports from international institutions) to review published articles on buprenorphine and methadone monitoring during pregnancy.. Buprenorphine and methadone and their metabolites were quantified in the meconium, umbilical cord, placenta, and maternal and neonatal hair. Methadone concentrations in the meconium and hair were typically higher than those in other matrices, although the concentrations in the placenta and umbilical cord were more suitable for predicting neonatal outcomes. Buprenorphine concentrations were lower and required sensitive instrumentation, as measuring buprenorphine glucuronidated metabolites is critical to predict neonatal outcomes.. Unconventional matrices are good alternatives to conventional ones for monitoring drug exposure during pregnancy. However, data are currently scarce on buprenorphine and methadone during pregnancy to accurately interpret their concentrations. Clinical studies should be conducted with larger cohorts, considering confounding factors such as illicit drug co-exposure.

Topics: Analgesics, Opioid; Buprenorphine; Drug Monitoring; Female; Hair; Humans; Meconium; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Prenatal Exposure Delayed Effects; Umbilical Cord

Topics: Buprenorphine; Dose-Response Relationship, Drug; Humans; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders

The United States continues to experience an opioid epidemic of unprecedented proportions despite FDA approval of life saving medications, such as buprenorphine. This paper describes a novel group-based buprenorphine treatment model and summarizes patient characteristics and treatment retention. This model, known as the Comprehensive Opioid Addiction Treatment (COAT) program, was developed in West Virginia, the epicenter of the opioid epidemic.. Data on 454 patients actively enrolled in the COAT program were extracted from an administrative clinical data set and electronic medical records and analyzed using descriptive and quantitative analysis to determine long-term retention in treatment using frequencies and means.. The characteristics of the 454 patients are as follows: average age of 39, 53% female, predominantly white (94%) and Medicaid was the primary insurance provider (68%). Analysis of retention showed 37.8% of patents were retained less than one year and 14.7% were retained 10 or more years. Initiating treatment at a younger age was associated with long-term retention.. Opioid use disorder is a chronic relapsing disease and treatment models that retain patients long-term have the greatest benefit. The COAT model has been successful in retaining patients long-term in a rural setting where barriers to treatment are many.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Female; Humans; Male; Medicaid; Opioid-Related Disorders; United States; West Virginia

The use of buprenorphine, a mixed opioid agonist-antagonist, for the management of chronic pain and/or opioid use disorder is increasing. As such, medical providers will more frequently encounter patients on this therapy. In this paper, we synthesize existing knowledge (derived through keyword searches using MEDLINE databases) in a novel conceptual framework for patients on buprenorphine presenting with acute pain or for those requiring surgical or invasive procedures. This framework is based on three unique domains: the patient, the features of the acute pain insult, and the environment. We discuss important considerations regarding the unique aspects of buprenorphine formulations and dosing, and we describe the importance of multidisciplinary planning and multimodal analgesic strategies. We also highlight important differences in management strategies based upon the presence or absence of opioid use disorder. All medical providers must be prepared to guide the patient on buprenorphine safely through the acute care episode, which includes adequate treatment of acute pain and avoidance of iatrogenic harm, including both short-term complications (eg, respiratory depression) and long-term complications (eg, relapse to opioid use).

Topics: Acute Pain; Buprenorphine; Dose-Response Relationship, Drug; Female; Humans; Male; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Pain, Postoperative

Prior to approval in the European Union, a systematic benefit-risk assessment was required to compare buprenorphine implant to sublingual buprenorphine as part of the license application to the European Medicines Agency.. The Benefit-Risk Action Team framework was used to describe the overall benefit-risk of buprenorphine implant in comparison to sublingual buprenorphine.. A value tree of key benefits and risks related to the implant formulation of buprenorphine was constructed. Risk differences (RD) or reporting ORs (ROR) and corresponding 95% CIs were calculated for each outcome, along with the number needed to treat and number needed to harm. Swing weighting was assigned to outcomes and the weighted net clinical benefit (wNCB) was calculated.. Key benefits assessed: reduced risk of illicit opioid use (RD=0.09, 95% CI 0.01 to 0.17), reduced risk of misuse and diversion (ROR=0.13, 95% CI 0.02 to 0.94), improved compliance and convenience (RD=0.20) and quality of life measures (RD=0.03). Key risks assessed: clinically significant implant breakage (RD=0.01, 95% CI 0.00 to 0.01), migration/missing implant (RD=0.01, 95% CI 0.00 to 0.02), infection at insertion/removal site (RD=0.08, 95% CI 0.03 to 0.12) and implant-related allergic reaction (RD=0.07, 95% CI 0.03 to 0.11). The wNCB for buprenorphine implant was 4.96, which suggests a favourable benefit-risk profile.. The benefit-risk profile of buprenorphine implant is considered favourable in comparison to sublingual buprenorphine, based on this semiquantitative analysis using available data. Further data from real-world use on benefits and risks should be used for ongoing monitoring of the benefit-risk profile of buprenorphine implants in the postmarketing setting.

Topics: Buprenorphine; Humans; Opioid-Related Disorders; Quality of Life; Risk Assessment; Risk Management

Emergency rooms across the United States regularly treat patients with opioid use disorder and patients experiencing opioid overdose. Four to six million people in the US are estimated to have opioid use disorder. Over half of overdose related deaths in 2016 resulted from the use of opioids. The majority of deaths involved the use of fentanyl. There is an opioid epidemic plaguing the nation and with emergency rooms at the forefront of the proverbial battlefield; they can potentially play a key role in addressing the problem. Currently, there are three FDA approved, evidence-based medications for the treatment of opioid use disorder. These are buprenorphine, methadone and extendedrelease naltrexone. Buprenorphine induction in emergency room settings has shown great promise. Research suggests that it is an effective, safe and cost-effective treatment to initiate in emergency rooms. In order to successfully treat opioid use disorder and overdose in emergency rooms, they must have waivered providers and they must be equipped with the necessary resources. The VA Connecticut has been able to overcome some of the challenges to initiating buprenorphine in the emergency room setting and has established a feasible model for treating opioid overdose and managing opioid use disorder.

Topics: Analgesics, Opioid; Buprenorphine; Emergency Service, Hospital; Humans; Methadone; Naltrexone; Opioid-Related Disorders; United States

The number of children with prenatal opioid exposure to medication for addiction treatment (MAT) with methadone and buprenorphine for maternal opioid use disorder is increasing, but the associations of this exposure with cognitive outcomes are not well understood.. To examine the strength and consistency of findings in the medical literature regarding the association of prenatal exposure to MAT with early childhood cognitive development, particularly when accounting for variables outside MAT exposure.. A search strategy obtained publications from PubMed, CINAHL, PsycINFO, Web of Science, and Embase from January 1972 to June 2019. Reference lists from identified articles were searched.. Inclusion criteria were cohort studies, studies including children aged 1 to 60 months with at least 2 months of prenatal MAT exposure, studies using standardized direct-observation testing scales, and studies reporting means and SDs. Case reports, case series, historical controls, and reviews were excluded.. Two authors independently selected studies for inclusion, extracted data, and assessed study quality. Data extracted included demographic characteristics, covariates, sources of bias, and effect estimates. Meta-analysis was performed using random-effects models. This study was conducted according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Data extraction and synthesis were conducted between January 2018 and August 2019.. Cognitive test scores and demographic variability between exposed and unexposed groups.. A total of 16 unique cohorts, described in 27 articles and including 1086 children (485 [44.7%] with MAT exposure), were included in a quantitative synthesis. On meta-analysis, MAT exposure was associated with lower cognitive development scores (pooled standardized mean difference, -0.57; 95% CI, -0.93 to -0.21; I2 = 81%). Multiple subanalyses on demographic characteristics (ie, maternal education, race/ethnicity, socioeconomic status, prenatal tobacco exposure, infant sex) were conducted. In the subanalysis of studies with comparable prenatal exposure to tobacco smoke, the association of MAT exposure with cognitive scores was no longer statistically significant and became homogeneous (standardized mean difference, -0.11; 95% CI, -0.42 to 0.20; I2 = 0%).. In this study, predefined subanalyses demonstrated how poor recruitment, particularly imbalances in maternal tobacco use, could contribute to a negative overall association of cognitive development test scores with prenatal MAT exposure. Promoting tobacco cessation for pregnant women with opioid use disorder should be prioritized in this high-risk population.

Topics: Analgesics, Opioid; Buprenorphine; Child Development; Child, Preschool; Cognition; Cognitive Dysfunction; Female; Humans; Infant; Infant, Newborn; Male; Maternal Exposure; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Risk Factors

Acute pain management in patients on buprenorphine opioid agonist therapy (BOAT) can be challenging. It is unclear whether BOAT should be continued or interrupted for optimization of postoperative pain control.. To determine an evidence-based approach for pain management in patients on BOAT in the perioperative setting, particularly whether BOAT should be continued or interrupted with or without bridging to another mu opioid agonist and to identify benefits and harms of either perioperative strategy.. Systematic literature review with qualitative data synthesis.. Hospital, perioperative.. The study protocol was registered on PROSPERO (Registration number 9030276355). Medline via OVID, EMBASE, CINAHL, and the Cochrane CENTRAL register of trials were searched for prospective or retrospective observational or controlled studies, case series, and case reports that described perioperative or acute pain care for patients on BOAT. References of narrative and systematic reviews addressing acute pain management in patients on BOAT and references of included articles were hand-searched to identify additional original articles for inclusion. The full text of publications were reviewed for final inclusion, and data were extracted using a standardized data extraction form. Results were summarized qualitatively. Primary outcomes were postoperative pain intensity and total opioid use and identification of benefits and harms of perioperative strategies.. Eighteen publications presenting data on the perioperative management of patients on BOAT were identified: 10 case reports, 5 case series, and 3 retrospective cohort studies. Eleven articles reported continuation of BOAT, 2 concerned bridging BOAT, and 4 articles described stopping BOAT without planned bridging. In one retrospective cohort study, BOAT was continued in half and interrupted in half of patients. Patients on BOAT may have pain that is more difficult to treat than those who are not on OAT. There is no clear evidence that one particular strategy provides superior postoperative pain control, but interruption of BOAT may result in harm, including failure to return to baseline BOAT doses, continuing non-BOAT opioid use, or relapse of opioid use disorder.. There were a limited number of articles relevant to the study question consisting of case reports and retrospective observational studies. Some omitted relevant details. No prospective studies were found.. There is no clear benefit to bridging or stopping BOAT but failure to restart it may pose concerns for relapse. We recommend continuing BOAT in the perioperative period when possible and incorporating an interdisciplinary approach with multimodal analgesia.. Opioid use disorder, opiate substitution treatment, buprenorphine, buprenorphine-naloxone, buprenorphine opioid agonist therapy, postoperative pain, acute pain, multimodal analgesia.

Topics: Analgesics, Opioid; Buprenorphine; Drug Administration Schedule; Humans; Observational Studies as Topic; Opiate Substitution Treatment; Opioid-Related Disorders; Pain Management; Pain, Postoperative; Prospective Studies; Retrospective Studies

The use of pharmacological treatments for opioid use disorders, including methadone, buprenorphine and naltrexone has been associated with a reduction in mortality compared with illicit opioid use. However, these treatments can also contribute significantly to the risk of death. The opioid agonists methadone and buprenorphine achieve clinical efficacy in patients with an opioid use disorder through suppressing craving and diminishing the effectiveness of illicit opioid doses, while the antagonist naltrexone blocks the action of opioids. Pharmacological differences between opioid pharmacotherapies then create different temporal patterns of protection and mortality risk, different risks of relapse to illicit opioid use, and variations in direct and indirect toxicity, which are revealed in clinical and epidemiological studies. Induction onto methadone and the cessation of oral naltrexone treatment are associated with an elevated risk of opioid poisoning, which is not apparent in patients treated with buprenorphine or sustained-release naltrexone. Beyond drug-related mortality, these pharmacotherapies can impact a participant's risk of death. Buprenorphine may also have some advantages over methadone in patients with depressive disorders or cardiovascular abnormalities. Naltrexone, which is also commonly prescribed to manage problem alcohol use, may reduce deaths in chronic co-alcohol users. Understanding these pharmacologically driven patterns then guides the judicious choice of drug and dosing schedule and the proactive risk management that is crucial to minimising the risk of death in treatment.

Topics: Analgesics, Opioid; Buprenorphine; Drug Administration Schedule; Humans; Methadone; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Risk Management

The volatile opioid epidemic is associated with higher levels of opioid use disorder (OUD) and negative health outcomes in adolescents and young adults. Medications for opioid use disorder (MOUD) demonstrate the best evidence for treating OUD. Adherence to and retention in MOUD, defined as continuous engagement in treatment, among adolescents and young adults, however, is incompletely understood. We examined the state of the literature regarding the association of age with adherence to and retention in MOUD using methadone, buprenorphine, or naltrexone among persons aged 10-24 years, along with related facilitators and barriers. All studies of MOUD were searched for that examined adherence, retention, or related concepts as an outcome variable and included adolescents or young adults. Search criteria generated 10,229 records; after removing duplicates and screening titles and abstracts, 587 studies were identified for full-text review. Ultimately, 52 articles met inclusion criteria for abstraction and 17 were selected for qualitative coding and analysis. Younger age was consistently associated with shorter retention, although the overall quality of included studies was low. Several factors at the individual, interpersonal, and institutional levels, such as concurrent substance use, MOUD adherence, family conflict, and MOUD dosage and flexibility, appeared to have roles in MOUD retention among adolescents and young adults. Ways MOUD providers can tailor treatment to increase retention of adolescents and young adults are highlighted, as is the need for more research explaining MOUD adherence and retention disparities in this age group.

Topics: Adolescent; Buprenorphine; Child; Humans; Methadone; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Young Adult

The burden of chronic pain in the United States is staggering. Concurrently, the problems associated with use of opioids for treatment of chronic pain have been prominently scrutinized in recent years. Buprenorphine is an opioid that is available for treatment of both chronic pain and opioid use disorder. Its use for chronic pain has been hampered by various factors including complex and often misunderstood pharmacology, challenges to transition and induction to buprenorphine from other opioids, provider perceptions around the legality of prescribing sublingual buprenorphine for pain, and insurance coverage limitations. This article reviews the pharmacology and clinical effectiveness of buprenorphine in the context of chronic pain treatment.

Topics: Analgesics, Opioid; Buprenorphine; Chronic Pain; Humans; Opioid-Related Disorders; Pain Management

The rising prevalence of opioid use disorder (OUD) and related complications in North America coupled with limited numbers of specialists in addiction medicine has led to large gaps in treatment. Primary care providers (PCPs) are ideally suited to diagnose and care for people with OUD and are increasingly being called upon to improve access to care. This review will highlight the recent literature pertaining to the care of patients with OUD by PCPs.. The prevalence of patients with OUD in primary care practice is increasing, and models of office-based opioid treatment (OBOT) are evolving to meet local needs of both ambulatory practices and patients. OBOT has been shown to increase access to care and demonstrates comparable outcomes when compared to more specialty-driven care. OBOT is an effective means of increasing access to care for patients with OUD. The ideal structure of OBOT depends on local factors. Future research must explore ways to increase the identification and diagnosis of patients with OUD, improve treatment retention rates, reduce stigma, and promote interdisciplinary approaches to care.

Topics: Buprenorphine; Humans; North America; Opiate Substitution Treatment; Opioid-Related Disorders; Primary Health Care

We assessed how opioid agonist treatment (OAT) for opioid use disorder (OUD), specifically methadone and buprenorphine, including buprenorphine-naloxone, is delivered in routine clinical practice, with a focus on factors that affect access to and delivery of these services. The aims of this review were to summarize eligibility criteria for entry to OAT, doses in routine clinical practice, access to and eligibility for unsupervised dosing and urine drug screening practices in OAT programs globally.. We completed searches of PubMed, Embase, and grey literature databases for cross-sectional or observational cohort studies of OAT using either methadone or buprenorphine. Dose data extracted from eligible studies were compared with guidelines provided by WHO.. We found 140 reports from 41 countries that contained data for at least one of the relevant indicators. A diagnosis of opioid dependence or opioid use disorder was the most common eligibility requirement for OAT (13 or 17 countries). Reported mean or median doses for methadone ranged from 16-131 mg whereas range for buprenorphine was 2.5-19 mg. Access to unsupervised dosing under some conditions was reported in 18 of 27 countries. Frequency of regular urine drug screenings (UDS) ranged from several times a week to eight times per year (methadone) or as clinically indicated.. Opioid agonist treatment practices, including doses prescribed, vary greatly both within and across countries. Of particular concern is the persistence of lower dose prescribing practices, in which patients may be prescribed doses below those proven to yield significant clinical benefits.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Humans; Methadone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders

Buprenorphine induction can lead to precipitated opioid withdrawal, even when using novel techniques such as transdermal buprenorphine. Involuntary limb movements are a distressing symptom of precipitated withdrawal that can be difficult to treat. We report a case of a military veteran transitioning from methadone to buprenorphine for the treatment of opioid use disorder (OUD) using small doses of transdermal buprenorphine. Herein, we review the literature associated with opioid withdrawal-related restlessness. Despite the known risk of concurrent benzodiazepine and buprenorphine administration, including decreased respiratory rate and death, we present a clinical presentation in which this medication combination may be necessary while under medical supervision. We suggest a stepwise algorithm for pharmacotherapy in patients experiencing involuntary limb movements associated with precipitated withdrawal. To safeguard the success of medication-assisted treatment (MAT) for opioid addiction, clinicians should be aware of potential clinical challenges when managing precipitated opioid withdrawal in patients with complex psychiatric comorbidities.

Topics: Buprenorphine; Humans; Methadone; Opioid-Related Disorders; Psychotic Disorders; Substance Withdrawal Syndrome; Veterans

The objective was to perform a systematic review and meta-analysis of the literature on the effects of buprenorphine on chronic pain outcomes (i.e., patient-reported pain intensity) in patients with and without opioid use disorder (OUD).. Ovid/Medline, PubMed, Embase, and the Cochrane Library were searched for studies that explored the effectiveness (in reducing pain) of buprenorphine treatment for chronic pain patients with and without a history of OUD. Randomized controlled trials and observational studies were included in the review.. Two separate searches were conducted to identify buprenorphine trials that included chronic pain patients either with or without OUD. Five studies used validated pain report measures and included a chronic pain population with OUD. Nine studies used validated report measures and included chronic pain patients without OUD. Meta-analysis was performed using the R, version 3.2.2, Metafor package, version 1.9-7.. The meta-analysis revealed that buprenorphine has a beneficial effect on pain intensity overall, with a small mean effect size in patients with comorbid chronic pain and OUD and a moderate- to large-sized effect in chronic pain patients without OUD.. Our results indicate that buprenorphine is modestly beneficial in reducing pain intensity in patients without OUD. Although informative, these findings should be carefully interpreted due to the small amount of data available and the variation in study designs.

Topics: Analgesics, Opioid; Buprenorphine; Chronic Pain; Humans; Opioid-Related Disorders

Opioid abuse and related overdose deaths continue to rise in the United States, contributing to the current national opioid crisis. Although several opioid-based pharmacotherapies are available (e.g., methadone, buprenorphine, naloxone), they show limited effectiveness in long-term relapse prevention. In response to the opioid crisis, the National Institute on Drug Abuse proposed a list of pharmacological targets of highest priority for medication development for the treatment of opioid use disorders (OUD). Among these are antagonists of dopamine D3 receptors (D3R). In this review, we first review recent progress in research of the dopamine hypothesis of opioid reward and abuse and then describe the rationale and recent development of D3R ligands for the treatment of OUD. Herein, an emphasis is placed on the effectiveness of newly developed D3R antagonists in the animal models of OUD. These new drug candidates may also potentiate the analgesic effects of clinically used opioids, making them attractive as adjunctive medications for pain management and treatment of OUD.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Drug Development; Methadone; Opioid-Related Disorders; Receptors, Dopamine D3; United States

Buprenorphine- Naloxone Fixed Dose Combination (BNX) is widely used to manage opioid use disorders. Contrary to evidence based concepts about sublingual bio-availability of naloxone, a few small studies have reported non-negligible amounts absorbed sublingually. But the extent to which these amounts exert opioid antagonist effects is yet to be established. We hereby report the first case of opioid dependence who developed a rare phenomenon of moderate to severe opioid withdrawal symptoms on administration of sublingual BNX after several days of being stabilized on plain buprenorphine (BUP). The case demonstrates the need to consider using buprenorphine monotherapy whenever such adverse effects are encountered. We also discuss the possible pharmacological explanations behind this rare side effect.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders

Amidst the opioid overdose crisis, there are increased efforts to expand access to medications for opioid use disorder (MOUD). Hospitalization for the complications of substance use in the United States (US) provides an opportunity to initiate methadone, buprenorphine, and extended release naltrexone and link high-risk, not otherwise engaged, patients into outpatient care. However, treatment options for patients are quickly exhausted when these medications are not desired, tolerated, or beneficial. As an example, we discuss the case of a man who was hospitalized 27 times over 2 years for complications related to his opioid use disorder (OUD), including recurring methicillin-resistant Staphylococcus aureus vertebral osteomyelitis, increasing antimicrobial resistance, new infections, and multiple overdoses in and out of the hospital. The patient suffered these complications despite efforts to treat his OUD with methadone and buprenorphine while hospitalized, and repeated attempts to link him to outpatient care. We use this case to review evidence-based treatments for refractory OUD, which are not approved in the US, but are available in Canada. If hospitalized in Vancouver, Canada, this patient could have been offered slow-release oral morphine and injectable opioid agonist therapy, as well as access to sterile syringes and injection equipment at an in-hospital supervised injection facility. Each of these approaches is supported by evidence and has been implemented successfully in Canada, yet none are available in the US. In order to combat the multiple harms from opioids, it is critical that we consider every evidence-based tool.

Topics: Analgesics, Opioid; Buprenorphine; Canada; Humans; Male; Methadone; Methicillin-Resistant Staphylococcus aureus; Opiate Substitution Treatment; Opioid-Related Disorders; United States

The diagnosis of opioid use disorder (OUD) is often overlooked or inadequately managed during the inpatient admission. When recognized, a common strategy is opioid detoxification, an approach that is often ineffective and can be potentially dangerous because of loss of tolerance and subsequent risk for overdose. Medication for addiction treatment (MAT), including methadone and buprenorphine, is effective and can be dispensed in the hospital for both opioid withdrawal and initiation of maintenance treatment. Hospitalists should be knowledgeable about diagnosing and managing patients with OUD, including how to manage acute pain or MAT during the perioperative setting.

Topics: Analgesics, Opioid; Buprenorphine; Harm Reduction; Hospitalization; Humans; Methadone; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Education as Topic

The opioid crisis has risen dramatically in North America in the new millennium, due to both illegal and prescription opioid use. While emergency departments (EDs) represent a potentially strategic setting for interventions to reduce harm from opioid use disorder (OUD), the absence of a recent synthesis of literature limits implementation and scalability. To fill this gap, we conducted a systematic review of the literature on interventions targeting OUDs initiated in EDs.. Using an explicit search strategy (PROSPERO), the MEDLINE, CINAHL Complete, EMBASE, and EBM reviews databases were searched from 1980 to October 4, 2019. The gray literature was explored using Google Scholar. Study characteristics were abstracted independently. The methodologic quality and risk of bias were assessed.. Twelve of 2,270 studies met the inclusion criteria (two of high quality). In addition to the heterogeneity of the outcome measures used (retention in treatment, opioid consumption, and overdose), brief intervention and buprenorphine initiation (six of 12 studies) were the most documented with mixed effects for the former and positive short-term and confined to single ED sites effects for the latter.. Emergency departments can be an appropriate setting for initiating opioid agonist treatment, but to be sustained, it likely needs to be coupled with community-based follow-up and support to ensure longer-term retention. The scarcity of high-quality evidence on OUD interventions initiated in emergency settings highlights the need for future research.

Topics: Analgesics, Opioid; Buprenorphine; Drug Overdose; Emergency Service, Hospital; Humans; Opioid-Related Disorders

Pregnant and postpartum women with opiate use disorder present a challenge in perinatal care. It is important for health care teams to provide sensitive and compassionate evidence-based care for these women, who often are stigmatized during the prenatal, delivery, and postpartum periods. Women with opiate use disorder are at risk for inadequate prenatal and postpartum care and for complications. Infants are at risk for neonatal abstinence syndrome and are expected to require neonatal intensive care. Pain management during labor and for cesarean delivery requires consultation and collaboration with providers who have expertise in management of addiction. Postpartum follow-up is essential.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Cesarean Section; Female; Humans; Infant, Newborn; Labor, Obstetric; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pain Management; Perinatal Care; Postpartum Period; Pregnancy; Pregnancy Complications

Opioid use disorder (OUD) represents a major public health problem that affects millions of people in the USA and worldwide. The relapsing and recurring aspect of OUD, driven by lasting neurobiological adaptations at different reward centres in the brain, represents a major obstacle towards successful long-term remission from opioid use. Currently, three drugs that modulate the function of the opioidergic receptors, methadone, buprenorphine and naltrexone have been approved by the US Food and Drug Administration (FDA) to treat OUD. In this review, we discuss the limitations and challenges associated with the current maintenance and medication-assisted withdrawal strategies commonly used to treat OUD. We further explore the involvement of glutamatergic, endocannabinoid and orexin signaling systems in the development, maintenance and expression of addiction-like behaviours in animal models of opioid addiction, and as potential and novel targets to expand therapeutic options to treat OUD. Despite a growing preclinical literature highlighting the role of these potential targets in animal models of opioid addiction, clinical and translational studies for novel treatments of OUD remain limited and inconclusive. Further preclinical and clinical investigations are needed to expand the arsenal of primary treatment options and adjuncts to maximise efficacy and prevent relapse.

Topics: Analgesics, Opioid; Animals; Behavior, Addictive; Brain; Buprenorphine; Disease Models, Animal; Endocannabinoids; Glutamic Acid; Humans; Methadone; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Orexins; Reward; Secondary Prevention; Signal Transduction; Treatment Outcome

Opioid use disorder (OUD), a leading cause of morbidity and mortality in the USA, can be effectively treated with buprenorphine. However, the same pharmacologic properties (e.g., high affinity, partial agonism, long half-life) that make it ideal as a treatment for OUD often cause concern among clinicians that buprenorphine will prevent effective management of acute pain with full agonist opioid analgesics. Because of this concern, many patients are asked to stop buprenorphine preoperatively or at the onset of acute pain, placing them at high risk for both relapse and a difficult transition back to buprenorphine after acute pain has resolved. The purpose of this review is to summarize the existing literature for acute pain and perioperative management in patients treated with buprenorphine for OUD and to provide practical management recommendations for generalist practitioners based on evidence and clinical experience. In short, evidence suggests that sufficient analgesia can be achieved with maintenance of buprenorphine and use of both opioid and non-opioid analgesic options for breakthrough pain. We recommend that clinicians (1) continue buprenorphine in the perioperative or acute pain period for patients with OUD; (2) use a multi-modal analgesic approach; (3) pay attention to care coordination and discharge planning when making an analgesic plan for patients with OUD treated with buprenorphine; and (4) use an individualized approach founded upon shared decision-making. Clinical examples involving mild and severe pain are discussed to highlight important management principles.

Topics: Acute Pain; Analgesics, Opioid; Buprenorphine; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Pain Management

In this large population-based cohort, individuals with more-severe obesity, central obesity, or genetic predisposition for obesity are at higher risk of developing severe-COVID-19.. The use of different references for the classification of a high %BF implied a difference in the diagnostic sensitivity of the BMI. Higher cutoff points resulted in greater sensitivity and ability to differentiate individuals with and without obesity.

Topics: Acyclic Monoterpenes; Adipose Tissue; Adolescent; Adult; Aged; Aged, 80 and over; Air Pollutants; Air Pollutants, Occupational; Amino Acid Transport Systems; Analgesics, Opioid; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Arthrobacter; Bacteria; Bacteriological Techniques; Benzaldehydes; Biodegradation, Environmental; Biofilms; Biological Transport; Biomarkers; Biomass; Bioreactors; Body Composition; Body Mass Index; Brassica; Brazil; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Caco-2 Cells; Cadmium; Calcium; Calcium Carbonate; Calcium Channels; Catalysis; Cell Degranulation; Cell Line; Cell Membrane; Chitosan; Chromatography, High Pressure Liquid; Chromium; Cobalt; Cohort Studies; Colony Count, Microbial; Composting; Copper; COVID-19; Cross-Sectional Studies; Cytoplasm; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Diarrhea; Diethylhexyl Phthalate; Dose-Response Relationship, Drug; Drug Implants; Drug Stability; Drug Synergism; Electroplating; Endometrial Neoplasms; Endometrium; Environmental Monitoring; Environmental Restoration and Remediation; Estradiol; Estrogens; Feces; Female; Food Microbiology; Food Preservation; Fruit and Vegetable Juices; Gasotransmitters; Gastrointestinal Diseases; Gastrointestinal Microbiome; Gene Expression Regulation, Developmental; Genetic Predisposition to Disease; Glutathione; Gold; Graphite; Growth Hormone; Harm Reduction; Hot Temperature; Humans; Hydrocortisone; Hydrogen; Hydrogen Peroxide; Hydrogen Sulfide; Hydrogen-Ion Concentration; Ileum; Imidazoles; Injections, Intraperitoneal; Insecticides; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor Binding Protein 2; Insulin-Like Growth Factor Binding Protein 5; Insulin-Like Growth Factor I; Intestinal Absorption; Light; Lignin; Liver; Magnetics; Male; Manganese; Mast Cells; Melanoma; Membrane Potentials; Metals; Methadone; Microbial Viability; Microplastics; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission; Middle Aged; Mitochondrial Swelling; Molecular Dynamics Simulation; Monophenol Monooxygenase; Morocco; Naloxone; Naltrexone; Nanocomposites; Nanomedicine; Nanoparticles; Narcotic Antagonists; Neonicotinoids; Nitric Oxide; Nitro Compounds; Nitrogen; Nitrogen Compounds; Obesity; Obesity, Abdominal; Occupational Exposure; Ontario; Opiate Substitution Treatment; Opioid-Related Disorders; Oryza; Overweight; Oxidative Stress; Oxides; Oxygen; Perception; Photoelectron Spectroscopy; Plants; Plastics; Point Mutation; Polychlorinated Biphenyls; Polycyclic Aromatic Hydrocarbons; Potassium; Premenopause; Prodrugs; Prospective Studies; Protons; Pyrolysis; Qualitative Research; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Resins, Synthetic; Rhodamines; Risk Factors; ROC Curve; Salmo salar; SARS-CoV-2; Seawater; Severity of Illness Index; Sewage; Social Media; Soil; Soil Microbiology; Soil Pollutants; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis, Raman; Staining and Labeling; Stainless Steel; Steel; Stress, Physiological; Substance Abuse Treatment Centers; Symporters; T-Lymphocytes; Toluene; Triclosan; Ultraviolet Rays; Waist Circumference; Waste Disposal, Fluid; Wastewater; Water Purification; Welding; X-Ray Diffraction; Young Adult

Topics: Analgesics, Opioid; Buprenorphine; Cognitive Behavioral Therapy; Humans; Narcotic Antagonists; Opioid-Related Disorders; Randomized Controlled Trials as Topic

Opioid-related harms have been increasing in Australia over the last 5 years. Patients with opioid use disorder are over-represented in ED presentations. Opioid agonist treatment is the most effective community-based treatment. Buprenorphine is considered the safest of these treatments to use in the ED setting. This rapid review investigated the effectiveness of initiating buprenorphine in the ED setting. Medline, Embase, Emcare, PSYCinfo, CINAHL and Cochrane Central Register of Controlled Trials databases were searched. Randomised and non-randomised studies published in peer-reviewed journals that involved the initiation of buprenorphine in the ED setting were considered eligible. The search revealed 350 articles of which 11 were included in the review; three articles representing two randomised controlled trials (RCTs) and eight observational studies. Data were extracted from included papers and risk of bias assessed on the RCTs. One well-conducted RCT showed that buprenorphine initiated in the ED does improve treatment engagement up to 2 months after an ED visit. Eight observational studies, one with a comparator group reported positive results for this intervention. There is strong evidence that clinicians should consider commencing buprenorphine in the ED for patients with opioid use disorder when combined with a direct and supported referral or 'warm handover' to community care. Further implementation studies and investigation of long-acting injectable buprenorphine treatment are required.

Topics: Analgesics, Opioid; Buprenorphine; Emergency Service, Hospital; Humans; Opiate Substitution Treatment; Opioid-Related Disorders

Despite high rates of cannabis use during medication-based treatment of opioid use disorder (MOUD), uncertainty remains around how cannabis influences treatment outcomes. We sought to investigate the relationship between cannabis use during MOUD and a number of patient outcomes. We searched seven databases for original peer-reviewed studies documenting the relationship between cannabis use and at least one primary outcome (opioid use, treatment adherence, or treatment retention) among patients enrolled in methadone-, buprenorphine-, or naltrexone-based therapy for OUD. In total, 41 articles (including 23 methadone, 7 buprenorphine, 6 naltrexone, and 5 mixed modalities) were included in this review. For each primary outcome area, there was a small number of studies that produced findings suggestive of a supportive or detrimental role of concurrent cannabis use, but the majority of studies reported that cannabis use was not statistically significantly associated with the outcome. No studies of naltrexone treatment demonstrated significantly worse outcomes for cannabis users. We identified methodological shortcomings and future research priorities, including exploring the potential role of adjunct cannabis use for improving opioid craving and withdrawal during MOUD. While monitoring for cannabis use may help guide clinicians towards an improved treatment plan, cannabis use is unlikely to independently threaten treatment outcomes.

Topics: Buprenorphine; Cannabis; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders

The opioid epidemic is a public health crisis. Medications for opioid use disorder (MOUD) include: 1) buprenorphine, 2) methadone, and 3) extended-release naltrexone (XR-NTX). Research should investigate patients' and providers' perspectives of MOUD since they can influence prescription, retention, and recovery.. This systematic review focused on patients' and providers' perceptions of MOUD. The review eligibility criteria included inclusion of the outcome of interest, in English, and involving persons ≥18 years. A PubMed database search yielded 1692 results; we included 152 articles in the final review.. There were 63 articles about buprenorphine, 115 articles about methadone, and 16 about naltrexone. Misinformation and stigma associated with MOUD were common patient themes. Providers reported lack of training and resources as barriers to MOUD.. This review suggests that patients have significant misinformation regarding MOUD. Due to the severity of the opioid epidemic, research must consider the effects of patients' and providers' perspectives on treatment for OUD, including the effects on the type of MOUD prescribed, patient retention and adherence, and ultimately the number of patients treated for OUD, which will aid in curbing the opioid epidemic.

Topics: Buprenorphine; Humans; Methadone; Naltrexone; Opiate Substitution Treatment; Opioid-Related Disorders

Despite evidence that medications to treat opioid use disorder (OUD) are effective, most people who could benefit from this treatment do not receive it. This rapid review synthesizes evidence on current barriers and facilitators to buprenorphine/naloxone and naltrexone at the patient, provider, and system levels to inform future interventions aimed at expanding treatment.. We systematically searched numerous bibliographic databases through May 2020 and selected studies published since 2014. Study selection, data abstraction, coding of barriers and facilitators, and quality assessment were first completed by one reviewer and checked by a second.. We included 40 studies of buprenorphine (5 also discussed naltrexone). Four types of patient and provider-level barriers to OUD medication use emerged-stigma related to OUD medications, treatment experiences and beliefs (positive or negative), logistical issues (time and costs as well as insurance and regulatory requirements), and knowledge (high or low) of OUD and the role of medications. Stigma was the most common barrier among patients, while logistical issues were the most common barriers among providers. Facilitators for both patients and providers included peer supports. Most administrator-identified or system-level barriers and facilitators fit into the category of logistical issues. We have moderate confidence in buprenorphine findings but low confidence in naltrexone findings due to the small number of studies.. Stigma, treatment experiences, logistical issues, and knowledge gaps are the main barriers associated with low utilization of OUD medications. These barriers can overlap and mutually reinforce each other, but given that, it is plausible that reducing one barrier may lead to reductions in others. The highest priority for future research is to evaluate interventions to reduce stigma. Other priorities for future research include better identification of barriers and facilitators for specific populations, such as those with OUD related to prescription opioids, and for naltrexone use.. PROSPERO; CRD42019133394.

Topics: Analgesics, Opioid; Buprenorphine; Humans; Naltrexone; Opiate Substitution Treatment; Opioid-Related Disorders

Managing acute pain in patients with opioid use disorder (OUD) on medication (methadone, buprenorphine, or naltrexone) can be complicated by patients' higher baseline pain sensitivity and need for higher opioid doses to achieve pain relief. This review aims to evaluate the benefits and harms of acute pain management strategies for patients taking OUD medications and whether strategies vary by OUD medication type or cause of acute pain.. We systematically searched multiple bibliographic sources until April 2020. One reviewer used prespecified criteria to assess articles for inclusion, extract data, rate study quality, and grade our confidence in the body of evidence, all with second reviewer checking.. We identified 12 observational studies-3 with control groups and 9 without. Two of the studies with control groups suggest that continuing buprenorphine and methadone in OUD patients after surgery may reduce the need for additional opioids and that ineffective pain management in patients taking methadone can result in disengagement in care. A third controlled study found that patients taking OUD medications may need higher doses of additional opioids for pain control, but provided insufficient detail to apply results to clinic practice. The only case study examining naltrexone reported that postoperative pain was managed using tramadol. We have low confidence in these findings as no studies directly addressed our question by comparing pain management strategies and few provided adequate descriptions of the dosage, timing, or rationale for clinical decisions.. We lack rigorous evidence on acute pain management in patients taking medication for OUD; however, evidence supports the practice of continuing methadone or buprenorphine for most patients during acute pain episodes. Well-described, prospective studies of adjuvant pain management strategies when OUD medications are continued would add to the existing literature base. Studies on nonopioid treatments are also needed for patients taking naltrexone.. PROSPERO; CRD42019132924.

Topics: Acute Pain; Analgesics, Opioid; Buprenorphine; Humans; Naltrexone; Opiate Substitution Treatment; Opioid-Related Disorders; Prospective Studies

The prevalence of opiate use among pregnant women can range from 1% to 2% to as high as 21%. Just in the United States alone, among pregnant women with hospital delivery, a fourfold increase in opioid use is reported from 1999 to 2014 (Haight 2018). Heroin crosses the placenta, and pregnant, opiate-dependent women experience a six-fold increase in maternal obstetric complications such as low birth weight, toxaemia, third trimester bleeding, malpresentation, puerperal morbidity, fetal distress and meconium aspiration. Neonatal complications include narcotic withdrawal, postnatal growth deficiency, microcephaly, neuro-behavioural problems, increased neonatal mortality and a 74-fold increase in sudden infant death syndrome. This is an updated version of the original Cochrane Review first published in 2008 and last updated in 2013.. To assess the effectiveness of any maintenance treatment alone or in combination with a psychosocial intervention compared to no intervention, other pharmacological intervention or psychosocial interventions alone for child health status, neonatal mortality, retaining pregnant women in treatment, and reducing the use of substances.. We updated our searches of the following databases to February 2020: the Cochrane Drugs and Alcohol Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, and Web of Science. We also searched two trials registers and checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs).. Randomised controlled trials which assessed the efficacy of any pharmacological maintenance treatment for opiate-dependent pregnant women.. We used the standard methodological procedures expected by Cochrane.. We found four trials with 271 pregnant women. Three compared methadone with buprenorphine and one methadone with oral slow-release morphine. Three out of four studies had adequate allocation concealment and were double-blind. The major flaw in the included studies was attrition bias: three out of four had a high dropout rate (30% to 40%), and this was unbalanced between groups. Methadone versus buprenorphine: There was probably no evidence of a difference in the dropout rate from treatment (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.37 to 1.20, three studies, 223 participants, moderate-quality evidence). There may be no evidence of a difference in the use of primary substances between methadone and buprenorphine (RR 1.81, 95% CI 0.70 to 4.68, two studies, 151 participants, low-quality evidence). Birth weight may be higher in the buprenorphine group in the two trials that reported data MD;-530.00 g, 95%CI -662.78 to -397.22 (one study, 19 particpants) and MD: -215.00 g, 95%CI -238.93 to -191.07 (one study, 131 participants) although the results could not be pooled due to very high heterogeneity (very low-quality of evidence). The third study reported that there was no evidence of a difference. We found there may be no evidence of a difference in the APGAR score (MD: 0.00, 95% CI -0.03 to 0.03, two studies,163 participants, low-quality evidence). Many measures were used in the studies to assess neonatal abstinence syndrome. The number of newborns treated for neonatal abstinence syndrome, which is the most critical outcome, may not differ between groups (RR 1.19, 95% CI 0.87 to1.63, three studies, 166 participants, low-quality evidence). Only one study which compared methadone with buprenorphine reported side effects. We found there may be no evidence of a difference in the number of mothers with serious adverse events (AEs) (RR 1.69, 95% CI 0.75 to 3.83, 175 participants, low-quality evidence) and we found there may be no difference in the numbers of newborns with serious AEs (RR 4.77, 95% CI 0.59, 38.49,131 participants, low-quality evidence). Methadone versus slow-release morphine: There were no dropouts in either treatment group. Oral slow-release morphine may be superior to methadone for abstinence from heroin use during pregnancy (RR 2.40, 95% CI 1.00 to 5.77, one study, 48 participants, low-quality evidence). In the comparison between methadone and slow-release morphine, no side effects were reported for the mother. In contrast, one child in. Methadone and buprenorphine may be similar in efficacy and safety for the treatment of opioid-dependent pregnant women and their babies. There is not enough evidence to make conclusions for the comparison between methadone and slow-release morphine. Overall, the body of evidence is too small to make firm conclusions about the equivalence of the treatments compared. There is still a need for randomised controlled trials of adequate sample size comparing different maintenance treatments.

Topics: Birth Weight; Buprenorphine; Delayed-Action Preparations; Female; Humans; Infant; Infant, Newborn; Methadone; Morphine; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Dropouts; Pregnancy; Pregnancy Complications; Randomized Controlled Trials as Topic

Recent evidence shows that emergency physicians (EP) can help patients obtain evidence-based treatment for Opioid Use Disorder by starting medication for addiction treatment (MAT) directly in the Emergency Department (ED). Many EDs struggle to provide options for maintenance treatment once patients are discharged from the ED. Health systems around the country are in need of a care delivery structure to link ED patients with OUD to care following initiation of buprenorphine. This paper reviews the three most common approaches to form effective partnerships between EDs and primary care/addiction medicine services: the Project Alcohol and Substance Abuse Services and Referral to Treatment (ASSERT) model, Bridge model, and ED-Bridge model.The ASSERT Model is characterized by peer educators or community workers in the ED directly referring patients suffering from OUD in the ED to local addiction treatment services. The Bridge model encourages prescribing physicians in an ED to screen patients for OUD, provide a short-term prescription for buprenorphine, and then refer the patient directly to an outpatient Bridge Clinic that is co-located in the same hospital but is a separate from the ED. This Bridge Clinic is staffed by addiction trained physicians and mid-level clinicians. The ED-Bridge model employs physicians trained in both emergency medicine and addiction medicine to serve within the ED as well as in the follow up addiction clinic.Distinct from the Bridge Clinic model above, EPs in the ED-Bridge model are both able to screen at-risk patients in the ED, often starting treatment, and to longitudinally follow patients in a regularly scheduled addiction clinic. This paper provides examples of these three models as well as implementation and logistical details to support a health system to better address OUD in their communities.

Topics: Aftercare; Analgesics, Opioid; Buprenorphine; Emergency Service, Hospital; Humans; Opioid-Related Disorders; Physicians; Referral and Consultation

Telemedicine is increasingly being used to treat patients with opioid use disorder (OUD). It has particular value in rural areas of the United States impacted by the opioid crisis as these areas have a shortage of trained addiction medicine providers. Patient satisfaction significantly impacts positive clinical outcomes in OUD treatment and thus is of great clinical interest. Yet little is known regarding patient satisfaction with the increasingly important platform of telemedicine-delivered medications for opioid use disorder (tMOUD). The goal of this review is to provide a summary of the existing literature regarding patient satisfaction with tMOUD. We also submit a novel survey based on an existing framework designed to assess tMOUD satisfaction, and present pilot data (

Topics: Adult; Buprenorphine; Humans; Narcotic Antagonists; Opiate Substitution Treatment; Opioid Epidemic; Opioid-Related Disorders; Patient Satisfaction; Rural Population; Surveys and Questionnaires; Telemedicine; United States

Opioid use during pregnancy has serious consequences for mother and baby. The true extent of the problem is unknown and there is a need for better screening. Existing guidelines with respect to the management of pregnant women with opioid use are based on limited evidence. To improve recommendations for optimal identification, management, and treatment, publications on opioids in pregnancy were reviewed. Published literature from 2007 to 2017 was searched in PubMed, Cochrane and Embase databases. The review employed 60 publications from 210 studies identified, that were of varying quality and included randomized controlled trials, systematic reviews, meta-analyses, and Cochrane reviews. The prevalence of opioid use in pregnancy is underestimated. Screening by urine testing and self-reporting is acceptable to identify fetal exposure. To minimize risk, opioid agonist pharmacotherapy should replace the continued use of opioids or detoxification. Current guidelines recommend methadone and buprenorphine equally. However, recent studies indicate that buprenorphine has advantages over methadone. Accordingly, we suggest buprenorphine as first-line therapy. Future studies should elaborate on better objective screening methods to prevent the consequences of fetomaternal opioid exposure.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Female; Humans; Maternal-Fetal Exchange; Methadone; Narcotic Antagonists; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications

Topics: Adolescent; Ambulatory Care; Analgesics, Opioid; Buprenorphine; Child, Foster; Female; Humans; Lost to Follow-Up; Methadone; Naltrexone; Opiate Substitution Treatment; Opioid-Related Disorders; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications; Pregnancy in Adolescence

Opioid maintenance treatment with methadone or buprenorphine is an established first-line treatment for opioid dependence. In addition to the novel weekly and monthly subcutaneously injectable buprenorphine depot CAM 2038 (Buvidal®), which is already available in Germany, two other long-acting buprenorphine formulations may be introduced in the near future: the monthly depot formulation RBP-6000 (Sublocade™) and a 6-month buprenorphine depot implant (Probuphine™). Basic pharmacological and clinical data of these three medications are given and possible clinical applications are discussed.

Topics: Analgesics, Opioid; Buprenorphine; Delayed-Action Preparations; Germany; Humans; Opiate Substitution Treatment; Opioid-Related Disorders

Opioid agonist therapies are effective medications that can greatly improve the quality of life of individuals with opioid use disorder. However, there is significant uncertainty about the risks of cause-specific mortality in and out of treatment.. This systematic review and meta-analysis explored the association between methadone and buprenorphine with cause-specific mortality among opioid-dependent persons.. We searched six online databases to identify relevant cohort studies, calculating all-cause and overdose-specific mortality rates during periods in and out of treatment. We pooled mortality estimates using multivariate random effects meta-analysis of the crude mortality rate per 1000 person-years of follow-up as well as relative risks comparing mortality in vs. out of treatment.. A total of 32 cohort studies (representing 150 235 participants, 805 423.6 person-years, and 9112 deaths) met eligibility criteria. Crude mortality rates were substantially higher among methadone cohorts than buprenorphine cohorts. Relative risk reduction was substantially higher with methadone relative to buprenorphine when time in-treatment was compared to time out-of-treatment. Furthermore, the greatest mortality reduction was conferred during the first 4 weeks of treatment. Mortality estimates were substantially heterogeneous and varied significantly by country, region, and by the nature of the treatment provider.. Precautions are necessary for the safer implementation of opioid agonist therapy, including baseline assessments of opioid tolerance, ongoing monitoring during the induction period, education of patients about the risk of overdose, and coordination within healthcare services.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Case-Control Studies; Cohort Studies; Databases, Factual; Drug Overdose; Drug Tolerance; Female; Humans; Male; Methadone; Monitoring, Physiologic; Narcotic Antagonists; Opioid-Related Disorders; Patient Education as Topic; Quality of Life; Risk

People infected with HIV through injection drug use are more likely to experience progression to AIDS, death due to AIDS, and all-cause mortality even when controlling for access to care and antiretroviral therapy. While high-risk behavior and concurrent infections most certainly are contributors, chronic immune activation, downstream metabolic comorbidities may play an important role.. Altered intestinal integrity plays a major role in HIV-related immune activation and microbial translocation markers are heightened in active heroin users. Additionally, greater injection frequency drives systemic inflammation and is associated with HIV viral rebound. Finally, important systemic inflammation markers have been linked with frailty and mortality in people who inject drugs with and without concurrent HIV infection. Heroin use may work synergistically with HIV infection to cause greater immune activation than either factor alone. Further research is needed to understand the impact on downstream metabolic comorbidities including cardiovascular disease. Medication-assisted treatment for opioid use disorder with methadone or buprenorphine may ameliorate some of this risk; however, there is presently limited research in humans, including in non-HIV populations, describing changes in immune activation on these treatments which is of paramount importance for those with HIV infection.

Topics: Analgesics, Opioid; Buprenorphine; Cardiovascular Diseases; HIV Infections; Humans; Inflammation; Methadone; Opioid Epidemic; Opioid-Related Disorders; Substance Abuse, Intravenous

Methadone, buprenorphine, and naltrexone are evidence-based treatments for opioid use disorder (OUD). A large body of evidence supports their effectiveness in adults with OUD. However, few studies have tested their efficacy in adolescents. This study summarizes the clinical benefits and risks of three medications for the treatment of OUD in adolescents.. We review and synthesize the published evidence about the efficacy and potential risks (including safety concerns) associated with methadone, buprenorphine, or naltrexone for the treatment of OUD in adolescents and compare their benefits and risks with that of no treatment or treatment without medications. We also discuss adolescent-specific treatment needs and strategies to overcome potential challenges in prescribing medications for adolescents with OUD.. Methadone appears to be effective in promoting treatment retention among adolescents with heroin use disorder. Data from three randomized controlled trials suggest that buprenorphine treatment improves the likelihood of opioid abstinence and treatment retention. Although these medications have a potential risk of overdose when misused or used illegally, evidence suggests this risk is much lower for buprenorphine than methadone. Emerging data also suggest that naltrexone is a safe and feasible option for adolescents. Vast evidence demonstrates that the risks of untreated OUD far outweigh the risks of any of the previously discussed medications.. Little published evidence specifically examines the efficacy and safety of using medications for OUD in adolescents, and more research is needed. It is essential for healthcare professionals to determine whether their adolescent patients may benefit from medications for the treatment of OUD.

Topics: Adolescent; Adolescent Behavior; Analgesics, Opioid; Buprenorphine; Humans; Methadone; Naltrexone; Opiate Substitution Treatment; Opioid-Related Disorders

The United States is in the midst of a national opioid epidemic. Physicians are encouraged both to prevent and treat opioid-use disorders (OUDs). Although there are 3 Food and Drug Administration-approved medications to treat OUD (methadone, buprenorphine, and naltrexone) and there is ample evidence of their efficacy, they are not used as often as they should. We provide a brief review of the 3 primary medications used in the treatment of OUD. Using data from available medical literature, we synthesize existing knowledge and provide a framework for how to determine the optimal approach for outpatient management of OUD with medication-assisted treatments.

Topics: Algorithms; Buprenorphine; Decision Trees; Humans; Methadone; Naltrexone; Opiate Substitution Treatment; Opioid-Related Disorders

Opioid use disorder is highly prevalent and can be fatal. At least 2.1 million Americans 12 years and older had opioid use disorder in 2016, and approximately 47,000 Americans died from opioid overdoses in 2017. Opioid use disorder is a chronic relapsing condition, the treatment of which falls within the scope of practice of family physicians. With appropriate medication-assisted treatment, patients are more likely to enter full recovery. Methadone and buprenorphine are opioid agonists that reduce mortality, opioid use, and HIV and hepatitis C virus transmission while increasing treatment retention. Intramuscular naltrexone is not as well studied and is harder to initiate than opioid agonists because of the need to abstain for approximately one week before the first dose. However, among those who start naltrexone, it can reduce opioid use and craving. Choosing the correct medication for a given patient depends on patient preference, local availability of opioid treatment programs, anticipated effectiveness, and adverse effects. Discontinuation of pharmacotherapy increases the risk of relapse; therefore, patients should be encouraged to continue treatment indefinitely. Many patients with opioid use disorder are treated in primary care, where effective addiction treatment can be provided. Family physicians are ideally positioned to diagnose opioid use disorder, provide evidence-based treatment with buprenorphine or naltrexone, refer patients for methadone as appropriate, and lead the response to the current opioid crisis.

Topics: Analgesics, Opioid; Buprenorphine; Chronic Disease; Evidence-Based Medicine; Female; Humans; Male; Mass Screening; Methadone; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy

The incidence of neonatal abstinence syndrome owing to prenatal opioid exposure has grown rapidly in recent decades and it disproportionately affects rural, non-white, and public insurance-dependent populations. Treatment consists of pharmacologic and nonpharmacologic interventions with wide variability in approaches across the United States. Standardizing clinical assessment, minimizing unnecessary interruptions, and prioritizing nonpharmacologic and family-centered care seems to improve hospital outcomes. Neonatal abstinence syndrome may have long-term developmental and biological effects, but understanding is limited owing in part confounding biosocial factors. Early intervention and longitudinal support of the infant and family promote better outcomes.

Topics: Analgesics, Opioid; Breast Feeding; Buprenorphine; Female; Humans; Hypnotics and Sedatives; Infant, Newborn; Intensive Care Units, Neonatal; Length of Stay; Methadone; Morphine; Neonatal Abstinence Syndrome; Nurseries, Hospital; Opiate Substitution Treatment; Opioid-Related Disorders; Parents; Phenobarbital; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Rooming-in Care; Severity of Illness Index; Treatment Outcome

Topics: Analgesia; Buprenorphine; Humans; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Perioperative Care; Practice Guidelines as Topic

Perinatal opioid use is a major public health problem and is associated with a number of deleterious maternal and fetal effects. We review recent evidence of perinatal outcomes and treatment of opioid use disorder (OUD) during pregnancy.. Opioid exposure in pregnancy is associated with multiple obstetric and neonatal adverse outcomes, with the most common being neonatal opioid withdrawal syndrome (NOWS). Treatment with buprenorphine or methadone is associated with NOWS, but neither medication appears to have significant adverse effects on early childhood development. Buprenorphine appears to be superior to methadone in terms of incidence and severity of NOWS in exposed infants. The long-term effects of opioid exposure in utero have been inconclusive, but recent longitudinal studies point to potential differences in brain morphology that may increase vulnerability to future stressors. Maintenance therapy with methadone or buprenorphine remains the standard of care for pregnant women with OUD given its consistent superiority to placebo in terms of rates of illicit drug use and pregnancy outcomes. New non-pharmacologic management options for NOWS appear promising. Future research is needed to further evaluate the effects of opioid exposure in utero and determine the optimal delivery model for maintenance therapy.

Topics: Buprenorphine; Child Development; Female; Humans; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Treatment Outcome

Memantine is commonly used for the treatment of moderate-to-severe Alzheimer's disease. Due to its antagonism of the N-methyl-d-aspartate (NMDA) receptor, which has been shown to block rewarding and reinforcing effects of morphine, memantine has been investigated for potential utilization in opioid use disorder (OUD). The objective of this systematic review is to assess the evidence available to determine the safety and efficacy of memantine as treatment for OUD. Pubmed (1946-August 2019) and Embase (1947-August 2019) were queried using the following search terms: opioid-related disorders, opioids, substance withdrawal syndrome, withdrawal syndrome, opiate addiction, opiate, opiate dependence, opiate substitution treatment, managed opioid withdrawal, or drug withdrawal and memantine. After assessing studies appropriate for the objective, one single-blind and five double-blind, placebo-controlled trials were included. Of the included studies, four demonstrated beneficial effects of memantine either as monotherapy or adjunct to methadone or buprenorphine on reducing opioid cravings and methadone dose, increasing retention rates, and improving cognitive performance in patients with OUD. Two studies did not show benefit on patient retention rates with memantine adjunct to naltrexone. Study durations ranged from 3 to 13 weeks, and memantine dosing ranged from 5 to 60 mg/day. Memantine was well tolerated with similar rates of adverse effects between treatment groups. Based on the reviewed literature, memantine appears most beneficial as an adjunctive treatment for OUD when combined with methadone or buprenorphine, but not naltrexone. Larger studies with longer periods of treatment and follow-up are needed to support the use of memantine in the management of OUD.

Topics: Analgesics, Opioid; Buprenorphine; Drug Therapy, Combination; Excitatory Amino Acid Antagonists; Humans; Memantine; Methadone; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Outcome Assessment, Health Care; Substance Withdrawal Syndrome

Opioid use disorder (OUD) is associated with a high risk of premature death. Medication-assisted treatment (MAT) is the primary treatment for opioid dependence. We comprehensively assessed the effects of different MAT-related characteristics on mortality among those with OUD by a systematic review and meta-analysis. The all-cause and overdose crude mortality rates (CMRs) and relative risks (RRs) by treatment status, different type, period, and dose of medication, and retention time were pooled using random effects, subgroup analysis, and meta-regression. Thirty cohort studies involving 370,611 participants (1,378,815 person-years) were eligible in the meta-analysis. From 21 studies, the pooled all-cause CMRs were 0.92 per 100 person-years (95% CI: 0.79-1.04) while receiving MAT, 1.69 (1.47-1.91) after cessation, and 4.89 (3.54-6.23) for untreated period. Based on 16 studies, the pooled overdose CMRs were 0.24 (0.20-0.28) while receiving MAT, 0.68 (0.55-0.80) after cessation of MAT, and 2.43 (1.72-3.15) for untreated period. Compared with patients receiving MAT, untreated participants had higher risk of all-cause mortality (RR 2.56 [95% CI: 1.72-3.80]) and overdose mortality (8.10 [4.48-14.66]), and discharged participants had higher risk of all-cause death (2.33 [2.02-2.67]) and overdose death (3.09 [2.37-4.01]). The all-cause CMRs during and after opioid substitution treatment with methadone or buprenorphine were 0.93 (0.76-1.10) and 1.79 (1.47-2.10), and corresponding estimate for antagonist naltrexone treatment were 0.26 (0-0.59) and 1.97 (0-5.18), respectively. Retention in MAT of over 1-year was associated with a lower mortality rate than that with retention ≤1 year (1.62, 1.31-1.93 vs. 5.31, -0.09-10.71). Improved coverage and adherence to MAT and post-treatment follow-up are crucial to reduce the mortality. Long-acting naltrexone showed positive advantage on prevention of premature death among persons with OUD.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Cohort Studies; Drug Overdose; Female; Humans; Male; Methadone; Naltrexone; Opiate Substitution Treatment; Opioid-Related Disorders; Risk

We sought to compare the efficacy and safety of detoxification from opioids compared with opioid replacement therapy (ORT) during pregnancy.. We searched PubMed, Embase, Cochrane Library, and ClinicalTrials.gov from inception to June 2017 for English-language randomized-controlled trials or cohort studies that compared detoxification with ORT. We sought studies with outcomes data on maternal abstinence at the time of delivery, neonatal abstinence syndrome (NAS), stillbirth, and preterm birth (PTB). We calculated pooled relative risks (RRs) with a random-effects model, assessed heterogeneity using the chi-square test for heterogeneity, and quantified heterogeneity using the. Three cohort studies met the inclusion criteria; eligible studies included 235 women with opioid use disorder in pregnancy. Maternal detoxification was associated with increased risk of relapse (RR = 1.91; 95% confidence interval [CI] = 1.14-3.21); however, no treatment differences were observed for the rates of NAS (RR = 0.99; 95% CI = 0.38-2.53) or PTB (RR = 0.39; 95% CI = 0.10-1.60).. Our findings suggest an increased risk of relapse with detoxification treatment compared with ORT; however, detoxification does not alter the risk of PTB or NAS. Further studies should confirm our findings and explore mechanisms to fight the current opioid epidemic.

Topics: Analgesics, Opioid; Buprenorphine; Female; Humans; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth; Recurrence

Opioid use disorder (OUD) is increasing in prevalence throughout the world, with approximately three million individuals in the United States affected. Buprenorphine is a medication designed, researched, and effectively used to assist in OUD recovery.. This narrative review discusses an approach to initiating buprenorphine in the emergency department (ED) for opioid-abuse recovery.. Buprenorphine is a partial mu-opioid receptor agonist with high affinity and low intrinsic activity. Buprenorphine's long half-life, high potency, and 'ceiling effect' for both euphoric sensation and adverse effects make it an optimal treatment alternative for patients presenting to the ED with opioid withdrawal. While most commonly provided as a sublingual film or tablet, buprenorphine can also be delivered via transbuccal, transdermal, subdermal (implant), subcutaneous, and parenteral routes. Prior to ED administration, caution is recommended to avoid precipitation of buprenorphine-induced opioid withdrawal. Following the evaluation of common opioid withdrawal symptoms, a step-by-step approach to buprenorphine can by utilized to reach a sustained withdrawal relief. A multimodal medication-assisted treatment (MAT) plan involving pharmacologic treatment, as well as counseling and behavioral therapy, is essential to maintaining opioid remission. Patients may be safely discharged with safe-use counseling, close outpatient follow-up, and return precautions for continued management of their OUD. Establishing a buprenorphine program in the ED involves a multifactorial approach to establish a pro-buprenorphine culture.. Buprenorphine is an evidence-based, safe, effective treatment option for OUD in an ED-setting. Though successfully utilized by many ED-based treatment programs, the stigma of 'replacing one opioid with another' remains a barrier. Evidence-based discussions on the safety and benefits of buprenorphine are essential to promoting a culture of acceptance and optimizing ED OUD treatment.

Topics: Behavior Therapy; Buprenorphine; Combined Modality Therapy; Directive Counseling; Dosage Forms; Emergency Service, Hospital; Humans; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Substance Withdrawal Syndrome

There is no consensus on the optimal perioperative management of patients on buprenorphine (BUP) for opioid use disorder (OUD). This article will review the available literature on BUP and the analgesic efficacy of BUP combined with full mu-opioid agonists and discuss the conflicting management strategies in the context of acute pain and our institution's protocol for the periprocedural management of BUP.. We searched published data on BUP periprocedural management from inception through March 2018 without language restrictions. Study selection included publications reporting outcomes on perioperative pain management in OUD patients maintained on BUP.. Our search resulted in four case reports supporting periprocedural discontinuation of BUP and two case series, one secondary observational study, one prospective matched cohort study, and four retrospective cohort studies supporting periprocedural continuation of BUP. No clinical trials were identified.. Maintaining BUP perioperatively does not lead to worsened clinical outcomes. Patients can receive adequate pain control from mu-opioid agonists while maintained on BUP. Based upon available evidence, we recommend continuing BUP at a reduced dose when indicated to avoid withdrawal symptoms and to facilitate the analgesic efficacy of mu-opioid agonists administered in combination for acute postoperative pain.

Topics: Buprenorphine; Humans; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Pain Management; Pain, Postoperative

Inappropriate and excessive opioid prescribing practices for treatment of chronic nonmalignant pain contributed to rising rates of opioid related mortality. Effective and widely available opioid addiction treatment resources are needed to ensure successful resolution of the "opioid epidemic". This chapter outlines the basic pathophysiology of addiction as well as principles of opioid addiction management focusing on the pharmacological and nonpharmacological aspects of care. Pharmacological treatment focuses on opioid substitution therapy, with aim at prevention of opioid cravings and opioid withdrawal symptoms. Nonpharmacological treatment involves psychological and supportive approaches to addiction such as group meetings, psychological counseling, and mindfulness training.

Topics: Analgesics, Opioid; Buprenorphine; Cognitive Behavioral Therapy; Humans; Methadone; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Practice Patterns, Physicians'

Topics: Buprenorphine; Emergency Service, Hospital; Evidence-Based Medicine; Female; Humans; Male; Narcotic Antagonists; Opioid-Related Disorders; Practice Guidelines as Topic; Substance Withdrawal Syndrome

Recent HIV outbreaks have occurred as a result of the current US opioid epidemic. Providing medications for opioid use disorder (MOUD) with methadone, buprenorphine, and extended-release naltrexone is essential to achieving optimal HIV treatment outcomes including viral suppression and retention in treatment. This review describes the pharmacology of MOUD with specific attention to interactions with antiretroviral therapy, and to the effect of MOUD on HIV treatment outcomes.. Methadone and buprenorphine both improve HIV viral suppression, adherence to antiretroviral therapy, and overall mortality for persons with opioid use disorder (OUD). Extended-release naltrexone has been most extensively studied in persons with HIV leaving incarcerated settings, and improves HIV viral suppression in that context. Strategies that integrate MOUD and HIV treatment are crucial to optimize viral suppression. The differing pharmacokinetic and delivery characteristics of these MOUD offer diverse options. Given the chronic and relapsing nature of both HIV and OUD, long-term approaches are required.

Topics: Buprenorphine; HIV Infections; Humans; Methadone; Naltrexone; Opioid-Related Disorders; Treatment Outcome

The escalation of the opioid crisis has led to an increase in the treatment of opioid use disorder. In particular, recent legislation has allowed for office-based treatment with buprenorphine, a partial µ-opioid agonist that is believed to be safer than methadone due to a ceiling effect on respiratory depression in adults. An increasing number of children are being exposed to buprenorphine as more adults in US households receive take-home prescriptions. The ceiling effect seen in adults does not seem to apply to young children, and intoxication with severe symptoms including fatalities can occur. This article outlines the pharmacology of buprenorphine and reviews the current literature on overdose in children. We conclude with practical recommendations for limiting potential exposure and damage to children from accidental buprenorphine overdose.

Topics: Accidents, Home; Age Factors; Analgesics, Opioid; Buprenorphine; Child; Child, Preschool; Drug Overdose; Female; Humans; Male; Opioid-Related Disorders; Prevalence; Risk Assessment; United States

Women with opioid use disorder who become pregnant are a particularly vulnerable population and require a comprehensive treatment approach for mother and fetus. Research is continuing on opioid use disorder, effects of opioid use on the fetus, and best treatment approaches. This article reviews current recommendations and guidelines for treatment.

Topics: Adolescent; Adult; Analgesics, Opioid; Buprenorphine; Cognitive Behavioral Therapy; Female; Fetal Diseases; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Physician Assistants; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications; Professional Role; Regional Health Planning; Young Adult

Pharmacotherapy, or medication-assisted treatment (MAT), is a critical component of a comprehensive treatment plan for the pregnant woman with opioid use disorder (OUD). Methadone and buprenorphine are two types of opioid-agonist therapy which prevent withdrawal symptoms and control opioid cravings. Methadone is a long-acting mu-opioid receptor agonist that has been shown to increase retention in treatment programs and attendance at prenatal care while decreasing pregnancy complications. However methadone can only be administered by treatment facilities when used for OUD. In contrast, buprenorphine is a mixed opioid agonist-antagonist medication that can be prescribed outpatient. The decision to use methadone vs buprenorphine for MAT should be individualized based upon local resources and a patient-specific factors. There are limited data on the use of the opioid antagonist naltrexone in pregnancy. National organizations continue to recommend MAT over opioid detoxification during pregnancy due to higher rates of relapse with detoxification.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Female; Guidelines as Topic; Humans; Methadone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnant Women

Despite proven clinical utility, use of sublinugual buprenorphine is fraught with issues of potential diversion among patients with opioid dependence. Transdermal buprenorphine patches provide an alternative delivery model that can be utilized to reduce such diversion. This narrative review discusses the transdermal buprenorphine formulations, and its pharmacology, drug interaction and tolerability profile. The studies utilizing buprenorphine transdermal patches in the treatment of opioid dependence are examined, while the potential of using such patches for maintenance treatment of opioid dependence is examined.

Topics: Buprenorphine; Humans; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Secondary Prevention; Transdermal Patch

This study examined the state of the literature on the effectiveness of medication assisted treatment (MAT; methadone, buprenorphine, naltrexone) delivered in prisons and jails on community substance use treatment engagement, opioid use, recidivism, and health risk behaviors following release from incarceration. Randomized controlled trials (RCTs) and quasi-experimental studies published through December 2017 that examined induction to or maintenance on methadone (n = 18 studies), buprenorphine (n = 3 studies), or naltrexone (n = 3 studies) in correctional settings were identified from PsycINFO and PubMed databases. There were a sufficient number of methadone RCTs to meta-analyze; there were too few buprenorphine or naltrexone studies. All quasi-experimental studies were systematically reviewed. Data from RCTs involving 807 inmates (treatment n = 407, control n = 400) showed that methadone provided during incarceration increased community treatment engagement (n = 3 studies; OR = 8.69, 95% CI = 2.46; 30.75), reduced illicit opioid use (n = 4 studies; OR = 0.22, 95% CI = 0.15; 0.32) and injection drug use (n = 3 studies; OR = 0.26, 95% CI = 0.12; 0.56), but did not reduce recidivism (n = 4 studies; OR = 0.93, 95% CI = 0.51; 1.68). Data from observational studies of methadone showed consistent findings. Individual review of buprenorphine and naltrexone studies showed these medications were either superior to methadone or to placebo, or were as effective as methadone in reducing illicit opioid use post-release. Results provide the first meta-analytic summary of MATs delivered in correctional settings and support the use of MATs, especially with regard to community substance use treatment engagement and opioid use; additional work is needed to understand the reduction of recidivism and other health risk behaviors.

Topics: Buprenorphine; Humans; Methadone; Naltrexone; Opiate Substitution Treatment; Opioid-Related Disorders; Prisons; Randomized Controlled Trials as Topic; Recidivism; Risk-Taking

Opioid use disorder is a major health concern in North America. Currently, buprenorphine is one of the most common pharmacological interventions used to treat opioid use disorder. Despite increasing prevalence of opioid use disorder among females, little is known about sex considerations in relation to treatment with buprenorphine.. CINAHL, PsycINFO, EMBASE, PubMed/MEDLINE and Cochrane Central were searched for randomized controlled trials examining buprenorphine maintenance versus other medication-assisted treatment, placebo, or withdrawal management to determine if there were any sex differences in treatment outcomes reported.. This review included 25 studies and found that only 52% included information related to sex differences in treatment outcomes or discussed any sex considerations in their studies. Of the 6,466 patients represented by these studies, only 26% were female. Of the studies conducting sex-specific analyses, seven studies examined treatment retention, five examined opioid use, two examined other substance use and one examined sexual risk behaviours. However, due to mixed findings, small sample sizes, and inability to conduct meta-analyses, no conclusive statements can be made about sex differences in these outcomes. None of the studies described sex differences in quality of life, legal involvement or mental and physical health.. Low numbers of females have been included in randomized controlled trials examining buprenorphine compared to males. While sex differences in treatment outcomes were identified in this review, further research is needed in order to add to these findings. Future studies should include greater numbers of female participants and conduct sex-specific analyses.

Topics: Analgesics, Opioid; Buprenorphine; Clinical Trials as Topic; Female; Humans; Male; Methadone; North America; Opiate Substitution Treatment; Opioid-Related Disorders; Quality of Life; Sex Characteristics; Treatment Outcome

The opioid crisis has reached an unprecedented magnitude in the United States and worldwide, and data on opioid use and misuse in the obstetric population are extremely concerning. Despite an abundant number of studies evaluating strategies to prevent neonatal opioid withdrawal syndrome in babies born to mothers who are chronic opioid users, in babies born to mothers using chronic opioids, numerous questions remain unanswered, including (1) how to optimally manage postpartum pain in opioid-dependent patients (2) how to reconcile buprenorphine and methadone use with intrapartum and post-partum analgesia, so as to avoid opioid withdrawal during and after delivery (3) how to safely and effectively provide a stepwise multimodal approach that incorporates systemic opioid-sparing approaches, such as neuraxial opioids, clonidine, ketamine, gabapentin, and regional anesthetic blocks, to ensure adequate pain relief while avoiding opioid withdrawal (4) how to optimally manage post-partum recovery and (5) how to avoid excessive opioid prescription and possibly leftover opioids that may promote persistent use, misuse and diversion. With the recognition that an increasing number of pregnant women are taking chronic opioids, the goals of this review article are to summarize the existing literature on post-cesarean pain management in the obstetric patient with an opioid-use disorder; and to provide clinicians with a stepwise approach for management before, as well as during and after, cesarean delivery of women who have been chronically using opioids during their pregnancy.

Topics: Analgesia, Patient-Controlled; Buprenorphine; Cesarean Section; Female; Humans; Methadone; Naltrexone; Opioid-Related Disorders; Pain, Postoperative; Pregnancy; Pregnancy Complications

Substance use disorders (SUD) are serious public health problems worldwide. Although significant progress has been made in understanding the neurobiology of drug reward and the transition to addiction, effective pharmacotherapies for SUD remain limited and a majority of drug users relapse even after a period of treatment. The United States Food and Drug Administration (FDA) has approved several medications for opioid, nicotine, and alcohol use disorders, whereas none are approved for the treatment of cocaine or other psychostimulant use disorders. The medications approved by the FDA for the treatment of SUD can be divided into two major classes - agonist replacement therapies, such as methadone and buprenorphine for opioid use disorders (OUD), nicotine replacement therapy (NRT) and varenicline for nicotine use disorders (NUD), and antagonist therapies, such as naloxone for opioid overdose and naltrexone for promoting abstinence. In the present review, we primarily focus on the pharmacological rationale of agonist replacement strategies in treatment of opioid dependence, and the potential translation of this rationale to new therapies for cocaine use disorders. We begin by describing the neural mechanisms underlying opioid reward, followed by preclinical and clinical findings supporting the utility of agonist therapies in the treatment of OUD. We then discuss recent progress of agonist therapies for cocaine use disorders based on lessons learned from methadone and buprenorphine. We contend that future studies should identify agonist pharmacotherapies that can facilitate abstinence in patients who are motivated to quit their illicit drug use. Focusing on those that are able to achieve abstinence from cocaine will provide a platform to broaden the effectiveness of medication and psychosocial treatment strategies for this underserved population. This article is part of the Special Issue entitled 'New Vistas in Opioid Pharmacology'.

Topics: Analgesics, Opioid; Buprenorphine; Central Nervous System Stimulants; Cocaine-Related Disorders; Dextroamphetamine; Dopamine Plasma Membrane Transport Proteins; Dopamine Uptake Inhibitors; Drug Development; Humans; Methadone; Methylphenidate; Modafinil; Nicotinic Agonists; Opiate Substitution Treatment; Opioid-Related Disorders; Oxalates; Piperazines; Receptors, Opioid, mu; Tobacco Use Disorder; Tropanes; Varenicline

When opioid misuse rises in the United States, pregnant women and their neonates are affected. This article summarizes the use of Food and Drug Administration-approved products, including methadone, buprenorphine, and the combination formulation of buprenorphine and naloxone to treat adult opioid use disorder during the perinatal period. All labels include pregnancy, neonatal, and lactation information and note the accepted use of these medications during the perinatal period if the benefits outweigh the risks. A summary of the neonatal abstinence syndrome definition, its assessment tools, treatment approaches, and future genetic directions are provided.

Topics: Analgesia, Obstetrical; Analgesics; Analgesics, Opioid; Breast Feeding; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Clonidine; Female; Humans; Hypnotics and Sedatives; Infant, Newborn; Kangaroo-Mother Care Method; Maternal-Fetal Exchange; Methadone; Neonatal Abstinence Syndrome; Occupational Therapy; Opiate Substitution Treatment; Opioid-Related Disorders; Pain Management; Patient Education as Topic; Phenobarbital; Physical Therapy Modalities; Pregnancy; Pregnancy Complications; Rooming-in Care

Opioid use disorder affects over 26 million individuals worldwide. There are currently three World Health Organization-recommended and US Food and Drug Administration-approved medication treatments for opioid use disorder: the full opioid agonist methadone, the opioid partial agonist buprenorphine, and the opioid receptor antagonist naltrexone. We provide a review of the use of buprenorphine for the treatment of opioid use disorder and discuss the barriers, challenges, risks, and efficacy of buprenorphine treatment vs. other treatments. Although evidence from numerous studies has shown buprenorphine to be effective for the treatment of opioid use disorder, a majority of patients with opioid use disorder do not receive buprenorphine, or any other medical treatment. We review the different formulations of buprenorphine, including newer long-acting injectable formulations that may decrease the risk of diversion and improve adherence.

Topics: Buprenorphine; Humans; Medication Adherence; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Substance Withdrawal Syndrome

To summarize the best available evidence regarding various topics related to primary care management of opioid use disorder (OUD).. MEDLINE, Cochrane Library, Google, and the references of included studies and relevant guidelines.. Published systematic reviews and newer randomized controlled trials from the past 5 to 10 years that investigated patient-oriented outcomes related to managing OUD in primary care, diagnosis, pharmacotherapies (including buprenorphine, methadone, and naltrexone), tapering strategies, psychosocial interventions, prescribing practices, and management of comorbidities.. From 8626 articles, 39 systematic reviews and an additional 26 randomized controlled trials were included. New meta-analyses were performed where possible. One cohort study suggests 1 case-finding tool might be reasonable to assist with diagnosis (positive likelihood ratio of 10.3). Meta-analysis demonstrated that retention in treatment improves when buprenorphine or methadone are used (64% to 73% vs 22% to 39% for control), when OUD is treated in primary care (86% vs 67% in specialty care, risk ratio [RR] of 1.25, 95% CI 1.07 to 1.47), and when counseling is added to pharmacotherapy (74% vs 62% for controls, RR = 1.20, 95% CI 1.06 to 1.36). Retention was also improved with naltrexone (33% vs 25% for controls, RR = 1.35, 95% CI 1.11 to 1.64) and reduced with medication-related contingency management (eg, loss of take-home doses as a punitive measure; 68% vs 77% for no contingency, RR = 0.86, 95% CI 0.76 to 0.99).. There is reasonable evidence that patients with OUD should be managed in the primary care setting. Diagnostic criteria for OUD remain elusive, with 1 reasonable case-finding tool. Methadone and buprenorphine improve treatment retention, while medication-related contingency methods could worsen retention. Counseling is beneficial when added to pharmacotherapy.

Topics: Analgesics, Opioid; Buprenorphine; Counseling; Humans; Methadone; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Primary Health Care; Randomized Controlled Trials as Topic; Systematic Reviews as Topic

In order to address the current opioid crisis, research on treatment outcomes for persons with opioid use disorder (OUD) should account for biological factors that could influence individual treatment response. Women and men might have clinically meaningful differences in their experience in OUD treatment and might also have unique challenges in achieving successful, long-term recovery. This review summarizes and synthesizes the current literature on sex-based differences in OUD treatment outcomes.. Relevant literature was identified via automated and manual searches using the terms "opioid treatment outcome sex [or gender] differences" and "opiate treatment outcome sex [or gender] differences." Search methodology was consistent with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), and were conducted within the PubMed electronic database during March and April of 2018.. The initial PubMed search yielded 241 manuscripts and 31 original research articles that met inclusion/exclusion criteria were synthesized in this review. Several important trends emerged, including findings that women are more likely than men to present to treatment with co-occurring mental health conditions such as depression, and that women might respond particularly well to buprenorphine maintenance.. While much of the literature on this topic is subject to potential cohort effects, interventions that address co-occurring mental health conditions and psychosocial stress might improve treatment outcomes for women with OUD.. Funding agencies and researchers should focus attention toward human laboratory studies and clinical trials that are prospectively designed to assess sex-based differences in OUD recovery. (Am J Addict 2019;28:246-261).

Topics: Analgesics, Opioid; Buprenorphine; Combined Modality Therapy; Female; Humans; Male; Opiate Substitution Treatment; Opioid-Related Disorders; Psychotherapy; Sex Characteristics; Sex Factors; Treatment Outcome

Funding for this summary was contributed by the Laura and John Arnold Foundation, Blue Shield of California, and California Health Care Foundation to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from Aetna, AHIP Anthem, Blue Shield of California, CVS Caremark, Express Scripts, Harvard Pilgrim Health Care, Cambia Health Solutions, United Healthcare, Kaiser Permanente, Premera Blue Cross, AstraZeneca, Genentech, GlaxoSmithKline, Johnson & Johnson, Merck, National Pharmaceutical Council, Prime Therapeutics, Sanofi, Spark Therapeutics, Health Care Service Corporation, Editas, Alnylam, Regeneron, Mallinkrodt, Biogen, HealthPartners, and Novartis. Otuonye, Kumar, and Pearson are ICER employees. Banken received consulting fees from ICER for work on this report.

Topics: Analgesics, Opioid; Buprenorphine; Cost-Benefit Analysis; Delayed-Action Preparations; Humans; Methadone; Models, Economic; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Policy; Treatment Outcome; United States

Topics: Analgesics, Opioid; Buprenorphine; Chronic Pain; Drug Overdose; Humans; Methadone; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Risk Assessment; Substance Abuse Detection

Well-informed staff can help decrease risks and common misconceptions regarding opioid-tolerant patients, especially those taking methadone.. In 2015, opioid pain relievers were the second most used drug at 3.8 million. Overdose death was three times greater in 2015 than in 2000. Medication-assisted treatment was sought by more than 2 million individuals with substance use disorder, one of which is methadone. Chronic pain affects millions of adults in the USA. Opioid therapy is widely used among these adults. Related to the risk of abuse and dependence, guidelines suggest that opioid therapy may not be considered first-line treatment. A multidisciplinary approach, including thorough preoperative evaluation, the utilization of multimodal pain management strategies, and opioid-sparing techniques in both the intraoperative and postoperative periods will allow for the best possible outcome.

Topics: Analgesics, Opioid; Buprenorphine; Chronic Pain; Humans; Methadone; Opioid-Related Disorders; Pain Management

Topics: Analgesics, Opioid; Buprenorphine; Cost-Benefit Analysis; Delayed-Action Preparations; Humans; Narcotic Antagonists; Opioid-Related Disorders; Quality of Life; Randomized Controlled Trials as Topic; Treatment Outcome

Opioid use disorder (OUD) and opioid-related overdose mortality are major public health concerns in the United States. Recently, several community-based and professional innovations - including hybrid recovery community organizations, peer-based emergency department warm handoff programs, emergency department buprenorphine induction, and low-threshold OUD treatment programs - have emerged or expanded in an effort to address significant obstacles to providing patients the care needed for OUD and to reduce the risk of overdose. Additional innovations are needed to address the crisis. Building upon the foundational frameworks of each of these recent innovations, a new model of OUD pharmacotherapy is proposed and discussed: the Recovery Community Center Office-Based Opioid Treatment model. Additionally, two potential implementation scenarios, the overdose and non-overdose event protocols, are detailed for communities, peers, and practitioners interested in implementing the model. Potential barriers to implementation of the model include service reimbursement, licensing regulations, and organizational concerns. Future research should seek to validate the model and to identify actual implementation and sustainability barriers and best practices.

Topics: Buprenorphine; Community Health Centers; Drug Overdose; Emergency Service, Hospital; Humans; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Referral and Consultation; United States

The use of buprenorphine, methadone, and long-acting naltrexone for treatment of opioid use disorder (OUD) is discussed, including a review of current literature detailing treatment approaches and action steps to optimize treatment in acute care and office-based settings.. The U.S. epidemic of opioid-related deaths has been driven by misuse of prescription opioids and, increasingly, illicit drugs such as heroin, fentanyl, and fentanyl analogs, necessitating a refocusing of treatment efforts on expanding access to life-saving, evidence-based OUD pharmacotherapy. Inpatient treatment of opioid withdrawal includes acute symptom control through a combination of nonopioid medications and long-term pharmacotherapy to lessen opioid craving and facilitate stabilization and recovery. Methadone and buprenorphine reduce opioid craving, increase treatment retention, reduce illicit opioid use, and increase overall survival. Buprenorphine has logistical advantages over methadone, such as greater flexibility of treatment setting and less risk of adverse effects. Studies have shown the efficacy of long-acting injectable naltrexone to be comparable to that of buprenorphine if patients are detoxified prior to initiation of therapy; however, patients with active OUD are often not able to complete the week-long period of opioid abstinence needed prior to initiation of naltrexone injections. Although buprenorphine is preferred by many patients and can be prescribed in office-based settings, there remains a paucity of physicians certified to prescribe it.. Buprenorphine has become the medication of choice for many patients with OUD, but its use is limited by the low number of physicians certified to prescribe the agent. Other agents studied for treatment of OUD include methadone and naltrexone.

Topics: Analgesics, Opioid; Buprenorphine; Drug Prescriptions; Evidence-Based Medicine; Humans; Methadone; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders

Opioid use disorder (OUD) and its consequences are a major public health concern. The partial agonist buprenorphine is a safe and effective treatment for OUD, but concerns about abuse, misuse, and diversion of buprenorphine have been raised. This narrative review examined the rates and motives for use of illicit buprenorphine in the United States. Findings from the 17 included studies suggest the majority of study participants using illicit buprenorphine do so for reasons related to misuse (to manage opioid withdrawal symptoms or achieve or maintain abstinence from other opioids). A smaller percentage of study respondents reported using buprenorphine for reasons related to abuse (to get high). There appears to be a gap between need for buprenorphine and access to adequate treatment. Attenuation of policy-related barriers and adoption of appropriate buprenorphine use by the treatment community are critical tools in the continued effort to reduce the burdens associated with OUD.

Topics: Analgesics, Opioid; Buprenorphine; Health Services Accessibility; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Prescription Drug Misuse; United States

Opioid use disorder (OUD) has become a public health crisis in the U.S., and there is a need to develop effective clinical treatment strategies. Coupling buprenorphine/naloxone (B/N) maintenance with counseling is encouraged as a best practice, yet the efficacy research on individual counseling in B/N-based Office-Based Opioid Treatment (OBOT) has been equivocal to date. In contrast, models for integrating B/N prescribing through group-based counseling could potentially have a differential impact, yet no systematic reviews have focused on examining the extent of the literature on group-based models of B/N delivery.. We conducted a systematic literature review to identify existing studies characterizing the different formats of Group-Based Opioid Treatment (GBOT), which we defined as the coupling of B/N prescribing with required office-based group counseling. Using this definition of GBOT, B/N prescribing could occur either concurrently during a medical visit with group counseling (i.e., Shared Medical Appointment) or asynchronously (i.e., Group Psychotherapy). We assessed for all available scientific literature reporting on the feasibility, acceptability and/or efficacy of these different forms of GBOT. The systematic review protocol used PRISMA standards.. We included 10 peer-reviewed, full-text articles and 5 conference abstracts of office-based opioid use disorder treatment that reported data on the feasibility, acceptability, and efficacy of Group-Based Opioid Treatment with B/N. Of the ten full-text articles we included 4 studies describing a shared medical appointment (SMA) model and 6 studies describing a group psychotherapy model. Of these studies, all were low in quality due to study design and only three were randomized controlled trials. No studies were appropriately designed to rigorously compare the efficacy of a GBOT approach (i.e., B/N prescribing with required group-based counseling) versus B/N prescribing with required individual counseling; nor were they designed for rigorous comparison with medication management alone. Nevertheless, most studies reported on the feasibility and acceptability of various models representative of a GBOT approach.. The small number of studies and study design limited the conclusions that could be drawn about the feasibility, acceptability, and efficacy of group-based B/N treatment. More research is needed to determine whether benefits exist of GBOT with B/N.

Topics: Analgesics, Opioid; Appointments and Schedules; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Counseling; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Psychotherapy, Group; Treatment Outcome

Topics: Adolescent; Analgesics, Opioid; Buprenorphine; Clinical Protocols; Humans; Methadone; Naltrexone; Opiate Substitution Treatment; Opioid-Related Disorders; Primary Health Care

Starting with approval for clinical use in the treatment of opioid dependence in October 2002 by the Food and Drug Administration (FDA), buprenorphine has become an integral treatment option and in recent years, in chronic pain management. Buprenorphine possesses a unique pharmacodynamic and pharmacokinetic profile that can potentially make perioperative analgesia challenging.. To date no unified guidelines or recommendations are available for buprenorphine product management during the perioperative period. The present investigation aims to review the literature and provide recommendations when encountering a patient on buprenorphine therapy who is scheduled for a surgical or interventional pain procedure.. Clinical studies and reviews were searched using the PubMed National Center for Biotechnology Information database using MeSH terms buprenorphine, buprenorphine and naloxone, suboxone, perioperative, and postoperative pain.. PubMed National Center for Biotechnology Information database search resulted in one randomized control trial, one prospective case matched cohort, one retrospective cohort, 0 case series, 4 case reports, and 6 review articles. Key literature is reviewed and summarized.. Only 12 articles were included, which permits only limited recommendations drawn from this review.. The perioperative management of buprenorphine and buprenorphine/naloxone are dependent on several key factors. The nature of the surgery, namely the postoperative opioid requirement, elective versus emergency surgery, patient characteristics, formulation of buprenorphine, and indication for buprenorphine or buprenorphine/naloxone therapy must be considered when devising a plan. Several options exist when formulating a plan for the perioperative management, including continuing buprenorphine therapy or holding buprenorphine therapy for a defined period of time with or without bridging to alternative opioids. Additionally, social support people and patient motivation should be addressed and optimized, as well as nonopioid adjuvant therapy should be maximized as applicable to each patient undergoing a surgical or interventional pain procedure.. Buprenorphine, naloxone, surgery, pain management, anesthesia, suboxone, opioid abuse.

Topics: Adult; Analgesics, Non-Narcotic; Buprenorphine; Humans; Naloxone; Opiate Substitution Treatment; Opioid-Related Disorders; Pain Management

Et stadig høyere antall pasienter i legemiddelassistert rehabilitering dør av somatiske sykdommer, inkludert kreftsykdom. I det palliative sykdomsforløpet er særlig smertebehandlingen utfordrende.

Topics: Acetaminophen; Analgesics, Non-Narcotic; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Buprenorphine; Cancer Pain; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pain Management; Pain Measurement; Pain, Postoperative; Palliative Care; Terminal Care

Opioid misuse, including the use of heroin and the overprescribing, misuse, and diversion of opioid pain medications, has reached epidemic proportions in the United States. As a result, there has been a dramatic increase in opioid use disorder and associated overdoses and deaths. Addiction is a chronic brain disease with a genetic component that affects motivation, inhibition, and cognition. Patient characteristics associated with successful buprenorphine maintenance treatment include stable or controlled medical or psychiatric comorbidities and a safe, substance-free environment. As a partial opioid agonist, buprenorphine has a ceiling effect that limits respiratory depression and adds to its safety in accidental or intentional overdose. Buprenorphine and combinations of buprenorphine and naloxone are generally well tolerated; adverse effects include anxiety, constipation, dizziness, drowsiness, headache, nausea, and sedation. Family physicians who meet specific requirements can obtain a Drug Addiction Treatment Act of 2000 waiver by notifying the Substance Abuse and Mental Health Services Administration of their intent to begin dispensing and/or prescribing buprenorphine. Medication-assisted treatment with buprenorphine is as effective as methadone in terms of treatment retention and decreased opioid use when prescribed at fixed dosages of at least 7 mg per day; dosages of 16 mg per day are clearly superior to placebo. Sporadic opioid use is not uncommon in the first few months of medication-assisted treatment and should be addressed by increased visit frequency and more intensive engagement with behavioral therapies. Follow-up visits should include documentation of any relapses, reemergence of cravings or withdrawal, random urine drug testing, pill or wrapper counts, and checks of state prescription drug database records.

Topics: Buprenorphine; Drug Prescriptions; Humans; Narcotic Antagonists; Opioid-Related Disorders; Treatment Outcome

This systematic review synthesizes evidence on the effects of Medication-Assisted Treatment (MAT) for opioid use disorder (OUD) on functional outcomes, including cognitive (e.g., memory), physical (e.g., fatigue), occupational (e.g., return to work), social/behavioral (e.g., criminal activity), and neurological (e.g., balance) function. Five databases were searched from inception to July 2017 to identify English-language controlled trials, case control studies, and cohort comparisons of one or more groups; cross-sectional studies were excluded. Two independent reviewers screened identified literature, abstracted study-level information, and assessed the quality of included studies. Meta-analyses used the Hartung-Knapp method for random-effects models. The quality of evidence was assessed using the GRADE approach. A comprehensive search followed by 1411 full text publication screenings yielded 30 randomized controlled trials (RCTs) and 10 observational studies meeting inclusion criteria. The studies reported highly diverse functional outcome measures. Only one RCT was rated as high quality, but several methodologically sound observational studies were identified. The statistical power to detect differences in functional outcomes was unclear in most studies. When compared with matched "healthy" controls with no history of substance use disorder (SUD), in two studies MAT patients had significantly poorer working memory and cognitive speed. One study found MAT patients scored worse in aggressive responding than did "healthy" controls. A large observational study found that MAT users had twice the odds of involvement in an injurious traffic accident as non-users. When compared with persons with OUD not on MAT, one cohort study found lower fatigue rates among buprenorphine-treated OUD patients. No differences were reported for occupational outcomes and results for criminal activity and other social/behavioral areas were mixed. There were few differences among MAT drug types. A pooled analysis of three RCTs found a significantly lower prevalence of fatigue with buprenorphine compared to methadone, while a meta-analysis of the same RCTs found no statistical difference in insomnia prevalence. Three RCTs that focused on cognitive function compared the effects of buprenorphine to methadone; no statistically significant differences in memory, cognitive speed and flexibility, attention, or vision were reported. The quality of evidence for most functional outcomes was

Topics: Buprenorphine; Humans; Methadone; Naltrexone; Opiate Substitution Treatment; Opioid-Related Disorders

Opioid-related overdose deaths have reached epidemic levels within the last decade. The efforts to prevent, identify, and treat opioid use disorders (OUDs) mostly focus on the outpatient setting. Despite their frequent overrepresentation, less is known about the inpatient management of patients with OUDs. Specifically, the perioperative phase is a very vulnerable time for patients with OUDs, and little has been studied on the optimal management of acute pain in these patients. The preoperative evaluation should aim to identify those with OUDs and assess factors that may interfere with OUD treatment and pain management. Efforts should be made to provide education and assistance to patients and their support systems. For those who are actively struggling with opioid use, the perioperative phase can be an opportunity for engagement and to initiate treatment. Buprenorphine, methadone, and naltrexone medication treatment for OUD and opioid tolerance complicate perioperative pain management. A multidisciplinary team approach is crucial to provide clinically balanced pain relief without jeopardizing the patient's recovery. This article reviews the existing literature on the perioperative management of patients with OUDs and provides clinical suggestions for the optimal care of this patient population.

Topics: Analgesics, Opioid; Buprenorphine; Drug Overdose; Drug Tolerance; Humans; Interdisciplinary Communication; Methadone; Naltrexone; Opiate Substitution Treatment; Opioid-Related Disorders; Pain Management; Patient Discharge; Patient-Centered Care; Perioperative Care

Despite increasing opioid overdose mortality, problems persist in the availability and quality of treatment for opioid use disorder (OUD). Three FDA-approved medications (methadone, buprenorphine, and naltrexone) have high quality evidence supporting their use, but most individuals with OUD do not receive them and many experience relapse following care episodes. Developing and organizing quality measures under a unified framework such as a Cascade of Care could improve system level practice and treatment outcomes. In this context, a review was performed of existing quality measures relevant to the treatment of OUD and the literature assessing the utility of these measures in community practice.. Systematic searches of two national quality measure clearinghouses (National Quality Forum and Agency for Healthcare Research and Quality) were performed for measures that can be applied to the treatment of OUD. Measures were categorized as structural, process, or outcome measures. Second stage searches were then performed within Ovid/Medline focused on published studies investigating the feasibility, reliability, and validity of identified measures, predictors of their satisfaction, and related clinical outcomes.. Seven quality measures were identified that are applicable to the treatment of OUD. All seven were process measures that assess patterns of service delivery. One recently approved measure addresses retention in medication-assisted treatment for patients with OUD. Twenty-nine published studies were identified that evaluate the quality measures, primarily focused on initiation and engagement in care for addiction treatment generally. Most measures and related studies do not specifically incorporate the evidence base for the treatment of OUD or assess patient level outcomes such as overdose.. Despite considerable progress, gaps exist in quality measures for OUD treatment. Development of a unified quality measurement framework such as an OUD Treatment Cascade will require further elaboration and refinement of existing measures across populations and settings. Such a framework could form the basis for applying strategies at clinical, organizational, and policy levels to expand access to quality care and reduce opioid-related mortality.

Topics: Analgesics, Opioid; Buprenorphine; Drug Overdose; Humans; Methadone; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Treatment Outcome

Pharmacologic therapies for management of heroin withdrawal have been studied and reviewed widely. Opium dependence is generally associated with less severe dependence and milder withdrawal symptoms than heroin. The evidence on withdrawal management of heroin might therefore not be exactly applicable for opium.. To assess the effectiveness and safety of various pharmacologic therapies for the management of the acute phase of opium withdrawal.. We searched the following sources up to September 2017: CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, regional and national databases (IMEMR, Iranmedex, and IranPsych), main electronic sources of ongoing trials, and reference lists of all relevant papers. In addition, we contacted known investigators to obtain missing data or incomplete trials.. Controlled clinical trials and randomised controlled trials on pharmacological therapies, compared with no intervention, placebo, other pharmacologic treatments, different doses of the same drug, and psychosocial intervention, to manage acute withdrawal from opium in a maximum duration of 30 days.. We used the standard methodological procedures expected by Cochrane.. We included 13 trials involving 1096 participants. No pooled analysis was possible. Studies were carried out in three countries, Iran, India, and Thailand, in outpatient and inpatient settings. The quality of the evidence was generally very low.When the mean of withdrawal symptoms was provided for several days, we mainly focused on day 3. The reason for this was that the highest severity of opium withdrawal is in the second to fourth day.Comparing different pharmacological treatments with each other, clonidine was twice as good as methadone for completion of treatment (risk ratio (RR) 2.01, 95% confidence interval (CI) 1.69 to 2.38; 361 participants, 1 study, low-quality evidence). All the other results showed no differences between the considered drugs: baclofen versus clonidine (RR 1.06, 95% CI 0.63 to 1.80; 66 participants, 1 study, very low-quality evidence); clonidine versus clonidine plus amantadine (RR 1.03, 95% CI 0.86 to 1.24; 69 participants, 1 study); clonidine versus buprenorphine in an inpatient setting (RR 1.04, 95% CI 0.90 to 1.20; 1 study, 35 participants, very low-quality evidence); methadone versus tramadol (RR 0.95, 95% CI 0.65 to 1.37; 1 study, 72 participants, very low-quality evidence); methadone versus methadone plus gabapentin (RR 1.17, 95% CI 0.96 to 1.43; 1 study, 40 participants, low-quality evidence), and tincture of opium versus methadone (1 study, 74 participants, low-quality evidence).Comparing different pharmacological treatments with each other, adding amantadine to clonidine decreased withdrawal scores rated at day 3 (mean difference (MD) -3.56, 95% CI -5.97 to -1.15; 1 study, 60 participants, very low-quality evidence). Comparing clonidine with buprenorphine in an inpatient setting, we found no difference in withdrawal symptoms rated by a physician (MD -1.40, 95% CI -2.93 to 0.13; 1 study, 34 participants, very low-quality evidence), and results in favour of buprenorpine when rated by participants (MD -11.80, 95% CI -15.56 to -8.04). Buprenorphine was superior to clonidine in controlling severe withdrawal symptoms in an outpatient setting (RR 0.35, 95% CI 0.19 to 0.64; 1 study, 76 participants). We found no difference in the comparison of methadone versus tramadol (MD 0.04, 95% CI -2.68 to 2.76; 1 study, 72 participants) and in the comparison of methadone versus methadone plus gabapentin (MD -2.20, 95% CI -6.72 to 2.32; 1 study, 40 participants).Comparing clonidine versus buprenorphine in an outpatient setting, more adve. Results did not support using any specific pharmacological approach for the management of opium withdrawal due to generally very low-quality evidence and small or no differences between treatments. However, it seems that opium withdrawal symptoms are significant, especially at days 2 to 4 after discontinuation of opium. All of the assessed medications might be useful in alleviating symptoms. Those who receive clonidine might experience hypotension.

Topics: Amantadine; Amines; Baclofen; Buprenorphine; Clonidine; Cyclohexanecarboxylic Acids; Gabapentin; gamma-Aminobutyric Acid; Humans; Methadone; Opioid-Related Disorders; Opium; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome; Tramadol

As part of a national effort to combat the current US opioid epidemic, use of currently Food and Drug Administration-approved drugs for the treatment of opioid use disorder/opioid addiction (buprenorphine, methadone, and naltrexone) is on the rise. To provide optimal pain control and minimize the risk of relapse and overdose, providers need to have an in-depth understanding of how to manage these medications in the perioperative setting. This article reviews key principles and discusses perioperative considerations for patients with opioid use disorder on buprenorphine, methadone, or naltrexone.

Topics: Buprenorphine; Humans; Methadone; Naltrexone; Opioid-Related Disorders; Pain Management; Perioperative Care

: Medication-assisted treatment for opioid use disorder (OUD), which incorporates methadone, buprenorphine, or naltrexone, has been shown to reduce all-cause mortality rates in patients with this disease-and the numbers of patients receiving such treatment is substantial. In 2016, among U.S. patients with OUD, nearly 350,000 were treated with methadone, more than 60,000 were treated with buprenorphine, and more than 10,000 were treated with naltrexone. Managing acute pain in patients receiving this treatment can be a significant nursing challenge. The authors discuss the attributes of the three medications used to treat OUD and, through a composite patient case, review how to manage acute pain effectively in patients receiving this type of treatment.This article is one in a series on palliative care developed in collaboration with the Hospice and Palliative Nurses Association (https://advancingexpertcare.org), which offers education, certification, advocacy, leadership, and research on palliative care.

Topics: Analgesics, Opioid; Buprenorphine; Female; Humans; Methadone; Middle Aged; Naltrexone; Narcotic Antagonists; Nurse's Role; Opiate Substitution Treatment; Opioid-Related Disorders; Pain Management; Palliative Care; Substance Withdrawal Syndrome

Buprenorphine has been used internationally for the treatment of opioid use disorder (OUD) since the 1990s and has been available in the United States for more than a decade. Initial practice recommendations were intentionally conservative, were based on expert opinion, and were influenced by methadone regulations. Since 2003, the American crisis of OUD has dramatically worsened, and much related empirical research has been undertaken. The findings in several important areas conflict with initial clinical practice that is still prevalent. This article reviews research findings in the following 7 areas: location of buprenorphine induction, combining buprenorphine with a benzodiazepine, relapse during buprenorphine treatment, requirements for counseling, uses of drug testing, use of other substances during buprenorphine treatment, and duration of buprenorphine treatment. For each area, evidence for needed updates and modifications in practice is provided. These modifications will facilitate more successful, evidence-based treatment and care for patients with OUD.

Topics: Benzodiazepines; Buprenorphine; Central Nervous System Agents; Counseling; Drug Therapy, Combination; Evidence-Based Medicine; Humans; Induction Chemotherapy; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Patient-Centered Care; Practice Guidelines as Topic; Recurrence; Substance Abuse Detection

Opioid use disorder continues to be a significant source of morbidity and mortality in the USA and the world. Pharmacologic treatment with methadone and buprenorphine has been shown to be effective at retaining people in treatment programs, decreasing illicit opioid use, decreasing rates of hepatitis B, and reducing all cause and overdose mortality. Unfortunately, barriers exist in accessing these lifesaving medications: users wishing to start buprenorphine therapy require a waivered provider to prescribe the medication, while some states have no methadone clinics. As such, users looking to wean themselves from opioids or treat their opioid dependence will turn to alternative agents. These agents include using prescription medications, like clonidine or gabapentin, off-label, or over the counter drugs, like loperamide, in supratherapeutic doses. This review provides information on the pharmacology and the toxic effects of pharmacologic agents that are used to treat opioid use disorder. The xenobiotics reviewed in depth include buprenorphine, clonidine, kratom, loperamide, and methadone, with additional information provided on lofexidine, akuamma seeds, kava, and gabapentin.

Topics: Buprenorphine; Humans; Methadone; Narcotic Antagonists; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders

Opioid addiction rates are at a national high, with significant morbidity and mortality. In women, rates have been steadily increasing to be at par with addiction rates in men. Women tend to have quicker addiction and shorter duration to adverse outcomes. Treatment of women has the best outcomes when it is gender-specific, trauma-informed, connected with access to psychiatric services, and integrated into the medical home. Improved outcomes can be achieved with coordinated systems of care based on the harm-reduction model, with integration of medication-assisted therapy in a patient-centered medical home.

Topics: Buprenorphine; Chronic Disease; Female; Humans; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Primary Health Care; Risk Factors; Women's Health

Pharmacotherapy for opioid addiction with methadone, buprenorphine, and naltrexone has proven efficacy in reducing illicit opioid use. These treatments are under-utilized among opioid-addicted individuals on parole, probation, or in drug courts. This paper examines the peer-reviewed literature on the effectiveness of pharmacotherapy for opioid addiction of adults under community-based criminal justice supervision in the US. Compared to general populations, there are relatively few papers addressing the separate impact of pharmacotherapy on individuals under community supervision. Tentative conclusions can be drawn from the extant literature. Reasonable evidence exists that illicit opioid use and self-reported criminal behaviour decline after treatment entry, and that these outcomes are as favourable among individuals under criminal justice supervision as the general treatment population. Surprisingly, there is no conclusive evidence regarding the extent to which pharmacotherapy impacts the likelihood of arrest and incarceration among individuals under supervision. However, given the proven efficacy of these three medications in reducing illicit opioid use and the evidence that, in the general population, methadone and buprenorphine treatment are associated with reduction in overdose mortality, the use of all three pharmacotherapies among patients under criminal justice supervision should be expanded while more data are collected on their impact on arrest and incarceration.

Topics: Buprenorphine; Criminal Law; Humans; Methadone; Naltrexone; Opiate Substitution Treatment; Opioid-Related Disorders; Prisons

Individuals who receive buprenorphine treatment for opioid use disorder in office-based settings may be at risk for, or have a history of, polysubstance use. Urine drug testing is an important clinical tool for monitoring medication adherence and patient stability; and screening for illicit drug use and dangerous drug-drug interactions. This article is intended to educate practitioners in office-based opioid treatment settings on selecting appropriate substances for a definitive drug testing panel that are known to be used concurrently, sequentially, or in combination with buprenorphine for opioid use disorder. It is also intended to educate such practitioners on selecting appropriate testing technology to reduce risks to the health and safety of patients prescribed buprenorphine for opioid use disorder. In developing this article, the author conducted a search from May 2018 through December 2017 of peer-reviewed and government-supported articles in electronic databases. The literature showed that several common substances are often abused in conjunction with certain other substances, increasing the risk of serious adverse events, including death. Whether used on their own, concurrently, sequentially, or in combination, substances of abuse carry significant health risks. Definitive urine drug testing, given its high specificity and sensitivity, can accurately identify the use of specific prescription medications and illicit substances that, especially when taken with buprenorphine or other substances, may cause harm to a patient. When testing for buprenorphine and other opioids; sedatives, hypnotics, and anxiolytics; cocaine; amphetamines; and PCP and other club drugs, providers in office-based opioid treatment settings are strongly advised to use definitive urine drug tests as the primary testing methodology. In addition, practitioners must be able to identify all other substances that a patient may be consuming, taking into consideration the patient's historical and current drugs of choice, given that concurrent use with buprenorphine or other substances may cause serious adverse events. This article highlights the pressing market demand for comprehensive, definitive urine drug testing at a more reasonable cost.

Topics: Buprenorphine; Drug Interactions; Humans; Illicit Drugs; Opiate Substitution Treatment; Opioid-Related Disorders; Substance Abuse Detection

Kappa opioid receptor (KOP) is a G-protein coupled receptor mainly expressed in the cerebral cortex and hypothalamus. It is implicated in nociception, diuresis, emotion, cognition, and immune system functions. KOP agonists possess a strong analgesic effect accompanied by a feeling of dysphoria. On the other hand, antagonists of this receptor were found to block depression, anxiety, and drug-seeking behaviors in animal models. Recently, great interest has been given to the development of selective KOP antagonists as an addiction treatment that does not cause dependence itself or show high relapse rates like the currently used agents. This review provides a comprehensive survey of the KOP antagonists developed for this purpose together with their in vivo studies and clinical trials. In addition, a future perspective and recommendations for the work needed to develop clinically relevant KOP antagonists are presented.

Topics: Animals; Humans; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Pain; Receptors, Opioid, kappa

Opioid abuse and dependence continues to rise in both the general population and pregnancy, with opioid overdose deaths having quadrupled in the last 15 years. Illicit drug use in last 30 days of pregnancy was over 4% with almost 0.6% documented maternal opiate use at time of birth. The management of the opioid-tolerant, buprenorphine-dependent or methadone-dependent patient in the peripartum period is reviewed. Options for treatment of opioid dependence, acute pain management, and perioperative multimodal analgesia are discussed. The effects of maternal management on neonatal abstinence syndrome are also reviewed.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Female; Humans; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Peripartum Period; Pregnancy; Pregnancy Complications; Treatment Outcome

Topics: Buprenorphine; Drug Overdose; Humans; Methadone; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Risk

Deaths due to heroin overdoses are increasing and are the leading cause of death among intravenous heroin users. Although medication-assisted treatment (MAT) improves morbidity and mortality in patients with opioid use disorders, it is underutilized. Most efforts to expand access to MAT have focused on outpatient settings. Although the inpatient medical setting presents a critical opportunity to initiate treatment, general hospitals are often unfamiliar with MAT, creating a number of barriers to its use. In this report, we describe the case of a woman with heroin use disorder who was initiated on buprenorphine maintenance treatment while hospitalized for cardiac disease related to her intravenous heroin use. Barriers to initiating buprenorphine in this case included patient, practitioner, and organizational factors, and, ultimately, shared misperceptions about the feasibility of administering buprenorphine in a general medical hospital. These barriers were addressed, buprenorphine was initiated, and the patient demonstrated reduced craving, improved postoperative pain control, improved overall well-being, increased engagement in discharge planning, and acceptance of referral for addiction specialty aftercare. Our experience with this patient suggests that it is feasible to initiate buprenorphine in acute medical settings and that such treatment can improve patient outcomes. Our review of the literature reveals emerging evidence supporting the value of this practice.

Topics: Adult; Buprenorphine; Female; Heroin Dependence; Hospitals, General; Humans; Inpatients; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Referral and Consultation

Topics: Analgesics, Opioid; Buprenorphine; Chronic Disease; Humans; Opioid-Related Disorders; Pain; Pain Management

The recent heroin and prescription opioid misuse epidemic has led to a sharp increase in the number of opioid overdose deaths in the USA. Notwithstanding the availability of three FDA-approved medications (methadone, buprenorphine, and naltrexone) to treat opioid use disorder, these medications are underutilized. This paper provides an update from the recent peer-reviewed literature on barriers to the use of these medications.. These barriers are interrelated and can be categorized as financial, regulatory, geographic, attitudinal, and logistic. While financial barriers are common to all three medications, other barriers are medication-specific. The adverse impact of the current opioid epidemic on public health can be reduced by increasing access to effective pharmacotherapy for opioid use disorder.

Topics: Analgesics, Opioid; Buprenorphine; Health Services Accessibility; Humans; Methadone; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; United States

Although methadone (an opioid agonist) and buprenorphine (a partial opioid agonist) have evidence to support their use in treating opioid use disorder, they remain misunderstood and underutilized. In this article, we outline the risks and benefits of using these drugs as maintenance therapy in opioid-dependent patients.

Topics: Analgesics, Opioid; Buprenorphine; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Prevalence; United States

Opioid pharmacotherapies play an important role in the treatment of opioid-dependent women; however, very little is known about the safety of naltrexone in pregnant patients.. This study examined the obstetric health of opioid-dependent women who were treated with implant naltrexone during pregnancy, and compared them with women treated with methadone and/or buprenorphine and a cohort of non-opioid-dependent controls.. Women treated with implant naltrexone, oral methadone or sublingual buprenorphine between 2001 and 2010, along with a cohort of age-matched controls, were linked with records from midwives, hospital and emergency departments (EDs) and the death registry to identify pregnancy and health events that occurred during pregnancy and in the post-partum period.. Overall rates of pregnancy loss (requiring hospital or ED attendance) were significantly elevated in naltrexone-treated women compared with buprenorphine-treated women (p = 0.018) and controls (p < 0.001); however, they were not statistically different to methadone-treated women (p = 0.210). Birth rates in women on naltrexone implant treatment were significantly higher than in all three comparison groups (p < 0.001). Rates of hospital and ED attendance during pregnancy in the naltrexone-treated women were not statistically different to those of either the methadone or buprenorphine groups, and neither were overall complications during pregnancy and labour. Overall rates of complications during pregnancy were significantly higher in the naltrexone-treated women than in the controls.. Opioid-dependent women treated with naltrexone implant had higher rates of birth than the other three groups (methadone- or buprenorphine-treated women, or age-matched controls). Overall rates of complications during pregnancy were elevated in naltrexone-treated women when compared with the control group, but were generally not significantly different to rates in methadone- or buprenorphine-treated women.

Topics: Administration, Oral; Administration, Sublingual; Buprenorphine; Drug Implants; Female; Humans; Methadone; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Retrospective Studies

Pregnant women with opioid use disorder can be treated with methadone, buprenorphine, or naltrexone to reduce opioid use and improve retention to treatment. In this review, we compare the pregnancy outcomes of methadone, buprenorphine, and naltrexone in clinical trials and discuss the potential behavioral and developmental effects of these agents seen in offspring in animal studies. Important clinical considerations in the management of opioid use disorder in pregnant women and their infants are also discussed. Outside of pregnancy, buprenorphine is used in combination with naloxone to reduce opioid abuse and diversion. During pregnancy, however, the use of buprenorphine as a single agent is preferred to prevent prenatal naloxone exposure. Both methadone and buprenorphine are widely used to treat opioid use disorder; however, compared with methadone, buprenorphine is associated with shorter treatment duration, less medication needed to treat neonatal abstinence syndrome (NAS) symptoms, and shorter hospitalizations for neonates. Despite being the standard of care, medication-assisted treatment with methadone or buprenorphine is still underused, making it apparent that more options are necessary. Naltrexone is not a first-line treatment primarily because both detoxification and an opioid-free period are required. More research is needed to determine naltrexone safety and benefits in pregnant women. Animal studies suggest that changes in pain sensitivity, developmental processes, and behavioral responses may occur in children born to mothers receiving methadone, buprenorphine, or naltrexone and is an area that warrants future studies.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Female; Humans; Infant, Newborn; Methadone; Naltrexone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Treatment Outcome

Opioid addiction to prescription and illicit drugs is a serious and growing problem. In the US alone, >2.4 million people suffer from opioid use disorder. Government and pharmaceutical agencies have begun to address this crisis with recently released and revised task forces and medication-assisted therapies (MAT). For decades, oral or intravenous (IV) MATs have helped patients in their recovery by administration of opioid agonists (methadone, buprenorphine, oxycodone), antagonists (naltrexone, naloxone), and combinations of the two (buprenorphine/naloxone). While shown to be successful, particularly when combined with psychological counseling, oral and IV forms of treatment come with constraints and challenges. Patients can become addicted to the agonists themselves, and there is increased risk for diversion, abuse, or missed dosages. Consequently, long-acting implants have begun to be developed as a potentially preferable method of agonist delivery. To date, the newest implant approved by the US Food and Drug Administration (May 2016) is Probuphine

Topics: Analgesics, Opioid; Buprenorphine; Delayed-Action Preparations; Drug Implants; Humans; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders

Opioid use disorder (OUD) in pregnancy has increased significantly in the past 10 years. Women with OUD may often be undertreated or untreated because of limited accessibility to treatment, particularly in rural areas. Because detoxification is not recommended during pregnancy due to the potential for adverse outcomes in the fetus and a high risk of relapse for the woman, more primary care providers need to be well versed in opioid-assisted therapy. In addition, recent changes in Food and Drug Administration regulations now allow nurse practitioners and physician assistants with specialized training to provide buprenorphine treatment for pregnant women with OUD in primary care settings. The purpose of this article is to provide information and guidance for clinicians working with and treating this population.

Topics: Analgesics, Opioid; Buprenorphine; Female; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnant Women

Opioid use disorder is a chronic, relapsing disease that encompasses use of both prescription opioids and heroin and is associated with a high annual rate of overdose deaths. Medical treatment has proven more successful than placebo treatment or psychosocial intervention, and the partial µ-opioid receptor agonist and κ-opioid receptor antagonist buprenorphine is similar in efficacy to methadone while offering lower risk of respiratory depression. However, frequent dosing requirements and potential for misuse and drug diversion contribute to significant complications with treatment adherence for available formulations. Areas covered: This review describes the development of and preliminary data from clinical trials of an implantable buprenorphine formulation. Efficacy and safety data from comparative studies with other administrations of buprenorphine, including tablets and sublingual film, will be described. Key premises of the Risk Evaluation and Mitigation Strategy program for safely administering buprenorphine implants, which all prescribing physicians must complete, are also discussed. Expert commentary: Long-acting implantable drug formulations that offer consistent drug delivery and lower risk of misuse, diversion, or accidental pediatric exposure over traditional formulations represent a promising development for the effective treatment of opioid use disorder.

Topics: Analgesics, Opioid; Buprenorphine; Delayed-Action Preparations; Drug Implants; Humans; Methadone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders

The challenge of managing acute pain in opioid-addicted patients is a question of fully understanding the pharmacological effects of the illegal drugs and to prevent overdosing or withdrawal symptoms. It requires a thorough knowledge of the patient's daily consumption of legal and illegal drugs and an understanding obtained through an accepting and empathetic communication with the patient. Substitution management aims to prevent opioid withdrawal symptoms and is not a means of managing pain. When planning the pain management the patient must receive at least 25% of the daily methadone dose, recalculated into equipotent substitute morphine.

Topics: Acute Pain; Analgesics, Opioid; Buprenorphine; Humans; Methadone; Morphine; Opiate Substitution Treatment; Opioid-Related Disorders; Pain Management; Pain Measurement; Professional-Patient Relations

Opioid use disorders (OUDs) have long been a global problem, but the prevalence rates have increased over 20 years to epidemic proportions in the US, with concomitant increases in morbidity and all-cause mortality, but especially opioid overdose. These increases are in part attributable to a several-fold expansion in the prescription of opioid pain medications over the same time period. Opioid detoxification and psychosocial treatments alone have each not yielded sufficient efficacy for OUD, but μ-opioid receptor agonist, partial agonist, and antagonist medications have demonstrated the greatest overall benefit in OUD treatment. Buprenorphine, a μ-opioid receptor partial agonist, has been used successfully on an international basis for several decades in sublingual tablet and film preparations for the treatment of OUD, but the nature of formulation, which is typically self-administered, renders it susceptible to nonadherence, diversion, and accidental exposure. This article reviews the clinical trial data for novel buprenorphine delivery systems in the form of subcutaneous depot injections, transdermal patches, and subdermal implants for the treatment of OUD and discusses both the clinical efficacy of longer-acting formulations through increasing consistent medication exposure and their potential utility in reducing diversion. These new delivery systems also offer new dosing opportunities for buprenorphine and strategies for dosing intervals in the treatment of OUD.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Delayed-Action Preparations; Drug Delivery Systems; Humans; Opiate Substitution Treatment; Opioid-Related Disorders

Primary care-based models for Medication-Assisted Treatment (MAT) have been shown to reduce mortality for Opioid Use Disorder (OUD) and have equivalent efficacy to MAT in specialty substance treatment facilities.. The objective of this study is to systematically analyze current evidence-based, primary care OUD MAT interventions and identify program structures and processes associated with improved patient outcomes in order to guide future policy and implementation in primary care settings.. PubMed, EMBASE, CINAHL, and PsychInfo.. We included randomized controlled or quasi experimental trials and observational studies evaluating OUD treatment in primary care settings treating adult patient populations and assessed structural domains using an established systems engineering framework.. We included 35 interventions (10 RCTs and 25 quasi-experimental interventions) that all tested MAT, buprenorphine or methadone, in primary care settings across 8 countries. Most included interventions used joint multi-disciplinary (specialty addiction services combined with primary care) and coordinated care by physician and non-physician provider delivery models to provide MAT. Despite large variability in reported patient outcomes, processes, and tasks/tools used, similar key design factors arose among successful programs including integrated clinical teams with support staff who were often advanced practice clinicians (nurses and pharmacists) as clinical care managers, incorporating patient "agreements," and using home inductions to make treatment more convenient for patients and providers.. The findings suggest that multidisciplinary and coordinated care delivery models are an effective strategy to implement OUD treatment and increase MAT access in primary care, but research directly comparing specific structures and processes of care models is still needed.

Topics: Adult; Buprenorphine; Delivery of Health Care; Humans; Methadone; Opioid-Related Disorders; Primary Health Care

Management of patients with opioid use disorder (OUD) commonly includes opioid agonist therapy (OAT) as a part of an integrated treatment plan. These interventions are associated with proven benefits to the individual and society. Areas covered: The use of methadone and buprenorphine within an integrated treatment plan in the management of patients with OUD: this work provides consensus recommendation on pharmacotherapy in OUD to assist clinicians with practical decision making in this field. Expert opinion: Pharmacotherapy is recommended as part of an integrated OUD treatment approach with psychosocial interventions, with the goal of reducing risks of illicit opioid use, overdose mortality, infection with HIV or HCV, improving health, psychological and social outcomes. Access to OAT should be prioritised in the treatment of OUD. Treatment choices in OUD pharmacotherapy should be based on the needs of the individual and characteristics of medications. Recommendations for choices of OAT are based on clinical efficacy, safety, patient preference, side effects, pharmacological interactions, quality of life, dose titration potential and outcomes (control craving, ongoing opioids consumption or other drugs, and potentially psychiatric comorbidities). Special groups, pregnant women, prisoners, patients with mental health problems have specific needs which must be addressed with expert input.

Topics: Buprenorphine; Consensus; Europe; Humans; Mental Disorders; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Preference; Quality of Life; Risk Reduction Behavior

Increased physician prescribing of opioids to treat chronic nonprogressive pain has been accompanied by an increase in opioid addiction. Twin studies of opioid addiction are consistent with an inherited component of risk, approximately 50%. Several genome-wide association study (GWAS) reports indicate that genetic risk for opioid addiction is conveyed by many alleles of small effect (odds ratios <1.5). These reports have detected alleles in potassium-ion-channel genes (. El aumento de las prescripciones médicas de opioides, para tratar el dolor crónico no progresivo, se ha acompañado de un incremento en la adicción a opioides. Los estudios en gemelos de la adicción a opioides son consistentes con una herencia del componente de riesgo de aproximadamente el 50%. Algunos reportes de los estudios de asociación del genoma completo (GWAS, Genome Wide Association Study) señalan que el riesgo genético para la adicción a opioides se transmite por muchos alelos de pequeño efecto (con una probabilidad <1,5). Estos estudios han detectado alelos en genes para el canal de potasio (KCNC1 y KCNG2) y para una proteína auxiliar del receptor de glutamato (CNIH3). Además, parece promisoria una variante en el gen del receptor opioide mu (OPRM1), que regula la expresión de OPRM1. En la farmacogenética de las adicciones a opioides, la dosis de metadona puede ser regulada por variantes en el citocromo P450 2B6 (CYP2B6), por una enzima que metaboliza la metadona y por el locus 300kb 5' de OPMR1. Un polimorfismo del nucleótido único del gen del receptor opioide delta puede predecir la respuesta terapéutica a metadona versus buprenorfina. Para poder progresar más se necesitan muestras más grandes para investigar los GWAS, las cuales deben incluir controles con exposición crónica a opioides, pero sin adicción. Para un progreso en la farmacogenética se requiere de ensayos clínicos con muestras grandes que comparen farmacoterapias efectivas para la adicción a opioides (naltrexona, metadona y buprenorfina).. L'augmentation des prescriptions médicales d'opioïdes pour traiter la douleur chronique stable s'accompagne d'une augmentation de l'addiction aux opioïdes. Les études de jumeaux sur l'addiction aux opioïdes sont cohérentes avec une composante héréditaire du risque, d'environ 50 %. D'après plusieurs rapports d'étude d'association pangénomique (GWAS : Genome Wide Association Study), le risque génétique pour l'addiction aux opioïdes est transmis par de nombreux allèles à l'effet minime (rapport de risque <1,5). Ces rapports ont détecté des allèles dans les gènes des canaux potassiques (KCNC1 et KCNG2) et dans une protéine auxiliaire du récepteur au glutamate (CNIH3). De plus, un variant du gène du récepteur aux opioïdes µ (OPRM1) régulant l'expression de OPRM1 semble prometteur. Dans la pharmacogénétique de l'addiction aux opioïdes, la dose de méthadone peut être régulée par des variants du cytochrome P450 2B6 (CYP2B6), une enzyme métabolisant la méthadone, et par le locus situé à 300 kb en en amont du gène OPRM1. Un polymorphisme nucléotidique du gène du récepteur δ aux opioïdes peut prédire la réponse au traitement à la méthadone versus buprénorphine. Afin de mieux progresser, les études d'association pangénomique nécessitent des échantillons plus grands, comportant des témoins ayant une exposition chronique aux opioïdes mais sans addiction. De grandes études cliniques comparant les traitements pharmacologiques efficaces pour l'addiction aux opioïdes (naltrexone, méthadone et buprénorphine) sont nécessaires pour le progrès pharmacogénétique.

Topics: Buprenorphine; Cytochrome P-450 CYP2B6; Genome-Wide Association Study; Humans; Narcotic Antagonists; Opioid-Related Disorders; Pharmacogenetics; Polymorphism, Single Nucleotide; Potassium Channels; Receptors, Opioid, mu

Opioid maintenance treatment is the first-line approach in opioid dependence. Both the full opioid agonist methadone (MET) and the partial agonist buprenorphine (BUP) are licensed for the treatment of opioid dependence. BUP differs significantly from MET in its pharmacology, side effects, and safety issues. For example, the risk of respiratory depression is lower than with MET. The risk of diversion and injection of BUP have been reduced by also making it available as a tablet containing the opioid antagonist naloxone. This review summarizes the clinical effects of BUP and examines possible factors that can support decisions regarding the use of BUP or MET in opioid-dependent people.. La primera elección para el tratamiento de la dependencia a opioides es la terapia de mantenimiento con opioides. Tanto la metadona (MET), agonista opioide total, como la buprenorfina (BUP), un agonista parcial, están autorizados para el tratamiento de la dependencia a opioides. La BUP se diferencia significativamente de la MET en su farmacología, los efectos indeseables y la seguridad. Por ejemplo, el riesgo de depresión respiratoria es menor con BUP que con MET. El riesgo del uso recreativo y de la inyección de BUP se ha reducido al tenerla disponible también en forma de comprimidos que contienen el antagonista opioide naloxona. Esta revisión resume los efectos clínicos de la BUP y analiza posibles factores que puedan sustentar decisiones en relación con el uso de BUP o MET en personas dependientes de opioides.. Le traitement d'entretien aux opioïdes est l'approche de première ligne dans la dépendance à ces substances. La méthadone (MET), agoniste complet des opioïdes, et la buprénorphine (BUP), agoniste partiel, sont autorisés tous les deux pour le traitement de la dépendance aux opioïdes. La pharmacologie, les effets secondaires et les problèmes de sécurité d'emploi de la BUP sont très différents de celle de la MET. Par exemple, le risque de dépression respiratoire est plus faible qu'avec la MET. Le risque de détournement et d'injection de la BUP a été réduit en la présentant aussi sous forme de comprimés contenant de la naloxone, un antagoniste des opioïdes. Cet article résume les effets cliniques de la BUP et s'intéresse aux facteurs susceptibles d'influer sur la décision d'utiliser la BUP ou la MET chez les personnes dépendantes aux opioïdes.

Topics: Buprenorphine; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders

Increase in the number of opioid-dependent pregnant women delivering babies at risk for neonatal abstinence syndrome prompted a US Government Accountability Office report documenting deficits in research and provider knowledge about care of the maternal/fetal unit and the neonate. There are 3 general sources of dependence: untreated opioid use disorder, pain management, and medication-assisted treatment with methadone or buprenorphine. A survey of methadone patients' experiences when telling a physician of their pregnancy and opioid dependence demonstrated physician confusion about proper care, frequent negative interactions with the mother, and failures to provide appropriate referral. Patients in pain management were discharged without referral when the physician was told of the pregnancy. Methadone and buprenorphine were frequently seen negatively because they "caused" neonatal abstinence syndrome. Most mothers surveyed had to find opioid treatment on their own. How dependence is managed medically is a critical determinant of the level of stress on both mother and fetus, and therefore another determinant of neonatal health. The effects of both opioid withdrawal stress and maternal emotional stress on neonatal and developmental outcomes are reviewed. Currently, there have been efforts to criminalize maternal opioid dependence and to encourage or coerce pregnant women to undergo withdrawal. This practice poses both acute risks of fetal hypoxia and long-term risks of adverse epigenetic programming related to catecholamine and corticosteroid surges during withdrawal. Contemporary studies of the effects of withdrawal stress on the developing fetal brain are urgently needed to elucidate and quantify the risks of such practices. At birth, inconsistencies in the hospital management of neonates at risk for neonatal abstinence syndrome have been observed. Neglect of the critical role of maternal comforting in neonatal abstinence syndrome management is an iatrogenic and preventable cause of poor outcomes and long hospitalizations. Rooming-in allows for continuous care of the baby and maternal/neonatal attachment, often unwittingly disrupted by the neonatal intensive care unit environment. Recommendations are made for further research into physician/patient interactions and into optimal dosing of methadone and buprenorphine to minimize maternal/fetal withdrawal.

Topics: Brain Diseases; Buprenorphine; Female; Fetal Diseases; Humans; Methadone; Opioid-Related Disorders; Pregnancy; Pregnancy Complications

Greater integration of medication-assisted treatment (MAT) for opioid use disorder (OUD) in U.S. primary care settings would expand access to treatment for this condition. Models for integrating MAT into primary care vary in structure. This article summarizes findings of a technical report for the Agency for Healthcare Research and Quality describing MAT models of care for OUD, based on a literature review and interviews with key informants in the field. The report describes 12 representative models of care for integrating MAT into primary care settings that could be considered for adaptation across diverse health care settings. Common components of existing care models include pharmacotherapy with buprenorphine or naltrexone, provider and community education, coordination and integration of OUD treatment with other medical and psychological needs, and psychosocial services and interventions. Models vary in how each component is implemented. Decisions about adopting MAT models of care should be individualized to address the unique milieu of each implementation setting.

Topics: Buprenorphine; Combined Modality Therapy; Education, Medical, Continuing; Health Education; Humans; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Primary Health Care; Psychotherapy

Although counseling is a required part of office-based buprenorphine treatment of opioid use disorders, the nature of what constitutes appropriate counseling is unclear and controversial. The authors review the literature on the role, nature, and intensity of behavioral interventions in office-based buprenorphine treatment.. The authors conducted a review of randomized controlled studies testing the efficacy of adding a behavioral intervention to buprenorphine maintenance treatment.. Four key studies showed no benefit from adding a behavioral intervention to buprenorphine plus medical management, and four studies indicated some benefit for specific behavioral interventions, primarily contingency management. The authors examined the findings from the negative trials in the context of six questions: 1) Is buprenorphine that effective? 2) Is medical management that effective? 3) Are behavioral interventions that ineffective in this population? 4) How has research design affected the results of studies of buprenorphine plus behavioral treatment? 5) What do we know about subgroups of patients who do and those who do not seem to benefit from behavioral interventions? 6) What should clinicians aim for in terms of treatment outcome in buprenorphine maintenance?. High-quality medical management may suffice for some patients, but there are few data regarding the types of individuals for whom medical management is sufficient. Physicians should consider a stepped-care model in which patients may begin with relatively nonintensive treatment, with increased intensity for patients who struggle early in treatment. Finally, with 6-month retention rates seldom exceeding 50% and poor outcomes following dropout, we must explore innovative strategies for enhancing retention in buprenorphine treatment.

Topics: Behavior Therapy; Buprenorphine; Cocaine-Related Disorders; Combined Modality Therapy; Heroin Dependence; Humans; Long-Term Care; Methadone; Opioid-Related Disorders; Outcome and Process Assessment, Health Care; Patient Compliance; Patient Preference; Randomized Controlled Trials as Topic

To systematically review the quantitative and qualitative evidence base pertaining to the prevalence, practice of, and treatment response to the diversion of prescribed opiates in the prison setting.. Medline, Embase, CINAHL, PsycINFO, Google Scholar, ASSIA and Science Direct databases were searched for papers from 1995 to the present relevant to the abuse of prescribed opiate medication. Identified journals and their reference lists were hand searched for other relevant articles. Of the abstracts identified as relevant, full text papers were retrieved and critiqued against the inclusion criteria for the review.. Three hundred and fifty-five abstracts were identified, leading to 42 full-text articles being retrieved. Of those, 10 papers were included in the review. Significant differences in abuse behaviours between different countries were reported. However, a key theme emerged from the data regarding a culture of nasal administration of prescribed sublingual buprenorphine within some prisons due to both reduced prevalence of injection within prison and reduced supplies of illicit drugs within prison. The buprenorphine/naloxone preparation appears to be less amenable to abuse. The review highlighted a paucity of empirical research pertaining to both prevalence of the phenomenon and treatment responses.. Healthcare providers within prisons need to prescribe opioids in the least abuseable preparation since the risk of abuse is significant, despite widespread processes of supervised dispensing. Prescription medication abuse is not limited to opioids and the predominant drug of abuse in an individual prison can rapidly change according to availability.

Topics: Administration, Sublingual; Analgesics, Opioid; Buprenorphine; Drug Prescriptions; Humans; Illicit Drugs; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Prescription Drug Misuse; Prevalence; Prisons; Treatment Outcome

Managed withdrawal is a necessary step prior to drug-free treatment or as the endpoint of substitution treatment.. To assess the effects of buprenorphine versus tapered doses of methadone, alpha. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 11, 2016), MEDLINE (1946 to December week 1, 2016), Embase (to 22 December 2016), PsycINFO (1806 to December week 3, 2016), and the Web of Science (to 22 December 2016) and handsearched the reference lists of articles.. Randomised controlled trials of interventions using buprenorphine to modify the signs and symptoms of withdrawal in participants who were primarily opioid dependent. Comparison interventions involved reducing doses of methadone, alpha. We used standard methodological procedures expected by Cochrane.. We included 27 studies involving 3048 participants. The main comparators were clonidine or lofexidine (14 studies). Six studies compared buprenorphine versus methadone, and seven compared different rates of buprenorphine dose reduction. We assessed 12 studies as being at high risk of bias in at least one of seven domains of methodological quality. Six of these studies compared buprenorphine with clonidine or lofexidine and two with methadone; the other four studies compared different rates of buprenorphine dose reduction.For the comparison of buprenorphine and methadone in tapered doses, meta-analysis was not possible for the outcomes of intensity of withdrawal or adverse effects. However, information reported by the individual studies was suggestive of buprenorphine and methadone having similar capacity to ameliorate opioid withdrawal, without clinically significant adverse effects. The meta-analyses that were possible support a conclusion of no difference between buprenorphine and methadone in terms of average treatment duration (mean difference (MD) 1.30 days, 95% confidence interval (CI) -8.11 to 10.72; N = 82; studies = 2; low quality) or treatment completion rates (risk ratio (RR) 1.04, 95% CI 0.91 to 1.20; N = 457; studies = 5; moderate quality).Relative to clonidine or lofexidine, buprenorphine was associated with a lower average withdrawal score (indicating less severe withdrawal) during the treatment episode, with an effect size that is considered to be small to moderate (standardised mean difference (SMD) -0.43, 95% CI -0.58 to -0.28; N = 902; studies = 7; moderate quality). Patients receiving buprenorphine stayed in treatment for longer, with an effect size that is considered to be large (SMD 0.92, 95% CI 0.57 to 1.27; N = 558; studies = 5; moderate quality) and were more likely to complete withdrawal treatment (RR 1.59, 95% CI 1.23 to 2.06; N = 1264; studies = 12; moderate quality). At the same time there was no significant difference in the incidence of adverse effects, but dropout due to adverse effects may be more likely with clonidine (RR 0.20, 95% CI 0.04 to 1.15; N = 134; studies = 3; low quality). The difference in treatment completion rates translates to a number needed to treat for an additional beneficial outcome of 4 (95% CI 3 to 6), indicating that for every four people treated with buprenorphine, we can expect that one additional person will complete treatment than with clonidine or lofexidine.For studies comparing different rate. Buprenorphine is more effective than clonidine or lofexidine for managing opioid withdrawal in terms of severity of withdrawal, duration of withdrawal treatment, and the likelihood of treatment completion.Buprenorphine and methadone appear to be equally effective, but data are limited. It remains possible that the pattern of withdrawal experienced may differ and that withdrawal symptoms may resolve more quickly with buprenorphine.It is not possible to draw any conclusions from the available evidence on the relative effectiveness of different rates of tapering the buprenorphine dose. The divergent findings of studies included in this review suggest that there may be multiple factors affecting the response to the rate of dose taper. One such factor could be whether or not the initial treatment plan includes a transition to subsequent relapse prevention treatment with naltrexone. Indeed, the use of buprenorphine to support transition to naltrexone treatment is an aspect worthy of further research.Most participants in the studies included in this review were male. None of the studies reported outcomes on the basis of sex, preventing any exploration of differences related to this variable. Consideration of sex as a factor influencing response to withdrawal treatment would be relevant research for selecting the most appropriate type of intervention for each individual.

Topics: Acute Disease; Buprenorphine; Clonidine; Female; Humans; Male; Methadone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome

Opioid dependence is a chronic condition with substantial health, economic and social costs. The study objective was to conduct a systematic review of published health-economic models of opioid agonist therapy for non-prescription opioid dependence, to review the different modelling approaches identified, and to inform future modelling studies.. Literature searches were conducted in March 2015 in eight electronic databases, supplemented by hand-searching reference lists and searches on six National Health Technology Assessment Agency websites. Studies were included if they: investigated populations that were dependent on non-prescription opioids and were receiving opioid agonist or maintenance therapy; compared any pharmacological maintenance intervention with any other maintenance regimen (including placebo or no treatment); and were health-economic models of any type.. A total of 18 unique models were included. These used a range of modelling approaches, including Markov models (n = 4), decision tree with Monte Carlo simulations (n = 3), decision analysis (n = 3), dynamic transmission models (n = 3), decision tree (n = 1), cohort simulation (n = 1), Bayesian (n = 1), and Monte Carlo simulations (n = 2). Time horizons ranged from 6 months to lifetime. The most common evaluation was cost-utility analysis reporting cost per quality-adjusted life-year (n = 11), followed by cost-effectiveness analysis (n = 4), budget-impact analysis/cost comparison (n = 2) and cost-benefit analysis (n = 1). Most studies took the healthcare provider's perspective. Only a few models included some wider societal costs, such as productivity loss or costs of drug-related crime, disorder and antisocial behaviour. Costs to individuals and impacts on family and social networks were not included in any model.. A relatively small number of studies of varying quality were found. Strengths and weaknesses relating to model structure, inputs and approach were identified across all the studies. There was no indication of a single standard emerging as a preferred approach. Most studies omitted societal costs, an important issue since the implications of drug abuse extend widely beyond healthcare services. Nevertheless, elements from previous models could together form a framework for future economic evaluations in opioid agonist therapy including all relevant costs and outcomes. This could more adequately support decision-making and policy development for treatment of non-prescription opioid dependence.

Topics: Buprenorphine; Cost-Benefit Analysis; Drug Overdose; Humans; Models, Economic; Narcotic Antagonists; Nonprescription Drugs; Opioid-Related Disorders

Topics: Adult; Analgesics, Opioid; Buprenorphine; Female; Humans; Male; Narcotic Antagonists; Opioid-Related Disorders; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome; Treatment Outcome; United States

Retention in medication-assisted treatment among opiate-dependent patients is associated with better outcomes. This systematic review (55 articles, 2010-2014) found wide variability in retention rates (i.e., 19%-94% at 3-month, 46%-92% at 4-month, 3%-88% at 6-month, and 37%-91% at 12-month follow-ups in randomized controlled trials), and identified medication and behavioral therapy factors associated with retention. As expected, patients who received naltrexone or buprenorphine had better retention rates than patients who received a placebo or no medication. Consistent with prior research, methadone was associated with better retention than buprenorphine/naloxone. And, heroin-assisted treatment was associated with better retention than methadone among treatment-refractory patients. Only a single study examined retention in medication-assisted treatment for longer than 1 year, and studies of behavioral therapies may have lacked statistical power; thus, studies with longer-term follow-ups and larger samples are needed. Contingency management showed promise to increase retention, but other behavioral therapies to increase retention, such as supervision of medication consumption, or additional counseling, education, or support, failed to find differences between intervention and control conditions. Promising behavioral therapies to increase retention have yet to be identified.

Topics: Behavior Therapy; Buprenorphine; Heroin; Humans; Methadone; Naltrexone; Narcotic Antagonists; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Randomized Controlled Trials as Topic; Treatment Outcome

Buprenorphine represents a safe and effective therapy for treating opioid dependence, alleviating craving and withdrawal symptoms in opioid-dependent patients. Buprenorphine has a "blocking" effect against the action of other opioids at the mu-receptor, preventing not only opioid-induced euphoria, but CNS and respiratory depressant effects as well. Buprenorphine was approved for the treatment of opioid dependence in 2002 after the passage of Drug Abuse Treatment Act 2000 (DATA 2000) which allowed clinicians to treat opioid-dependent patients with specifically named opioid agonist therapies in an office setting. Buprenorphine programs reduce the prevalence of HIV and hepatitis C and reduce criminal behaviors associated with illicit drug use. Patients stabilized on buprenorphine have increased employment, enhanced engagement with social services, and better overall health and well-being.

Topics: Analgesics, Opioid; Behavior, Addictive; Buprenorphine; Craving; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Quality of Life; Risk Factors; Substance Abuse Treatment Centers; Toxicology; Treatment Outcome

Opioid substitution therapy (OST) has been established as the gold standard in treating opioid use disorders. Nevertheless, there is still a debate regarding the qualitative characteristics that define the optimal OST intervention, namely the treatment threshold. The aim of this review is twofold: first, to provide a summary and definition of "treatment thresholds", and second, to outline these thresholds and describe how they related to low and high threshold treatment characteristics and outcomes.. We searched the main databases of Medline, PubMed, PsycInfo, EMBASE, CINAHL and the Cochrane Library. Original published research papers, reviews, and meta-analyses, containing the eligible keywords: "opioid substitution", "OST", "low threshold", "high threshold" were searched alone and in combination, up to June, 2015.. Treatment thresholds were defined as barriers a patient may face prior to and during treatment. The variables of these barriers were classified into treatment accessibility barriers and treatment design barriers. There are increasing numbers of studies implementing low threshold designs with an increasing body of evidence suggesting better treatment outcomes compared to high threshold designs.. Clinical characteristics of low threshold treatments that were identified to increase the effectiveness of OST intervention include increasing accessibility so as to avoid waiting lists, using personalized treatment options regarding medication choice and dose titration, flexible treatment duration, a treatment design that focuses on maintenance and harm reduction with emphasis on the retention of low adherence patients.

Topics: Buprenorphine; Health Services Accessibility; Humans; Methadone; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Compliance; Waiting Lists

Perioperative management of patients receiving opioid addiction therapy presents a unique challenge for the anesthesiologist. The goal of pain management in this patient population is to effectively manage postoperative pain, to improve patient satisfaction and outcomes, and to reduce the cost of health care. Multimodal analgesics, including nonsteroid anti-inflammatory drugs, intravenous acetaminophen, gabapentanoid agents, and low-dose ketamine infusions, have been used to improve postoperative pain and to reduce postoperative opioid use. Patients on long-term opioid management therapy with methadone and buprenorphine require special considerations. Recommendations and options for treating postoperative pain in patients on methadone and buprenorphine are outlined below. Other postoperative pain management options include patient-controlled analgesia, intravenous, and transdermal, in addition to neuraxial and regional anesthesia techniques. Special patient populations include the parturient on long-term opioid therapy. Recommendations for use of opioids in these patients during labor and delivery and in the postpartum period are discussed.

Topics: Buprenorphine; Drug Administration Schedule; Female; Humans; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pain Management; Pain, Postoperative; Postpartum Period; Practice Guidelines as Topic; Pregnancy; Pregnancy Outcome

Four decades of concerted pharmacotherapy research has netted us three medications approved for the treatment of opioid addiction. The clinical pharmacology, safety, efficacy, and clinical use of these medications are familiar to most clinical researchers and clinicians in addiction medicine. Less common is an understanding of the social and political forces behind the choice of these particular agents for their development and how these forces continue to influence how clinicians interact with patients who have opioid use disorder. This review brings into focus those forces and puts into context how we came to have these particular medications. What we know determines our views of the world we live in, including our patients and ourselves, as well as those to whom we give power to govern us. The issues are raised by the author, who does not provide resolutions; answers to the questions of how to address the issues must come from the reader.

Topics: Analgesics, Opioid; Buprenorphine; Humans; Methadone; Naltrexone; Opiate Substitution Treatment; Opioid-Related Disorders

Although there is an abundance of interventional studies to increase breastfeeding rates, little is known about how to support and promote breastfeeding among mothers on opioid maintenance treatment (OMT). The studies on maternal OMT mainly focus on medication excreted in breast milk and breastfeeding benefits for infants with neonatal abstinence syndrome (NAS). We aim to review interventions to improve breastfeeding outcomes among mothers on OMT to make recommendations for practice and future research. We searched CINAHL, PubMed, PsycINFO, and the Cochrane Database of Systematic Reviews for articles, preferably experimental/quasi-experimental studies published within the past 10 years, that examined interventions to increase rates of breastfeeding initiation and duration among mothers on OMT. Nine studies met our inclusion criteria, comprising 5 categories: 4 combined obstetric and addiction care, 1 rooming-in, 1 Baby-Friendly hospital, 2 inpatient/outpatient NAS treatment, and 1 divided methadone dose. Breastfeeding rates were relatively higher for divided methadone dose (81% initiated any breastfeeding) and rooming-in (62% initiated any breastfeeding); lower in Baby-Friendly hospital (24%) and inpatient/outpatient NAS treatment (45% and 24%, respectively); and mixed in combined obstetric and addiction care programs (2 studies reported 70% and 76%; 2 studies reported 17% and 28%). Studies that included both methadone and buprenorphine did not specify breastfeeding results by medication. We recommend future research to differentiate breastfeeding types and duration by OMT medication. Qualitative studies are needed to explore maternal view on breastfeeding regarding need, barrier, and motivating factors in order to develop effective interventions to promote breastfeeding among mothers on OMT.

Topics: Analgesics, Opioid; Breast Feeding; Buprenorphine; Female; Health Promotion; Humans; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders

As a result of the prescription opioid epidemic in the United States, there has been an increasing need for effective treatment interventions, both pharmacological and nonpharmacological. Buprenorphine has emerged as a critical component of the treatment of opioid use disorder, yet its adoption has not been without some concerns. This article first reviews the pharmacology, clinical use, and US legislative action related to buprenorphine, followed by a discussion of the misuse and diversion of buprenorphine in the United States as well as internationally. We then explore the impact of buprenorphine abuse as well as discussing strategies for its reduction, including changes in policy, prescription and pharmacy monitoring, and continuing medical education for guiding and improving clinical practice.

Topics: Buprenorphine; Drug Prescriptions; Humans; Legislation, Medical; Narcotic Antagonists; Opioid-Related Disorders; United States

People who inject drugs (PWID) and other individuals with opioid use disorders have a dramatically higher prevalence of hepatitis C virus (HCV) infection than the general population. The availability of novel direct acting antivirals (DAAs) for the treatment of HCV infection with very high efficacy, improved tolerability and shortened treatment durations have led to global efforts to ramp up treatment for all HCV-infected individuals to prevent or delay complications of the disease. Individuals with opioid use disorders, including those on medication-assisted therapy such as methadone or buprenorphine, are a key demographic group that can benefit from HCV treatment given their high HCV prevalence; however, pharmacokinetic and pharmacodynamic drug interactions could blunt their utility.. We performed a comprehensive literature review of published and unpublished data from PubMed database, relevant conference abstracts/proceedings and FDA approved drug package inserts, to review the pharmacokinetic (PK) profile and drug interactions between currently approved HCV DAAs and methadone and buprenorphine.. The paper highlights specific drug combinations which result in altered opioid drug levels including telaprevir/methadone, daclatasvir/buprenorphine, and Abbvie 3D combination regimen (paritaprevir, ritonavir, ombitasvir and dasabuvir)/buprenorphine. However, concurrent pharmacodynamics assessments did not reveal significant signs and symptoms of opioid withdrawal or toxicity that would preclude concurrent administration.

Topics: Animals; Antiviral Agents; Buprenorphine; Drug Interactions; Hepatitis C; Humans; Methadone; Opioid-Related Disorders; Substance Abuse, Intravenous

There are increasing concerns regarding pharmaceutical opioid harms including overdose and dependence, with an associated increase in treatment demand. People dependent on pharmaceutical opioids appear to differ in important ways from people who use heroin, yet most opioid agonist treatment research has been conducted in people who use heroin.. To assess the effects of maintenance agonist pharmacotherapy for the treatment of pharmaceutical opioid dependence.. The search included the Cochrane Drugs and Alcohol Group's Specialised Register of Trials; the Cochrane Central Register of Controlled Trials (CENTRAL, 2015, Issue 5); PubMed (January 1966 to May 2015); EMBASE (Ovid) (January 1974 to May 2015); CINAHL (EBSCOhost) (1982 to May 2015); ISI Web of Science (to May 2014); and PsycINFO (Ovid) (1806 to May 2014).. We included randomised controlled trials examining maintenance opioid agonist treatments that made the following two comparisons:1. full opioid agonists (methadone, morphine, oxycodone, levo-alpha-acetylmethadol (LAAM), or codeine) versus different full opioid agonists or partial opioid agonists (buprenorphine) for maintenance treatment and2. full or partial opioid agonist maintenance versus placebo, detoxification only, or psychological treatment (without opioid agonist treatment).. We used standard Cochrane methodological procedures.. We identified six randomised controlled trials that met inclusion criteria (607 participants).We found moderate quality evidence from two studies of no difference between methadone and buprenorphine in self reported opioid use (risk ratio (RR) 0.37, 95% confidence interval (CI) 0.08 to 1.63) or opioid positive urine drug tests (RR 0.81, 95% CI 0.56 to 1.18). There was low quality evidence from three studies of no difference in retention between buprenorphine and methadone maintenance treatment (RR 0.69, 95% CI 0.39 to 1.22). There was moderate quality evidence from two studies of no difference between methadone and buprenorphine on adverse events (RR 1.10, 95% CI 0.64 to 1.91).We found low quality evidence from three studies favouring maintenance buprenorphine treatment over detoxification or psychological treatment in terms of fewer opioid positive urine drug tests (RR 0.63, 95% CI 0.43 to 0.91) and self reported opioid use in the past 30 days (RR 0.54, 95% CI 0.31 to 0.93). There was no difference on days of unsanctioned opioid use (standardised mean difference (SMD) -0.31, 95% CI -0.66 to 0.04). There was moderate quality evidence favouring buprenorphine maintenance over detoxification or psychological treatment on retention in treatment (RR 0.33, 95% CI 0.23 to 0.47). There was moderate quality evidence favouring buprenorphine maintenance over detoxification or psychological treatment on adverse events (RR 0.19, 95% CI 0.06 to 0.57).The main weaknesses in the quality of the data was the use of open-label study designs.. There was low to moderate quality evidence supporting the use of maintenance agonist pharmacotherapy for pharmaceutical opioid dependence. Methadone or buprenorphine appeared equally effective. Maintenance treatment with buprenorphine appeared more effective than detoxification or psychological treatments.Due to the overall low to moderate quality of the evidence and small sample sizes, there is the possibility that the further research may change these findings.

Topics: Analgesics, Opioid; Buprenorphine; Humans; Methadone; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Prescription Drug Misuse; Randomized Controlled Trials as Topic

To evaluate maternal and neonatal safety outcomes for methadone and buprenorphine in the obstetric population.. A literature search of PubMed (1966 to March 2016) and EMBASE (1973 to March 2016) was completed using the search terms buprenorphine, methadone, pregnancy, opioid, and neonatal abstinence syndrome Priority was given to randomized controlled trials and trials directly comparing buprenorphine and methadone during pregnancy. The bibliographies were reviewed for other relevant articles.. All human studies published in English, that compared methadone and buprenorphine use in pregnancy were evaluated. Because of the limited number of obstetric studies, only 5 critical studies were found.. Buprenorphine significantly improved or had similar outcomes to methadone for development of neonatal abstinence syndrome (NAS), percentage of infants requiring treatment for NAS (20%-47% vs 45.5%-57%, respectively), total amount of morphine used to treat NAS (0.472-3.4 vs 1.862-10.4 mg, respectively), duration of NAS (4.1-5.6 vs 5.3-9.9 days, respectively), peak NAS (3.9-11 vs 4.9-12.8 score, respectively), infant hospital stay (6.8-10.6 vs 8.1-17.5 days, respectively), and gestational age at delivery (38.8-39.7 vs 37.9-38.8 weeks, respectively). No difference was found with other neonatal or maternal outcomes.. Both methadone and buprenorphine are effective agents, with improved safety compared with continued nonmedical opioid use during pregnancy. There is evidence to suggest that buprenorphine should be considered as an equivalent option to methadone for use in pregnancy; however, larger studies are still needed to fully evaluate buprenorphine safety and advantages over methadone in the obstetric population.

Topics: Buprenorphine; Female; Humans; Infant; Infant, Newborn; Length of Stay; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Randomized Controlled Trials as Topic

To assess the safety of buprenorphine compared with methadone to treat pregnant women with opioid use disorder.. We searched PubMed, Embase and the Cochrane Library from inception to February 2015 for randomized controlled trials (RCT) and observational cohort studies (OBS) that compared buprenorphine with methadone for treating opioid-dependent pregnant women. Two reviewers assessed independently the titles and abstracts of all search results and full texts of potentially eligible studies reporting original data for maternal/fetal/infant death, preterm birth, fetal growth outcomes, fetal/congenital anomalies, fetal/child neurodevelopment and/or maternal adverse events. We ascertained each study's risk of bias using validated instruments and assessed the strength of evidence for each outcome using established methods. We computed effect sizes using random-effects models for each outcome with two or more studies.. Three RCTs (n = 223) and 15 cohort OBSs (n = 1923) met inclusion criteria. In meta-analyses using unadjusted data and methadone as comparator, buprenorphine was associated with lower risk of preterm birth [RCT risk ratio (RR) = 0.40, 95% confidence interval (CI) = 0.18, 0.91; OBS RR = 0.67, 95% CI = 0.50, 0.90], greater birth weight [RCT weighted mean difference (WMD) = 277 g, 95% CI = 104, 450; OBS WMD = 265 g, 95% CI = 196, 335] and larger head circumference [RCT WMD = 0.90 cm, 95% CI = 0.14, 1.66; OBS WMD = 0.68 cm, 95% CI = 0.41, 0.94]. No treatment differences were observed for spontaneous fetal death, fetal/congenital anomalies and other fetal growth measures, although the power to detect such differences may be inadequate due to small sample sizes.. Moderately strong evidence indicates lower risk of preterm birth, greater birth weight and larger head circumference with buprenorphine treatment of maternal opioid use disorder during pregnancy compared with methadone treatment, and no greater harms.

Topics: Abnormalities, Drug-Induced; Analgesics, Opioid; Birth Weight; Buprenorphine; Female; Fetal Death; Fetal Development; Humans; Infant, Newborn; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Safety; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth; Prenatal Care; Randomized Controlled Trials as Topic; Sudden Infant Death

This article reviews the current pharmacotherapy options available for the treatment of patients with substance use disorders. In the United States there are medications available to treat tobacco use disorders (nicotine replacement, bupropion, and varenicline), alcohol use disorders (naltrexone and acamprosate), and opioid use disorders (methadone and buprenorphine). These medications are likely underused and physicians should more readily prescribe for eligible patients.

Topics: Age Factors; Alcohol Deterrents; Alcoholism; Antidepressive Agents; Buprenorphine; Bupropion; Drug Therapy, Combination; Humans; Methadone; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Recurrence; Substance Withdrawal Syndrome; Substance-Related Disorders; Tobacco Use Cessation Devices; Tobacco Use Disorder; Varenicline

Opioid use and addiction in adolescents and young adults is a health problem of epidemic proportions, with devastating consequences for youth and their families. Opioid overdose is a life-threatening emergency that should be treated with naloxone, and respiratory support if necessary. Overdose should always be an opportunity to initiate addiction treatment. Detoxification is often a necessary, but never sufficient, component of treatment for OUDs. Treatment for OUDs is effective but treatment capacity is alarmingly limited and under-developed. Emerging consensus supports the incorporation of relapse prevention medications such as buprenorphine and extended release naltrexone into comprehensive psychosocial treatment including counseling and family involvement.

Topics: Adolescent; Analgesics, Opioid; Buprenorphine; Drug Overdose; Humans; Naloxone; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders

Treatment of opioid dependence with buprenorphine improves outcomes. Typical dosing ranges for all patients from clinical evidence and as defined in the product information are wide. For specific groups with complex clinical scenarios, there is no clear consensus on dosing choices to achieve best possible outcomes.. The doses of buprenorphine used in 6 European countries was reviewed. A review of published evidence supported rapid induction with buprenorphine and the benefits of higher doses but did not identify clearly useful guidance on dosing choices for groups with complex clinical scenarios. An expert group of physicians with experience in addiction care participated in a discussion meeting to share clinical practice experience and develop a consensus on dosing choices.. There was general agreement that treatment outcomes can be improved by optimising buprenorphine doses in specific subgroups. Specific groups in whom buprenorphine doses may be too low and who could have better outcomes with optimised dosing were identified on the basis of clinical practice experience. These groups include people with severe addiction, high tolerance to opioids, and psychiatric comorbidities. In these groups it is recommended to review dosing choices to ensure buprenorphine dosing is sufficient.

Topics: Analgesics, Opioid; Buprenorphine; Europe; Expert Testimony; Humans; Narcotic Antagonists; Opioid-Related Disorders; Treatment Outcome

Topics: Adrenergic alpha-Agonists; Buprenorphine; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Substance Withdrawal Syndrome

Opioid use disorder is a leading cause of morbidity and mortality among US youth. Effective treatments, both medications and substance use disorder counseling, are available but underused, and access to developmentally appropriate treatment is severely restricted for adolescents and young adults. Resources to disseminate available therapies and to develop new treatments specifically for this age group are needed to save and improve lives of youth with opioid addiction.

Topics: Adolescent; Buprenorphine; Humans; Medication Adherence; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders

Topics: Acute Pain; Analgesics, Non-Narcotic; Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Drug Overdose; Hospitalization; Humans; Methadone; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Respiration, Artificial; Substance Withdrawal Syndrome

Opioid Use Disorder (OUD) is a significant public health concern, negatively impacting the medical, psychological, and social domains of an individual's life as well as creating substantial burdens for society. Effective treatment interventions are necessary for reduction of OUD and its consequences. Pharmacotherapy represents a central component of management. Areas covered: This review focuses on pharmacologic strategies for OUD treatment, discussing both primary as well as adjunctive therapy modalities. We will discuss both medications used during detoxification to treat withdrawal, as well as those used as maintenance therapy. Detox medications include alpha-2 adrenergic agonists, such as clonidine, as well as the μ-opioid agonist, methadone, and the μ-opioid partial agonist, buprenorphine. Opioid maintenance treatment (OMT) is also discussed, focusing on those medications meant to substitute abused opioids and includes the agonists, methadone and buprenorphine, as well as supervised intravenous heroin, and opioid antagonist, naltrexone. Expert opinion: Medication therapy for treatment of OUD has demonstrated efficacy and is of great clinical benefit. While agonist treatment with methadone or buprenorphine remains the gold standard, there is an important place for use of long-acting antagonist therapy with naltrexone. Continued investigation into treatment paradigms and behavioral platforms which optimize medication therapy is most needed.

Topics: Adrenergic alpha-2 Receptor Agonists; Buprenorphine; Clonidine; Combined Modality Therapy; Humans; Methadone; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Treatment Outcome

Opioid dependence is a severe medical disorder with a high psychiatric and somatic comorbidity and mortality rate. The opioid agonist methadone, mixed agonist-antagonist buprenorphine and the combination of buprenorphine with the opioid antagonist naloxone are the first-line maintenance treatments for opioid dependence. Risk of diversion and accidental intoxications, especially in children, are of great concern. To lower these risks, a novel buprenorphine-naloxone film has been developed and introduced in the USA and Australia.. This review evaluates the available preclinical and clinical data on the novel buprenorphine-naloxone film for treatment of opioid dependence. Literature was identified through a comprehensive PubMed search. Data sources also included official FDA information and material made public by the manufacturer.. Few preclinical and clinical data on safety and efficacy have been published. The pharmacological differences between the novel film and the conventional buprenorphine/naloxone are small. In an experimental study, the new formulation suppressed symptoms of opioid withdrawal. The spectrum of adverse events seems to be similar to that of the conventional sublingual tablet. Recent data show that patients prefer the novel film over the conventional sublingual tablet. Emerging surveillance data indicate a lower risk of accidental poisoning in children compared with the conventional formulation. Further clinical and preclinical data are needed to explore additional possible advantages of the new formulation.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Chemistry, Pharmaceutical; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Tablets

Maintenance therapy with methadone or buprenorphine is an established and first-line treatment for opioid dependence. Clinical studies indicate that about a third of patients in opioid maintenance therapy show increased alcohol consumption and alcohol use disorders. Comorbid alcohol use disorders have been identified as a risk factor for clinical outcome and can cause poor physical and mental health, including liver disorders, noncompliance, social deterioration and increased mortality risk. The effects of opioid maintenance therapy on alcohol consumption are controversial and no clear pattern has emerged. Most studies have not found a change in alcohol use after initiation of maintenance therapy. Methadone and buprenorphine appear to carry little risk of liver toxicity, but further research on this topic is required. Recent data indicate that brief intervention strategies may help reduce alcohol intake, but the existing evidence is still limited. This review discusses further clinical implications of alcohol use disorders in opioid dependence.

Topics: Alcohol Drinking; Alcohol-Related Disorders; Brain; Buprenorphine; Chemical and Drug Induced Liver Injury; Comorbidity; Humans; Methadone; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Prevalence

Smoking is associated with adverse effects on pregnancy and fetal development, yet 88-95% of pregnant women in medication-assisted treatment for an opioid use disorder smoke cigarettes. This review summarizes existing knowledge about smoking cessation treatments for pregnant women on buprenorphine or methadone, the two forms of medication-assisted treatment for opioid use disorder indicated for prenatal use. We performed a systematic review of the literature using indexed terms and key words to capture the concepts of smoking, pregnancy, and opioid substitution and found that only three studies met search criteria. Contingency management, an incentive based treatment, was the most promising intervention: 31% of participants achieved abstinence within the 12-week study period, compared to 0% in a non-contingent behavior incentive group and a group receiving usual care. Two studies of brief behavioral interventions resulted in reductions in smoking but not cessation. Given the growing number of pregnant women in medication-assisted treatment for an opioid use disorder and the negative consequences of smoking on pregnancy, further research is needed to develop and test effective cessation strategies for this group.

Topics: Analgesics, Opioid; Behavior Therapy; Buprenorphine; Female; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Smoking Cessation; Tobacco Use Disorder; Treatment Outcome

Buprenorphine maintenance therapy (BMT) is increasingly the preferred opioid maintenance agent due to its reduced toxicity and availability in an office-based setting in the United States. Although BMT has been shown to be highly efficacious, it is often discontinued soon after initiation. No current systematic review has yet investigated providers' or patients' reasons for BMT discontinuation or the outcomes that follow. Hence, provider and patient perspectives associated with BMT discontinuation after a period of stable buprenorphine maintenance and the resultant outcomes were systematically reviewed with specific emphasis on pre-buprenorphine-taper parameters predictive of relapse following BMT discontinuation. Few identified studies address provider or patient perspectives associated with buprenorphine discontinuation. Within the studies reviewed providers with residency training in BMT were more likely to favor long term BMT instead of detoxification, and providers were likely to consider BMT discontinuation in the face of medication misuse. Patients often desired to remain on BMT because of fear of relapse to illicit opioid use if they were to discontinue BMT. The majority of patients who discontinued BMT did so involuntarily, often due to failure to follow strict program requirements, and 1 month following discontinuation, rates of relapse to illicit opioid use exceeded 50% in every study reviewed. Only lower buprenorphine maintenance dose, which may be a marker for attenuated addiction severity, predicted better outcomes across studies. Relaxed BMT program requirements and frequent counsel on the high probability of relapse if BMT is discontinued may improve retention in treatment and prevent the relapse to illicit opioid use that is likely to follow BMT discontinuation.

Topics: Analgesics, Opioid; Buprenorphine; Humans; Opioid-Related Disorders; Withholding Treatment

Opioid abuse has reached epidemic levels. Evidence-based treatments such as buprenorphine maintenance therapy (BMT) remain underutilized. Offering BMT in primary care settings has the potential to reduce overall costs of care, decrease medical morbidity associated with opioid dependence, and improve treatment outcomes. However, access to BMT, especially in rural areas, remains limited. This article will present a review of barriers to adoption of BMT among family physicians in a primarily rural area in the USA.. An anonymous survey of family physicians practicing in Vermont or New Hampshire, two largely rural states, was conducted. The survey included both quantitative and qualitative questions, focused on BMT adoption and physician opinions of opioids. Specific factors assessed included physician factors, physicians' understanding of patient factors, and logistical issues.. One-hundred and eight family physicians completed the survey. Approximately 10% were buprenorphine prescribers. More than 80% of family physicians felt they regularly saw patients addicted to opiates. The majority (70%) felt that they, as family physicians, bore responsibility for treating opiate addiction. Potential logistical barriers to buprenorphine adoption included inadequately trained staff (88%), insufficient time (80%), inadequate office space (49%), and cumbersome regulations (37%). Common themes addressed in open-ended questions included lack of knowledge, time, or interest; mistrust of people with addiction or buprenorphine; and difficult patient population.. This study aims to quantify perceived barriers to treatment and provide insight expanding the community of family physicians offering BMT. The results suggest family physicians are excellent candidates to provide BMT, as most report regularly seeing opioid-addicted patients and believe that treating opioid addiction is their responsibility. Significant barriers remain, including inadequate staff training, lack of access to addiction experts, and perceived efficacy of BMT. Addressing these barriers may lower resistance to buprenorphine adoption and increase access to BMT in rural areas.

Topics: Buprenorphine; Confidentiality; Female; Health Knowledge, Attitudes, Practice; Health Services Accessibility; Humans; Inservice Training; Male; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Perception; Physicians, Family; Practice Patterns, Physicians'; Primary Health Care; Time Factors; Trust

Increasing use of opioids has led to an increase in the number of pregnant and postpartum women in medication assisted treatment (MAT) for opioid use disorder.. We (1) conducted a systematic review of published literature on MAT discontinuation (methadone and buprenorphine) in pregnant and postpartum women and (2) determined methadone discontinuation rates in a retrospective cohort (2006-2013) of pregnant and postpartum women in a university affiliated methadone clinic.. We found limited generalizable literature reports of discontinuation rates, with a range of prenatal discontinuation rates from 0 to 33% and rates which spanned various prenatal and postnatal periods from 26 to 64%. In our cohort of 229 women, 251 pregnancies were reported, with a prenatal methadone discontinuation rate of 11.0%. Based on a Cox proportional hazards model controlling for age, pregnancy outcome, and duration of treatment prior to delivery, the probability of methadone discontinuation at or before 6 months postpartum was 56.0%. Duration of methadone treatment prior to delivery was inversely associated with risk for postpartum discontinuation of treatment (HR = 0.98, 95% CI (0.96, 0.99)).. We conclude that the postpartum period is a time of increased risk for discontinuation of MAT. More accurate assessment of rates of pre- and postpartum MAT discontinuation, as well as further investigation of factors affecting these rates, is warranted. Development and testing of interventions to encourage early prenatal enrollment in MAT and improve postnatal retention in MAT would benefit pregnant women and new mothers with opioid use disorder.

Topics: Buprenorphine; Female; Humans; Kaplan-Meier Estimate; Methadone; Narcotic Antagonists; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Dropouts; Postpartum Period; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Retrospective Studies

In Denmark, approximately 7,600 patients receive maintenance therapy with methadone or buprenorphine because of opioid addiction. These patients have an increased risk of inadequate pain treatment during hospitalization, among others because of tolerance to opioids and poor communication with the staff. The present article describes four common misconceptions among health-care providers that underlie inadequate pain treatment and provides practical recommendations for the analgesic management of acute pain in patients receiving methadone or buprenorphine.

Topics: Acute Pain; Analgesics, Opioid; Buprenorphine; Drug Tolerance; Drug Users; Humans; Methadone; Morphine; Opiate Substitution Treatment; Opioid-Related Disorders; Pain Management

Opioid misuse during pregnancy is associated with negative outcomes for both mother and fetus due not only to the physiological effects of the drug but also to the associated social, medical and mental health problems that accompany illicit drug use. An interdisciplinary approach to the treatment of opioid use disorder during pregnancy is most effective. Ideally, obstetric and substance use treatment are co-located and ancillary support services are readily available. Medication-assisted treatment with methadone or buprenorphine is intrinsic to evidence-based care for the opioid-using pregnant woman. Women who are not stabilized on an opioid maintenance medication experience high rates of relapse and worse outcomes. Methadone has been the mainstay of maintenance treatment for nearly 50 years, but recent research has found that both methadone and buprenorphine maintenance treatments significantly improve maternal, fetal and neonatal outcomes. Although methadone remains the current standard of care, the field is beginning to move towards buprenorphine maintenance as a first-line treatment for pregnant women with opioid use disorder, because of its greater availability and evidence of better neonatal outcomes than methadone. However, there is some evidence that treatment dropout may be greater with buprenorphine relative to methadone.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Female; Humans; Infant, Newborn; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications

Opiate drugs are psychoactive substances used to manage severe pain. However, their chronic use is associated with the development of addiction. Opiate addiction represents a significant public health concern.. This review focuses on the most recent advances in the pharmacological treatment of opiate addiction, from those being tested in clinical trials (Phase I and II), to preclinical studies that point to new targets. Readers will gain knowledge of the wide variety of treatments used to treat opiate addiction, including their strengths and weaknesses, and the promising pharmacological targets identified by preclinical research.. Among the currently available agonist therapies, new dosage forms of buprenorphine can increase patient acceptability and compliance. New extended-release forms of naltrexone are building hope of retaining opiate-dependent subjects in a drug-free state. Unfortunately, the review of the literature shows that successful preclinical studies are often followed by discouraging results in human clinical trials. Nevertheless, all targets of potential interest should be tested exhaustively. Indeed, a number of new targets and research lines (genetics and neuroinflammation approaches) may lead to breakthroughs in the future.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Drug Design; Humans; Molecular Targeted Therapy; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders

Medication-assisted treatment (MAT) is a key component in overdose prevention, reducing illicit opiate use and risk of blood-borne virus infection. By retaining participants in MAT programs for longer periods of time, more noticeable and permanent changes in drug use, risk behavior and quality of life can be achieved. Many studies have documented retention in MAT programs in high-income countries, using a 50% average 12-month follow-up retention rate as a marker for a successful MAT program. This study contributes to a systematic understanding of how successful programs have been in retaining participants in low- and middle-income countries (LMIC) over time.. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a systematic literature search to identify MAT program studies that documented changes in retention over time for participants in buprenorphine and methadone programs in LMIC. Retention was measured for participants by length of follow-up, type of MAT and treatment dosage.. There were 58 MAT program studies, with 27 047 participants eligible for inclusion in the review. Overall average retention after 12 months was 54.3% [95% confidence interval (CI) = 46.2, 63.7%]. Overall average retention was moderately good for both buprenorphine (48.3%, 95% CI = 22.1, 74.6%) and methadone (56.6%, 95% CI = 45.9%, 67.3%) after 12 months of treatment. Among programs using methadone there was no statistically significant difference in average retention by dosage level, and the 10 highest and lowest dosage programs obtained similar average retention levels after 12 months.. Medication-assisted treatment programs in low- and middle-income countries achieve an average 50% retention rate after 12 months, with wide variation across programs but little difference between those using buprenorphine versus methadone.

Topics: Analgesics, Opioid; Buprenorphine; Developing Countries; Humans; Medication Adherence; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders

Buprenorphine maintenance treatment (BMT) and methadone maintenance treatment (MMT) are pharmacological treatment programs for individuals with opioid use disorders. MMT is discussed in a companion article. This article describes BMT and reviews available research on its efficacy.. Authors reviewed meta-analyses, systematic reviews, and individual studies of BMT from 1995 through 2012. Databases surveyed were PubMed, PsycINFO, Applied Social Sciences Index and Abstracts, Sociological Abstracts, Social Services Abstracts, and Published International Literature on Traumatic Stress. They chose from three levels of evidence (high, moderate, and low) based on benchmarks for the number of studies and quality of their methodology. They also described the evidence of service effectiveness.. Sixteen adequately designed randomized controlled trials of BMT indicated a high level of evidence for its positive impact on treatment retention and illicit opioid use. Seven reviews or meta-analyses were also included. When the medication was dosed adequately, BMT and MMT showed similar reduction in illicit opioid use, but BMT was associated with less risk of adverse events. Results suggested better treatment retention with MMT. BMT was associated with improved maternal and fetal outcomes in pregnancy, compared with no medication-assisted treatment. Rates of neonatal abstinence syndrome were similar for mothers treated with BMT and MMT during pregnancy, but symptoms were less severe for infants whose mothers were treated with BMT.. BMT is associated with improved outcomes compared with placebo for individuals and pregnant women with opioid use disorders. BMT should be considered for inclusion as a covered benefit.

Topics: Analgesics, Opioid; Buprenorphine; Female; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications

For many years, methadone has been recognized as an effective maintenance treatment for opioid dependence. However, of the many adverse events reported, sexual dysfunction is one of the most common side effects.. We conducted a meta-analysis to evaluate the prevalence of sexual dysfunction among male patients on methadone and buprenorphine treatments.. Relevant studies published from inception until December 2012 were identified by searching PubMed, OVID, and Embase. Studies were selected using prior defined criteria. Heterogeneity, publication bias, and odds ratio were assessed thoroughly.. To examine the prevalence and odds ratio of sexual dysfunctions among the methadone and buprenorphine groups.. A total of 1,570 participants from 16 eligible studies were identified in this meta-analysis. The studies provided prevalence estimates for sexual dysfunction among methadone users with a meta-analytical pooled prevalence of 52% (95% confidence interval [CI], 0.39-0.65). Only four studies compared sexual dysfunction between the two groups, with a significantly higher combined odds ratio in the methadone group (OR = 4.01, 95% CI, 1.52-10.55, P = 0.0049).. Evidence showed that the prevalence of sexual dysfunction was higher among the users of methadone compared with buprenorphine. Patients with sexual difficulty while on methadone treatment were advised to switch to buprenorphine.

Topics: Buprenorphine; Humans; Male; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Prevalence; Sexual Dysfunction, Physiological; Sexual Dysfunctions, Psychological

Buprenorphine maintenance treatment has been evaluated in randomised controlled trials against placebo medication, and separately as an alternative to methadone for management of opioid dependence.. To evaluate buprenorphine maintenance compared to placebo and to methadone maintenance in the management of opioid dependence, including its ability to retain people in treatment, suppress illicit drug use, reduce criminal activity, and mortality.. We searched the following databases to January 2013: Cochrane Drugs and Alcohol Review Group Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Current Contents, PsycLIT, CORK, Alcohol and Drug Council of Australia, Australian Drug Foundation, Centre for Education and Information on Drugs and Alcohol, Library of Congress, reference lists of identified studies and reviews. We sought published/unpublished randomised controlled trials (RCTs) from authors.. Randomised controlled trials of buprenorphine maintenance treatment versus placebo or methadone in management of opioid-dependent persons.. We used Cochrane Collaboration methodology.. We include 31 trials (5430 participants), the quality of evidence varied from high to moderate quality.There is high quality of evidence that buprenorphine was superior to placebo medication in retention of participants in treatment at all doses examined. Specifically, buprenorphine retained participants better than placebo: at low doses (2 - 6 mg), 5 studies, 1131 participants, risk ratio (RR) 1.50; 95% confidence interval (CI) 1.19 to 1.88; at medium doses (7 - 15 mg), 4 studies, 887 participants, RR 1.74; 95% CI 1.06 to 2.87; and at high doses (≥ 16 mg), 5 studies, 1001 participants, RR 1.82; 95% CI 1.15 to 2.90. However, there is moderate quality of evidence that only high-dose buprenorphine (≥ 16 mg) was more effective than placebo in suppressing illicit opioid use measured by urinanalysis in the trials, 3 studies, 729 participants, standardised mean difference (SMD) -1.17; 95% CI -1.85 to -0.49, Notably, low-dose, (2 studies, 487 participants, SMD 0.10; 95% CI -0.80 to 1.01), and medium-dose, (2 studies, 463 participants, SMD -0.08; 95% CI -0.78 to 0.62) buprenorphine did not suppress illicit opioid use measured by urinanalysis better than placebo.There is high quality of evidence that buprenorphine in flexible doses adjusted to participant need,was less effective than methadone in retaining participants, 5 studies, 788 participants, RR 0.83; 95% CI 0.72 to 0.95. For those retained in treatment, no difference was observed in suppression of opioid use as measured by urinalysis, 8 studies, 1027 participants, SMD -0.11; 95% CI -0.23 to 0.02 or self report, 4 studies, 501 participants, SMD -0.11; 95% CI -0.28 to 0.07, with moderate quality of evidence.Consistent with the results in the flexible-dose studies, in low fixed-dose studies, methadone (≤ 40 mg) was more likely to retain participants than low-dose buprenorphine (2 - 6 mg), (3 studies, 253 participants, RR 0.67; 95% CI: 0.52 to 0.87). However, we found contrary results at medium dose and high dose: there was no difference between medium-dose buprenorphine (7 - 15 mg) and medium-dose methadone (40 - 85 mg) in retention, (7 studies, 780 participants, RR 0.87; 95% CI 0.69 to 1.10) or in suppression of illicit opioid use as measured by urines, (4 studies, 476 participants, SMD 0.25; 95% CI -0.08 to 0.58) or self report of illicit opioid use, (2 studies, 174 participants, SMD -0.82; 95% CI -1.83 to 0.19). Similarly, there was no difference between high-dose buprenorphine (≥ 16 mg) and high-dose metha. Buprenorphine is an effective medication in the maintenance treatment of heroin dependence, retaining people in treatment at any dose above 2 mg, and suppressing illicit opioid use (at doses 16 mg or greater) based on placebo-controlled trials.However, compared to methadone, buprenorphine retains fewer people when doses are flexibly delivered and at low fixed doses. If fixed medium or high doses are used, buprenorphine and methadone appear no different in effectiveness (retention in treatment and suppression of illicit opioid use); however, fixed doses are rarely used in clinical practice so the flexible dose results are more relevant to patient care. Methadone is superior to buprenorphine in retaining people in treatment, and methadone equally suppresses illicit opioid use.

Topics: Buprenorphine; Humans; Maintenance Chemotherapy; Methadone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Randomized Controlled Trials as Topic

Buprenorphine-naloxone (bup/nal in 4:1 ratio; Suboxone; Reckitt Benckiser Pharmaceuticals Incorporation, Richmond, VA) is approved by the Food and Drug Administration for outpatient office-based addiction treatment. In the past few years, bup/nal has been increasingly prescribed off-label for chronic pain management. The current data suggest that bup/nal may provide pain relief in patients with chronic pain with opioid dependence or addiction. However, the unique pharmacological profile of bup/nal confers it to be a weak analgesic that is unlikely to provide adequate pain relief for patients without opioid dependence or addiction. Possible mechanisms of pain relief by bup/nal therapy in opioid-dependent patients with chronic pain may include reversal of opioid-induced hyperalgesia and improvement in opioid tolerance and addiction. Additional studies are needed to assess the implication of bup/nal therapy in clinical anesthesia and perioperative pain management.

Topics: Ambulatory Care; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Chronic Pain; Drug Combinations; Humans; Naloxone; Opioid-Related Disorders; Pain Management; Treatment Outcome

The scientific literature examining effective treatments for opioid dependent adults clearly indicates that pharmacotherapy is a necessary and acceptable component of effective treatments for opioid dependence. Nevertheless, no studies have been published that systematically assess the effectiveness of the pharmacological detoxification among adolescents.. To assess the effectiveness of any detoxification treatment alone or in combination with psychosocial intervention compared with no intervention, other pharmacological intervention or psychosocial interventions on completion of treatment, reducing the use of substances and improving health and social status.. We searched the Cochrane Central Register of Controlled Trials (2014, Issue 1), PubMed (January 1966 to January 2014), EMBASE (January 1980 to January 2014), CINHAL (January 1982 to January 2014), Web of Science (1991-January 2014) and reference lists of articles.. Randomised controlled clinical trials comparing any pharmacological interventions alone or associated with psychosocial intervention aimed at detoxification with no intervention, placebo, other pharmacological intervention or psychosocial intervention in adolescents (13 to 18 years).. We used standard methodological procedures recommended by The Cochrane Collaboration. Two trials involving 190 participants were included. One trial compared buprenorphine with clonidine for detoxification. No difference was found for drop out: risk ratio (RR) 0.45 (95% confidence interval (CI): 0.20 to 1.04) and acceptability of treatment: withdrawal score mean difference (MD): 3.97 (95% CI -1.38 to 9.32). More participants in the buprenorphine group initiated naltrexone treatment: RR 11.00 (95% CI 1.58 to 76.55), quality of evidence moderate.The other trial compared maintenance treatment versus detoxification treatment: buprenorphine-naloxone maintenance versus buprenorphine detoxification. For drop out the results were in favour of maintenance treatment: RR 2.67 (95% CI 1.85, 3.86), as well as for results at follow-up RR 1.36 [95% CI 1.05to 1.76); no differences for use of opiate, quality of evidence low.. It is difficult to draw conclusions on the basis of two trials with few participants. Furthermore, the two studies included did not consider the efficacy of methadone that is still the most frequent drug utilised for the treatment of opioid withdrawal. One possible reason for the lack of evidence could be the difficulty in conducting trials with young people due to practical and ethical reasons.

Topics: Adolescent; Buprenorphine; Clonidine; Humans; Maintenance Chemotherapy; Naloxone; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Dropouts; Randomized Controlled Trials as Topic

Buprenorphine and methadone are opioid-receptor agonists used as opioid substitution therapy during pregnancy to limit exposure of the fetus to cycles of opioid withdrawal and reduce the risk of infectious comorbidities of illicit opioid use. As part of a comprehensive care plan, such therapy may result in improved access to prenatal care, reduced illicit drug use, reduced exposure to infections associated with intravenous drug use, and improved maternal nutrition and infant birth weight. This article describes differences in patient selection between the two drugs, their relative safety during pregnancy, and changes in daily doses as a guide for prescribing clinicians.

Topics: Analgesics, Opioid; Buprenorphine; Drug Administration Schedule; Female; Humans; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications; Pregnant Women; Prenatal Exposure Delayed Effects; Substance-Related Disorders; Treatment Outcome

The scientific literature examining effective treatments for opioid-dependent adults clearly indicates that pharmacotherapy is a necessary and acceptable component. Nevertheless, no reviews have been published that systematically assess the effectiveness of pharmacological maintenance treatment in adolescents.. To assess the effectiveness of any maintenance treatment alone or in combination with psychosocial intervention compared to no intervention, other pharmacological intervention or psychosocial interventions for retaining adolescents in treatment, reducing the use of substances and improving health and social status.. We searched the Cochrane Drugs and Alcohol Group's Trials Register (January 2014), the Cochrane Central Register of Controlled Trials (2014, Issue 1), PubMed (January 1966 to January 2014), EMBASE (January 1980 to January 2014), CINAHL (January 1982 to January 2014), Web of Science (1991 to January 2014) and reference lists of articles.. Randomised and controlled clinical trials of any maintenance pharmacological interventions either alone or associated with psychosocial intervention compared with no intervention, placebo, other pharmacological intervention, pharmacological detoxification or psychosocial intervention in adolescents (13 to 18 years).. We used the standard methodological procedures expected by The Cochrane Collaboration.. We included two trials involving 189 participants. One study, with 35 participants, compared methadone with levo-alpha-acetylmethadol (LAAM) for maintenance treatment lasting 16 weeks, after which patients were detoxified. The other study, with 154 participants, compared maintenance treatment with buprenorphine-naloxone and detoxification with buprenorphine. We did not perform meta-analysis because the two studies assessed different comparisons.In the study comparing methadone and LAAM, the authors declared that there was no difference in the use of a substance of abuse or social functioning (data not shown). The quality of the evidence was very low. No side effects, such as nausea, vomiting, constipation, weakness or fatigue, were reported by study participants.In the comparison between buprenorphine maintenance and buprenorphine detoxification, maintenance treatment appeared to be more efficacious in retaining patients in treatment (drop-out risk ratio (RR) 0.37; 95% confidence interval (CI) 0.26 to 0.54), but not in reducing the number of patients with a positive urine test at the end of the study (RR 0.97; 95% CI 0.78 to 1.22). Self reported opioid use at one-year follow-up was significantly lower in the maintenance group, even though both groups reported a high level of opioid use (RR 0.73; 95% CI 0.57 to 0.95). More patients in the maintenance group were enrolled in other addiction treatment programmes at 12-month follow-up (RR 1.33; 95% CI 0.94 to 1.88). The quality of the evidence was low. No serious side effects attributable to buprenorphine-naloxone were reported by study participants and no patients were removed from the study due to side effects. The most common side effect was headache, which was reported by 16% to 21% of patients in both groups. It is difficult to draft conclusions on the basis of only two trials. One of the possible reasons for the lack of evidence could be the difficulty of conducting trials with young people for practical and ethical reasons.There is an urgent need for further randomised controlled trials comparing maintenance treatment with detoxification treatment or psychosocial treatment alone before carrying out studies that compare different pharmacological maintenance treatments. These studies should have long follow-up and measure relapse rates after the end of treatment and social functioning (integration at school or at work, family relationships).

Topics: Adolescent; Buprenorphine; Humans; Maintenance Chemotherapy; Methadone; Methadyl Acetate; Naloxone; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Randomized Controlled Trials as Topic

Increasing rates of maternal opioid use during pregnancy and neonatal withdrawal, termed neonatal abstinence syndrome (NAS), are public health concerns. Prenatal buprenorphine maintenance treatment (BMT) versus methadone maintenance treatment (MMT) may improve neonatal outcomes, but associations vary. To summarize evidence, we used a random-effects meta-analysis model and estimated summary measures of BMT versus MMT on several outcomes. Sensitivity analyses evaluated confounding, publication bias, and heterogeneity. Subjects were 515 neonates whose mothers received BMT and 855 neonates whose mothers received MMT and who were born from 1996 to 2012 and who were included in 12 studies. The unadjusted NAS treatment risk was lower (risk ratio=0.90, 95% confidence interval (CI): 0.81, 0.98) and mean length of hospital stay shorter (-7.23 days, 95% CI: -10.64, -3.83) in BMT-exposed versus MMT-exposed neonates. In treated neonates, NAS treatment duration was shorter (-8.46 days, 95% CI: -14.48, -2.44) and morphine dose lower (-3.60 mg, 95% CI: -7.26, 0.07) in those exposed to BMT. BMT-exposed neonates had higher mean gestational age and greater weight, length, and head circumference at birth. Fewer women treated with BMT used illicit opioids near delivery (risk ratio=0.44, 95% CI: 0.28, 0.70). Simulations suggested that confounding by indication could account for some of the observed differences. Prenatal BMT versus MMT may improve neonatal outcomes, but bias may contribute to this protective association. Further evidence is needed to guide treatment choices.

Topics: Buprenorphine; Female; Humans; Infant, Newborn; Methadone; Models, Statistical; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Treatment Outcome

Buprenorphine follows the success of methadone as another milestone in the history of treatment for opioid addiction. Buprenorphine can be used in an office-based setting where it is clearly effective, highly accepted by patients and has a favorable safety profile and less abuse potential. However, the adoption of buprenorphine treatment has been slow in the USA.. This article first reviews the history of medication-assisted opioid addiction treatment and the current epidemic opioid addiction, followed by a review of the efficacy, pharmacology and clinical prescription of buprenorphine in office-based care. We then explore the possible barriers in using buprenorphine and the ways to overcome these barriers, including new formulations, educational programs and policy regulations that strike a balance between accessibility and reducing diversion.. Buprenorphine can align addiction treatment with treatments for other chronic medical illnesses. However, preventing diversion will require graduate and continuing medical education and integrated care models for delivery of buprenorphine to those in need.

Topics: Analgesics, Opioid; Buprenorphine; Humans; Narcotic Antagonists; Opioid-Related Disorders; Prescription Drugs

Sublingual formulations of buprenorphine (BUP) and BUP/naloxone have well-established pharmacokinetic and pharmacodynamic profiles, and are safe and effective for treating opioid use disorder. Since approvals of these formulations, their clinical use has increased. Yet, questions have arisen as to how BUP binding to mu-opioid receptors (μORs), the neurobiological target for this medication, relate to its clinical application. BUP produces dose- and time-related alterations of μOR availability but some clinicians express concern about whether doses higher than those needed to prevent opioid withdrawal symptoms are warranted, and policymakers consider limiting reimbursement for certain BUP dosing regimens.. We review scientific data concerning BUP-induced changes in μOR availability and their relationship to clinical efficacy.. Withdrawal suppression appears to require ≤50% μOR availability, associated with BUP trough plasma concentrations ≥1 ng/mL; for most patients, this may require single daily BUP doses of 4 mg to defend against trough levels, or lower divided doses. Blockade of the reinforcing and subjective effects of typical doses of abused opioids require <20% μOR availability, associated with BUP trough plasma concentrations ≥3 ng/mL; for most individuals, this may require single daily BUP doses >16 mg, or lower divided doses. For individuals attempting to surmount this blockade with higher-than-usual doses of abused opioids, even larger BUP doses and <10% μOR availability would be required.. For these reasons, and given the complexities of studies on this issue and comorbid problems, we conclude that fixed, arbitrary limits on BUP doses in clinical care or limits on reimbursement for this care are unwarranted.

Topics: Administration, Sublingual; Analgesics, Opioid; Buprenorphine; Health Policy; Humans; Naloxone; Opiate Substitution Treatment; Opioid-Related Disorders; Protein Binding; Receptors, Opioid, mu

Opioid painkiller dependence is a growing problem and best-practice management is not well defined. We report a case of a young woman exhibiting dependence on codeine, originally prescribed for myalgic encephalopathy, after escalating use over a 10-year period. In 2012, a consultation with a new general practitioner, who had extensive experience of patients with substance abuse, revealed the underlying dependence. After building trust for 6 months, she was able to admit to medication abuse, and was referred to the community drug and alcohol team. On presentation to the team, the patient had no pain issues and the dihydrocodeine use--600 tablets/week--solely reflected her dependence. The patient successfully underwent rapid induction with buprenorphine/naloxone as opioid substitution treatment over 2 days. She is currently stable, engaged with recovery support services and psychosocial counselling, and has just returned to work. She is maintained on a therapeutic dose of buprenorphine 10 mg/naloxone 2.5 mg.

Topics: Acetaminophen; Analgesics, Opioid; Buprenorphine; Chronic Pain; Codeine; Counseling; Fatigue Syndrome, Chronic; Female; Follow-Up Studies; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Primary Health Care; Risk Assessment; Severity of Illness Index; Treatment Outcome; Young Adult

Topics: Administration, Sublingual; Adolescent; Adolescent Health; Analgesics, Opioid; Behavior, Addictive; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Dose-Response Relationship, Drug; Drug Overdose; Humans; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Care Team; Patient Compliance; Practice Guidelines as Topic; Receptors, Opioid, mu; Substance Abuse Detection

The aim of this review was to update and summarize the scientific knowledge on the long term outcomes of the different pharmacological treatment options for opioid dependence currently available and to provide a critical discussion on the different treatment options based on these results. We performed a literature search using the PubMed databases and the reference lists of the identified articles. Data from research show that the three pharmacological options reviewed are effective treatments for opioid dependence with positive long term outcomes. However, each one has its specific target population and setting. While methadone and buprenorphine are first line options, heroin-assisted treatment is a second line option for those patients refractory to treatment with methadone with concomitant severe physical, mental, social and/or functional problems. Buprenorphine seems to be the best option for use in primary care offices. The field of opioid dependence treatment is poised to undergo a process of reinforcement and transformation. Further efforts from researchers, clinicians and authorities should be made to turn new pharmacological options into clinical reality and to overcome the structural and functional obstacles that maintenance programmes face in combatting opioid dependence.

Topics: Buprenorphine; Heroin; Heroin Dependence; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Time Factors; Treatment Outcome

For people seeking treatment, the course of heroin addiction tends to be chronic and relapsing, and longer duration of treatment is associated with better outcomes. Heroin addiction is strongly associated with deviant behaviour and crime, and the objectives in treating heroin addiction have been a blend of humane support, rehabilitation, public health intervention and crime control. Reduction in street heroin use is the foundation on which all these outcomes are based. The pharmacological basis of maintenance treatment of dependent individuals is to minimize withdrawal symptoms and attenuate the reinforcing effects of street heroin, leading to reduction or cessation of street heroin use. Opioid maintenance treatment can be moderately effective in suppressing heroin use, although deviations from evidence-based approaches, particularly the use of suboptimal doses, have meant that treatment as delivered in practice may have resulted in poorer outcomes than predicted by research. Methadone treatment has been 'programmatic', with a one-size-fits-all approach that in part reflects the perceived need to impose discipline on deviant individuals. However, differences in pharmacokinetics and in side-effects mean that many patients do not respond optimally to methadone. Injectable diamorphine (heroin) provides a more reinforcing medication for some 'nonresponders' and can be a valuable option in the rehabilitation of demoralized, socially excluded individuals. Buprenorphine, a partial agonist, is a less reinforcing medication with different side-effects and less risk of overdose. Not only is it a different medication, but also it can be used in a different paradigm of treatment, office-based opioid treatment, with less structure and offering greater patient autonomy.

Topics: Buprenorphine; Drug Overdose; Heroin; Heroin Dependence; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Reinforcement, Psychology; Substance Withdrawal Syndrome; Time Factors

Pharmacologic therapies for maintenance treatment of heroin dependence have been used and studied widely. Systematic reviews have demonstrated the effectiveness of such therapies. Opium dependence is associated with less problems and impairments and is less likely to be used by injecting, with consequent reductions in risk of overdose and blood-borne diseases. Although it is a common substance use disorder in many countries, a systematic review of the literature is lacking on the maintenance treatment for opium dependence.. To evaluate the effectiveness and safety of various pharmacological therapies on maintenance of opium dependence (alone or in combination with psychosocial interventions) compared to no intervention, detoxification, different doses of the same intervention, other pharmacologic interventions and any psychosocial interventions.. We searched the following sources up to February 2012: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, PsycINFO, regional databases (IMEMR and ASCI), national databases (Iranmedex and Iranpsych), main electronic sources of ongoing trials and reference lists of all relevant papers. Also, we contacted known investigators from some Asian countries to obtain details about unpublished trials.. Randomised controlled clinical trials (RCTs) comparing any maintenance pharmacologic intervention versus no intervention, other pharmacologic or non-pharmacologic intervention for opium dependence.. Two reviewers assessed the risks of biases and extracted data, independently.. Three RCTs recruiting 870 opium dependents were included. The studies made different comparisons so it was not possible to pool data. Only retention rate was assessed by the studies. Two studies compared different doses of buprenorphine: in one study, 4 mg/day of buprenorphine was compared with doses of 2 mg/day and 1 mg/day and in another study, 8 mg/day of buprenorphine was compared with doses of 3 mg/day and 1 mg/day. Comparisons showed a statistically significant difference between groups; higher doses of buprenorphine increased the probability of retention in treatment. The studies had high risks of biases. In the third study, after a process of detoxification, baclofen (60 mg/day) was compared with placebo for maintenance treatment. The difference in retention rate between groups was high, but it was not statistically significant.. It is not possible to conclude about the use of any kind of pharmacologic therapies for maintenance treatment of opium dependence.

Topics: Baclofen; Buprenorphine; Drug Administration Schedule; Humans; Maintenance Chemotherapy; Narcotic Antagonists; Opioid-Related Disorders; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome

Opioid maintenance therapy with methadone or buprenorphine is an established and first-line treatment for opioid dependence. Risk of diversion and toxicity of opioid prescription drugs, including buprenorphine, causes significant concerns. This is particularly the case in the United States, where the number of related emergency visits is increasing, especially in children. A systematic literature research (Medline, Pubmed) was performed to assess the risk associated with buprenorphine. The search, which was not limited to particular publication years, was performed with the key words buprenorphine AND toxicity (114 counts ) AND children (4 counts) and buprenorphine AND mortality AND children (5 counts). In addition, the author obtained information from relevant websites (NIDA, SAMSHA) and pharmacovigilance data from the manufacturer of buprenorphine. Clinical and toxicological data suggest a low risk for fatal intoxications associated with bupreorphine in adults. Data from emergency units indicate a dramatic, 20-fold increase in buprenorphine exposure in children over the past decade, mostly in those under 6. The US 'Researched Abuse, Diversion and Addiction-Related Surveillance' (RADARS) system indicates a lower risk of severe opioid intoxications with buprenorphine than with other opioids, with no fatal outcomes recorded. Correspondingly, data from spontaneous reports to the surveillance programme of the manufacturer of buprenorphine (13,600 buprenorphine exposures, 4879 of these in children under six) show a serious medical outcome in 34% of children under the age of six but only one fatal outcome. Although exposure to buprenorphine and other opioids remains a significant concern in children, the drug seems rather to be safe with respect to severe outcomes, in particular death.

Topics: Age Factors; Buprenorphine; Drug Therapy, Combination; Humans; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Pharmacovigilance; Prescription Drug Diversion

Methadone and buprenorphine are maintenance replacement therapies for opioid dependence; they are also used for pain management. Methadone and buprenorphine (to a lesser extent) have seen sharp increases in mortality associated with their use. They have distinct routes of metabolism (mostly cytochrome P450 dependent), and distinct pharmacologic activity of metabolites. As such, metabolism may play a role in differences in their toxicity.. This article reviews peer-reviewed literature obtained from PubMed searches and literature referenced within. The review considers first an overview of drug use and mortality over the past decade. It then provides extensive detail on the in vitro and in vivo human metabolism of methadone and buprenorphine. Using both human and experimental animal studies it then presents the pharmacodynamic activity of parent drug and metabolites at the mu-opioid receptor, as P-glycoprotein substrates and plasma/brain concentration ratios, and activity at the hERG K(+) channel. Lessons learned from drug interaction studies in humans are then examined in an attempt to bring together the combined information.. The use and misuse of these drugs contributes to the epidemic in opioid-associated mortalities. A better understanding of metabolism-, transport- and co-medication-induced changes will contribute to their safer use.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Drug Interactions; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pain

Topics: Antiretroviral Therapy, Highly Active; Buprenorphine; Comorbidity; Evidence-Based Medicine; Harm Reduction; HIV Infections; Humans; Incidence; Medication Adherence; Methadone; Needle Sharing; Opiate Substitution Treatment; Opioid-Related Disorders; Risk Factors; Substance Abuse, Intravenous; Tuberculosis; Unsafe Sex

Pregnancy in opioid users poses a number of problems to treating physicians. Most guidelines recommend maintenance treatment to manage opioid addiction in pregnancy, with methadone being the gold standard. More recently, buprenorphine has been discussed as an alternate medication. The use and efficacy of buprenorphine in pregnancy is still controversial. This article reviews the current database on the basis of a detailed and critical literature search performed in MEDLINE (206 counts). Most of the relevant studies (randomised clinical trials and one national cohort sample) were published in the last 2 years and mainly compared buprenorphine with methadone. Some studies are related to maternal outcomes, others to foetal, neonatal or older child outcomes. With respect to maternal outcomes, most studies suggest that buprenorphine has similar effects to methadone. Very few data from small studies discuss an effect of buprenorphine on neurodevelopment of the foetus. Neonatal abstinence syndrome is common in infants of both buprenorphine- and methadone-maintained mothers. As regards neonatal outcomes, buprenorphine has the same clinical outcome as methadone, although some newer studies suggest that it causes fewer withdrawal symptoms. Since hardly any studies have investigated the combination of buprenorphine with naloxone (which has been suggested to possibly have teratogenic effects) in pregnant women, a switch to buprenorphine monotherapy is recommended in women who become pregnant while receiving the combination product. These novel findings indicate that buprenorphine is emerging as a first-line treatment for pregnant opioid users.

Topics: Animals; Buprenorphine; Child; Female; Humans; Infant, Newborn; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications

Topics: Buprenorphine; Humans; Medicaid; Opiate Substitution Treatment; Opioid-Related Disorders; United States

Current trends in the United States suggest that chronic narcotic use has increased in reproductive aged women over the past 10 years. Regular exposure to such substances during pregnancy has maternal and fetal implications. Appropriate prenatal care is critical to optimizing outcomes. Management options for narcotic dependence should be patient-specific and may include discontinuation of narcotics with careful observation, limitation of prescription dispensing, or substitution therapy with methadone or buprenorphine. A multidisciplinary, collaborative approach is highly recommended. This review discusses usage of narcotic medications, associated maternal and fetal risks, and management strategies for the antepartum, intrapartum, and postpartum periods.

Topics: Analgesics, Opioid; Buprenorphine; Female; Humans; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Prenatal Care

Managing opioid dependence in pregnant women is a complex and potentially challenging task. Drug-dependent women may be difficult to engage in antenatal care and opioid substitution requires careful dose titration. Pregnancy, however, can be an opportune time to effect behaviour change, and supporting an opioid-dependent woman through pregnancy can be a rewarding clinical experience.. This article provides an overview of treatment principles for managing opioid dependence in pregnancy, and reviews current treatment guidelines for use of opioid-substitution therapy in pregnant women.. The management of opioid dependence during pregnancy requires holistic and comprehensive assessment and referral to specialist services is often appropriate. Specific issues that may need to be addressed include decision-making regarding the choice of opioid-substitution therapy and the potential for neonatal abstinence syndrome in the newborn. General practitioners are often well placed to support and coordinate care of their opioid-dependent pregnant patients.

Topics: Adult; Buprenorphine; Female; General Practice; Humans; Methadone; Narcotics; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications; Prenatal Care; Young Adult

Preoperative evaluation of patients with chronic pain is important because it may lead to multidisciplinary preoperative treatment of patients' pain and a multimodal analgesia plan for effective pain control. Preoperative multidisciplinary management of chronic pain and comorbid conditions, such as depression, anxiety, deconditioning, and opioid tolerance, can improve patient satisfaction and surgical recovery. Multimodal analgesia using pharmacologic and nonpharmacologic strategies shifts the burden of analgesia away from simply increasing opioid dosing. In more complicated chronic pain patients, multidisciplinary treatment, including pain psychology, physical therapy, judicious medication management, and minimally invasive interventions by pain specialists, can improve patients' satisfaction and surgical outcome.

Topics: Analgesia; Analgesics, Opioid; Buprenorphine; Chronic Pain; Humans; Opioid-Related Disorders; Pain Measurement; Pain, Postoperative; Perioperative Period; Preoperative Care

The prevalence of opiate use among pregnant women can range from 1% to 2% to as high as 21%. Heroin crosses the placenta and pregnant, opiate-dependent women experience a six-fold increase in maternal obstetric complications such as low birth weight, toxaemia, third trimester bleeding, malpresentation, puerperal morbidity, fetal distress and meconium aspiration. Neonatal complications include narcotic withdrawal, postnatal growth deficiency, microcephaly, neuro-behavioural problems, increased neonatal mortality and a 74-fold increase in sudden infant death syndrome.. To assess the effectiveness of any maintenance treatment alone or in combination with psychosocial intervention compared to no intervention, other pharmacological intervention or psychosocial interventions for child health status, neonatal mortality, retaining pregnant women in treatment and reducing the use of substances.. We searched the Cochrane Drugs and Alcohol Group Trials Register (September 2013), PubMed (1966 to September 2013), CINAHL (1982 to September 2013), reference lists of relevant papers, sources of ongoing trials, conference proceedings and national focal points for drug research. We contacted authors of included studies and experts in the field.. Randomised controlled trials assessing the efficacy of any maintenance pharmacological treatment for opiate-dependent pregnant women.. We used the standard methodological procedures expected by The Cochrane Collaboration.. We found four trials with 271 pregnant women. Three compared methadone with buprenorphine and one methadone with oral slow-release morphine. Three out of four studies had adequate allocation concealment and were double-blind. The major flaw in the included studies was attrition bias: three out of four had a high drop-out rate (30% to 40%) and this was unbalanced between groups.Methadone versus buprenorphine: the drop-out rate from treatment was lower in the methadone group (risk ratio (RR) 0.64, 95% confidence interval (CI) 0.41 to 1.01, three studies, 223 participants). There was no statistically significant difference in the use of primary substance between methadone and buprenorphine (RR 1.81, 95% CI 0.70 to 4.69, two studies, 151 participants). For both, we judged the quality of evidence as low. Birth weight was higher in the buprenorphine group in the two trials that could be pooled (mean difference (MD) -365.45 g (95% CI -673.84 to -57.07), two studies, 150 participants). The third study reported that there was no statistically significant difference. For APGAR score neither of the studies which compared methadone with buprenorphine found a significant difference. For both, we judged the quality of evidence as low. Many measures were used in the studies to assess neonatal abstinence syndrome. The number of newborns treated for neonatal abstinence syndrome, which is the most critical outcome, did not differ significantly between groups. We judged the quality of evidence as very low.Methadone versus slow-release morphine: there was no drop-out in either treatment group. Oral slow-release morphine seemed superior to methadone for abstinence from heroin use during pregnancy (RR 2.40, 95% CI 1.00 to 5.77, one study, 48 participants). We judged the quality of evidence as moderate.Only one study which compared methadone with buprenorphine reported side effects. For the mother there was no statistically significant difference; for the newborns in the buprenorphine group there were significantly fewer serious side effects.In the comparison between methadone and slow-release morphine no side effects were reported for the mother, whereas one child in the methadone group had central apnoea and one child in the morphine group had obstructive apnoea.. We did not find sufficient significant differences between methadone and buprenorphine or slow-release morphineto allow us to conclude that one treatment is superior to another for all relevant outcomes. While methadone seems superior in terms of retaining patients in treatment, buprenorphine seems to lead to less severe neonatal abstinence syndrome. Additionally, even though a multi-centre, international trial with 175 pregnant women has recently been completed and its results published and included in this review, the body of evidence is still too small to draw firm conclusions about the equivalence of the treatments compared. There is still a need for randomised controlled trials of adequate sample size comparing different maintenance treatments.

Topics: Birth Weight; Buprenorphine; Delayed-Action Preparations; Female; Humans; Infant; Infant, Newborn; Methadone; Morphine; Narcotics; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Randomized Controlled Trials as Topic

The present paper considers naltrexone to treat opioid dependence during pregnancy. The public health problem of opioid dependence and its treatment during pregnancy is reviewed first. Next, the naltrexone and opioid dependence treatment literature is summarized, with overviews of the pre-clinical and clinical research on prenatal naltrexone exposure. Finally, considerations and recommendations for future medication research for the treatment of opioid dependence in pregnant women are provided. The efficacy of long-acting injectable naltrexone relative to placebo, its blockade of opioid agonist euphoric effects, its lack of abuse and tolerance development and its modest adverse effect profile make it a potential medication for opioid-dependent pregnant women. However, it is not without seriously concerning potential drawbacks, including the difficulty surrounding medication induction that may lead to vulnerability with regard to relapse, physical dependence re-establishment, increased risk behaviors, treatment dropout and resulting opioid overdose. Before embarking on future research with this medication, the benefits and risks for the mother-embryo/fetus/child dyad should be weighed carefully. Should future research be conducted, a multi-level commitment to proactive ethical research is needed to reach the ultimate goal of improving the lives of women and children affected by opioid dependence.

Topics: Buprenorphine; Female; Humans; Infant, Newborn; Methadone; Naltrexone; Narcotic Antagonists; Narcotics; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Risk Assessment; Risk Factors; Treatment Outcome

Here we describe methods for preclinical evaluation of candidate medications to treat opioid abuse and dependence. Our perspective is founded on the propositions that (1) drug self-administration procedures provide the most direct method for assessment of medication effects, (2) procedures that assess choice between opioid and nondrug reinforcers are especially useful, and (3) the states of opioid dependence and withdrawal profoundly influence both opioid reinforcement and the effects of candidate medications. Effects of opioid medications on opioid choice in nondependent and opioid-dependent subjects are reviewed. Various nonopioid medications have also been examined, but none yet have been identified that safely and reliably reduce opioid choice. Future research will focus on (1) strategies for increasing safety and/or effectiveness of opioid medications, and (2) continued development of nonopioids such as inhibitors of endocannabinoid catabolic enzymes or inhibitors of opioid-induced glial activation.

Topics: Analgesics, Opioid; Buprenorphine; Choice Behavior; Endocannabinoids; Evidence-Based Medicine; Humans; Methadone; Naltrexone; Narcotic Antagonists; Narcotics; Neuroglia; Opioid-Related Disorders; Receptors, Opioid, mu; Reinforcement, Psychology; Self Administration; Substance Withdrawal Syndrome; Treatment Outcome

To review evidence on the effectiveness of opioid maintenance treatment (OMT) in prison and post-release.. Systematic review of experimental and observational studies of prisoners receiving OMT regarding treatment retention, opioid use, risk behaviours, human immunodeficiency virus (HIV)/hepatitis C virus (HCV) incidence, criminality, re-incarceration and mortality. We searched electronic research databases, specialist journals and the EMCDDA library for relevant studies until January 2011. Review conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.. Twenty-one studies were identified: six experimental and 15 observational. OMT was associated significantly with reduced heroin use, injecting and syringe-sharing in prison if doses were adequate. Pre-release OMT was associated significantly with increased treatment entry and retention after release if arrangements existed to continue treatment. For other outcomes, associations with pre-release OMT were weaker. Four of five studies found post-release reductions in heroin use. Evidence regarding crime and re-incarceration was equivocal. There was insufficient evidence concerning HIV/HCV incidence. There was limited evidence that pre-release OMT reduces post-release mortality. Disruption of OMT continuity, especially due to brief periods of imprisonment, was associated with very significant increases in HCV incidence.. Benefits of prison OMT are similar to those in community settings. OMT presents an opportunity to recruit problem opioid users into treatment, to reduce illicit opioid use and risk behaviours in prison and potentially minimize overdose risks on release. If liaison with community-based programmes exists, prison OMT facilitates continuity of treatment and longer-term benefits can be achieved. For prisoners in OMT before imprisonment, prison OMT provides treatment continuity.

Topics: Buprenorphine; Cocaine-Related Disorders; Continuity of Patient Care; Crime; Epidemiologic Methods; Heroin Dependence; Humans; Illicit Drugs; Methadone; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Compliance; Prisoners; Risk-Taking; Treatment Outcome

This review will discuss the complex nature of maternal and other factors that can affect the infant's display of neonatal abstinence syndrome (NAS), clinical presentation and treatment of NAS, and the impact of recent findings on future directions for research.. NAS has traditionally been described as a constellation of signs/symptoms displayed by the neonate upon withdrawal of gestational opioid exposure; however, recent research has advanced our understanding of this disorder. Other psychoactive substances, such as increasingly prescribed serotonin reuptake inhibitors, may produce an independent or synergistic discontinuation syndrome. The wide variability in NAS presentation has generated interest in the interplay of prenatal and postnatal environmental and genetic factors that may moderate or mediate its expression. Finally, recent advances in the treatment of opioid-dependent pregnant women have suggested buprenorphine as an alternative treatment to methadone during pregnancy, largely due to reduced NAS severity in exposed neonates.. Physicians should be aware of the complexity of the maternal, fetal, and infant factors that combine to create the infant's display of NAS, and incorporate these aspects into comprehensive assessment and care of the dyad. Further research regarding the pathophysiology and treatment of NAS is warranted.

Topics: Buprenorphine; Female; Humans; Infant, Newborn; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects

To review the current evidence on buprenorphine-naloxone for the treatment of opioid-related disorders, with a focus on primary care settings.. MEDLINE and the Cochrane Database of Systematic Reviews were searched. Evidence is mainly level I.. Buprenorphine is a partial μ-opioid agonist and κ-opioid antagonist with a long half-life and less abuse potential than methadone. For detoxification, buprenorphine is at least equivalent to methadone and is superior to clonidine. For maintenance treatment, buprenorphine is clearly superior to placebo. Methadone has a slight advantage in terms of retention in treatment, but a stepped approach with initial use of buprenorphine-naloxone is as efficacious. Use of buprenorphine in the primary care setting is feasible, safe, and effective. Authorization to prescribe buprenorphine can be obtained after completing online training.. Buprenorphine is a safe and effective agent for detoxification from opioids. It can be used as a first-line agent in maintenance programs, owing to its lower abuse potential relative to other opioids. Its effectiveness in primary care settings makes it a useful therapeutic tool for family physicians.

Topics: Analgesics, Opioid; Buprenorphine; Humans; Inactivation, Metabolic; Opioid-Related Disorders; Substance-Related Disorders

Constant refinement of opioid dependence (OD) therapies is a condition to promote treatment access and delivery. Among other applications, the partial opioid agonist buprenorphine has been studied to improve evidence-based interventions for the transfer of patients from opioid agonist to antagonist medications. This paper summarizes PubMed-searched clinical investigations and conference papers on the transition from methadone maintenance to buprenorphine and from buprenorphine to naltrexone, discussing challenges and advances. The majority of the 26 studies we examined were uncontrolled investigations. Many small clinical trials have demonstrated the feasibility of in- or outpatient transfer to buprenorphine from low to moderate methadone doses (up to 60-70 mg). Results on the conversion from higher methadone doses, on the other hand, indicate significant withdrawal discomfort, and need for ancillary medications and inpatient treatment. Tapering high methadone doses before the transfer to buprenorphine is not without discomfort and the risk of relapse. The transition buprenorphine-naltrexone has been explored in several pilot studies, and a number of treatment methods to reduce withdrawal intensity warrant further investigation, including the co-administration of buprenorphine and naltrexone. Outpatient transfer protocols using buprenorphine, and direct comparisons with other modalities of transitioning from opioid agonist to antagonist medications are limited. Given its potential salience, the information gathered should be used in larger clinical trials on short and long-term outcomes of opioid agonist-antagonist transition treatments. Future studies should also test new pharmacological mechanisms to help reduce physical dependence, and identify individualized approaches, including the use of pharmacogenetics and long-acting opioid agonist and antagonist formulations.

Topics: Biological Availability; Buprenorphine; Chemistry, Pharmaceutical; Humans; Methadone; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Substance Withdrawal Syndrome

The goal of this meta-analysis is to provide evidence based information about proper dosing for buprenorphine maintenance treatment to improve treatment outcome. To be selected for the review and inclusion in the meta-analysis, articles had to be randomized, controlled, or double-blind clinical trials, with buprenorphine as the study drug; the length of buprenorphine maintenance treatment had to be 3 weeks or longer; doses of buprenorphine had to be clearly stated; outcome measures had to include retention rates in buprenorphine treatment; outcome measures had to include illicit opioid use based on analytical determination of drugs of abuse in urine samples as outcome variables; and outcome measures had to include illicit cocaine use based on analytical determination of drugs of abuse in urine samples as outcome variables. Twenty-nine articles were excluded because they did not meet the inclusion criteria. The authors present the results of 21 articles that met inclusion criteria. The higher buprenorphine dose (16-32 mg per day) predicted better retention in treatment compared with the lower dose (less than 16 mg per day) (P = .009, R(2) adjusted = 0.40), and the positive urine drug screens for opiates predicted dropping out of treatment (P = .019, R(2) Adjusted = 0.40). Retention in treatment predicted less illicit opioid use (P = .033, R(2) Adjusted = 0.36), and the positive urine drug screens for cocaine predicted more illicit opioid use (P = .021, R(2) Adjusted = 0.36). Strong evidence exists based on 21 randomized clinical trials that the higher buprenorphine dose may improve retention in buprenorphine maintenance treatment.

Topics: Buprenorphine; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Medication Adherence; Narcotic Antagonists; Opioid-Related Disorders; Randomized Controlled Trials as Topic; Treatment Outcome

Opioid dependence is a significant public health problem associated with high risk for relapse if treatment is not ongoing. While maintenance on opioid agonists (i.e., methadone, buprenorphine) often produces favorable outcomes, detoxification followed by treatment with the μ-opioid receptor antagonist naltrexone may offer a potentially useful alternative to agonist maintenance for some patients.. Treatment approaches for making this transition are described here based on a literature review and solicitation of opinions from several expert clinicians and scientists regarding patient selection, level of care, and detoxification strategies.. Among the current detoxification regimens, the available clinical and scientific data suggest that the best approach may be using an initial 2-4 mg dose of buprenorphine combined with clonidine, other ancillary medications, and progressively increasing doses of oral naltrexone over 3-5 days up to the target dose of naltrexone. However, more research is needed to empirically validate the best approach for making this transition.

Topics: Adrenergic alpha-2 Receptor Agonists; Buprenorphine; Clinical Protocols; Clonidine; Drug Administration Schedule; Drug Therapy, Combination; Humans; Methadone; Naltrexone; Narcotic Antagonists; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Substance Withdrawal Syndrome

This article provides an overview and discussion of the collective maternal, fetal and neonatal outcome research on women maintained on methadone or buprenorphine during pregnancy. Its focus is on an assessment of the comparative effectiveness of methadone and buprenorphine pharmacotherapy, with particular attention given to recent findings from the literature. Recommendations for clinical practice are outlined, and directions for future research are presented. Findings from comparative studies of methadone and buprenorphine underscore the efficacy of both medications in preventing relapse to illicit opioid use in the treatment of opioid-dependent pregnant patients, as well as the simplicity of induction onto methadone and patient retention while receiving such therapy. Fetal monitoring suggests that buprenorphine results in less fetal cardiac and movement suppression than does methadone. The clinical implications of these findings need future exploration. For the neonate, evidence from studies using a wide range of designs, including retrospective chart reviews, prospective observational studies, and randomized clinical trials, show consistent results, with prenatal exposure to buprenorphine resulting in less severe neonatal abstinence syndrome relative to methadone. Any medication given to pregnant women should be prescribed only after considering the risk : benefit ratio for the maternal-fetal dyad. Medication choices for each opioid-dependent patient during pregnancy need to be made on a patient-by-patient basis, taking into consideration the patient's opioid dependence history, previous and current treatment experiences, medical circumstances and treatment preferences. Moreover, for a full remission of opioid addiction to be sustainable, both post-partum and across the lifespan, treatment providers must not rely solely on medication to treat their patients but should also utilize women-specific comprehensive treatment models that address the underlying multifaceted complexities of their patient's lives.

Topics: Analgesics, Opioid; Buprenorphine; Female; Humans; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Randomized Controlled Trials as Topic

Opioid dependence is a chronic relapsing condition which requires comprehensive care; pharmacological agents form the mainstay of its long term treatment. The two most popular approaches are the harm reduction method using agonists and the complete abstinence method using antagonists. Currently, particularly from the harm minimization perspective and the low feasibility of an abstinence based approach, there is an increasing trend toward agonist treatment. The use of buprenorphine has gained popularity in view of its safety profile and the availability of the buprenorphine-naloxone combination has made it popular as a take-home treatment. This review outlines the pharmacological advances and controversies in this area.

Topics: Buprenorphine; Drug Therapy, Combination; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders

Illicit use of opiates is the fastest growing substance use problem in the United States, and the main reason for seeking addiction treatment services for illicit drug use throughout the world. It is associated with significant morbidity and mortality related to human immunodeficiency virus, hepatitis C, and overdose. Treatment for opiate addiction requires long-term management. Behavioral interventions alone have extremely poor outcomes, with more than 80% of patients returning to drug use. Similarly poor results are seen with medication-assisted detoxification. This article provides a topical review of the three medications approved by the Food and Drug Administration for long-term treatment of opiate dependence: the opioid-agonist methadone, the partial opioid-agonist buprenorphine, and the opioid-antagonist naltrexone. Basic mechanisms of action and treatment outcomes are described for each medication. Results indicate that maintenance medication provides the best opportunity for patients to achieve recovery from opiate addiction. Extensive literature and systematic reviews show that maintenance treatment with either methadone or buprenorphine is associated with retention in treatment, reduction in illicit opiate use, decreased craving, and improved social function. Oral naltrexone is ineffective in treating opiate addiction, but recent studies using extended-release naltrexone injections have shown promise. Although no direct comparisons between extended-release naltrexone injections and either methadone or buprenorphine exist, indirect comparison of retention shows inferior outcome compared with methadone and buprenorphine. Further work is needed to directly compare each medication and determine individual factors that can assist in medication selection. Until such time, selection of medication should be based on informed choice following a discussion of outcomes, risks, and benefits of each medication.

Topics: Analgesics, Opioid; Buprenorphine; Humans; Long-Term Care; Methadone; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Substance Withdrawal Syndrome; Treatment Outcome

Opioid dependence is a chronic relapsing disorder that shows excess mortality and comorbidity with somatic and psychiatric disorders. Methadone and buprenorphine/naloxone are widely accepted and are used as first-line maintenance treatments for opioid dependence. Fatal intoxications with these agents, risk of diversion, and accidental intoxications, especially in children, are apparent risks and are of increasing public concern. Buprenorphine/naloxone sublingual tablet is an established treatment for opioid dependence. A novel buprenorphine/naloxone film has been developed with improved pharmacokinetics and a hopefully lower risk of diversion and accidental intoxications.. This review evaluates the available preclinical and clinical data on the novel buprenorphine/naloxone film for the treatment of opioid dependence. Literature was identified though a comprehensive PubMed search and data sources included official FDA information.. This is an interesting new formulation of a well-established medication in opioid dependence. However, few data have been published on its safety and efficacy. In an experimental study, the new formulation suppressed symptoms of opioid withdrawal as expected. Results of an unpublished study made public by the FDA suggest a spectrum of adverse events similar to that of the conventional sublingual tablet. Some data show patients may prefer the novel film over the sublingual tablet. The estimated lower risk for diversion and especially for accidental poisoning in children cannot be assessed in clinical studies but requires data from emergency room visits.

Topics: Animals; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Drug Carriers; Drug Combinations; Drug Compounding; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Tablets

The increased use of opioid pain medication has been mirrored by the increased misuse and abuse of these drugs. As part of a multidisciplinary approach to this epidemic, pharmaceutical companies, with the encouragement of the Food and Drug Administration, have increased the development of abuse-deterrent formulations. While all have the goal of treating pain while mitigating misuse and abuse, there are different technologies utilized to impart the abuse-deterrent properties. The goal of this paper is to review the basis of abuse-deterrent formulations, the different types and approaches of some of the abuse-deterrent products, and their current regulatory status in the USA.

Topics: Analgesics, Opioid; Buprenorphine; Chemistry, Pharmaceutical; Dextroamphetamine; Humans; Lisdexamfetamine Dimesylate; Morphine; Naltrexone; Opioid-Related Disorders; Pain; Prescription Drug Misuse; United States; United States Food and Drug Administration

This paper reviews the published literature regarding outcomes following maternal treatment with buprenorphine in five areas: maternal efficacy, fetal effects, neonatal effects, effects on breast milk and longer-term developmental effects.. Within each outcome area, findings are summarized first for the three randomized clinical trials and then for the 44 non-randomized studies (i.e. prospective studies, case reports and series and retrospective chart reviews), only 28 of which involve independent samples.. Results indicate that maternal treatment with buprenorphine has comparable efficacy to methadone, although difficulties may exist with current buprenorphine induction methods. The available fetal data suggest buprenorphine results in less physiological suppression of fetal heart rate and movements than methadone. Regarding neonatal effects, perhaps the single definitive conclusion is that prenatal buprenorphine treatment results in a clinically significant less severe neonatal abstinence syndrome (NAS) than treatment with methadone. The limited research suggests that, like methadone, buprenorphine is compatible with breastfeeding. Data available thus far suggest that there are no deleterious effects of in utero buprenorphine exposure on infant development.. While buprenorphine produces a less severe neonatal abstinence syndrome than methadone, both methadone and buprenorphine are important parts of a complete comprehensive treatment approach for opioid-dependent pregnant women.

Topics: Buprenorphine; Child Development; Female; Fetus; Humans; Infant, Newborn; Length of Stay; Methadone; Milk, Human; Morphine; Narcotic Antagonists; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pain Management; Patient Dropouts; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Randomized Controlled Trials as Topic; Substance Abuse Detection; Treatment Outcome

The Maternal Opioid Treatment: Human Experimental Research (MOTHER) project, an eight-site randomized, double-blind, double-dummy, flexible-dosing, parallel-group clinical trial is described. This study is the most current--and single most comprehensive--research effort to investigate the safety and efficacy of maternal and prenatal exposure to methadone and buprenorphine.. The MOTHER study design is outlined, and its basic features are presented.. At least seven important lessons have been learned from the MOTHER study: (i) an interdisciplinary focus improves the design and methods of a randomized clinical trial; (ii) multiple sites in a clinical trial present continuing challenges to the investigative team due to variations in recruitment, patient populations and hospital practices that, in turn, differentially impact recruitment rates, treatment compliance and attrition; (iii) study design and protocols must be flexible in order to meet the unforeseen demands of both research and clinical management; (iv) staff turnover needs to be addressed with a proactive focus on both hiring and training; (v) the implementation of a protocol for the treatment of a particular disorder may identify important ancillary clinical issues worthy of investigation; (vi) timely tracking of data in a multi-site trial is both demanding and unforgiving; and (vii) complex multi-site trials pose unanticipated challenges that complicate the choice of statistical methods, thereby placing added demands on investigators to effectively communicate their results.

Topics: Buprenorphine; Double-Blind Method; Drug Administration Schedule; Female; Humans; Infant, Newborn; Narcotic Antagonists; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Selection; Pregnancy; Pregnancy Complications; Randomized Controlled Trials as Topic; Treatment Outcome; United States

The purpose of this review is to discuss the incidence, risks, pregnancy complications, and maintenance options for treatment of opioid addiction in pregnancy.. Opioid dependence in pregnancy carries clear identifiable maternal and fetal risk. Providing care for patients with dependence is best done in a multidisciplinary care model addressing the particular needs of this population. There are limited data on maternal detoxification, with data still emerging surrounding the safety profile of this practice. Historically, methadone has been the recommended maintenance treatment; however, recent data on buprenorphine identify this as a safe and effective option. The majority of births from women with opioid dependence result in neonatal abstinence syndrome requiring prolonged neonatal hospitalization. Intrapartum pain management should not differ from the general obstetric population. Postpartum pain is magnified in this population, and particular attention should be focused on this issue. Breast-feeding is recommended regardless of maintenance dose, unless other conditions restricting breast-feeding are present. Comprehensive postpartum care and transition of care to addiction specialists are highly recommended.. Obstetricians and gynecologists, family physicians, addiction specialists.. After completing this CME activity, physicians should be better able to assess the treatment options available to patients with opioid addiction during pregnancy, compare the risk/safety profiles of methadone and buprenorphine, and evaluate the recommendations and current data surrounding breast-feeding while on opioid maintenance treatment.

Topics: Analgesics, Opioid; Breast Feeding; Buprenorphine; Female; Humans; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pain Management; Pregnancy; Pregnancy Complications

Pregnancy in substance-abusing women with HIV/AIDS presents a complex clinical challenge. Opioid-dependent women need treatment with opioid therapy during pregnancy to protect the health of mother and developing fetus. However, opioid therapies, methadone and buprenorphine, may have drug interactions with some HIV medications that can have adverse effects leading to suboptimal clinical outcomes. Further, many opioid-dependent individuals have problems with other forms of substance abuse, for example, cocaine abuse, that could also contribute to poor clinical outcomes in a pregnant woman. Physiological changes, including increased plasma volume and increased hepatic and renal blood flow, occur in the pregnant woman as the pregnancy progresses and may alter medication needs with the potential to exacerbate drug interactions, although there is sparse literature on this issue. Knowledge of possible drug interactions between opioids, other abused substances such as cocaine, HIV therapeutics, and other frequently required medications such as antibiotics and anticonvulsants is important to assuring the best possible outcomes in the pregnant woman with opioid dependence and HIV/AIDS.

Topics: Anti-HIV Agents; Buprenorphine; Cocaine; Drug Interactions; Female; HIV Infections; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnancy Complications, Infectious; Substance-Related Disorders

Topics: Buprenorphine; Child; Female; Fetus; Humans; Narcotic Antagonists; Opioid-Related Disorders; Pain, Postoperative; Pregnancy

Opioid dependence is becoming a more common problem in the United States that gives rise to many negative health and social consequences for both individuals and society as a whole. Opioid dependence presents a challenging issue for physicians to identify and treat. Understanding and managing withdrawal symptoms is often a necessary first step on the road to recovery for these patients. Long-term therapy options include detoxification, nonpharmacologic treatment plans, and maintenance replacement treatment with either methadone or buprenorphine. Physicians meeting necessary requirements have the option of implementing office-based opioid-assisted maintenance therapy.

Topics: Analgesics, Opioid; Behavior Therapy; Buprenorphine; Cognitive Behavioral Therapy; Humans; Methadone; Narcotic Antagonists; Opioid-Related Disorders; Psychotherapy; Substance Withdrawal Syndrome; United States

To review the use of buprenorphine for opioid-addicted patients in primary care.. The MEDLINE database was searched for literature on buprenorphine from 1980 to 2009. Controlled trials, meta-analyses, and large observational studies were reviewed.. Buprenorphine is a partial opioid agonist that relieves opioid withdrawal symptoms and cravings for 24 hours or longer. Buprenorphine has a much lower risk of overdose than methadone and is preferred for patients at high risk of methadone toxicity, those who might need shorter-term maintenance therapy, and those with limited access to methadone treatment. The initial dose should be given only after the patient is in withdrawal. The therapeutic dose range for most patients is 8 to 16 mg daily. It should be dispensed daily by the pharmacist with gradual introduction of take-home doses. Take-home doses should be introduced more slowly for patients at higher risk of abuse and diversion (eg, injection drug users). Patients who fail buprenorphine treatment should be referred for methadone- or abstinence-based treatment.. Buprenorphine is an effective treatment of opioid addiction and can be safely prescribed by primary care physicians.

Topics: Buprenorphine; Humans; Opioid-Related Disorders; Primary Health Care

The diversion, misuse, and non-medically supervised use of buprenorphine and buprenorphine/naloxone by opioid users are reviewed. Buprenorphine and buprenorphine/naloxone are used globally as opioid analgesics and in the treatment of opioid dependency. Diversion of buprenorphine and buprenorphine/naloxone represents a complex medical and social issue, and has been widely documented in various geographical regions throughout the world. We first discuss the clinical properties of buprenorphine and its abuse potential. Second, we discuss its diversion and illicit use on an international level, as well as motivations for those activities. Third, we examine the medical risks and benefits of buprenorphine's non-medically supervised use and misuse. These risks and benefits include the effect of buprenorphine's use on HIV risk and the risk of its concomitant use with other medications and drugs of abuse. Finally, we discuss the implications of diversion, misuse, and non-medically supervised use (including potential measures to address issues of diversion); and potential areas for further research.

Topics: Buprenorphine; Drug Overdose; HIV Infections; Humans; Illicit Drugs; Motivation; Naloxone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Risk-Taking

The amount of opioid users receiving opioid maintenance therapy has increased significantly over the last few years. As a result, an increasing number of children are prenatally exposed to long-lasting opioids such as methadone and buprenorphine. This article reviews the literature on the cognitive development of children born to mothers in opioid maintenance therapy. Topics discussed are the effects of prenatal exposure on prematurity, somatic growth, brain volume, myelination, and the endocrine and neurotransmitter system. Social-environmental factors, including parental functioning, as well as genetic factors are also described. Areas requiring further research are identified.

Topics: Analgesics, Opioid; Buprenorphine; Child; Child Development; Cognition; Female; Humans; Male; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Prenatal Exposure Delayed Effects

Research on clinical application of oral naltrexone agrees on several things. From a pharmacological perspective, naltrexone works. From an applied perspective, the medication compliance and the retention rates are poor.. To evaluate the effects of naltrexone maintenance treatment versus placebo or other treatments in preventing relapse in opioid addicts after detoxification.. We searched: Cochrane Central Register of Controlled Trials (CENTRAL - The Cochrane Library issue 6 2010), PubMed (1973- June 2010), CINAHL (1982- June 2010). We inspected reference lists of relevant articles and contacted pharmaceutical producers of naltrexone, authors and other Cochrane review groups.. All randomised controlled clinical trials which focus on the use of naltrexone maintenance treatment versus placebo, or other treatments to reach sustained abstinence from opiate drugs. Three reviewers independently assessed studies for inclusion and extracted data. One reviewer carried out the qualitative assessments of the methodology of eligible studies using validated checklists.. Thirteen studies, 1158 participants, met the criteria for inclusion in this review.Comparing naltrexone versus placebo or no pharmacological treatments, no statistically significant difference were noted for all the primary outcomes considered. The only outcome statistically significant in favour of naltrexone is re incarceration, RR 0.47 (95%CI 0.26-0.84), but results come only from two studies. Considering only studies were patients were forced to adherence a statistical significant difference in favour of naltrexone was found for retention and abstinence, RR 2.93 (95%CI 1.66-5.18).Comparing naltrexone versus psychotherapy, in the two considered outcomes, no statistically significant difference was found in the single study considered.Naltrexone was not superior to benzodiazepines and to buprenorphine for retention and abstinence and side effects. Results come from single studies.. The findings of this review suggest that oral naltrexone did not perform better than treatment with placebo or no pharmacological agent with respect to the number of participants re-incarcerated during the study period. If oral naltrexone is compared with other pharmacological treatments such as benzodiazepine and buprenorphine, no statistically significant difference was found. The percentage of people retained in treatment in the included studies is however low (28%). The conclusion of this review is that the studies conducted have not allowed an adequate evaluation of oral naltrexone treatment in the field of opioid dependence. Consequently, maintenance therapy with naltrexone cannot yet be considered a treatment which has been scientifically proved to be superior to other kinds of treatment.

Topics: Administration, Oral; Benzodiazepines; Buprenorphine; Female; Humans; Male; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Randomized Controlled Trials as Topic

The management of pregnancy and delivery of a woman on opiate-substitution therapy with buprenorphine requires a coordinated team approach by social services, addiction medicine, obstetrics, and pediatrics. Her obstetrical care is further complicated by the unique pharmacology of buprenorphine and the issues of pain management. Obstetrical providers should be familiar with the complex issues surrounding the optimal care of these women.

Topics: Buprenorphine; Female; Humans; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy

The association between buprenorphine taper duration and treatment outcomes is not well understood. This review evaluated whether duration of outpatient buprenorphine taper is significantly associated with treatment outcomes.. Studies that were published in peer-reviewed journals, administered buprenorphine as an outpatient taper to opioid-dependent participants, and provided data on at least one of three primary treatment outcome measures (opioid abstinence, retention, peak withdrawal severity) were reviewed. Primary treatment outcomes were evaluated as a function of taper duration using hierarchical linear regressions with pre-taper maintenance duration as a cofactor.. Twenty-eight studies were reviewed. Taper duration significantly predicted percent of opioid-negative samples provided during treatment, however pre-taper maintenance period predicted percent participants abstinent on the final day of treatment. High rates of relapse were reported. No significant association between taper duration and retention in treatment or peak withdrawal severity was observed.. The data reviewed here suggest taper duration is associated with opioid abstinence achieved during detoxification but not with other markers of treatment outcome. The reviewed studies varied widely on several parameters (e.g., frequency of urinalysis testing, provision of ancillary medications) that may influence treatment outcome and thus could have interfered with the ability to identify relationships between taper duration and outcomes. Future studies evaluating opioid detoxification should utilize rigorous experimental methods and report a wider range of outcome measures in order to help advance our understanding of the association between taper duration and treatment outcomes.

Topics: Buprenorphine; Drug Administration Schedule; Humans; Narcotic Antagonists; Opioid-Related Disorders; Outpatients; Substance Withdrawal Syndrome; Substance-Related Disorders; Treatment Outcome

Injecting drug users are vulnerable to infection with Human Immunodeficiency Virus (HIV) and other blood borne viruses as a result of collective use of injecting equipment as well as sexual behaviour. To assess the effect of oral substitution treatment for opioid dependent injecting drug users on risk behaviours and rates of HIV infections. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and PsycINFO to May 2011. We also searched reference lists of articles, reviews and conference abstracts. Studies were required to consider the incidence of risk behaviours, or the incidence of HIV infection related to substitution treatment of opioid dependence. All types of original studies were considered. Two authors independently assessed each study for inclusion. Two authors independently extracted key information from each of the included studies. Any differences were resolved by discussion or by referral to a third author.. Thirty-eight studies, involving some 12,400 participants, were included. The majority were descriptive studies, or randomisation processes did not relate to the data extracted, and most studies were judged to be at high risk of bias. Studies consistently show that oral substitution treatment for opioid-dependent injecting drug users with methadone or buprenorphine is associated with statistically significant reductions in illicit opioid use, injecting use and sharing of injecting equipment. It is also associated with reductions in the proportion of injecting drug users reporting multiple sex partners or exchanges of sex for drugs or money, but has little effect on condom use. It appears that the reductions in risk behaviours related to drug use do translate into reductions in cases of HIV infection. However, because of the high risk of bias and variability in several aspects of the studies, combined totals were not calculated.. Oral substitution treatment for injecting opioid users reduces drug-related behaviours with a high risk of HIV transmission, but has less effect on sex-related risk behaviours. The lack of data from randomised controlled studies limits the strength of the evidence presented in this review.

Topics: Administration, Oral; Buprenorphine; HIV Infections; Humans; Methadone; Narcotics; Opioid-Related Disorders; Randomized Controlled Trials as Topic; Risk-Taking; Sexual Behavior; Substance Abuse, Intravenous

Different pharmacological approaches aimed at opioid detoxification are effective. Nevertheless a majority of patients relapse to heroin use, and relapses are a substantial problem in the rehabilitation of heroin users. Some studies have suggested that the sorts of symptoms which are most distressing to addicts during detoxification are psychological rather than physiological symptoms associated with the withdrawal syndrome.. To evaluate the effectiveness of any psychosocial plus any pharmacological interventions versus any pharmacological alone for opioid detoxification, in helping patients to complete the treatment, reduce the use of substances and improve health and social status.. We searched the Cochrane Drugs and Alcohol Group trials register (June 2011), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 6, 2011), PUBMED (1996 to June 2011); EMBASE (January 1980 to June 2011); CINAHL (January 2003 to June 2008); PsycINFO (1985 to April 2003) and reference list of articles.. Randomised controlled trials and controlled clinical trial which focus on any psychosocial associated with any pharmacological intervention aimed at opioid detoxification. People less than 18 years of age and pregnant women were excluded.. Two authors independently assessed trials quality and extracted data.. Eleven studies, 1592 participants, fulfilled the criteria of inclusion and were included in the review. The studies considered five different psychosocial interventions and two pharmacological treatments (methadone and buprenorphine). Compared to any pharmacological treatment alone, the association of any psychosocial with any pharmacological was shown to significantly reduce dropouts RR 0.71 (95% CI 0.59 to 0.85), use of opiate during the treatment, RR 0.82 (95% CI 0.71 to 0.93), at follow up RR 0.66 (95% IC 0.53 to 0.82) and clinical absences during the treatment RR 0.48 (95%CI 0.38 to 0.59). Moreover, with the evidence currently available, there are no data supporting a single psychosocial approach.. Psychosocial treatments offered in addition to pharmacological detoxification treatments are effective in terms of completion of treatment, use of opiate, participants abstinent at follow-up and clinical attendance. The evidence produced by this review is limited due to the small number of participants included in the studies, the heterogeneity of the assessment or the lack of detailed outcome information that prevented the possibility of cumulative analysis for several outcomes. Nevertheless it seems desirable to develop adjunct psychosocial approaches that might make detoxification more effective.

Topics: Adult; Buprenorphine; Combined Modality Therapy; Female; Humans; Male; Methadone; Narcotics; Opioid-Related Disorders; Psychotherapy; Randomized Controlled Trials as Topic

Dependence on opioids is a multifactorial condition involving genetic and psychosocial factors. There are three stages to treating opioid dependence. Stabilisation is usually by opioid substitution treatments, and aims to ensure that the drug use becomes independent of mental state (such as craving and mood) and independent of circumstances (such as finance and physical location). The next stage is to withdraw (detox) from opioids. The final stage is relapse prevention. This treatment process contributes to recovery of the individual, which also includes improved overall health and wellbeing, as well as engagement in society.. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments for stabilisation (maintenance) in people with opioid dependence? What are the effects of drug treatments for withdrawal in people with opioid dependence? What are the effects of drug treatments for relapse prevention in people with opioid dependence? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).. We found 26 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.. In this systematic review, we present information relating to the effectiveness and safety of the following interventions: buprenorphine; clonidine; lofexidine; methadone; naltrexone; and ultra-rapid withdrawal regimens.

Topics: Analgesics, Opioid; Buprenorphine; Evidence-Based Medicine; Heroin Dependence; Humans; Incidence; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Treatment Outcome

The number of opiate addicted patients treated with opioid replacement therapy is continuously increasing. In Germany, 57.7% of these patients are treated with methadone and 18.6% with buprenorphine. This maintenance therapy provides several advantages while addicted pregnant women and their foetus have a high benefit from appropriate replacement therapy. However, the recommendations concerning breast feeding during an opioid replacement therapy are discussed controversially, because methadone as well as buprenorphine accumulate in breast milk. This accumulation might cause damages to the newborn's health; so, child benefits of breast feeding have to be balanced with possible health risks.This review provides an overview of a selective literature search based on the PubMed-database and german consensus recommendations. Used search terms included: (methadone*) AND (breastfeeding OR lactation), (methadone*) AND (human milk), (buprenorphine*) AND (breastfeeding OR lactation) and (buprenorphine*) AND (human milk).According to the available literature, addicted women, substinated with methadone or buprenorphine are allowed to breast feed their newborns. The advantages of breast feeding prevail the risks of an infant opiate intoxication caused by methadone or buprenorphine.

Topics: Analgesics, Opioid; Breast Feeding; Buprenorphine; Contraindications; Dose-Response Relationship, Drug; Female; Germany; Humans; Infant; Infant, Newborn; Male; Metabolic Clearance Rate; Methadone; Milk, Human; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy

In Australia and New Zealand, in parallel with other developed countries, the number of patients prescribed opioids on a long-term basis has grown rapidly over the last decade. The burden of chronic pain is more widely recognised and there has been an increase in the use of opioids for both cancer and non-cancer indications. While the prevalence of illicit opioid use has remained relatively stable, the diversion and abuse of prescription opioids has escalated, as has the number of individuals receiving methadone or buprenorphine pharmacotherapy for opioid addiction. As a result, the proportion of opioid-tolerant patients requiring acute pain management has increased, often presenting clinicians with greater challenges than those faced when treating the opioid-naïve. Treatment aims include effective relief of acute pain, prevention of drug withdrawal, assistance with any related social, psychiatric and behavioural issues, and ensuring continuity of long-term care. Pharmacological approaches incorporate the continuation of usual medications (or equivalent), short-term use of sometimes much higher than average doses of additional opioid, and prescription of non-opioid and adjuvant drugs, aiming to improve pain relief and attenuate opioid tolerance and/or opioid-induced hyperalgesia. Discharge planning should commence at an early stage and may involve the use of a 'Reverse Pain Ladder' aiming to limit duration of additional opioid use. Legislative requirements may restrict which drugs can be prescribed at the time of hospital discharge. At all stages, there should be appropriate and regular consultation and liaison with the patient, other treating teams and specialist services.

Topics: Acute Disease; Analgesics; Analgesics, Opioid; Animals; Australia; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Drug Tolerance; Humans; Hyperalgesia; Illicit Drugs; Methadone; Naloxone; Narcotic Antagonists; Narcotics; New Zealand; Opiate Substitution Treatment; Opioid-Related Disorders; Pain; Pain, Postoperative; Patient Discharge; Preoperative Care; Substance Withdrawal Syndrome

Many opiate users require prescribed medication to help them achieve abstinence, commonly taking the form of a detoxification regime. In UK prisons, drug users are nearly universally treated for their opiate use by primary care clinicians, and once released access GP services where 40% of practices now treat drug users. There is a paucity of evidence evaluating methadone and buprenorphine (the two most commonly prescribed agents in the UK) for opiate detoxification.. To evaluate whether buprenorphine or methadone help to achieve drug abstinence at completion of a reducing regimen for heroin users presenting to UK prison health care for detoxification.. Open-label, pragmatic, randomised controlled trial in three prison primary healthcare departments in the north of England.. Prisoners (n = 306) using illicit opiates were recruited and given daily sublingual buprenorphine or oral methadone, in the context of routine care, over a standard reduced regimen of not more than 20 days. The primary outcome measure was abstinence from illicit opiates at 8 days post detoxification, as indicated by urine test (self-report/clinical notes where urine sample was not feasible). Secondary outcomes were also recorded.. Abstinence was ascertained for 73.7% at 8 days post detoxification (urine sample = 52.6%, self report = 15.2%, clinical notes = 5.9%). There was no statistically significant difference in the odds of achieving abstinence between methadone and buprenorphine (odds ratio [OR] = 1.69; 95% confidence interval [CI] = 0.81 to 3.51; P = 0.163). Abstinence was associated solely with whether or not the participant was still in prison at that time (15.22 times the odds; 95% CI = 4.19 to 55.28). The strongest association for lasting abstinence was abstinence at an earlier time point.. There is equal clinical effectiveness between methadone and buprenorphine in achieving abstinence from opiates at 8 days post detoxification within prison.

Topics: Administration, Oral; Administration, Sublingual; Adult; Aged; Buprenorphine; Humans; Methadone; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Prisoners; Young Adult

The aim of this systematic review was to compare the efficacy of methadone, buprenorphine, clonidine and lofexidine for opioid detoxification. Mixed treatment comparison meta-analyses were used to synthesise the data as it is designed for data-sets where limitations in standard pairwise meta-analyses make comparisons difficult to interpret.. A systematic search was conducted using the following databases: CENTRAL, CINAHL, Embase, HMIC, Medline and PsycINFO.. RCTs that included opioid dependent participants over a mean age of 16 receiving opioid detoxification using buprenorphine, methadone, clonidine or lofexidine were included in the systematic review. Included studies were quality assessed and the completion of treatment data was extracted by the author and a research assistant independently. Mixed treatment comparison methods were used to synthesise the data.. There were 23 RCTs included in the systematic review (and 20 included in the meta-analysis) comprising a total of 2112 participants. Buprenorphine and methadone were ranked as the most effective methods of opioid detoxification followed by lofexidine and clonidine respectively.. Buprenorpine and methadone appear to be the most effective detoxification treatments. While the analysis suggests buprenorphine is the most effective method of detoxification there is some uncertainty on whether it is more effective than methadone and requires further research to confirm this result.

Topics: Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Buprenorphine; Clonidine; Data Interpretation, Statistical; Humans; Methadone; Narcotic Antagonists; Narcotics; Odds Ratio; Opioid-Related Disorders; Randomized Controlled Trials as Topic; Treatment Outcome

This article reviews the main pharmacotherapies that are currently being used to treat opioid addiction. Treatments include detoxification using tapered methadone, buprenorphine, adrenergic agonists such as clonidine and lofexidine, and forms of rapid detoxification. In opioid maintenance treatment (OMT), methadone is most widely used. OMT with buprenorphine, buprenorphine-naloxone combination, or other opioid agonists is also discussed. The use of the opioid antagonists naloxone (for the treatment of intoxication and overdose) and oral and sustained-release formulations of naltrexone (for relapse prevention) is also considered. Although recent advances in the neurobiology of addictions may lead to the development of new pharmacotherapies for the treatment of addictive disorders, a major challenge lies in delivering existing treatments more effectively. Pharmacotherapy of opioid addiction alone is usually insufficient, and a complete treatment should also include effective psychosocial support or other interventions. Combining pharmacotherapies with psychosocial support strategies that are tailored to meet the patients' needs represents the best way to treat opioid addiction effectively.

Topics: Adrenergic Agonists; Analgesics, Opioid; Buprenorphine; Clonidine; Drug Therapy, Combination; Humans; Inactivation, Metabolic; Methadone; Naloxone; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Social Support; Substance Withdrawal Syndrome

Patients on drug-assisted rehabilitation have the same right to pain relief as others. Techniques that reduce the need for opioids should be used when possible in opioid-dependent individuals who need treatment of acute and post-operative pain. Substitution treatment should always be continued. In some situations a switch to a different opioid or route of administration is required. Higher doses of opioids than those needed in other patients may be required for analgesia. Well-designed clinical studies are lacking in this field.

Topics: Acetaminophen; Acute Disease; Analgesics, Non-Narcotic; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Buprenorphine; Glucocorticoids; Humans; Ketamine; Methadone; Opioid-Related Disorders; Pain; Pain, Postoperative; Surgical Procedures, Operative

While street drugs appear unlikely to alter the metabolism of antiretroviral (ARV) medications, several ARVs may induce or inhibit metabolism of various street drugs. However, research on these interactions is limited. Case reports have documented life-threatening overdoses of ecstasy and gamma-hydroxybutyrate after starting ritonavir, an ARV that inhibits several metabolic enzymes. For opioid addiction, methadone or buprenorphine are the treatments of choice. Because a number of ARVs decrease or increase methadone levels, patients should be monitored for methadone withdrawal or toxicity when they start or stop ARVs. Most ARVs do not cause buprenorphine withdrawal or toxicity, even if they alter buprenorphine levels, with rare exceptions to date including atazanavir/ritonavir associated with significant increases in buprenorphine and adverse events related to sedation and mental status changes in some cases. There are newer medications yet to be studied with methadone or buprenorphine. Further, there are many frequently used medications in treatment of complications of HIV disease that have not been studied. There is need for continuing research to define these drug interactions and their clinical significance.

Topics: Analgesics, Opioid; Anti-HIV Agents; Buprenorphine; Drug Interactions; HIV Infections; Humans; Illicit Drugs; Methadone; Opioid-Related Disorders; Ritonavir

Topics: Analgesics, Opioid; Buprenorphine; Counseling; Humans; Methadone; Opioid-Related Disorders; United States

Heroin craving is a trigger for relapse and dropping out of treatment. Methadone has been the standard medication for the management of heroin craving.. We explored the medication options other than methadone which may have heroin anticraving properties.. To be selected for the review, articles had to include outcome measures of the effect of the studied medication on subjective and/or objective opiate craving and be of the following two types: (1) randomized, controlled, and/or double-blind clinical trials (RCTs) examining the relationship between the studied medication and heroin craving; (2) nonrandomized and observational studies (NRSs) examining the relationship between the studied medication and heroin craving. Thirty-three articles were initially included in the review. Twenty-one were excluded because they did not meet the inclusion criteria. We present the results of 12 articles that met all the inclusion criteria.. Some new medications have been under investigation and seem promising for the treatment of opiate craving. Buprenorphine is the second most studied medication after methadone for its effect on opiate craving. At doses above 8 mg daily, it seems very promising and practical for managing opiate craving in patients receiving long-term opioid maintenance treatment.. In doses higher than 8 mg daily, buprenorphine is an appropriate treatment for opiate craving. More research with rigorous methodology is needed to study the effect of buprenorphine on heroin craving. Also more studies are needed to directly compare buprenorphine and methadone with regard to their effects on heroin craving.

Topics: Buprenorphine; Heroin; Heroin Dependence; Humans; Methadone; Naltrexone; Narcotic Antagonists; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome

Opioid abuse is a devastating, costly, and growing problem in the United States, and one for which treatment can be complicated by barriers such as access to care and legal issues. Only 12% to 15% of the opioid-dependent population is enrolled in methadone maintenance programs. A significant breakthrough occurred with passage of the Drug Addiction Treatment Act of 2000 (DATA 2000). For the first time in approximately 80 years, physicians could legally prescribe opioid medications for the treatment of opioid addiction. The opiate, so designated, was buprenorphine (Subutex).

Topics: Anesthesia; Buprenorphine; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Renal Insufficiency

Buprenorphine/naloxone (Suboxone) comprises the partial mu-opioid receptor agonist buprenorphine in combination with the opioid antagonist naloxone in a 4 : 1 ratio. When buprenorphine/naloxone is taken sublingually as prescribed, the naloxone exerts no clinically significant effect, leaving the opioid agonist effects of buprenorphine to predominate. However, when buprenorphine/naloxone is parenterally administered in patients physically dependent on full agonist opioids, the opioid antagonism of naloxone causes withdrawal effects, thus reducing the abuse potential of the drug combination. Buprenorphine/naloxone is an effective maintenance therapy for opioid dependence and has generally similar efficacy to methadone, although more data are needed. Less frequent dispensing of buprenorphine/naloxone (e.g. thrice weekly) does not appear to compromise efficacy and can improve patient satisfaction. Buprenorphine/naloxone is more effective than clonidine as a medically-supervised withdrawal therapy. Moreover, buprenorphine/naloxone is a generally well tolerated medically-supervised withdrawal and maintenance treatment. Thus, sublingual buprenorphine/naloxone is a valuable pharmacotherapy for the treatment of opioid dependence.

Topics: Buprenorphine; Clinical Trials as Topic; Drug Combinations; Drug Interactions; Humans; Methadone; Naloxone; Narcotic Antagonists; Opioid-Related Disorders

The scientific literature examining effective treatments for opioid dependent adults clearly indicates that pharmacotherapy is a necessary and acceptable component of effective treatments for opioid dependence. Nevertheless no studies have been published which systematically assess the effectiveness of the pharmacological detoxification among adolescents.. To assess the effectiveness of any detoxification treatment alone or in combination with psychosocial intervention compared to no intervention, other pharmacological intervention or psychosocial interventions on completion of treatment, reducing the use of substances and improving health and social status.. We searched the Cochrane Central Register of Controlled Trials (August 2008), MEDLINE (January 1966 to August 2008), EMBASE (January 1980 to August 2008), CINHAL (January 1982 to August) and reference lists of articles.. Randomised and controlled clinical trials comparing any pharmacological interventions alone or associated with psychosocial intervention aimed at detoxification with no intervention, placebo, other pharmacological intervention or psychosocial intervention in adolescents (13-18 years).. Two reviewers independently assessed trial quality and extracted data.. One trial involving 36 participants was included. It compares buprenorphine with clonidine for detoxification. No difference was found for drop out: RR 0.45 (95%CI: 0.20 - 1.04) and acceptability of treatment: withdrawal score WMD: 3.97 (95%CI -1.38, 9.32). More participants in the buprenorphine group initiated naltrexone treatment: RR 11.00 [95%CI 1.58, 76.55].. It is difficult to draft conclusions on the basis of only one trial with few participants. Furthermore, the only study included did not consider the efficacy of methadone that is still the most frequent drug utilized for the treatment of opioid withdrawal. One possible reason for the lack of evidence could be the difficulty in conducting trials with young people for to practical and ethical reasons.

Topics: Adolescent; Buprenorphine; Clonidine; Humans; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders

The scientific literature examining effective treatments for opioid dependent adults clearly indicates that pharmacotherapy is a necessary and acceptable component of effective treatments for opioid dependence. Nevertheless no studies have been published which systematically assess the effectiveness of the pharmacological maintenance treatment among adolescent.. To assess the effectiveness of any maintenance treatment alone or in combination with psychosocial intervention compared to no intervention, other pharmacological intervention or psychosocial interventions on retaining adolescents in treatment, reducing the use of substances and reducing health and social status. We searched the Cochrane Drugs and Alcohol Group's trials register (august 2008), MEDLINE (January 1966 to august 2008), EMBASE (January 1980 to august 2008), CINHAL (January 1982 to august 2008) and reference lists of articles. Randomised and controlled clinical trials comparing any maintenance pharmacological interventions alone or associated with psychosocial intervention with no intervention, placebo, other pharmacological intervention included pharmacological detoxification or psychosocial intervention in adolescent (13-18 years). Two reviewers independently assessed trial quality and extracted data. Two trials involving 187 participants were included. One study compared methadone with LAAM for maintenance treatment lasting 16 weeks after which patients were detoxified, the other compared maintenance treatment with buprenorphine - naloxone with detoxification with buprenorphine. No meta-analysis has been performed because the two studies assessed different comparisons. Maintenance treatment seems more efficacious in retaining patients in treatment but not in reducing patients with positive urine at the end of the study. Self reported opioid use at 1 year follow up was significantly lower in the maintenance group even if both group reported high level of opioid use and more patients in the maintenance group were enrolled in other addiction treatment at 12 month follow up.. It is difficult to draft conclusions on the basis of only two trials. One of the possible reason for the lack of evidence could be the difficulty to conduct trial with young people due to practical and ethic reasons.

Topics: Adolescent; Buprenorphine; Humans; Methadone; Methadyl Acetate; Naloxone; Narcotics; Opioid-Related Disorders; Randomized Controlled Trials as Topic; Young Adult

Topics: Buprenorphine; Counseling; Drug Delivery Systems; Drug Tolerance; Humans; Methadone; Narcotics; Opioid-Related Disorders; Patient Education as Topic; Pharmacies

Buprenorphine is a partial mu agonist opioid that is FDA-approved to manage opioid addiction in settings outside of traditional methadone clinics. The clinical uses, pharmacokinetics, pharmacodynamics, toxicology, and management of overdoses of buprenorphine are reviewed.

Topics: Analgesics, Opioid; Buprenorphine; Drug Overdose; Humans; Narcotic Antagonists; Opioid-Related Disorders; Pain

The development of effective treatments for opioid dependence is of great importance given the devastating consequences of the disease. Pharmacotherapies for opioid addiction include opioid agonists, partial agonists, opioid antagonists, and alpha-2-adrenergic agonists, which are targeted toward either detoxification or long-term agonist maintenance. Agonist maintenance therapy is currently the recommended treatment for opioid dependence due to its superior outcomes relative to detoxification. Detoxification protocols have limited long-term efficacy, and patient discomfort remains a significant therapy challenge. Buprenorphine's effectiveness relative to methadone remains a controversy and may be most appropriate for patients in need of low doses of agonist treatment. Buprenorphine appears superior to alpha-2 agonists, however, and office-based treatment with buprenorphine in the USA is gaining support. Studies of sustained-release formulations of naltrexone suggest improved effectiveness for retention and sustained abstinence; however, randomized clinical trials are needed.

Topics: Adrenergic alpha-Agonists; Analgesics, Opioid; Buprenorphine; Clinical Trials as Topic; Humans; Methadone; Narcotic Antagonists; Opioid-Related Disorders; Substance Withdrawal Syndrome

Managed withdrawal is a necessary step prior to drug-free treatment or as the end point of substitution treatment.. To assess the effectiveness of interventions involving the use of buprenorphine to manage opioid withdrawal, for withdrawal signs and symptoms, completion of withdrawal and adverse effects.. We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3, 2008), MEDLINE (January 1966 to July 2008), EMBASE (January 1985 to 2008 Week 31), PsycINFO (1967 to 7 August 2008) and reference lists of articles.. Randomised controlled trials of interventions involving the use of buprenorphine to modify the signs and symptoms of withdrawal in participants who were primarily opioid dependent. Comparison interventions involved reducing doses of methadone, alpha(2)-adrenergic agonists, symptomatic medications or placebo, or different buprenorphine-based regimes.. One author assessed studies for inclusion and methodological quality, and undertook data extraction. Inclusion decisions and the overall process was confirmed by consultation between all authors.. Twenty-two studies involving 1736 participants were included. The major comparisons were with methadone (5 studies) and clonidine or lofexidine (12 studies). Five studies compared different rates of buprenorphine dose reduction.Severity of withdrawal is similar for withdrawal managed with buprenorphine and withdrawal managed with methadone, but withdrawal symptoms may resolve more quickly with buprenorphine. It appears that completion of withdrawal treatment may be more likely with buprenorphine relative to methadone (RR 1.18; 95% CI 0.93 to 1.49, P = 0.18) but more studies are required to confirm this.Relative to clonidine or lofexidine, buprenorphine is more effective in ameliorating the symptoms of withdrawal, patients treated with buprenorphine stay in treatment for longer (SMD 0.92, 95% CI 0.57 to 1.27, P < 0.001), and are more likely to complete withdrawal treatment (RR 1.64; 95% CI 1.31 to 2.06, P < 0.001). At the same time there is no significant difference in the incidence of adverse effects, but drop-out due to adverse effects may be more likely with clonidine.. Buprenorphine is more effective than clonidine or lofexidine for the management of opioid withdrawal. Buprenorphine may offer some advantages over methadone, at least in inpatient settings, in terms of quicker resolution of withdrawal symptoms and possibly slightly higher rates of completion of withdrawal.

Topics: Acute Disease; Buprenorphine; Clonidine; Humans; Narcotic Antagonists; Opioid-Related Disorders; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome

Topics: Buprenorphine; France; Health Policy; Humans; Legislation, Medical; Mental Disorders; Methadone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Substance-Related Disorders

The widely used term "overdose" denotes a toxic effect: opioid-induced intoxication and a mechanism: the poisoning results only from an overdose. Surprisingly, our understanding of the pathophysiology of this deadly complication is limited. In drug users, we attempted to: (1) improve knowledge of drug-induced respiratory effects; (2) clarify the mechanisms of drug interactions; (3) identify factors of variability and vulnerability. A prospective study of opioid overdoses confirmed that poisonings involving buprenorphine do exist. However, the mechanisms of buprenorphine poisoning are more complex than only an overdose, particularly the severity is less than that induced by heroin. In contrast, methadone overdose is life-threatening. Experimental studies addressed several clinical questions and also showed limited discrepancies. At pharmacological doses, opioids decrease the ventilatory response to CO(2). However, this effect does not account for the morbimortality of opioid poisonings. The mechanisms of opioid-induced morbimortality are different. Buprenorphine at doses near its median lethal dose did not induce acute respiratory failure as defined by a decrease in the partial pressure of oxygen in arterial blood (PaO(2)). In contrast, the combination of buprenorphine with flunitrazepam results in a decrease in PaO(2). This harmful interaction does not exist with other benzodiazepines in the rat, except for very high doses of nordazepam. The interaction results from a pharmacokinetic process. In contrast, methadone causes a dose-dependent decrease in PaO(2,) even significant before hypercapnia. We are assessing the relationships between on one hand alterations of ventilatory pattern and of arterial blood gas and on the other hand the different types of opiate receptors in the rats.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Drug Interactions; Drug Overdose; France; Humans; Methadone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Respiratory System

The needs of drug users for substitution therapy and drug-use-related care can vary greatly, a source of conflict between users and health care professionals and sometimes generating dysfunction of the health care system. For example, in France the lack of injection formulations for substitution therapy has led users to inject their substitution product (Subutex or Skenan) creating a bogus relationship with the pharmacist or physician who do not know how they should react. Beliefs held by health care professionals and the lack of drug abuse training in the pharmacy and medicine curricula can also lead to a dangerous situation for users: physicians may prescribe a dose too low for substitution with the risk of pushing the user into the black market to search for a complement. We detail here the way users would like to use substitution, focusing on the points where they are in agreement or disagreement with health care professionals. We explain why, in our opinion, it is fundamental to take into consideration the users' point of view.

Topics: Buprenorphine; Chemistry, Pharmaceutical; Consumer Behavior; France; Humans; Interprofessional Relations; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Pharmacists; Physicians

Widespread diffusion of opiate substitution therapy (OST), particularly with high-dose buprenorphine (BHD) has led to a considerable decline in the number of intravenous drug users (IVDU) in France, in parallel with a reduction in the volume of over-the-counter syringe sales, the number of overdoses, the use of heroin, and the associated delinquency, and HIV prevalence. OST also plays a crucial role in improving observance of anti-HIV, and anti-HCV treatments as well as an improvement in the quality-of-life of IVDUs. But fraudulent behavior (resellers, dealers), and misuse (sniff, inhalation, injection for BHD, fractionated or excessive doses, association with other psychoactive products for BHD and methadone) have also developed. Misuse is related either to the difficult, and progressive adhesion process during the early phases of OST or to a situation of therapeutic failure after long-term appropriate OST. Unless access to care is facilitated with new therapeutic options capable of matching the benefits of OST, healthcare professionals will have little to offer in the event of therapeutic failure.

Topics: Attitude of Health Personnel; Buprenorphine; France; Humans; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Physicians; Quality of Life

Opioid dependence is a chronic relapsing condition for which long-term opioid substitution treatment (OST) is effective. However, safety and community acceptance of OST is compromised by diversion of prescribed medication. The development of a formulation combining buprenorphine and naloxone is designed to reduce the likelihood of intravenous misuse, and the therefore the value of the medication if diverted to the black market.. To evaluate the evidence for 4:1 buprenorphine-naloxone as an efficacious OST, and as a deterrent to diversion and intravenous misuse.. The literature on buprenorphine-naloxone in a 4:1 ratio is reviewed.. The addition of naloxone does not appear to affect the efficacy of buprenorphine as a maintenance drug. While offering some deterrence of injection through precipitated withdrawal, there are many circumstances where injecting of buprenorphine-naloxone is reinforcing rather than aversive. The combination will reduce, but not eliminate, intravenous misuse; clinicians therefore need to monitor patients in OST, and be selective in providing patients with medication to be taken without observation.

Topics: Buprenorphine; Clinical Trials as Topic; Drug Combinations; Drug Interactions; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders

Buprenorphine/naloxone (Suboxone) comprises the partial micro-opioid receptor agonist buprenorphine in combination with the opioid antagonist naloxone in a 4 : 1 ratio. When buprenorphine/naloxone is taken sublingually as prescribed, the naloxone exerts no clinically significant effect, leaving the opioid agonist effects of buprenorphine to predominate. However, when buprenorphine/naloxone is parenterally administered in patients physically dependent on full agonist opioids, the opioid antagonism of naloxone causes withdrawal effects, thus reducing the abuse potential of the drug combination. Buprenorphine/naloxone is an effective maintenance therapy for opioid dependence and has generally similar efficacy to methadone, although more data are needed. Less frequent dispensing of buprenorphine/naloxone (e.g. thrice weekly) does not appear to compromise efficacy and can improve patient satisfaction. Buprenorphine/naloxone is more effective than clonidine as a medically supervised withdrawal therapy. Moreover, buprenorphine/naloxone is a generally well tolerated medically supervised withdrawal and maintenance treatment. Thus, sublingual buprenorphine/naloxone is a valuable pharmacotherapy for the treatment of opioid dependence.

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Drug Combinations; Humans; Naloxone; Opioid-Related Disorders; Randomized Controlled Trials as Topic; Treatment Outcome

Rising rates of opioid use among teenagers and young adults are a public health concern. Despite short durations of opioid use compared with those of adults, youth with opioid dependence have a host of co-occurring conditions, including polysubstance abuse, psychiatric disorders, hepatitis C infection, HIV risk, and high-risk sexual and criminal behaviors. Opioid-dependent youth typically are offered outpatient/residential treatment with brief detoxification, but one study showed that heroin users fare worse following residential treatment. Although abundant research supports the use of medication-assisted treatment for opioid-dependent adults, research is only recently emerging for youth. Buprenorphine, a partial opioid agonist, was proven safe and effective in improving abstinence from opioids in two controlled clinical trials. More research is needed to determine several clinically relevant areas: appropriate duration of agonist treatment, ways to enhance medication adherence, the value of integrated treatments for co-occurring conditions, and the role of opioid antagonists in opioid-dependent youth.

Topics: Adolescent; Adult; Buprenorphine; Clinical Trials as Topic; Humans; Narcotic Antagonists; Opioid-Related Disorders; Young Adult

To determine the efficacy of Opiate Maintenance Therapy (OMT) and adjunctive interventions for dual heroin and cocaine dependence by means of a meta-analysis.. We searched for and retrieved randomized controlled clinical trials. We used RevMan 5.0 with random effects modeling for statistical analysis and for comparisons of relative risk, effect sizes, and confidence intervals. Subsequent moderator variables and sensitivity analyses were performed.. Thirty-seven studies, which have enrolled 3,029 patients, have been included in this meta-analysis. High doses of OMT were more efficacious than lower ones in the achievement of sustained heroin abstinence (RR = 2.24 [1.54, 3.24], p < .0001) but had no effect on cocaine abstinence. At equivalent doses, methadone was more efficacious than buprenorphine on cocaine abstinence (RR = 1.63 [1.20, 2.22], p = .002) and also appeared to be superior on heroin abstinence (RR = 1.39 [1.00, 1.93], p = .05). Several pharmacological and psychological potentiation strategies have been investigated. An improvement on sustained cocaine abstinence was achieved with indirect dopaminergic agonists (RR = 1.44 [1.05, 1.98], p = .03) and with contingency management (CM) focusing on cocaine abstinence (RR = 3.11 [1.80, 5.35], p < .0001).. Dual opioid and cocaine dependence can be effectively treated with OMT in combination with adjunctive interventions. Higher OMT doses are preferable to lower ones and methadone to buprenorphine. OMT can be enhanced with indirect dopaminergic drugs and with CM focusing on cocaine abstinence.

Topics: Behavior Therapy; Buprenorphine; Cocaine-Related Disorders; Humans; Methadone; Narcotics; Opioid-Related Disorders; Treatment Outcome

Dependence on opioids is a multifactorial condition involving genetic and psychosocial factors. There are three approaches to treating opioid dependence. Stabilisation is usually by opioid substitution treatments, and aims to ensure that the drug use becomes independent of mental state (such as craving and mood) and independent of circumstances (such as finance and physical location). The next stage is to withdraw (detox) from opioids. The final aim is relapse prevention.. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments for stabilisation (maintenance) in people with opioid dependence? What are the effects of drug treatments for withdrawal in people with opioid dependence? What are the effects of drug treatments for relapse prevention in people with opioid dependence? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2008 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).. We found 23 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.. In this systematic review, we present information relating to the effectiveness and safety of the following interventions: buprenorphine; clonidine; lofexidine; methadone; naltrexone; and ultra-rapid withdrawal regimes.

Topics: Analgesics, Opioid; Buprenorphine; Evidence-Based Medicine; Heroin Dependence; Humans; Incidence; Methadone; Naltrexone; Opioid-Related Disorders

A systematic review was undertaken to examine studies of buprenorphine detoxification that has included post-treatment outcomes as well as more immediate aspects of progress. Studies were required to report details of buprenorphine withdrawal regime and post-treatment outcomes including abstinence rates. Only five studies met these criteria, with buprenorphine regimes lasting 3 days to several weeks, and with variable follow-up. Detoxification completion rates were 65-100%, but relatively few treatment completers were then drug free at their follow-up appointments. In subsequent prescribing, more patients had returned to opioid maintenance than complied with naltrexone. Our preliminary review indicates that buprenorphine is a suitable medication for the process of opiate detoxification but that this newer treatment option has not led to higher rates of abstinence following withdrawal. Further studies are required to more substantially examine abstinence outcomes, as well as characteristics which predict success.

Topics: Buprenorphine; Humans; Opioid-Related Disorders; Residence Characteristics; Substance Abuse Treatment Centers; Substance Withdrawal Syndrome; Treatment Outcome

Psychiatric pharmacogenetics involves the use of genetic tests that can predict the effectiveness of treatments for individual patients with mental illness such as drug dependence. This review aims to cover these developments in the pharmacotherapy of alcohol and opiates, two addictive drugs for which we have the majority of our FDA approved pharmacotherapies.. We conducted a literature review using Medline searching terms related to these two drugs and their pharmacotherapies crossed with related genetic studies.. Alcohol's physiological and subjective effects are associated with enhanced beta-endorphin release. Naltrexone increases baseline beta-endorphin release blocking further release by alcohol. Naltrexone's action as an alcohol pharmacotherapy is facilitated by a putative functional single nucleotide polymorphism (SNP) in the opioid mu receptor gene (Al18G) which alters receptor function. Patients with this SNP have significantly lower relapse rates to alcoholism when treated with naltrexone. Caucasians with various forms of the CYP2D6 enzyme results in a 'poor metabolizer' phenotype and appear to be protected from developing opioid dependence. Others with a "ultra-rapid metabolizer" phenotype do poorly on methadone maintenance and have frequent withdrawal symptoms. These patients can do well using buprenorphine because it is not significantly metabolized by CYP2D6.. Pharmacogenetics has great potential for improving treatment outcome as we identify gene variants that affect pharmacodynamic and pharmacokinetic factors. These mutations guide pharmacotherapeutic agent choice for optimum treatment of alcohol and opiate abuse and subsequent relapse.

Topics: Alcoholism; beta-Endorphin; Buprenorphine; Cytochrome P-450 CYP2D6; Humans; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Polymorphism, Single Nucleotide; Predictive Value of Tests; Receptors, Opioid, mu

Through a novel synthesis of the literature and our own clinical experience, we have derived a set of evidence-based recommendations for consideration as guidance in the management of opioid-dependent pregnant women and infants.. PubMed literature searches were carried out to identify recent key publications in the areas of pregnancy and opioid dependence, neonatal abstinence syndrome (NAS) prevention and treatment, multiple substance abuse and psychiatric comorbidity.. Pregnant women dependent on opioids require careful treatment to minimize harm to the fetus and neonate and improve maternal health. Applying multi-disciplinary treatment as early as possible, allowing medication maintenance and regular monitoring, benefits mother and child both in the short and the long term. However, there is a need for randomized clinical trials with sufficient sample sizes.. Opioid maintenance therapy is the recommended treatment approach during pregnancy. Treatment decisions must encompass the full clinical picture, with respect to frequent complications arising from psychiatric comorbidities and the concomitant consumption of other drugs. In addition to standardized approaches to pregnancy, equivalent attention must be given to the treatment of NAS, which occurs frequently after opioid medication.. Methodological flaws and inconsistencies confound interpretation of today's literature. Based on this synthesis of available evidence and our clinical experience, we propose recommendations for further discussion.

Topics: Buprenorphine; Diagnosis, Dual (Psychiatry); Female; GABA Modulators; Humans; Infant, Newborn; Mental Disorders; Methadone; Narcotics; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Phenobarbital; Pregnancy; Pregnancy Complications

Opioids have been regarded for millennia as among the most effective drugs for the treatment of pain. Their use in the management of acute severe pain and chronic pain related to advanced medical illness is considered the standard of care in most of the world. In contrast, the long-term administration of an opioid for the treatment of chronic noncancer pain continues to be controversial. Concerns related to effectiveness, safety, and abuse liability have evolved over decades, sometimes driving a more restrictive perspective and sometimes leading to a greater willingness to endorse this treatment. The past several decades in the United States have been characterized by attitudes that have shifted repeatedly in response to clinical and epidemiological observations, and events in the legal and regulatory communities. The interface between the legitimate medical use of opioids to provide analgesia and the phenomena associated with abuse and addiction continues to challenge the clinical community, leading to uncertainty about the appropriate role of these drugs in the treatment of pain. This narrative review briefly describes the neurobiology of opioids and then focuses on the complex issues at this interface between analgesia and abuse, including terminology, clinical challenges, and the potential for new agents, such as buprenorphine, to influence practice.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Chronic Disease; Drug Tolerance; History, Ancient; Humans; Narcotic Antagonists; Nervous System; Opioid-Related Disorders; Pain; Substance Withdrawal Syndrome

Dependence on and abuse of prescription opioid drugs is now a major health problem, with initiation of prescription opioid abuse exceeding cocaine in young people. Coincident with the emergence of abuse and dependence on prescription opioids, there has been an increased emphasis on the treatment of pain. Pain is now the "5th vital sign" and physicians face disciplinary action for failure to adequately relieve pain. Thus, physicians are whipsawed between the imperative to treat pain with opioids and the fear of producing addiction in some patients. In this article, the authors characterize the emerging epidemic of prescription opioid abuse, discuss the utility of buprenorphine in the treatment of addiction to prescription opioids, and present illustrative case histories of successful treatment with buprenorphine.

Topics: Analgesics, Opioid; Buprenorphine; Disease Outbreaks; Humans; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Pain; Prescription Drugs; Substance-Related Disorders; United States

Opioids have been used for centuries to treat a variety of psychiatric conditions with much success. The so-called "opium cure" lost popularity in the early 1950s with the development of non-addictive tricyclic antidepressants and monoamine oxidase inhibitors. Nonetheless, recent literature supports the potent role of methadone, buprenorphine, tramadol, morphine, and other opioids as effective, durable, and rapid therapeutic agents for anxiety and depression. This article reviews the medical literature on the treatment of psychiatric disorders with opioids (notably, methadone and buprenorphine) in both the non-opioid-dependent population and in the opioid-dependent methadone maintenance population. The most recent neurotransmitter theories on the origin of depression and anxiety will be reviewed, including current information on the role of serotonin, N-Methyl d-Aspartate, glutamate, cortisol, catecholamine, and dopamine in psychiatric disorders. The observation that methadone maintenance patients with co-existing psychiatric morbidity (so called dual diagnosis patients) require substantially higher methadone dosages by between 20% and 50% will be explored and qualified. The role of methadone and other opioids as beneficial psychiatric medications that are independent of their drug abuse mitigating properties will be discussed. The mechanisms by which methadone and other opioids can favorably modulate the neurotransmitter systems controlling mood will also be discussed.

Topics: Anxiety Disorders; Brain; Buprenorphine; Comorbidity; Depressive Disorder; Diagnosis, Dual (Psychiatry); Dose-Response Relationship, Drug; Humans; Methadone; Narcotics; Opioid-Related Disorders; Receptors, Neurotransmitter

The increasing global public health burden of heroin dependence and prescription opioid dependence warrants further expansion of treatment models. The most effective intervention for opioid dependence remains maintenance with methadone, a full mu-opioid receptor agonist, or buprenorphine, a partial mu-opioid receptor agonist.A growing body of evidence supports the use of opioid receptor agonist maintenance in office-based settings. Office-based opioid treatment (OBOT) can expand treatment access in a less stigmatized environment, which enables integrated care of co-morbid conditions. The current review primarily examines OBOT in the US, although a comparison with the British and French models is provided, given that the public health impact and implementation of OBOT will likely vary between countries because of policy and logistical differences. The comparative effectiveness of maintenance treatment in office-based and traditional programme-based models of care requires further study. Clinical and practical considerations when providing treatment for opioid dependence in traditional versus office-based settings include patient selection and monitoring, health economics, management of co-morbid conditions, and access to ancillary psychosocial treatment. OBOT is not a replacement for more structured, traditional models of care, but provides an additional opportunity to help address the tremendous public health impact of opioid dependence.

Topics: Analgesics, Opioid; Buprenorphine; Humans; Methadone; Office Visits; Opioid-Related Disorders; Primary Health Care

Sublingual buphrenorphine is a unique opioid medication based on its pharmacokinetics and pharmacodynamic properties. It may be used "on label" as an alternative choice to methadone for the treatment of opioid addiction or "off-label" for the treatment of both acute and chronic pain. Because of high mu receptor affinity and resultant blockade, it has been suggested that this might interfere with the management of moderate to severe pain in patients on opioid agonist treatment. The following article will offer strategies and approaches to address some of these real and perceived challenges.

Topics: Acute Disease; Administration, Sublingual; Adult; Analgesics, Opioid; Buprenorphine; Chronic Disease; Drug Synergism; Female; Humans; Male; Middle Aged; Opioid-Related Disorders; Pain, Intractable; Receptors, Opioid

In recent years, we have seen regulatory approval being given for several new pharmacotherapies in the treatment of drug addiction disorders. Within the United States, the most noteworthy development has been the approval of buprenorphine in the treatment of opioid dependence, and its availability for prescribing in an office-based setting has resulted in thousands of additional patients going into treatment. Although approved medications for the treatment of cocaine and methamphetamine dependence are still lacking, the National Institute on Drug Abuse has devoted substantial effort toward meeting these clinical needs. Recent studies of modafinil for the treatment of cocaine dependence have been especially encouraging. Looking to the future, the looming challenge is polydrug addiction, a situation that is often complicated by co-occurring psychiatric disorders. As we strive to address the needs of these complicated patients, studies of buprenorphine/naltrexone may hold the key to a major advance.

Topics: Buprenorphine; Comorbidity; Delayed-Action Preparations; Drug Administration Schedule; Drug Design; Drug Therapy, Combination; Humans; Mental Disorders; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders

This article addresses common questions that clinicians face when treating pregnant women with opioid dependence. Guidance, based on both research evidence and the collective clinical experience of the authors, which include investigators in the Maternal Opioid Treatment: Human Experimental Research (MOTHER) project, is provided to aid clinical decision making. The MOTHER project is a double-blind, double-dummy, flexible-dosing, parallel-group clinical trial examining the comparative safety and efficacy of methadone and buprenorphine for the treatment of opioid dependence in pregnant women and their neonates. The article begins with a discussion of appropriate assessment during pregnancy and then addresses clinical management stages including maintenance medication selection, induction, and stabilization; opioid agonist medication management before, during, and after delivery; pain management; breast-feeding; and transfer to aftercare. Lastly, other important clinical issues including managing co-occurring psychiatric disorders and medication interactions are discussed.

Topics: Analgesics, Opioid; Buprenorphine; Clinical Trials as Topic; Decision Making; Female; Humans; Infant, Newborn; Methadone; Opioid-Related Disorders; Pain; Pregnancy; Pregnancy Complications

The management of opioid dependence during pregnancy has received considerable attention over the past three decades. Recent peer-reviewed literature in the fields of pregnancy and opioid dependence and neonatal abstinence syndrome has been evaluated and discussed.. Pregnant opioid-dependent women must be carefully managed to minimize harm to the fetus; therefore, standardized care for maternal health is required. In a multidisciplinary care system opioid maintenance therapy is the recommended treatment approach during pregnancy. Equivalent attention must be given to the treatment of neonatal abstinence syndrome, which occurs in 55-94% of neonates after intrauterine opioid exposure with a 60% likelihood of requiring treatment; heterogeneous rating scales as well as heterogeneous treatment approaches are often responsible for extended hospital stays.. Interpretation of available literature is confounded by several methodological flaws. In general, there is still a lack of evidence-based study designs for pharmacological treatment of these patients as well as neonatal abstinence syndrome.

Topics: Buprenorphine; Female; Humans; Methadone; Narcotics; Opioid-Related Disorders; Pregnancy

Buprenorphine has been reported as an alternative to methadone for maintenance treatment of opioid dependence, but differing results are reported concerning its relative effectiveness indicating the need for an integrative review.. To evaluate the effects of buprenorphine maintenance against placebo and methadone maintenance in retaining patients in treatment and in suppressing illicit drug use.. We searched the following databases up to October 2006: Cochrane Drugs and Alcohol Review Group Register, the Cochrane Controlled Trials Register, MEDLINE, EMBASE, Current Contents, Psychlit, CORK , Alcohol and Drug Council of Australia, Australian Drug Foundation, Centre for Education and Information on Drugs and Alcohol, Library of Congress databases, reference lists of identified studies and reviews, authors were asked about any other published or unpublished relevant RCT.. Randomised clinical trials of buprenorphine maintenance versus placebo or methadone maintenance.. Authors separately and independently evaluated the papers and extracted data for meta-analysis.. Twenty four studies met the inclusion criteria (4497 participants), all were randomised clinical trials, all but six were double-blind. The method of allocation concealment was not clearly described in the majority (20) of the studies, but where it was reported the methodological quality was good. Buprenorphine was statistically significantly superior to placebo medication in retention of patients in treatment at low doses (RR=1.50; 95% CI: 1.19 - 1.88), medium (RR=1.74; 95% CI: 1.06 - 2.87), and high doses (RR=1.74; 95% CI: 1.02 - 2.96). The high statistical heterogeneity prevented the calculation of a cumulative estimate. However, only medium and high dose buprenorphine suppressed heroin use significantly above placebo. Buprenorphine given in flexible doses was statistically significantly less effective than methadone in retaining patients in treatment (RR= 0.80; 95% CI: 0.68 - 0.95), but no different in suppression of opioid use for those who remained in treatment. Low dose methadone is more likely to retain patients than low dose buprenorphine (RR= 0.67; 95% CI: 0.52 - 0.87). Medium dose buprenorphine does not retain more patients than low dose methadone, but may suppress heroin use better. There was no advantage for medium dose buprenorphine over medium dose methadone in retention (RR=0.79; 95% CI:0.64 - 0.99) and medium dose buprenorphine was inferior in suppression of heroin use.. Buprenorphine is an effective intervention for use in the maintenance treatment of heroin dependence, but it is less effective than methadone delivered at adequate dosages.

Topics: Buprenorphine; Humans; Methadone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Randomized Controlled Trials as Topic

The prevalence of opiate use among pregnant women ranges from 1% to 2% to as much as 21%. Heroin crosses the placenta and pregnant opiate dependent women experience a six fold increase in maternal obstetric complications such as low birth weight, toxaemia, 3rd trimester bleeding, malpresentation, puerperal morbidity, fetal distress and meconium aspiration. Neonatal complications include narcotic withdrawal, postnatal growth deficiency, microcephaly, neurobehavioral problems, increased neonatal mortality and a 74-fold increase in sudden infant death syndrome.. To assess the effectiveness of any maintenance treatment alone or in combination with psychosocial intervention compared to no intervention, other pharmacological intervention or psychosocial interventions on child health status, neonatal mortality, retaining pregnant women in treatment, and reducing use of substances. We searched Cochrane Drugs and Alcohol Group' Register of Trials (June 2007), PubMed (1966 - June 2007), CINAHL (1982- June 2007), reference lists of relevant papers, sources of ongoing trials, conference proceedings, National focal points for drug research. Authors of included studies and experts in the field were contacted.. Randomised controlled trials enrolling opiate dependent pregnant women. The authors assessed independently the studies for inclusion and methodological quality. Doubts were solved by discussion.. We found three trials with 96 pregnant women. Two compared methadone with buprenorphine and one methadone with oral slow morphine. For the women there was no difference in drop out rate RR 1.00 (95% CI 0.41 to 2.44) and use of primary substance RR 2.50 (95% CI 0.11 to 54.87) between methadone and buprenorphine, whereas oral slow morphine seemed superior to methadone in abstaining women from the use of heroin RR 2.40 (95% CI 1.00 to 5.77)For the newborns in one trial buprenorphine performed better than methadone for birth weight WMD -530 gr (95% CI -662 to -397), this result is not confirmed in the other trial. For the APGAR score both studies didn't find significant difference . No differences for NAS measures used. Comparing methadone with oral slow morphine no differences for birth weight and mean duration of NAS. The APGAR score wasn't considered.. We didn't find any significant difference between the drugs compared both for mother and for child outcomes; the trials retrieved were too few and the sample size too small to make firm conclusion about the superiority of one treatment over another. There is an urgent need of big randomized controlled trials.

Topics: Birth Weight; Buprenorphine; Female; Humans; Infant; Infant, Newborn; Methadone; Narcotics; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Randomized Controlled Trials as Topic

The profile of opioid dependence in the United States is changing. Abuse of prescription opioids is more common than that of illicit opioids: Recent data indicate that approximately 1.6 million persons abuse or are dependent on prescription opioids, whereas 323,000 abuse or are dependent on heroin. Despite this prevalence, nearly 80% of opioid-dependent persons remain untreated. One option for expanding treatment is the use of buprenorphine and the buprenorphine-naloxone combination. Buprenorphine is a partial opioid agonist that can be prescribed by trained physicians and dispensed at pharmacies. This article addresses the clinical presentation of a patient with opioid dependence and describes the relatively new practice of office-based treatment with buprenorphine-naloxone. The different components of treatment; the role of the physician who provides this treatment; and the logistics of treating this growing, multifaceted patient population are also examined.

Topics: Adult; Buprenorphine; Drug Combinations; Female; Humans; Methadone; Naloxone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Patient Care Planning; Physician's Role; Primary Health Care

In England and Wales, estimates suggest around 250,000 people have serious drug problems such as dependency, that cause considerable harm to themselves and others, and give rise to high social and economic costs. The number of people receiving specialist treatment for drug problems has increased greatly in recent years. Many people dependent on opioids will require opioid substitution treatment at some time. This may involve long-term maintenance to reduce use of illicit drugs, and/or short-term detoxification to stop such use completely. Standard management involves methadone maintenance therapy. Buprenorphine (Subutex-Schering-Plough) is also licensed for the management of patients with opioid dependence. Here we review the evidence for the use of buprenorphine compared with methadone for opioid dependence.

Topics: Analgesics, Opioid; Buprenorphine; Humans; Methadone; Opioid-Related Disorders

Buprenorphine (Subutex) is a safe and effective treatment for opioid dependence, and has very low potential for abuse, especially when it is combined with naloxone (Narcan) in a single sublingual tablet (Suboxone). New regulations allow physicians who are certified in buprenorphine therapy to offer it in their offices, a development that can substantially increase patient access to treatment.

Topics: Buprenorphine; Drug Combinations; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders

In the era of highly effective anti-retroviral therapy (ART), data show a significant difference in treatment outcomes between injecting drug users (IDUs) and non-IDUs. Factors that may contribute to suboptimal treatment outcomes in IDUs include delayed access to ART, competing comorbid diseases, psychosocial barriers and poor long-term adherence to ART. This review describes and compares several studies on adherence to ART and its correlates in HIV-infected individuals in general, then IDUs and finally those IDUs on opioid substitution treatment (OST). It highlights how ongoing drug use or OST can modify the pattern of these correlates. The aim is to extend all the experience acquired from these studies in order to optimise both access to care and adherence in those countries where HIV infection is mainly driven by IDUs and where ART and OST are only starting to be scaled up. The role of OST in fostering access to care and adherence to ART together with the promising results achieved to date using modified directly observed therapy (DOT) programs for patients taking methadone, allow us to emphasize the efficacy of a comprehensive care model which integrates substance dependence treatment, psychiatric treatment, social services, and medical treatment. The review concludes by suggesting areas of future research targeted at improving the understanding of both the role of perceived toxicity and patient-provider relationship for patients on ART and OST.

Topics: Antiretroviral Therapy, Highly Active; Buprenorphine; HIV Infections; Humans; Methadone; Narcotics; Opioid-Related Disorders; Patient Compliance; Substance Abuse Treatment Centers; Substance Abuse, Intravenous

There is growing empirical evidence of buprenorphine's effectiveness in treating opioid dependence in community-based settings in the U.S. Decades of research indicates that in order for buprenorphine to have a sizable effect, it must be appropriately supported by behavioral counseling. Studies to date have not established the optimal behavioral counseling content for supporting buprenorphine treatment. The objective of this article is: 1) to review evidence of the key treatment-relevant issues posed by opioid-dependent patients in community-based settings in the U.S.; and 2) to review behavioral counseling content that may optimize the use of buprenorphine for treating opioid dependence in such settings. Evidence points toward the use of behavioral counseling aimed at enhancing patients' motivation during treatment entry followed by an emphasis on improving coping/relapse prevention skills during the primary phase of treatment.

Topics: Adaptation, Psychological; Buprenorphine; Cognitive Behavioral Therapy; Combined Modality Therapy; Counseling; Humans; Methadone; Motivation; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Patient Dropouts; Secondary Prevention; Substance Abuse Treatment Centers; Treatment Outcome; United States

The Drug Addiction Treatment Act of 2000 (DATA 2000) was established to create a new paradigm for medication-assisted treatment of persons with opiate addiction in the United States. Before enactment of DATA 2000, the use of opioid medications to treat patients with opioid addiction was permissible only in federally approved treatment programs, ie, "methadone clinics." The only medications permitted were Schedule II drugs (eg, methadone hydrochloride and l-alpha-acetylmethadol [LAAM]), which could only be dispensed, not prescribed. Under provisions of DATA 2000, qualified physicians in a medical office and other appropriate settings outside the opioid treatment program system may prescribe and/or dispense Schedule III, IV, and V opioid medications for treating persons with opioid addiction if such medications have been specifically approved by the US Food and Drug Administration for that indication. Opioid addiction treatment programs were commonly known as methadone clinics. Such programs now may also dispense buprenorphine hydrochloride and the buprenorphine hydrochloride-naloxone combination.

Topics: Buprenorphine; Humans; Narcotic Antagonists; Opioid-Related Disorders; Outcome Assessment, Health Care; United States

In France, all registered medical doctors have been allowed to prescribe buprenorphine without any special education or licensing since 1995. This has led to a rapidly increasing number of opiate-dependent users under buprenorphine treatment in primary care. French physician compensation mechanisms, pharmacy services, and medical insurance funding all have contributed to minimizing barriers to buprenorphine treatment. Approximately 20% of all physicians in France are prescribing buprenorphine to treat more than one half of the estimated 180,000 problem heroin users. Intravenous diversion of buprenorphine may occur in up to 20% of buprenorphine patients and has led to relatively rare overdoses in combination with sedatives, whereas total opiate overdose deaths have declined substantially. In France, buprenorphine maintenance treatment for problem opiate users was feasible and safe through office-based prescriptions in a relaxed regulatory environment.

Topics: Buprenorphine; Cause of Death; Cross-Sectional Studies; Drug Approval; Drug Overdose; Drug Prescriptions; Drug Utilization; Feasibility Studies; France; Heroin Dependence; Humans; Long-Term Care; Narcotics; National Health Programs; Opioid-Related Disorders; Primary Health Care; Substance Abuse, Intravenous

While opioid dependence has more treatment agents available than other abused drugs, none are curative. They can, however, markedly diminish withdrawal symptoms and craving, and block opioid effects due to lapses. The most effective withdrawal method is substituting and tapering methadone or buprenorphine. alpha-2 Adrenergic agents can ameliorate untreated symptoms or substitute for agonists if not available. Shortening withdrawal by precipitating it with narcotic antagonists has been studied, but the methods are plagued by safety issues or persisting symptoms. Neither the withdrawal agents nor the methods are associated with better long-term outcome, which appears mostly related to post-detoxification treatment. Excluding those with short-term habits, the best outcome occurs with long-term maintenance on methadone or buprenorphine accompanied by appropriate psychosocial interventions. Those with strong external motivation may do well on the antagonist naltrexone. Currently, optimum duration of maintenance on either is unclear. Better agents are needed to impact the brain changes related to addiction.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Humans; Inactivation, Metabolic; Methadone; Naloxone; Opioid-Related Disorders; Substance Withdrawal Syndrome

This literature review synthesizes and appraises evidence on the pharmaco-economic value of community maintenance for opiate dependence. Included studies enrolled opiate-dependent subjects aged 18 years or over participating in a community maintenance programme. Cost-effectiveness/cost-utility analyses provided some evidence supporting the value of methadone maintenance in combination with psychosocial services and of heroin co-prescription. Evidence on the pharmaco-economic profile of maintenance with buprenorphine as compared with methadone is mixed. Few studies carried out an economic evaluation alongside a randomised controlled trial and studies adopting a modelling approach suffered from problems with the quality and validity of parameter estimates. Studies were also limited in the range of costs and consequences considered. The cost-benefit literature showed positive net benefits from community maintenance programmes. A longer length of stay of subjects in methadone maintenance was associated with greater reductions in criminal activity. However, measurement of benefits was limited to savings from reduced crime rates. Health benefits were rarely considered. Cost-benefit studies based on a before-and-after comparison were not able to consider the impact of treatment on mortality of opiate-dependent subjects. There is a need for better-designed economic evaluations that examine whether treatment benefits exceed costs, in terms of both financial benefits and health gain.

Topics: Buprenorphine; Community Mental Health Services; Cost-Benefit Analysis; Evaluation Studies as Topic; Health Status; Humans; Methadone; Narcotics; Opioid-Related Disorders

This review summarizes current research on the management of opioid withdrawal and considers the selection of the approach in different situations.. The recent publication of three controlled trials makes firm conclusions about the relative effectiveness of newer approaches (antagonist-induced withdrawal under anaesthesia or with minimal sedation; buprenorphine) to the management of opioid withdrawal possible.. Antagonist-induced withdrawal under anaesthesia should not be pursued as it has an increased risk of life-threatening adverse events and has no additional benefits relative to antagonist-induced withdrawal under minimal sedation. Antagonist-induced withdrawal with minimal sedation is feasible and may be suitable for those who intend to enter antagonist-maintenance treatment with a clear commitment to abstinence and good support. Buprenorphine is suitable for quick withdrawal, supports transition to naltrexone maintenance treatment, is safe and effective in outpatient settings and can be extended into maintenance treatment if the detoxification attempt is unsuccessful. Adrenergic agonists (clonidine and lofexidine) remain an effective option for those who do not want to use an opioid and do not intend to transfer to naltrexone maintenance treatment, with lofexidine being preferable for outpatient settings. Through appropriate choice of approach, detoxification can be a gateway to multiple, long-term treatment options.

Topics: Adrenergic Agonists; Analgesics, Opioid; Anesthesia; Buprenorphine; Humans; Narcotic Antagonists; Opioid-Related Disorders; Substance Withdrawal Syndrome

Managed withdrawal is a necessary step prior to drug-free treatment. It may also represent the end point of maintenance treatment.. To assess the effectiveness of interventions involving the use of buprenorphine to manage opioid withdrawal, for withdrawal signs and symptoms, completion of withdrawal and adverse effects.. We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library, including the Cochrane Drugs and Alcohol Group trials register, Issue 3, 2005), MEDLINE (January 1966 to August 2005), EMBASE (January 1985 to August 2005), PsycINFO (1967 to August 2005), CINAHL(1982 to July 2005) and reference lists of articles.. Experimental interventions involved the use of buprenorphine to modify the signs and symptoms of withdrawal in participants who were primarily opioid dependent. Comparison interventions involved reducing doses of methadone, alpha2 adrenergic agonists, symptomatic medications or placebo, or different buprenorphine-based regimes.. One reviewer assessed studies for inclusion and methodological quality, and undertook data extraction. Inclusion decisions and the overall process was confirmed by consultation between all three reviewers.. Eighteen studies (14 randomised controlled trials), involving 1356 participants, were included. Ten studies compared buprenorphine with clonidine; four compared buprenorphine with methadone; one compared buprenorphine with oxazepam; three compared different rates of buprenorphine dose reduction; two compared different starting doses of buprenorphine. (Two studies included more than one comparison.)Relative to clonidine, buprenorphine is more effective in ameliorating the symptoms of withdrawal, patients treated with buprenorphine stay in treatment for longer, particularly in an outpatient setting (SMD 0.82, 95% CI 0.57 to 1.06, P < 0.001), and are more likely to complete withdrawal treatment (RR 1.73, 95% CI 1.21 to 2.47, P = 0.003). At the same time there is no significant difference in the incidence of adverse effects, but drop-out due to adverse effects may be more likely with clonidine. Severity of withdrawal is similar for withdrawal managed with buprenorphine and withdrawal managed with methadone, but withdrawal symptoms may resolve more quickly with buprenorphine. There is a trend towards completion of withdrawal treatment being more likely with buprenorphine relative to methadone (RR 1.30, 95% CI 0.97 to 1.73, P = 0.08).. Buprenorphine is more effective than clonidine for the management of opioid withdrawal. There appears to be no significant difference between buprenorphine and methadone in terms of completion of treatment, but withdrawal symptoms may resolve more quickly with buprenorphine.

Topics: Acute Disease; Buprenorphine; Clonidine; Humans; Narcotic Antagonists; Opioid-Related Disorders; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome

Historically, China has had extraordinarily high rates of opiate dependence. These rates declined drastically following the 1949 revolution; however, opiate abuse has re-emerged in the late 1980's and has spread quickly since then.. To describe the current situation of opiate addiction and treatments in China and make some suggestions.. A descriptive study based on literature searched from Medline and the China National Knowledge Infrastructure database (1996 to 2004) and hand-picked references.. The number of registered addicts in 2004 was 1.14 million (more than 75% of them heroin addicts), but the actual number is probably far higher. Opiate abuse contributes substantially to the spread of HIV/AIDS in China, with intravenous drug use the most prevalent route of transmission (51.2%). Currently, the main treatments for opiate dependence in China include short-term detoxification with opiate agonists or non-opiate agents, such as clonidine or lofexidine; Chinese herbal medicine and traditional non-medication treatments are also used. Methadone maintenance treatment (MMT) has not been officially approved by the Chinese government for widespread implementation, but some pilot studies are currently underway.. China faces substantial drug abuse problems that appear to be worsening with time. Opiate dependence is a major threat to the public health and social security of China because of its devastating medical effects, its impact on risk for HIV/AIDS and criminal behaviors, low rates of recovery and high rates of relapse. There is an urgent need to implement MMT and other modern treatments for opiate dependence more widely in China.

Topics: Buprenorphine; China; Clonidine; Drugs, Chinese Herbal; HIV Infections; Humans; Methadone; Naltrexone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Substance Abuse, Intravenous; Substance Withdrawal Syndrome; Sympatholytics

Legislation has enabled physicians to treat opioid-dependent patients with an office-based maintenance program using buprenorphine, a partial mu-opioid receptor agonist. Clinical studies indicate buprenorphine effectively manages opioid addiction. Buprenorphine is more effective than placebo for managing opioid addiction but may not be superior to methadone if high doses are needed. It is comparable to lower doses of methadone, however. Treatment phases include induction, stabilization, and maintenance. Buprenorphine therapy should be initiated at the onset of withdrawal symptoms and adjusted to address withdrawal symptoms and cravings. Advantages of buprenorphine include low abuse potential and high availability for office use. Disadvantages include high cost and possible lack of effectiveness in patients who require high methadone doses. Most family physicians are required to complete eight hours of training before they can prescribe buprenorphine for opioid addiction.

Topics: Ambulatory Care; Buprenorphine; Drug Prescriptions; Humans; Narcotic Antagonists; Opioid-Related Disorders; Treatment Outcome; United States

Injection drug use is a common risk factor for HIV infection, and opioid use and dependence is the underlying condition that often fuels HIV risk behaviour and subsequent HIV seroconversion among injection drug users (IDUs). Treatment of opioid dependence often requires continued opioid administration in the form of substitution therapy, which means that opioid-using IDUs often continue receiving opioids even after cessation of illicit drug use. The concurrent use of both antiretrovirals and opioids in HIV-positive individuals is thus common. This review was undertaken to summarise current knowledge on the interactions between the opioids and antiretrovirals and to make recommendations on the treatment of HIV-positive opioid-dependent patients.

Topics: Animals; Anti-HIV Agents; Buprenorphine; Drug Interactions; Humans; Methadone; Methadyl Acetate; Narcotic Antagonists; Narcotics; Opioid-Related Disorders

Although the synthetic opioid buprenorphine has been available clinically for almost 30 years, its use has only recently become much more widespread for the treatment of opioid addiction. The pharmacodynamic and pharmacokinetic profiles of buprenorphine make it unique in the armamentarium of drugs for the treatment of opioid addiction. Buprenorphine has partial mu-opioid receptor agonist activity and is a kappa-opioid receptor antagonist; hence, it can substitute for other micro-opioid receptor agonists, yet is less apt to produce overdose reactions or dysphoria. On the other hand, buprenorphine can block the effects of opioids such as heroin (diamorphine) and morphine, and can even precipitate withdrawal in individuals physically dependent upon these drugs. Buprenorphine has significant sublingual bioavailability and a long half-life, making administration on a less than daily basis possible. Furthermore, its discontinuation is associated with only a mild withdrawal syndrome. Clinical trials have demonstrated that sublingual buprenorphine is effective in both maintenance therapy and detoxification of individuals addicted to opioids. The introduction of a sublingual formulation combining naloxone with buprenorphine further reduces the risk of diversion to illicit intravenous use. Because of its relative safety and lower risk of illegal diversion, buprenorphine has been made available in several countries for treating opioid addiction in the private office setting, greatly enhancing treatment options for this condition.

Topics: Animals; Buprenorphine; Drug and Narcotic Control; Drug Therapy, Combination; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders

To provide an overview of published studies on agonist maintenance treatment options for opioid-dependent patients.. The recent publication of controlled trials confirms earlier clinical evidence of the efficacy of diamorphine (heroin) in the treatment of opioid dependence. Findings show not only efficacy with respect to improvement of health, reduction of illicit drug use, reduction of criminality and stabilization of social conditions, but also cost effectiveness in the treatment of chronic treatment-resistant heroin addicts.. Agonist maintenance treatment has become the first-line treatment for chronic opioid dependence. High-quality studies demonstrate the effectiveness of a growing number of different agonist maintenance treatments for opioid dependence such as methadone and buprenorphine. In addition, there is new evidence for the effectiveness of other agonists, mainly slow-release morphine, intravenous and inhalable diamorphine and possibly oral diamorphine. Maintenance treatment with intravenous or inhalable diamorphine should be implemented into the healthcare system to treat a group of severely dependent treatment-resistant patients. Furthermore, the opioid-dependent patients not under treatment need to be engaged in maintenance treatments through other harm reduction measures. Agonist maintenance treatment is very effective in stabilizing the health condition and social situation, while also reducing harm, thereby increasing life expectancy and quality of life.

Topics: Buprenorphine; Controlled Clinical Trials as Topic; Delayed-Action Preparations; Heroin; Humans; Methadone; Morphine; Narcotics; Opioid-Related Disorders; Quality of Life

Injecting drug use is a common mode of transmission among persons with HIV/AIDS. Many HIV-infected patients meet diagnostic criteria for opioid dependence, a chronic and relapsing brain disorder. Most HIV providers, however, receive little training in substance use disorders. Opioid agonist therapy (OAT) has a stabilizing effect on opioid-dependent patients and is associated with greater acceptance of antiretroviral (ARV) therapy, higher ARV adherence, and greater engagement in HIV-related health care. Although methadone maintenance has been the OAT gold standard, methadone is available for the treatment of opioid dependence only in strictly regulated narcotic treatment programs. Buprenorphine, a partial opioid agonist approved for the office-based treatment of opioid dependence in 2002, may result in better health and substance use treatment outcomes for patients with HIV disease.

Topics: Anti-HIV Agents; Buprenorphine; HIV Infections; Humans; Methadone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Primary Health Care; Substance Abuse, Intravenous

Drug abuse and infection with human immunodeficiency virus (HIV) are associated with high rates of morbidity and mortality, but, because of medical, social, and legal factors, opiate addiction/dependence is a major obstacle to successful treatment of disease--for example, treatment of acquired immunodeficiency syndrome (AIDS) with highly active antiretroviral therapy. In an effort to improve the opportunity for treatment of drug abuse and HIV infection, the Forum for Collaborative HIV Research, in collaboration with the Substance Abuse and Mental Health Services Administration, the National Institute on Drug Abuse, the Centers for Disease Control and Prevention, and other agencies, presented a workshop entitled "Buprenorphine in the Primary HIV Care Setting." Participants reviewed and discussed current issues, such as the introduction of and sources for the provision of buprenorphine in HIV primary care settings and strategies for integrating treatment of HIV-infected drug abusers, all of which are covered in this supplement.

Topics: Antiretroviral Therapy, Highly Active; Buprenorphine; Delivery of Health Care, Integrated; Female; Follow-Up Studies; Health Services Research; HIV Infections; Humans; Incidence; Male; Narcotic Antagonists; Opioid-Related Disorders; Primary Health Care; Primary Prevention; Risk Assessment; Survival Analysis; Treatment Outcome; United States

Opioid dependence is a chronic and relapsing medical disorder with a well-established neurobiological basis. Opioid agonist treatments, such as methadone and the recently approved buprenorphine, stabilize opioid receptors and the intracellular processes that lead to opioid withdrawal and craving. Both methadone and buprenorphine have been proven effective for the treatment of opioid dependence and can contribute to a decreased risk of human immunodeficiency virus (HIV) transmission. In addition, a buprenorphine/naloxone combination appears to have a decreased potential for abuse or diversion, compared with that associated with methadone. Largely because of these properties, recent legislation now affords an unprecedented opportunity for general physicians to offer opioid agonist treatment through their offices. This review focuses on the neurobiological basis of opioid dependence, the rationale for methadone and buprenorphine treatments, and issues in prescribing these medications to patients with HIV infection.

Topics: Buprenorphine; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Female; Humans; Male; Methadone; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Prognosis; Risk Assessment; Substance Abuse Detection; Substance Withdrawal Syndrome; Treatment Outcome

Untreated opioid dependence is a major obstacle to the successful treatment and prevention of human immunodeficiency virus (HIV) infection. In this review, we examine the interwoven epidemics of HIV infection and opioid dependence and the emerging role of buprenorphine in improving HIV treatment outcomes among infected individuals, as well as its role in primary and secondary prevention. This article addresses some of the emerging issues about integrating buprenorphine treatment into HIV clinical care settings and the various strategies that must be considered. Specifically, it addresses the role of buprenorphine in improving HIV treatment outcomes through engagement in care, access to antiretroviral therapy and preventive therapies for opportunistic infections, and the potential benefits of and pitfalls in integrating buprenorphine into HIV clinical care settings. We discuss the key research questions regarding buprenorphine in the area of improving HIV treatment outcomes and prevention, including a review of published studies of buprenorphine and antiretroviral treatment and currently ongoing studies, and provide insight into and models for integrating buprenorphine into HIV clinical care settings. Dialogue among practitioners and policy makers in the HIV care and substance abuse communities will facilitate an effective expansion of buprenorphine and ensure that these beneficial outcomes are achieved.

Topics: Buprenorphine; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; HIV Infections; Humans; Incidence; Male; Narcotic Antagonists; Opioid-Related Disorders; Risk Assessment; Severity of Illness Index; Substance Abuse Detection; Substance Abuse Treatment Centers; Survival Analysis; Treatment Outcome; United States

The Centers for Disease Control and Prevention's HIV Prevention Strategic Plan Through 2005 advocated for increasing the proportion of persons with human immunodeficiency virus (HIV) infection and in need of substance abuse treatment who are successfully linked to services for these 2 conditions. There is evidence that integrating care for HIV infection and substance abuse optimizes outcomes for patients with both disorders. Buprenorphine, a recently approved medication for the treatment of opioid dependence in physicians' offices, provides the opportunity to integrate the treatment of HIV infection and substance abuse in one clinical setting, yet little information exists on the models of care that will most successfully facilitate this integration. To promote the uptake of this type of integrated care, the current review provides a description of 4 recently implemented models for combining buprenorphine treatment with HIV primary care: (1) an on-site addiction/HIV specialist treatment model; (2) a HIV primary care physician model; (3) a nonphysician health professional model; and (4) a community outreach model.

Topics: Antiretroviral Therapy, Highly Active; Buprenorphine; Centers for Disease Control and Prevention, U.S.; Delivery of Health Care, Integrated; Female; Health Resources; Health Services Needs and Demand; HIV Infections; Humans; Male; Methadone; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Patient Selection; Primary Health Care; Program Evaluation; Risk Assessment; Substance Abuse Treatment Centers; United States

Buprenorphine is used for the treatment of opioid dependence. As the number of persons receiving buprenorphine treatment and antiretroviral therapy continues to grow, so too does the existence and clinical impact of drug interactions between buprenorphine and medications for treating human immunodeficiency virus (HIV) infection. Awareness that such interactions exist may deter some patients and physicians from initiating potentially lifesaving therapy or lead to complications among patients whose treatment is already under way. Complications include nonadherence to antiretroviral therapy and the development of viral resistance. Illicit drug use is a frequent consequence of adverse drug effects experienced by injection drug users. The occurrence of unrecognized drug interactions can lead to unsuccessful therapy for HIV infection and the treatment of substance dependence. The present review is organized to provide a working background of buprenorphine pharmacology. Review of the current state of knowledge regarding specific interactions between buprenorphine and antiretrovirals is followed by a review of the clinical applicability of these interactions.

Topics: Animals; Anti-Retroviral Agents; Buprenorphine; Clinical Trials as Topic; Drug Interactions; Drug Resistance, Viral; Female; HIV Infections; Humans; In Vitro Techniques; Male; Narcotic Antagonists; Opioid-Related Disorders; Risk Factors; Sensitivity and Specificity; Treatment Refusal

Treatment for substance abuse and human immunodeficiency virus (HIV) infection historically have come from different providers, often in separate locations, and have been reimbursed through separate funding streams. We describe policy and financing challenges faced by health care providers seeking to integrate buprenorphine, a new treatment for opioid dependence, into HIV primary care. Regulatory challenges include licensing and training restrictions imposed by the Drug Addiction Treatment Act of 2000 and confidentiality regulations for alcohol and drug treatment records. Potential responses include the development of local training programs and electronic medical records. Addressing the complexity of funding sources for integrated care will require administrative support, up-front investments, and federal and state leadership. A policy and financing research agenda should address evidence gaps in the rationales for regulatory restrictions and should include cost-effectiveness studies that quantify the "value for money" of investments in integrated care to improve health outcomes for HIV-infected patients with opioid dependence.

Topics: Antiretroviral Therapy, Highly Active; Buprenorphine; Delivery of Health Care, Integrated; Female; Financing, Government; Health Care Costs; Health Policy; Health Resources; HIV Infections; Humans; Insurance, Health, Reimbursement; Male; Narcotic Antagonists; Opioid-Related Disorders; Primary Health Care; Quality of Health Care; United States

Opiate dependence is a major health and social issue in many countries. A mainstay of therapy has been methadone maintenance treatment, but other treatments, particularly buprenorphine, are increasingly being considered.. To conduct a systematic review to synthesise and critically appraise the evidence on the effectiveness of community maintenance programmes with methadone or buprenorphine in treating opiate dependence.. A systematic review of databases, journals and the grey literature was carried out from 1990-2002. Inclusion criteria were: community-based, randomised controlled trials of methadone and/or buprenorphine for opiate dependence involving subjects who were aged 18 years old or over.. Trials were set in a range of countries, employed a variety of comparators, and suffered from a number of biases. The evidence indicated that higher doses of methadone and buprenorphine are associated with better treatment outcomes. Low-dose methadone (20 mg per day) is less effective than buprenorphine (2-8 mg per day). Higher doses of methadone (>50-65 mg per day) are slightly more effective than buprenorphine (2-8 mg per day). There was some evidence that primary care could be an effective setting to provide this treatment, but such evidence was sparse.. The literature supports the effectiveness of substitute prescribing with methadone or buprenorphine in treating opiate dependence. Evidence is also emerging that the provision of methadone or buprenorphine by primary care physicians is feasible and may be effective.

Topics: Adolescent; Adult; Aged; Buprenorphine; Community Health Services; Humans; Methadone; Middle Aged; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Primary Health Care; Randomized Controlled Trials as Topic

To summarize the major findings of the five Cochrane reviews on substitution maintenance treatments for opioid dependence.. We conducted a narrative and quantitative summary of systematic review findings. There were 52 studies included in the original reviews (12,075 participants, range 577-5894): methadone maintenance treatment (MMT) was compared with methadone detoxification treatment (MDT), no treatment, different dosages of MMT, buprenorphine maintenance treatment (BMT), heroin maintenance treatment (HMT), and l-alpha-acetylmethadol (LAAM) maintenance treatment (LMT).. Outcomes considered were retention in treatment, use of heroin and other drugs during treatment, mortality, criminal activity, and quality of life.. Retention in treatment: MMT is more effective than MDT, no treatment, BMT, LMT, and heroin plus methadone. MMT proved to be less effective than injected heroin alone. High doses of methadone are more effective than medium and low doses. Use of heroin: MMT is more effective than waiting list, less effective than LAAM, and not different from injected heroin. No significant results were available for mortality and criminal activity.. These findings confirm that MMT at appropriate doses is the most effective in retaining patients in treatment and suppressing heroin use but show weak evidence of effectiveness toward other relevant outcomes. Future clinical trials should collect data on a broad range of health outcomes and recruit participants from heterogeneous practice settings and social contexts to increase generalizability of results.

Topics: Buprenorphine; Humans; Information Dissemination; Methadone; Narcotic Antagonists; Opioid-Related Disorders; Research; Substance Abuse Treatment Centers

Buprenorphine has been in clinical use in anaesthesia for several decades. Recently, the high-dose sublingual formulation (Subutex, Reckitt Benckiser, Slough, U.K.) has been increasingly used as maintenance therapy in opioid dependence, as an alternative to methadone and other pharmacological therapies. Buprenorphine has unique pharmacological properties making it well suited for use as a maintenance therapy in opioid dependence. However, these same properties may cause difficulty in the perioperative management of pain. Buprenorphine is a partial opioid agonist, attenuating the effects of supplemental illicit or therapeutic opioid agonists. As a result of its high receptor affinity, supplemental opioids do not readily displace buprenorphine from the opioid receptor in standard doses. High-dose buprenorphine has an extended duration of action that prolongs both of these effects. The perioperative management of patients stabilized on high-dose buprenorphine and undergoing surgery requires consideration of the likely analgesic requirements. Where possible the buprenorphine should be continued. Pain management should focus on maximizing non-opioid analgesia, local anaesthesia and non-pharmacological techniques. Where pain may not be adequately relieved by these methods, the addition of a full opioid agonist such as fentanyl or morphine at appropriate doses should be considered, accompanied by close monitoring in a high dependency unit. In situations where this regimen is unlikely to be effective, preoperative conversion to morphine or methadone may be an option. Where available, liaison with a hospital-based alcohol and drug service should always be considered.

Topics: Analgesia; Analgesics, Opioid; Biological Availability; Buprenorphine; Drug Interactions; Half-Life; Humans; Hyperalgesia; Intraoperative Period; Opioid-Related Disorders; Perioperative Care; Tissue Distribution

Buprenorphine is a semi-synthetic opioid derived from thebaine, a naturally occurring alkaloid of the opium poppy, Papaver somniferum. The pharmacology of buprenorphine is unique in that it is a partial agonist at the opioid mu receptor. Buprenorphine undergoes extensive first-pass metabolism and therefore has very low oral bioavailability; however, its bioavailability sublingually is extensive enough to make this a feasible route of administration for the treatment of opioid dependence. The mean time to maximum plasma concentration following sublingual administration is variable, ranging from 40 minutes to 3.5 hours. Buprenorphine has a large volume of distribution and is highly protein bound (96%). It is extensively metabolised by N-dealkylation to norbuprenorphine primarily through cytochrome P450 (CYP) 3A4. The terminal elimination half-life of buprenorphine is long and there is considerable variation in reported values (mean values ranging from 3 to 44 hours). Most of a dose of buprenorphine is eliminated in the faeces, with approximately 10-30% excreted in urine. Naloxone has been added to a sublingual formulation of buprenorphine to reduce the abuse liability of the product. The presence of naloxone does not appear to influence the pharmacokinetics of buprenorphine. Buprenorphine crosses the placenta during pregnancy and also crosses into breast milk. Buprenorphine dosage does not need to be significantly adjusted in patients with renal impairment; however, since CYP3A activity may be decreased in patients with severe chronic liver disease, it is possible that the metabolism of buprenorphine will be altered in these patients. Although there is limited evidence in the literature to date, drugs that are known to inhibit or induce CYP3A4 have the potential to diminish or enhance buprenorphine N-dealkylation. It appears that the interaction between buprenorphine and benzodiazepines is more likely to be a pharmacodynamic (additive or synergistic) than a pharmacokinetic interaction. The relationship between buprenorphine plasma concentration and response in the treatment of opioid dependence has not been well studied. The pharmacokinetic and pharmacodynamic properties of buprenorphine allow it to be a feasible option for substitution therapy in the treatment of opioid dependence.

Topics: Biological Availability; Buprenorphine; Humans; Metabolic Clearance Rate; Opioid-Related Disorders

In 1989, the National Institute on Drug Abuse (NIDA) established its Medications Development Program. This program has concentrated on developing pharmacotherapies for opiate and cocaine dependence and, more recently, for methamphetamine and cannabis dependence. The major goals of this program are to optimize existing treatments and to expand treatment options for physicians and patients. This review will concentrate on the development of pharmacotherapies for the following substance abuse disorders: opiate, cocaine, methamphetamine, and cannabis dependence. Left untreated, opiate and stimulant dependence are responsible for significant morbidity and mortality. For example, use of illicit opiates is associated with an increased risk of hepatitis C infection, HIV infection, and other medical consequences, e.g., an overdose. The NIDA Medications Development Program has had success in developing, with pharmaceutical partners, levomethadyl acetate, buprenorphine, and buprenorphine/naloxone for opiate dependence. Moreover, several marketed medications have shown promise in reducing cocaine use. Of interest, these medications likely operate through diverse neurochemical mechanisms, suggesting that combination therapy may be a rational next step that could increase treatment gains further in cocaine-dependent patients. The Medications Development Program has also identified multiple neuronal mechanisms that are altered by chronic administration of drugs of abuse. Advances in neuroscience have identified changes in conditioned cueing, drug priming, stress-induced increases in drug intake, and reduced frontal inhibitory mechanisms as all being possible for the development of, maintenance of, and possible relapse to, addiction. Potential medications that modulate these mechanisms are highlighted.

Topics: Animals; Buprenorphine; Chemistry, Pharmaceutical; Clinical Trials as Topic; Cocaine-Related Disorders; Dopamine; Drug Design; Drug Industry; Drug Therapy, Combination; Humans; Methadyl Acetate; Naloxone; National Institutes of Health (U.S.); Opioid-Related Disorders; Program Development; Secondary Prevention; Substance-Related Disorders; United States

It appears that the literature on agonist maintenance therapies for opioid dependence pays more attention to outcomes during, rather than after, treatment. This review aims to (a) estimate to what extent opioid abstinence can be expected from former maintenance patients, (b) examine possible relationships between patient and treatment characteristics and abstinence rates and (c) assess the need for research in the field of abstinence-orientated maintenance treatment in general, and time-limited buprenorphine maintenance treatment in particular. Database searches supplemented by cross-references resulted in 12 studies included in the review. The studies were mostly naturalistic follow-up studies of former methadone maintenance patients, authored by US researchers in the 1970s. Buprenorphine was used in only one of the studies, and then as a transition between methadone and abstinence. There were considerable variations in definition and assessment of abstinence. Pooled abstinence rates ranged from 22% to 86%. The single factor associated most frequently with abstinence was voluntary participation in detoxification programmes with eligibility criteria ('therapeutic detoxification'). When 'therapeutic detoxification' was compared to 'non-therapeutic detoxification' the pooled abstinence rates were 48% and 22%, respectively. Abstinence-orientated maintenance therapy may be suitable for a subgroup of patients, but there is a substantial need for research updates.

Topics: Buprenorphine; Humans; Inactivation, Metabolic; Methadone; Narcotic Antagonists; Opioid-Related Disorders; Time Factors; Treatment Outcome

The Drug Addiction Treatment Act of 2000 (DATA 2000) was established to create a new paradigm for medication-assisted treatment of opiate addiction in the United States. Before enactment of DATA 2000, the use of opioid medications to treat opioid addiction was permissible only in federally approved treatment programs, ie, methadone clinics. The only medications permitted were Schedule II drugs (eg, methadone and l-a-acetylmethadol [LAAM]), which could only be dispensed, not prescribed. Under provisions of DATA 2000, qualified physicians in a medical office and other appropriate settings outside the opioid treatment program system may prescribe or dispense (or both), Schedule III, IV, and V opioid medications for treatment of opioid addiction if such medications have been specifically approved by the the US Food and Drug Administration for that indication. Opioid addiction treatment programs were commonly known as methadone clinics. They now may also dispense buprenorphine hydrochloride and the buprenorphine hydrochloride-naloxone combination. The information in this article is extracted (with revision) from: Center for Substance Abuse Treatment. Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. Treatment Improvement Protocol (TIP) Series 40. DHS Publication No. (SMA) 04-3939. Rockville, Md: Substance Abuse and Mental Health Services Administration; 2004. The Clinical Guidelines document is in the public domain except for material indicated as reprinted from a copyrighted source. The author served on both the Expert Panel and the Consensus Panel that produced the guidelines, available in portable document format at http://buprenorphine.samhsa.gov/Bup%20Guidelines.pdf.

Topics: Buprenorphine; Humans; Narcotic Antagonists; Office Visits; Opioid-Related Disorders; United States

Pharmacotherapy for substance abuse is a rapidly evolving field comprising both old and new effective treatments for substance use. Opiate agonist therapy has been shown to diminish and often eliminate opiate use. This behavior change has resulted in the reduced transmission of many infections, including HIV, hepatitis C virus (HCV), and an enhanced quality of life. For the past 35 years, the provision of opioid agonist therapy has been limited to opioid treatment programmes. Opioid treatment programmes treat approximately 200,000 of the estimated million opiate-addicted individuals in the United States. With the need to increase the number of treatment opportunities available for opioid-dependent patients, Congress passed the Drug Addiction Treatment Act of 2000, which allows for the treatment of opioid dependence using buprenorphine by a properly licensed physician, including HIV primary care physicians. The integration of buprenorphine treatment for opioid addiction into HIV primary care thus provides a new treatment paradigm to address substance abuse in patients with HIV and HCV infections.

Topics: Buprenorphine; Delivery of Health Care, Integrated; Hepatitis C; HIV Infections; Humans; Narcotic Antagonists; Opioid-Related Disorders; Primary Health Care; Substance Abuse Treatment Centers; United States

New federal regulations allow for office-based treatment of opioid dependent patients with opioid agonist medication (e.g., buprenorphine). We sought to evaluate the literature on office-based physicians' acceptance of this practice.. We searched the MEDLINE database for original research examining office-based providers' acceptance or satisfaction with office-based treatment. Articles included in the analysis met the following criteria: (1) discussed the treatment of patients with substance abuse disorders, (2) focused on the treatment of opioid dependent patients, (3) discussed treatment with opioid agonist therapy, (4) discussed treatment by office-based physicians, (5) presented original research, and (6) provided data examining physician acceptance or satisfaction.. Eight studies met the criteria. Their heterogeneity precluded aggregate analysis. Four of 8 studies revealed that providers had a positive perception concerning the efficacy of opioid agonist treatment, 4/8 indicated that providers believed that opioid dependent patients were more complex than others in their practices, and 3/8 studies indicated the need for additional support services.. There are few studies of provider satisfaction with office-based treatment of opioid dependence. This literature reveals overall provider acceptance of this practice but highlights the need for support services. Further research, designed to identify the barriers to provider satisfaction with office-based opioid agonist therapy, is needed to ensure that these barriers do not limit expansion of this practice.

Topics: Ambulatory Care; Attitude of Health Personnel; Buprenorphine; Cooperative Behavior; Humans; Methadone; Narcotics; Opioid-Related Disorders; Patient Care Team; Physician-Patient Relations; Physicians, Family

Buprenorphine is a new and attractive medication option for many opioid-addicted adults and their physicians. Before initiating buprenorphine treatment, providers must be aware of such critical factors as how the medication works, its efficacy and safety profile, how it is used in opioid withdrawal as well as maintenance treatment, and how patients can best be selected, educated about buprenorphine, and monitored throughout treatment. This article reviews these important issues as well as requirements for physician and staff training and needs for additional research on this unique medication.

Topics: Buprenorphine; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Interactions; Education, Continuing; Health Services Accessibility; Humans; Methadone; Naloxone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Patient Education as Topic; Patient Selection

Almost 3 million Americans have abused heroin. The most effective treatment for this concerning epidemic is opioid replacement therapy. Although, from a historical perspective, acceptance of this therapy has been slow, growing evidence supports its efficacy. There are 3 approved medications for opioid maintenance therapy: methadone hydrochloride, levomethadyl acetate, and buprenorphine hydrochloride. Each has unique characteristics that determine its suitability for an individual patient. Cardiac arrhythmias have been reported with methadone and levomethadyl, but not with buprenorphine. Due to concerns about cardiac risk, levomethadyl use has declined and the product may ultimately be discontinued. These recent safety concerns, specifics about opioid detoxification and maintenance, and new federal initiatives were studied. Opioid detoxification has a role in both preventing acute withdrawal and maintaining long-term abstinence. Although only a minority of eligible patients are engaged in treatment, opioid maintenance therapy appears to offer the greatest public health benefits. There is growing interest in expanding treatment into primary care, allowing opioid addiction to be managed like other chronic illnesses. This model has gained wide acceptance in Europe and is now being implemented in the United States. The recent Drug Addiction Treatment Act enables qualified physicians to treat opioid-dependent patients with buprenorphine in an office-based setting. Mainstreaming opioid addiction treatment has many advantages; its success will depend on resolution of ethical and delivery system issues as well as improved and expanded training of physicians in addiction medicine.

Topics: Analgesics, Opioid; Arrhythmias, Cardiac; Buprenorphine; Europe; Humans; Methadone; Methadyl Acetate; Opioid-Related Disorders; Prevalence; Primary Health Care; Substance Withdrawal Syndrome; United States

To provide an overview of 5 Cochrane reviews of different approaches for treating opioid withdrawal.. Narrative and quantitative summary of review findings.. There were 46 studies included in the original reviews with a total of 3350 participants (range 18-300).. The 5 reviews considered 46 studies covering seven different comparisons, the major ones being methadone compared with alpha2-adrenergic agonists and other opioid agonists, different alpha2-adrenergic agonists compared with each other and to antagonist-induced withdrawal and buprenorphine.. The outcomes considered were signs and symptoms of withdrawal, retention in treatment, completion rate, relapse rate and side effects.. Methadone detoxification results in higher retention in treatment, lower relapse rate and fewer side effects when compared with adrenergic agonists. No difference was observed when comparing different adrenergic agonists; buprenorphine appears to have an advantage over adrenergic agonists on withdrawal symptoms and side effects.. Despite the considerable number of trials that have been carried out on this topic, they are very heterogeneous as far as the comparisons and outcomes considered. This prevented many of them from being incorporated into a quantitative meta-analysis. Consensus in measurements and results should be reached among researchers involved in the evaluation of the effectiveness of treatments for opiate addiction in order to produce consistent outcomes in the measuring and reporting of results from clinical trials.

Topics: Adrenergic alpha-Agonists; Antidepressive Agents, Tricyclic; Buprenorphine; Humans; Methadone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Reproducibility of Results; Review Literature as Topic; Secondary Prevention; Substance Withdrawal Syndrome; Time Factors; Treatment Outcome

Buprenorphine has become of increasing interest to be an alternative to methadone in the treatment of heroin addicts. The aim of the paper is to review, from a clinical perspective, the current status of what is known about the pharmacology of buprenorphine, with a particular emphasis on the issues of maintenance therapy in heroin addiction. A systematic review of published follow-up data, from observational and experimental studies was done. Electronic databases Medline and PSYNDEXplus were searched from their earliest entries. Buprenorphine appears to be a well-tolerated drug, with a benign overall side effect. Buprenorphine is an additional treatment option for heroin dependent patients, especially for those who do not wish to start or continue with methadone or for those who do not seem to benefit from adequate dosages of methadone.

Topics: Animals; Buprenorphine; Clinical Trials as Topic; Female; Humans; Male; Narcotic Antagonists; Opioid-Related Disorders; Pregnancy; Substance Withdrawal Syndrome; Treatment Outcome

The recent approval of office-based treatment for opioid addiction and US Food and Drug Administration approval of buprenorphine will expand treatment options for opioid addiction. Buprenorphine is classified as a partial micro opioid agonist and a weak kappa antagonist. It has a high affinity for the micro receptor, with slow dissociation resulting in a long duration of action and an analgesic potency 25 to 40 times more potent than morphine. At higher doses, its agonist effects plateau and it begins to behave more like an antagonist, limiting the maximal analgesic effect and respiratory depression. This "ceiling effect" confers a high safety profile clinically, a low level of physical dependence, and only mild withdrawal symptoms on cessation after prolonged administration. Suboxone contains a mixture of buprenorphine and naloxone. The naloxone is poorly absorbed sublingually and is designed to discourage intravenous use. Subutex, buprenorphine only, will also be available primarily as an initial test dose. Clinicians will be using this drug for detoxification or for maintenance of opioid addiction. Patients with recent illicit opioid use may develop a mild precipitated withdrawal syndrome with the induction of buprenorphine. Acute buprenorphine intoxication may present with some diffuse mild mental status changes, mild to minimal respiratory depression, small but not pinpoint pupils, and relatively normal vital signs. Naloxone may improve respiratory depression but will have limited effect on other symptoms. Patients with significant symptoms related to buprenorphine should be admitted to the hospital for observation because symptoms will persist for 12 to 24 hours.

Topics: Buprenorphine; Drug and Narcotic Control; Drug Overdose; Emergency Medicine; Humans; Narcotic Antagonists; Opioid-Related Disorders; Pain; United States

Over the past century, a worldwide system for the control of drugs with abuse potential has developed through the adoption of a series of international treaties. The important multilateral conventions currently in force are the United Nations Single Convention on Narcotic Drugs, 1961 (Single Convention), the United Nations Convention on Psychotropic Substances, 1971 (Psychotropic Convention) and the United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances, 1988. From the beginning, the aim of these drug control treaties has been to control the abuse and trafficking of substances with abuse potential while assuring that the availability of these drugs for medical and scientific purposes is not unduly restricted. There is activity in the World Health Organization and the International Narcotics Control Board to determine whether the international control of buprenorphine, a partial mu-opioid agonist used as an analgesic and for the treatment of opioid addiction, should be changed from the Psychotropic Convention to the Single Convention. This change would result in the classification and regulation of buprenorphine as a narcotic drug rather than a psychotropic substance. Such a move is unwarranted medically and scientifically and would provoke increased controls on buprenorphine that would fundamentally disrupt the medical practice of pain management and opioid replacement therapy around the world. The negative impact of inappropriate regulatory controls when licensed medicines come under such scrutiny are described.

Topics: Analgesics, Opioid; Benzodiazepines; Buprenorphine; Drug and Narcotic Control; History, 20th Century; Humans; International Cooperation; Narcotic Antagonists; Opioid-Related Disorders; World Health Organization

This overview of the March 2003 conference on the U.S. national buprenorphine implementation program is developed to inform the practitioner about the positive experience that has been accumulated worldwide on the use of buprenorphine for office-based practice. The first paper delineates the challenges for American psychiatry in moving buprenorphine forward into general practice. Most psychiatrists are unprepared to work with opiate-dependent patients or to use buprenorphine. The international successes with office-based buprenorphine from France and Australia are presented in the next papers, followed by presentations on several U.S. studies using buprenorphine in the community for detoxification and office-based maintenance. These experiences have thus far confirmed buprenorphine's utility and promise for opiate addiction treatment in the U.S. Finally, two national monitoring programs have been implemented to assess the public health impact of this new treatment opportunity. This opportunity has a three-year window, however, and a critical need will be to attract a sufficient number of physicians into prescribing buprenorphine/naloxone in order to allow our patients increased access to this treatment.

Topics: Attitude of Health Personnel; Buprenorphine; Community Health Services; Cross-Cultural Comparison; Diffusion of Innovation; Family Practice; Heroin Dependence; Humans; Narcotic Antagonists; Narcotics; Office Visits; Opioid-Related Disorders; Product Surveillance, Postmarketing; Psychiatry; Treatment Outcome; United States

Buprenorphine has recently been reported to be an alternative to methadone and LAAM for maintenance treatment of opioid dependent individuals, differing results are reported concerning its relative effectiveness indicating the need for an integrative review.. To evaluate the effects of buprenorphine maintenance against placebo and methadone maintenance in retaining patients in treatment and in suppressing illicit drug use.. We searched the following databases up to 2001, inclusive: Cochrane Drugs and Alcohol Review Group Register, the Cochrane Controlled Trials Register, MEDLINE, EMBASE, Current Contents, Psychlit, CORK [www. state.vt.su/adap/cork], Alcohol and Drug Council of Australia (ADCA) [www.adca.org.au], Australian Drug Foundation (ADF -VIC) [www.adf.org.au], Centre for Education and Information on Drugs and Alcohol (CEIDA) [www.ceida.net.au], Australian Bibliographic Network (ABN), and Library of Congress databases, available NIDA monographs and the College on Problems of Drug Dependence Inc. proceedings, the reference lists of all identified studies and published reviews and authors of identified RCT's were asked about any other published or unpublished relevant RCT.. Randomised clinical trials of buprenorphine maintenance compared with either placebo or methadone maintenance for opioid dependence.. Reviewers evaluated the papers separately and independently, rating methodological quality of concealment of allocation; data were extracted independently for meta-analysis and double-entered.. Thirteen studies met the inclusion criteria, all were randomised clinical trials, all but one were double-blind. The method of concealment of allocation was not clearly described in 11 of the studies, otherwise methodological quality was good. Buprenorphine given in flexible doses appeared statistically significantly less effective than methadone in retaining patient in treatment (RR= 0.82; 95% CI: 0.69-0.96). Low dose buprenorphine is not superior to low dose methadone. High dose buprenorphine does not retain more patients than low dose methadone, but may suppress heroin use better. There was no advantage for high dose buprenorphine over high dose methadone in retention (RR=0.79; 95% CI:0.62-1.01), and high dose buprenorphine was inferior in suppression of heroin use. Buprenorphine was statistically significantly superior to placebo medication in retention of patients in treatment at low doses (RR=1.24; 95% CI: 1.06-1.45), high doses (RR=1.21; 95% CI: 1.02-1.44), and very high doses (RR=1.52; 95% CI: 1.23-1.88). However, only high and very high dose buprenorphine suppressed heroin use significantly above placebo.. Buprenorphine is an effective intervention for use in the maintenance treatment of heroin dependence, but it is not more effective than methadone at adequate dosages.

Topics: Buprenorphine; Humans; Methadone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Randomized Controlled Trials as Topic

Buprenorphine's physiological effects are produced when it attaches to specific opiate receptors that are designated mu, kappa, or delta. Buprenorphine, a partial agonist at the mu receptor and an antagonist at the kappa receptor, produces typical morphine-like effects at low doses. At higher doses, it produces opiate effects that are less than those of full opiate agonists. Knowledge of the physiological effects of opiate receptors and the way they interact with opiate agonists, partial opiate agonists, and opiate antagonists is fundamental to understanding the safety and efficacy of buprenorphine in treatment of pain and opiate addiction. Knowledge of the historical and social context of opiate agonist treatment of opiate dependence is fundamental to understanding how nonpharmacological factors may limit the clinical adoption and utility of a safe and effective medication in treatment of opiate dependence. This article reviews the pharmacology of sublingual buprenorphine and the historical context of opiate agonist therapy; delineates classes of opiate receptors and their interaction with opiate agonists, partial agonists, and antagonists; and describes the commercially available pharmaceutical formulations of buprenorphine. It focuses on sublingual buprenorphine tablets, Subutex and Suboxone, the FDA-approved formulations of buprenorphine for treatment of opiate dependence. Sublingual buprenorphine, and the combination of sublingual buprenorphine/naloxone, have unique pharmacological properties that make them a logical first-line intervention in the treatment of opioid dependence.

Topics: Administration, Sublingual; Buprenorphine; Drug Combinations; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Private Practice; United States

Although addiction to heroin and other opiates is a major public health issue in the United States and many other countries, advances in pharmacologic and nonpharmacologic treatment have been made. Some of these advances represent a major shift from traditional treatment philosophies, whereas others are characterized by more subtle, though important, improvements. This review discusses recent advances in opiate-addiction treatment in the context of three main domains: the use of buprenorphine and buprenorphine/naloxone in an office-based paradigm, psychosocial treatment and the addressing of medical and psychiatric comorbidity, and harm reduction strategies.

Topics: Buprenorphine; Comorbidity; Drug Therapy, Combination; Humans; Mental Disorders; Naloxone; Narcotic Antagonists; Office Visits; Opioid-Related Disorders; Psychotherapy

The federal Drug Abuse Treatment Act 2000 (DATA) opened a window of opportunity for patients with the disease of addiction by providing increased access to options for treatment. Previously, only methadone maintenance, approved for use only through specially regulated clinics, was available to treat opioid addiction. DATA allows any physician choosing to take a short specialty training course and become certified to prescribe buprenorphine. Buprenorphine and buprenorphine/ naloxone (Subutex, Suboxone) can be prescribed by certified physicians in a traditional office setting to treat patients with opioid dependence. Clinical studies indicate buprenorphine maintenance is as effective as methadone maintenance in retaining patients in substance abuse treatment and reducing illicit opioid use. Sublingual buprenorphine is more effective than clonidine or clonidine/naltrexone in short-term opioid detoxification treatment. Buprenorphine provides an additional tool to treat opioid addiction and improve the quality of lives of these patients. More physicians are needed to treat patients with addiction. DATA facilitates this by removing existing barriers and increasing access to treatment.

Topics: Biological Availability; Buprenorphine; Drug Interactions; Humans; Narcotic Antagonists; Opioid-Related Disorders; Randomized Controlled Trials as Topic

Buprenorphine and buprenorphine/naloxone (BUP) are newly approved for office-based treatment of opioid dependence. Federal and non-federal regulatory and monitoring agencies, national and international researchers, national professional organizations, researchers involved in monitoring, opioid treatment programs and the pharmaceutical industry met to synthesize and disseminate practical information to guide training, practice, monitoring, regulation and evaluation efforts with these medications. We performed a review of the literature, training curricula and practice guidelines and commissioned manuscripts describing recently completed, or still in progress, studies or field experiences with BUP treatment. A consensus process generated fifteen statements: (1) The federal government should collect baseline data on opioid-related deaths and morbidity to assess the effect of BUP on public health, (2) the patient limit for group practices should apply to individual physicians rather than group practices, (3 and 4) telephone and Internet-based physician and pharmacist support is needed, (5) clinicians who provide psychosocial services to opioid dependent patients should be informed of the role of BUP, (6) opioid-dependent patients should be instructed to present for induction in mild withdrawal, (7) the existing Center for Substance Abuse Treatment guidelines provide a reasonable induction protocol, (8) physicians should be prepared to use ancillary medications with BUP induction, (9) a physician or nurse must be available to the patient during the induction period, (10) concurrent counseling and support services are necessary, (11) detoxification without appropriate followup addiction treatment leads to rapid relapse and is not as effective as maintenance, (12) pregnant opioid-dependent women should be treated using good clinical practice including specialist addiction care and prenatal care, (13) BUP induction and withdrawal treatment may benefit from different designations for payment, (14) take-home medication options should be tailored to patients' needs, (15) there is a need for clinical and policy research in unique patient populations.

Topics: Ambulatory Care; Buprenorphine; Heroin Dependence; Humans; Narcotic Antagonists; Opioid-Related Disorders; Practice Guidelines as Topic; United States

Managed withdrawal (detoxification) is a necessary step prior to drug-free treatment. It may also represent the end point of long-term opioid replacement treatment such as methadone maintenance. The availability of managed withdrawal is essential to an effective treatment system.. To assess the effectiveness of interventions involving the use of buprenorphine to manage opioid withdrawal, in terms of withdrawal signs and symptoms, completion of withdrawal and adverse effects.. Multiple electronic databases (including Medline, Embase, PsycINFO, Australian Medical Index, Cochrane Clinical Trials Register) were systematically searched to October 2003. Reference lists of retrieved studies, reviews and conference abstracts were handsearched.. Controlled trials comparing buprenorphine with reducing doses of methadone, alpha2 adrenergic agonists, symptomatic medications or placebo, or comparing different buprenorphine-based regimes, to modify the signs and symptoms of withdrawal in participants who were primarily opioid dependent.. One reviewer assessed studies for inclusion and undertook data extraction. Inclusion decisions and the overall process were confirmed by consultation between all three reviewers. Included studies were assessed for methodological quality. Meta-analysis was undertaken where possible, with sensitivity analyses used to assess the impact of methodological quality.. Thirteen studies (10 RCTs), involving 744 participants, met the criteria for inclusion in the review. Seven studies compared buprenorphine with clonidine; 3 compared buprenorphine with methadone; 1 compared buprenorphine with oxazepam; 2 compared rapid and slow rates of tapering buprenorphine dose; 1 compared 3 different starting doses of buprenorphine. For groups treated with buprenorphine, withdrawal severity was less than that in groups treated with clonidine; peak severity was similar to those treated with methadone, but withdrawal symptoms may resolve more quickly with buprenorphine. Withdrawal is probably more severe when doses are tapered rapidly following a period of maintenance treatment. Buprenorphine is associated with fewer adverse effects than clonidine, and completion of withdrawal is significantly more likely with buprenorphine (Relative Risk 1.35, 95% confidence interval 1.13, 1.62). In the two available studies, there was no statistically significant difference in rates of completion of withdrawal for buprenorphine compared to methadone in reducing doses. Completion of withdrawal following buprenorphine maintenance treatment may be more likely when doses are reduced gradually.. Buprenorphine is more effective than clonidine for the management of opioid withdrawal. There appears to be no significant difference between buprenorphine and methadone in terms of completion of withdrawal, but withdrawal symptoms may resolve more quickly with buprenorphine. Many aspects of treatment protocol and relative effectiveness need to be investigated further in order to determine the most effective way of using buprenorphine to manage opioid withdrawal.

Topics: Acute Disease; Buprenorphine; Clonidine; Humans; Narcotic Antagonists; Opioid-Related Disorders; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome

Topics: Buprenorphine; Female; Humans; Mental Disorders; Methadone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Patient Selection; Physician's Role; Pregnancy; Pregnancy Complications; Prisoners; Psychotropic Drugs; Social Support

The practice of prescribing opioid drugs for opioid dependent patients in the U.S. has been subjected to special government scrutiny for almost 100 years. From 1920 until 1964, doctors who used opioids to treat addicts risked federal and/or state criminal prosecution. Although that period ended when oral methadone maintenance was established as legitimate medical practice, public concern about methadone diversion and accidental overdose fatalities, combined with political pressure from both hostile bureaucracies and groups committed to drug-free treatments, led to the development of unprecedented and detailed Food and Drug Administration (FDA) regulations that specified the manner in which methadone (and later, levo-alpha-acetyl methadol, or levomethadyl acetate, (LAAM)) could be provided. In 1974, Congress gave the Drug Enforcement Administration (DEA) additional oversight of methadone treatment programs. Efforts to liberalize the FDA regulations over the past 30 years have been resisted by both the DEA and existing treatment providers. Additional flexibility for clinicians may evolve from the most recent effort to create an accreditation system to replace some of the FDA regulations. The development of buprenorphine, a partial opioid agonist, as an effective treatment for opioid addiction reopened the possibility for having a less burdensome oversight process, especially because of its reduced toxicity if ingested by non-tolerant individuals. New legislation, the Drug Addiction Treatment Act (DATA) of 2000, created an opportunity for clinicians with special training to be exempted from both federal methadone regulations and the requirement to obtain a special DEA license when using buprenorphine to treat addicts. Some details of how the DATA was developed, moved through Congress, and signed into law are described.

Topics: Analgesics, Opioid; Behavior, Addictive; Buprenorphine; Humans; Methadone; Morphine; Opioid-Related Disorders; Substance Abuse Treatment Centers; United States; United States Food and Drug Administration

This paper will review clinical pharmacology studies on buprenorphine, a mixed opioid agonist-antagonist currently approved as a treatment for opioid dependence. The focus is on studies characterizing buprenorphine's pharmacodynamic actions, including its safety, abuse liability, withdrawal suppression and withdrawal precipitation capacity, physical dependence potential, cross-tolerance and duration of action as well as a review of the pharmacological profile of buprenorphine/naloxone combinations. The findings from these clinical pharmacology studies are synthesized and presented in a framework designed to (1) inform clinicians about the advantages and disadvantages of buprenorphine as an opioid maintenance agent, and (2) provide information about dosing procedures that may optimize the use of buprenorphine in the clinic.

Topics: Animals; Buprenorphine; Clinical Trials as Topic; Humans; Narcotic Antagonists; Opioid-Related Disorders; Pharmacology, Clinical

The sublingual combination tablet formulation of buprenorphine and naloxone at a fixed dose ratio of 4:1 has been shown to be as effective as the tablet formulation containing only buprenorphine in treating opiate addiction. The addition of naloxone does not affect the efficacy of buprenorphine for two reasons: (1) naloxone is poorly absorbed sublingually relative to buprenorphine and (2) the half-life for buprenorphine is much longer than for naloxone (32 vs. 1 h for naloxone). The sublingual absorption of buprenorphine is rapid and the peak plasma concentration occurs 1 h after dosing. The plasma levels for naloxone are much lower and decline much more rapidly than those for buprenorphine. Increasing dose results in increasing plasma levels of buprenorphine, although this increase is not directly dose-proportional. There is a large inter-subject variability in plasma buprenorphine levels. Due to the large individual variability in opiate dependence level and the large variability in the pharmacokinetics (PK) of buprenorphine, the effective dose or effective plasma concentration is also quite variable. Doses must be titrated to a clinically effective level for individual patients.

Topics: Administration, Sublingual; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Drug Combinations; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Tablets

Although only a partial mu-opiate agonist, buprenorphine can be abused and diverted from medical therapy to the illicit drug market. A combination of buprenorphine and naloxone for sublingual administration may discourage diversion and abuse by precipitating opiate withdrawal when taken parenterally. Because opiate-abusing populations are not homogeneous and have varying levels of opiate dependence, the efficacy of buprenorphine and naloxone in precipitating opiate withdrawal or in attenuating the pleasurable effects of buprenorphine may vary. This chapter describes the effects of sublingual and parenteral buprenorphine and naloxone combinations in several populations of opiate-dependent people. We conclude that buprenorphine and naloxone combinations should not diminish the efficacy of sublingual buprenorphine, but should have lower abuse liability than buprenorphine alone.

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Chemistry, Pharmaceutical; Clinical Trials as Topic; Drug Administration Routes; Drug Combinations; Drug Evaluation; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders

Buprenorphine has been studied extensively since 1978 when it was initially proposed as an alternative to methadone for treatment of opioid dependence. Early work by Jasinski et al., 1978; Mello and Mendelson, 1980; Mello et al., 1982; Mello et al., 1983 and Mendelson et al., 1984 and their colleagues demonstrated buprenorphine's low physical abuse potential and its ability to substitute for heroin and reduce heroin self-administration in opiate-dependent humans. The subsequent early clinical studies suggested that, in clinical settings, buprenorphine was a safe and efficacious opiate dependence pharmacotherapy. Formal approval for general clinical use, however, required that systematic data be gathered on buprenorphine's safety and efficacy in larger groups and a series of controlled clinical trials was designed to evaluate its utility from a medication development perspective. In general, these trials adhered to one of three basic protocol designs: comparison of buprenorphine to methadone; dose comparisons using dose response as an indicator of efficacy; and comparison of buprenorphine to placebo. Retention in treatment, reduction in illicit drug use and craving, and patient and staff ratings of improvements were the most frequently used outcome indicators in these trials. Additional data collected included optimum dosing and dosage schedules, adverse reactions and common side-effects, and other information intended to clarify buprenorphine's benefit-risk relationship and to help prepare guidelines for its safe marketing and utilization by physicians in general clinical practice. This paper presents a review of the buprenorphine/methadone comparison trials conducted in the United States and two such trials conducted in Europe. Also reviewed are three placebo-controlled trials and a buprenorphine/methadone detoxification study. Overall, this series of studies did firmly establish the efficacy of buprenorphine alone and in comparison to methadone.

Topics: Buprenorphine; Controlled Clinical Trials as Topic; Humans; Methadone; Narcotic Antagonists; Opioid-Related Disorders; Placebos; Substance Withdrawal Syndrome

The unique pharmacology of buprenorphine at the mu-opioid receptor (i.e. high affinity, low intrinsic activity and slow dissociation) results in buprenorphine having: (1) a good safety profile, (2) low physical dependence, and (3) flexibility in dose scheduling. Early studies assessed the effectiveness of buprenorphine for the treatment of opioid dependence using a sublingual solution formulation. More recently, a combination tablet (buprenorphine/naloxone in a 4:1 ratio) has been assessed with the goal of decreasing diversion and abuse. Controlled studies with buprenorphine solution, buprenorphine mono-tablet, and buprenorphine/naloxone combination tablet have uniformly demonstrated the effectiveness of buprenorphine for opioid dependence treatment and the combination tablet appears to decrease (but not eliminate) abuse potential. There is general agreement across studies regarding buprenorphine induction and maintenance dose schedules. The clinical effects of buprenorphine and buprenorphine/naloxone are similar and most patients can be treated initially with and maintained on a daily buprenorphine/naloxone dose of 4:1-24:6 mg. Dosing is possible on a less-than-daily schedule; however, multiples of the daily-dose should be administered to cover the increased interval between doses. If buprenorphine withdrawal is indicated, gradual dose reduction is recommended over a rapid dose reduction or abrupt cessation. Both tablet formulations are approved by the US FDA for opioid dependence treatment as Schedule III narcotics and are, therefore, available for use in office-based practice. The buprenorphine plus naloxone combination product should provide additional safeguards for use in office-based practice by decreasing risk of diversion, and office-based treatment should expand the availability of services to opioid dependent patients.

Topics: Buprenorphine; Clinical Trials as Topic; Dosage Forms; Drug Administration Routes; Drug Combinations; Humans; Narcotic Antagonists; Opioid-Related Disorders

It is estimated that 55-94% of infants born to opioid-dependent mothers in US will show signs of opioid withdrawal. Buprenorphine has been reported to produce little or no autonomic signs or symptoms of opioid withdrawal following abrupt termination in adults. To date, there have been 21 published reports representing approximately 15 evaluable cohorts of infants exposed to buprenorphine in utero. Of approximately 309 infants exposed, a neonatal abstinence syndrome (NAS) has been reported in 62% infants with 48% requiring treatment; apparently greater than 40% of these cases are confounded by illicit drug use. The NAS associated with buprenorphine generally appears within 12-48 h, peaks at approximately 72-96 h, and lasts for 120-168 h. These results appear similar to or less than that observed following in utero exposure to methadone. From a review of the literature, buprenorphine appears to be safe and effective in both mother and infant with an NAS that may differ from methadone both qualitatively and quantitatively.

Topics: Buprenorphine; Disease Management; Female; Humans; Infant, Newborn; Narcotic Antagonists; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects

Opiate dependence remains a fundamental challenge confronting health delivery systems and is often characterized as a social and moral issue. The impact of this disorder on healthcare policy is changing with the increased incidence of HIV, hepatitis C, and tuberculosis infections in opiate-dependent patients. These medical illnesses have substantial effect on escalating healthcare costs, and, therefore, also affect healthcare policy priorities, which are responsive to these costs. Pharmacological treatments for opiate dependence have had limited success; often the consequence of limited access to care. Hence, there is a need to develop new pharmacotherapies for opiate dependence that extend the range of clinical options, including new first-line treatment approaches. This paper will focus on the safety and health policy considerations related to the use of buprenorphine and buprenorphine/naloxone based on data derived from clinical trials and post-marketing surveillance that provide evidence for the use of the medications as first-line treatments in an office-based environment. The evaluation of this evidence formed the basis by the National Institute on Drug Abuse to support and pursue the evaluation and registration of buprenorphine/naloxone and buprenorphine in a public/private sector cooperative effort to become an office-based, first-line treatment for opiate dependence.

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Clinical Trials as Topic; Drug Combinations; Health Policy; Humans; Naloxone; Narcotic Antagonists; Office Visits; Opioid-Related Disorders; Treatment Outcome

Buprenorphine has recently been reported to be an alternative to methadone and LAAM for maintenance treatment of opioid dependent individuals, differing results are reported concerning its relative effectiveness indicating the need for an integrative review.. To evaluate the effects of buprenorphine maintenance against placebo and methadone maintenance in retaining patients in treatment and in suppressing illicit drug use.. We searched the following databases up to 2001, inclusive: Cochrane Drugs and Alcohol Review Group Register, the Cochrane Controlled Trials Register, MEDLINE, EMBASE, Current Contents, Psychlit, CORK [www. state.vt.su/adap/cork], Alcohol and Drug Council of Australia (ADCA) [www.adca.org.au], Australian Drug Foundation (ADF -VIC) [www.adf.org.au], Centre for Education and Information on Drugs and Alcohol (CEIDA) [www.ceida.net.au], Australian Bibliographic Network (ABN), and Library of Congress databases, available NIDA monographs and the College on Problems of Drug Dependence Inc. proceedings, the reference lists of all identified studies and published reviews and authors of identified RCT's were asked about any other published or unpublished relevant RCT.. Randomised clinical trials of buprenorphine maintenance compared with either placebo or methadone maintenance for opioid dependence.. Reviewers evaluated the papers separately and independently, rating methodological quality of concealment of allocation; data were extracted independently for meta-analysis and double-entered.. Thirteen studies met the inclusion criteria, all were randomised clinical trials, all but one were double-blind. The method of concealment of allocation was not clearly described in 11 of the studies, otherwise methodological quality was good. Buprenorphine given in flexible doses appeared statistically significantly less effective than methadone in retaining patient in treatment (RR= 0.82; 95% CI: 0.69-0.96). Low dose buprenorphine is not superior to low dose methadone. High dose buprenorphine does not retain more patients than low dose methadone, but may suppress heroin use better. There was no advantage for high dose buprenorphine over high dose methadone in retention (RR=0.79; 95% CI:0.62-1.01), and high dose buprenorphine was inferior in suppression of heroin use. Buprenorphine was statistically significantly superior to placebo medication in retention of patients in treatment at low doses (RR=1.24; 95% CI: 1.06-1.45), high doses (RR=1.21; 95% CI: 1.02-1.44), and very high doses (RR=1.52; 95% CI: 1.23-1.88). However, only high and very high dose buprenorphine suppressed heroin use significantly above placebo.. Buprenorphine is an effective intervention for use in the maintenance treatment of heroin dependence, but it is not more effective than methadone at adequate dosages.

Topics: Buprenorphine; Humans; Methadone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Randomized Controlled Trials as Topic

Substitution treatment (replacement therapy) is the most widespread and the most frequently researched therapeutic approach to heroin dependence. At present, the "gold standard" is methadone maintenance, but the use of other agonists and of combined compounds with antagonists are increasingly used, especially Buprenorphine. This paper reviews the main findings from research and their consequences for best practice rules. The evolution and organisation of substitution treatment in Europe is described, indicating a major discrepancy in administrative regulations. Emerging trends are also mentioned, as well as the merits and limitations that mark the place of substitution treatment in a comprehensive therapeutic network for opioid dependence.

Topics: Animals; Buprenorphine; Drug Therapy, Combination; Humans; Methadone; Opioid-Related Disorders

Although pharmacotherapy has been a mainstay in opiate addiction, not much research in the development of new opiate medications has been translated into clinical practice. In part, this is because opiate pharmacotherapy has not been an integral element of mainstream medical practice and because new medications developed by research are not available to clinicians. All that will change with the availability of buprenorphine for addiction treatment. For the first time in nearly a century, clinicians will be able to treat opiate addicts in the general medical setting, in the same manner they treat other patients. The unique pharmacological properties of buprenorphine, with its high patient acceptance, favorable safety profile, and ease of clinical administration, should facilitate its clinical integration. However, successful implementation will require changes in the understanding and attitude of clinicians, policymakers, and society.

Topics: Australia; Buprenorphine; Clinical Trials as Topic; France; Humans; Narcotic Antagonists; Opioid-Related Disorders; Substance Abuse Treatment Centers; United States

Opiate addiction is a chronic, relapsing disorder. Left untreated, high morbidity and mortality rates are seen. Pharmacotherapies for this disorder using mu opiate agonists (methadone and levomethadyl acetate) and partial agonists have been developed in the last 40 years. Agonist pharmacotherapy with oral methadone for the treatment of opiate dependence was developed in clinical pharmacology studies at Rockefeller University by Dole, Nyswander, and Kreek. Further studies by this laboratory and others established that moderate to high dose treatment with methadone (80-120 mg) reduced or eliminated opiate use in outpatient settings with consequent reductions in morbidity and up to 4-fold reductions in mortality. Levomethadyl acetate (LAAM), a congener of methadone, is biotransformed to active metabolites responsible for its longer duration of action. The Federal Regulations regarding the dispensation of methadone and LAAM have recently been revised to facilitate the treatment of patients under a "medical maintenance" model. Future regulatory reform will likely involve the establishment of rules for "office based opioid treatment."

Topics: Buprenorphine; Clinical Trials as Topic; History, 20th Century; Humans; Methadone; Methadyl Acetate; Naloxone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders

Buprenorphine, a long-acting opioid with both agonist and antagonist properties, binds to mu-opioid (OP(3)), kappa-opioid (OP(2)), delta-opioid (OP(1)), and nociceptin (ORL-1) receptors. Its actions at these receptors have not been completely characterized, although buprenorphine is generally regarded as a mu-opioid receptor partial agonist and a kappa-opioid receptor antagonist. Its pharmacology is further complicated by an active metabolite, norbuprenorphine. Although buprenorphine can be used as an analgesic agent, it is of greater importance in the treatment of opioid abuse. Because of its partial agonist activity at mu-opioid receptors and its long half-life, buprenorphine has proven to be an excellent alternative to methadone for either maintenance therapy or detoxification of the opioid addict. Although buprenorphine may ultimately prove to be superior to methadone in the maintenance of the pregnant addict, its effects on the developing fetus must be carefully evaluated.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Female; Humans; Infant, Newborn; Narcotic Antagonists; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Receptors, Opioid; Receptors, Opioid, delta; Receptors, Opioid, kappa; Receptors, Opioid, mu

Buprenorphine has recently been reported to be an alternative to methadone and LAAM for maintenance treatment of opioid dependent individuals, differing results are reported concerning its relative effectiveness indicating the need for an integrative review.. To evaluate the effects of buprenorphine maintenance against placebo and methadone maintenance in retaining patients in treatment and in suppressing illicit drug use.. We searched the following databases up to 2001, inclusive: Cochrane Drugs and Alcohol Review Group Register, the Cochrane Controlled Trials Register, MEDLINE, EMBASE, Current Contents, Psychlit, CORK [www. state.vt.su/adap/cork], Alcohol and Drug Council of Australia (ADCA) [www.adca.org.au], Australian Drug Foundation (ADF -VIC) [www.adf.org.au], Centre for Education and Information on Drugs and Alcohol (CEIDA) [www.ceida.net.au], Australian Bibliographic Network (ABN), and Library of Congress databases, available NIDA monographs and the College on Problems of Drug Dependence Inc. proceedings, the reference lists of all identified studies and published reviews and authors of identified RCT's were asked about any other published or unpublished relevant RCT.. Randomised clinical trials of buprenorphine maintenance compared with either placebo or methadone maintenance for opioid dependence.. Reviewers evaluated the papers separately and independently, rating methodological quality of concealment of allocation; data were extracted independently for meta-analysis and double-entered.. Thirteen studies met the inclusion criteria, all were randomised clinical trials, all but one were double-blind. The method of concealment of allocation was not clearly described in 11 of the studies, otherwise methodological quality was good. Buprenorphine given in flexible doses appeared statistically significantly less effective than methadone in retaining patient in treatment (RR= 0.82; 95% CI: 0.69-0.96). Low dose buprenorphine is not superior to low dose methadone. High dose buprenorphine does not retain more patients than low dose methadone, but may suppress heroin use better. There was no advantage for high dose buprenorphine over high dose methadone in retention (RR=0.79; 95% CI:0.62-1.01), and high dose buprenorphine was inferior in suppression of heroin use. Buprenorphine was statistically significantly superior to placebo medication in retention of patients in treatment at low doses (RR=1.24; 95% CI: 1.06-1.45), high doses (RR=1.21; 95% CI: 1.02-1.44), and very high doses (RR=1.52; 95% CI: 1.23-1.88). However, only high and very high dose buprenorphine suppressed heroin use significantly above placebo.. Buprenorphine is an effective intervention for use in the maintenance treatment of heroin dependence, but it is not more effective than methadone at adequate dosages.

Topics: Buprenorphine; Humans; Methadone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Randomized Controlled Trials as Topic

The efficacy of methadone maintenance in opioid addiction was assessed in terms of programme retention rate and reduction of illicit opioid use by means of a meta-analysis of randomised, controlled and double blind clinical trials. The results were compared with interventions using buprenorphine and levo-acetylmethadol (LAAM). Trials were identified from the PubMed database from 1966 to December 1999 using the major medical subject headings 'methadone' and 'randomised controlled trial'. Data for a total of 1944 opioid-dependent patients from 13 studies were analysed. Sixty-four percent of patients received methadone, administered either as fixed or adjusted doses. Thus, 890 patients received > or = 50 mg/day (high dose group) and 392 were given < 50 mg/day (low dose group). Of 662 controls, 131 received placebo, 350 buprenorphine (265 at doses > or = 8 mg/day and 85 at doses < 8 mg/day) and 181 LAAM. High doses of methadone were more effective than low doses in the reduction of illicit opioid use (odds ratio [OR] 1.72, 95% confidence interval [CI] 1.26--2.36). High doses of methadone were significantly more effective than low doses of buprenorphine (< 8 mg/day) for retention rates and illicit opioid use, but similar to high doses of buprenorphine (> or = 8 mg/day) for both parameters. Patients treated with LAAM had more risk of failure of retention than those receiving high doses of methadone (OR 1.92, 95% CI 1.32--2.78). It is proposed that in agonist-maintenance programmes, oral methadone at doses of 50 mg/day or higher is the drug of choice for opioid dependence.

Topics: Buprenorphine; Humans; Methadone; Methadyl Acetate; Narcotics; Opioid-Related Disorders; Patient Dropouts; Randomized Controlled Trials as Topic; Substance Abuse Detection; Treatment Outcome

To review opioid dependence (OD) and its treatment. Pharmacologic treatments, including the use of buprenorphine/naloxone, are presented. Pharmaceutical care functions for outpatient OD treatment are discussed.. Primary and review articles were identified by MEDLINE and HEALTHSTAR searches (from 1966 to November 2000) and through secondary sources. Tertiary sources were also reviewed regarding general concepts of OD and its treatment.. Relevant articles were reviewed after identification from published abstracts. Articles were selected based on the objectives for this article. Studies of the treatment of OD with buprenorphine were selected based on the topic (pharmacology, pharmacokinetics, adverse reactions) and study design (randomized, controlled clinical trials in patients with OD with active/placebo comparisons and/or comparisons of active OD treatments). Articles regarding pharmacists' activities in the treatment and prevention of OD were reviewed for the pharmaceutical care section.. OD is considered a medical disorder with costly adverse health outcomes. Although methadone maintenance treatment (MMT) is cost-effective for OD, only about 12% of individuals with OD receive this treatment. Psychological and pharmacologic modalities are used to treat OD, but patients often relapse. Drug therapy includes alpha 2-agonists for withdrawal symptoms, detoxification regimens with or without opioids, opioid antagonists, and opioid replacement including methadone, levomethadyl acetate, and buprenorphine. The Drug Addiction Treatment Act of 1999 allows for office-based opioid replacement therapies. Sublingual buprenorphine with naloxone can be used in this milieu. Buprenorphine with naloxone is currently under new drug application review with the Food and Drug Administration. Clinical research shows buprenorphine to be equal in effectiveness to methadone, but safer in overdose due to its ceiling effect on respiratory depression. It has lower abuse potential and fewer withdrawal symptoms when discontinued. Naloxone is included to decrease diversion and injection of the tablets. Pharmacists in outpatient settings who are familiar with OD have opportunities to provide pharmaceutical care to patients receiving this treatment. Pharmaceutical care functions for OD include ensuring appropriate drug administration, monitoring adverse effects, alleviating withdrawal symptoms, treating intercurrent illnesses, minimizing diversion, and preventing relapse.. OD is a critical unmet health problem in the US. Buprenorphine combined with naloxone represents an innovative treatment for OD in outpatient settings. This new treatment has advantages over MMT.

Topics: Administration, Sublingual; Buprenorphine; Clinical Trials as Topic; Databases, Bibliographic; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Treatment Outcome

Topics: Buprenorphine; Heroin Dependence; Humans; Methadone; Narcotics; Opioid-Related Disorders

Managed withdrawal (detoxification) is a necessary step prior to drug-free treatment. It may also represent the end point of long-term opioid replacement treatment such as methadone maintenance. The availability of managed withdrawal is essential to an effective treatment system.. To assess the effectiveness of interventions involving the short-term use of buprenorphine to manage the acute phase of opioid withdrawal.. Multiple electronic databases were searched using a strategy designed to retrieve references broadly addressing the management of opioid withdrawal. Reference lists of retrieved studies, reviews and conference abstracts were handsearched.. Randomised or quasi-randomised controlled clinical trials or prospective controlled cohort studies that compared different buprenorphine regimes, or that compared buprenorphine with another form of treatment (or placebo) to modify the signs and symptoms of withdrawal in participants who were primarily opioid dependent.. Potentially relevant studies were assessed for inclusion by one reviewer. Inclusion decisions were confirmed by consultation between reviewers. One reviewer undertook data extraction with the process confirmed by consultation between all three reviewers.. Six studies (5 RCTs and 1 controlled prospective study), involving 357 participants, met the criteria for inclusion in the review. Four studies compared buprenorphine with clonidine. All found withdrawal to be less severe in the buprenorphine treatment group. In three of these studies all participants were withdrawing from heroin. Participants in one study were withdrawing from methadone (10mg/day). Aches, restlessness, yawning, mydriasis, tremor, insomnia, nausea and mild anxiety were reported as being experienced by some participants. Rates of completion of withdrawal ranged from 65% to 100%. None of the studies included in the review reported adverse effects. However a single-group study which therefore did not meet the inclusion criteria, reported the occurrence in some participants of headaches, sedation, nausea, constipation, anxiety, dizziness and itchiness, particularly in the first 2-3 days of treatment. In one of the six studies, and in two studies that did not meet the inclusion criteria, treatment was provided on an outpatient basis.. Buprenorphine has potential as a medication to ameliorate the signs and symptoms of withdrawal from heroin, and possibly methadone, but many aspects of treatment protocol and relative effectiveness need to be investigated further.

Topics: Acute Disease; Buprenorphine; Humans; Narcotic Antagonists; Opioid-Related Disorders; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome

The unique pharmacological properties of buprenorphine may make it a useful maintenance therapy for opiate addiction. This meta-analysis considers the effectiveness of buprenorphine relative to methadone.. A systematic literature search identified five randomized clinical trials comparing buprenorphine to methadone. Data from these trials were obtained. Retention in treatment was analyzed with a Cox proportional hazards regression. Urinalyses for opiates were studied with analysis of variance and a common method of handling missing values. A meta-analysis was used to combine these results.. Subjects who received 8-12 mg/day buprenorphine had 1.26 times the relative risk of discontinuing treatment (95% confidence interval 1.01-1.57) and 8.3% more positive urinalyses (95% confidence interval 2.7-14%) than subjects receiving 50-80 mg/day methadone. Buprenophrine was more effective than 20-35 mg/day methadone. There was substantial variation in outcomes in the different trials.. The variation between trials may be due to differences in dose levels, patient exclusion criteria and provision of psychosocial treatment. The difference in the effectiveness of buprenorphine and methadone may be statistically significant, but the differences are small compared to the wide variance in outcomes achieved in different methadone treatment programs. Further research is needed to determine if buprenorphine treatment is more effective than methadone in particular settings or in particular subgroups of patients.

Topics: Analysis of Variance; Buprenorphine; Humans; Methadone; Narcotics; Opioid-Related Disorders; Patient Compliance; Patient Dropouts; Proportional Hazards Models; Treatment Outcome

To determine the cost-effectiveness of buprenorphine maintenance therapy for opiate addiction in the United States, particularly its effect on the HIV epidemic.. We developed a dynamic model to capture the effects of adding buprenorphine maintenance to the current opiate dependence treatment system. We evaluated incremental costs, including all health-care costs, and incremental effectiveness, measured as quality-adjusted life years (QALYs) of survival. We considered communities with HIV prevalence among injection drug users of 5% and 40%. Because no price has been set in the United States for a dose of buprenorphine, we considered three prices per dose: $5, $15, and $30.. If buprenorphine increases the number of individuals in maintenance treatment by 10%, but does not affect the number of individuals receiving methadone maintenance, the cost-effectiveness ratios for buprenorphine maintenance therapy are less than $45 000 per QALY gained for all prices, in both the low-prevalence and high-prevalence communities. If the same number of individuals enter buprenorphine maintenance (10% of the number currently in methadone), but half are injection drug users newly entering maintenance and half are individuals who switched from methadone to buprenorphine, the cost-effectiveness ratios in both communities are less than $45 000 per QALY gained for the $5 and $15 prices, and greater than $65 000 per QALY gained for the $30 price.. At a price of $5 or less per dose, buprenorphine maintenance is cost-effective under all scenarios we considered. At $15 per dose, it is cost-effective if its adoption does not lead to a net decline in methadone use, or if a medium to high value is assigned to the years of life lived by injection drug users and those in maintenance therapy. At $30 per dose, buprenorphine will be cost-effective only under the most optimistic modeling assumptions.

Topics: Buprenorphine; Cost-Benefit Analysis; Humans; Narcotic Antagonists; Opioid-Related Disorders; Quality-Adjusted Life Years; United States

Managed withdrawal, or detoxification, is not in itself a treatment for opioid dependence, but it is a required first step for many forms of longer-term treatment. It may also represent the end point of an extensive period of treatment such as methadone maintenance. As such, managed withdrawal is an essential component of an effective treatment system. This review is one of a series that aims to assess the evidence as to the effectiveness of the variety of approaches to managing opioid withdrawal.. To assess the effectiveness of interventions involving the short-term use of buprenorphine to manage the acute phase of opioid withdrawal.. Multiple electronic databases, including Medline, Embase, Psychlit, Australian Medical Index and Current Contents, were searched using a strategy designed to retrieve references broadly addressing the management of opioid withdrawal. Reference lists of retrieved studies, reviews and conference abstracts were handsearched.. We included randomised or quasi-randomised controlled clinical trials or prospective controlled cohort studies comparing buprenorphine (treatment 10 days or less) with another form of treatment. Studies were required to provide detailed information on the type and dose of drugs used and the characteristics of patients treated. Studies were also required to provide information on the nature of withdrawal signs and symptoms experienced, the occurrence of adverse effects OR rates of completion of the withdrawal episode.. Potentially relevant studies were assessed for inclusion by one reviewer (LG). Inclusion decisions were confirmed by consultation between reviewers. Included studies were assessed by all reviewers. One reviewer (LG) undertook data extraction with the process confirmed by consultation between all three reviewers.. Five studies met the criteria for inclusion in the review. No data tables are included in this review and no meta-analysis has been undertaken because of differences in treatment regimes and the assessment of outcomes in these studies. Four studies compared buprenorphine with clonidine. All found withdrawal to be less severe in the buprenorphine treatment group. In three of these studies all participants were withdrawing from heroin. Participants in one study were withdrawing from methadone, with doses reduced to 10mg/day prior to treatment with buprenorphine. Three of the studies commented on residual symptoms experienced by participants treated with buprenorphine to manage heroin withdrawal. Aches, restlessness, yawning, mydriasis, tremor, insomnia, nausea and mild anxiety were reported as being experienced by some participants. Rates of completion of withdrawal were able to be calculated for all studies included in the review but the definition of completion varied between studies. Rates ranged from 65% to 100%. None of the studies included in the review reported adverse effects. However, approximately approximately Lintzeris 1999a approximately approximately (a single-group study which therefore did not meet the inclusion criteria) reported 50% of participants withdrawing from heroin experienced headaches, 28% sedation, 21% nausea, 21% constipation, 21% anxiety, 17% dizziness and 17% itchiness during withdrawal. These adverse effects were most common in the first 2-3 days of treatment and then subsided. In four of the five studies treatment was undertaken on an inpatient basis. Only approximately approximately O'Connor 1997 approximately approximately provided outpatient treatment. However, two studies that did not meet the inclusion criteria ( approximately approximately Diamant 1998 approximately approximately and approximately approximately Lintzeris 1999a approximately approximately ) also provided outpatient treatment. The findings of these studies support the feasibility of heroin withdrawal being managed with buprenorphine on an outpatient basis

Topics: Acute Disease; Buprenorphine; Humans; Narcotic Antagonists; Opioid-Related Disorders; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome

Two new long-acting opioid agonists have recently been introduced for the substitutional treatment of opioid-dependent patients: Orlaam (LAAM) and Subutex (buprenorphine). Both have a dose-related duration of action two to three times that of methadone, and can be given only three times a week instead of daily, thus reducing the need for take-home doses. Further, the longer duration of action provides a smoother blood level with fewer fluctuations between doses. With the availability of buprenorphine and LAAM as alternatives to methadone, agonist treatment can be more differentiated, and one can hope that this will increase the quality of the treatment.

Topics: Analgesics, Opioid; Buprenorphine; Controlled Clinical Trials as Topic; Drug Interactions; Humans; Methadyl Acetate; Narcotic Antagonists; Opioid-Related Disorders

Increases in the use of illicit opiates have refocused attention on these drugs. One outgrowth of this attention has been the increased consideration of pharmacotherapies to provide alternatives to methadone maintenance. Buprenorphine is one new tool used in the attenuation of illicit opiate use. Like methadone, buprenorphine produces cross-tolerance to other opiates. However, it may have advantages over methadone including a longer duration, limited withdrawal syndrome, and increased safety. Buprenorphine's ability to serve as a replacement drug for illicit opiate use is well documented, and efforts have recently been made to compare the drug with methadone. The purpose of this study was to provide a meta-analysis of all available research reporting a controlled comparison of buprenorphine and methadone. This analysis provided a rating of the comparative efficacy of each drug, thus giving clinicians an additional guide when selecting an appropriate course of treatment. Findings suggest a relative equality in the efficacy of buprenorphine and methadone, although patients receiving methadone were less likely to test positive for illicit opiate use. Past experience with methadone maintenance acted as a moderating variable, however, such that those receiving buprenorphine were more likely to stay drug-free in studies that included patients with prior methadone experience.

Topics: Buprenorphine; Female; Humans; Male; Methadone; Opioid-Related Disorders; Substance Withdrawal Syndrome; Treatment Outcome

Topics: Analgesics, Opioid; Buprenorphine; Drug and Narcotic Control; Humans; Methadone; Methadyl Acetate; Opioid-Related Disorders; Treatment Outcome

Detoxification from opiate addiction has been a medical problem for as long as opiate drugs have been available. Treatment before the discovery of clonidine involved giving another opioid drug with less dangerous consequences of chronic use, such as the long-acting and orally administered once a day methadone, for another opioid mu agonist like heroin, which must be taken intravenously many times a day, thus making rehabilitation, work, and avoidance of hepatitis, HIV, and other illnesses difficult. Although methadone has proved to be very beneficial, it still has significant abuse potential. Naltrexone, because it blocks the effects of all opiates, has facilitated the transformation from addiction to a drug-free state for many recovering addicts. By alleviating withdrawal symptoms and by lessening the detoxification period, clonidine similarly has improved the prospect of recovery from opiate addiction. Relapse, whether withdrawal is treated with clonidine or other new agents or not, occurs with great regularity because repeated opiate use can induce a new acquired drive state--the drive for opiates. In addition, with powerful withdrawal symptoms during abstinence, opiate relapse is difficult to prevent without an adequate treatment program. The efficacy of clonidine and other medical magic bullets for withdrawal distress needs to be given as part of a long-term recovery program which not only allows the brain to re-establish normal homeostatic changes in the drug-free state but also provides sufficient motivation for new approaches to achieving and sustaining pleasurable existence.

Topics: Animals; Buprenorphine; Clonidine; Humans; Locus Coeruleus; Methadone; Naltrexone; Opioid-Related Disorders; Substance Withdrawal Syndrome

Topics: Animals; Buprenorphine; Cocaine; Heroin Dependence; Humans; Opioid-Related Disorders

Topics: Animals; Buprenorphine; Humans; Opioid-Related Disorders

Buprenorphine, a mixed opioid agonist/antagonist, has been examined not only for the treatment of opioid dependence, but also for concurrent dependence on both opioids and cocaine. Preliminary human studies have suggested that buprenorphine treatment may be associated with significantly less cocaine abuse than is treatment with methadone maintenance. Preclinical studies in both primates and rodents have also indicated that buprenorphine may reduce cocaine self-administration and attenuate place preference for cocaine. Two double-blind, randomized clinical trials comparing buprenorphine with methadone have failed to demonstrate that buprenorphine is superior to methadone in reducing cocaine abuse. However, the trial by Kosten and associates has suggested a larger reduction in cocaine abuse at 6 mg than at 2 mg daily of buprenorphine. This dose dependence is consistent with cocaine challenge studies in which buprenorphine attenuated cocaine effects at 4 mg, but not at 2 mg, daily.

Topics: Buprenorphine; Clinical Trials as Topic; Cocaine; Humans; Opioid-Related Disorders; Substance-Related Disorders

This month's guest authors are affiliated with the substance abuse treatment and treatment research unit of the Connecticut Mental Health Center and the department of psychiatry at Yale University School of Medicine, where Dr. Rosen is instructor and Dr. Kosten is associate professor. They discuss a promising new treatment that may reduce abuse of cocaine by drug addicts who use intravenous heroin and may indirectly reduce risk-taking behavior associated with transmission of the human immunodeficiency virus.

Topics: Acquired Immunodeficiency Syndrome; Buprenorphine; Cocaine; Humans; Methadone; Opioid-Related Disorders; Risk Factors; Substance Abuse, Intravenous; Substance-Related Disorders

Many aspects of the pharmacokinetics of methadone have been evaluated since 1970. Analytic techniques used to monitor urine and serum or plasma concentrations of methadone and its metabolites have improved with advances in chromatography and development of immunoassay techniques. On reviewing the literature on methadone since 1970, however, there were several recurring limitations of the experimental design in a large number of the studies reported. These include: 1. No appreciation for the effect of urinary pH on excretion of methadone 2. Small number of patients enrolled with inadequate control subjects 3. The effect of smoking cigarettes was not evaluated or adequately controlled 4. Urine collections were often obtained without supervision and correcting results to creatinine excretion 5. Blood specimens were generally not collected from 0-15 minutes after intravenous dosing 6. Incomplete excretion data (nonhydrolysis of glucuronide conjugates) in the urine 7. Most studies did not evaluate protein binding of methadone when attempting to correlate therapeutic control or failure with serum concentrations of methadone. In general, the literature supporting the use of naltrexone was more favorable than for methadone, buprenorphine, LAAM, and clonidine. The major limitation on the use of naltrexone, however, is the lack of incentive for the patient to keep taking the medication. If the use of naltrexone, LAAM, buprenorphine, or clonidine becomes widely available, robust analytic techniques must be developed for monitoring of these drugs, their metabolites, or both in the urine to verify patient compliance.

Topics: Buprenorphine; Clonidine; Humans; Methadone; Methadyl Acetate; Naltrexone; Opioid-Related Disorders

Topics: Analgesics, Opioid; Animals; Buprenorphine; Heroin Dependence; Humans; Nausea; Opioid-Related Disorders; Substance Withdrawal Syndrome

Topics: Buprenorphine; Cocaine; Desipramine; Female; Heroin Dependence; Humans; Male; Naltrexone; Opioid-Related Disorders; Sex Factors; Substance-Related Disorders

The reinforcing properties of drugs can be evaluated pre-clinically using self-administration procedures in laboratory animals. This paper reviews self-administration studies of the four opioid agonist/antagonist analgesics pentazocine, butorphanol, nalbuphine and buprenorphine, and compares these results to those from studies of morphine and cyclazocine. All four agonist/antagonists possess reinforcing properties under at least some test conditions. In this respect they more resemble morphine than cyclazocine. These results suggest that they all may have some potential for recreational use. On the other hand, some data point to a lower reinforcing efficacy for these agonist/antagonists than for the pure agonists such as morphine. Studies comparing the reinforcing efficacy among the agonist/antagonists are also reviewed, however more data are needed before definitive conclusions can be drawn within the class.

Topics: Animals; Buprenorphine; Butorphanol; Cyclazocine; Humans; Macaca mulatta; Morphinans; Morphine; Nalbuphine; Opioid-Related Disorders; Papio; Pentazocine; Rats; Reinforcement, Psychology; Self Administration

Buprenorphine is an opioid mixed agonist-antagonist that has potential usefulness as a pharmacotherapy for opiate addiction. Buprenorphine significantly suppressed opiate self-administration by heroin addicts. Buprenorphine also suppressed opiate self-administration in a primate model. Although buprenorphine is a positive reinforcer in rhesus monkey, it is less reinforcing than other opioids and some opioid mixed agonist-antagonists as evaluated in progressive ratio and drug substitution procedures. These data suggest that the abuse liability of buprenorphine should be less than that of other opioid drugs. The safety and potential therapeutic benefits of buprenorphine relative to other currently available pharmacotherapies probably overweigh the possible risks of abuse.

Topics: Adult; Animals; Buprenorphine; Conditioning, Operant; Eating; Heroin Dependence; Humans; Macaca; Male; Methadone; Morphinans; Naltrexone; Opioid-Related Disorders; Reinforcement, Psychology; Self Administration

Topics: Analgesics; Analgesics, Opioid; Buprenorphine; Buspirone; Double-Blind Method; Humans; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Substance Withdrawal Syndrome; Treatment Outcome

This randomized controlled trial tested whether external coaching influences addiction treatment providers' utilization of medications to treat opioid use disorder (MOUDs).. This study recruited 75 unique clinical sites in Florida, Ohio, and Wisconsin, including 61 sites in specialty treatment agencies and 14 behavioral health sites within health systems. The trial used external coaching to increase use of MOUDs in the context of a learning collaborative and compared it with no coaching and no learning collaborative (control condition). Outcome measures of MOUD capacity and utilization were monthly tabulations of licensed buprenorphine slots (i.e., the number of patients who could be treated based on the buprenorphine waiver limits of the site's providers), buprenorphine use, and injectable naltrexone administration.. The coaching and control arms showed no significant difference at baseline. Although buprenorphine slots increased in both arms during the 30-month trial, growth increased twice as fast at the coaching sites, compared with the control sites (average monthly rate of 6.1% vs. 3.0%, respectively, p<0.001). Buprenorphine use showed a similar pattern; the monthly growth rate in the coaching arm was more than twice the rate in the control arm (5.3% vs. 2.4%, p<0.001). Coaching did not have an impact on injectable naltrexone, which grew less than 1% in both arms over the trial period.. External coaching can increase organizational capacity for and growth of buprenorphine use. Future research should explore the dimensions of coaching practice, dose, and delivery modality to better understand and enhance the coaching function.

Topics: Analgesics, Opioid; Buprenorphine; Humans; Naltrexone; Ohio; Opiate Substitution Treatment; Opioid-Related Disorders

Opioid-related deaths continue to rise in the U.S. A shared decision-making (SDM) system to help primary care clinicians (PCCs) identify and treat patients with opioid use disorder (OUD) could help address this crisis.. In this cluster-randomized trial, primary care clinics in three healthcare systems were randomized to receive or not receive access to an OUD-SDM system. The OUD-SDM system alerts PCCs and patients to elevated risk of OUD and supports OUD screening and treatment. It includes guidance on OUD screening and diagnosis, treatment selection, starting and maintaining patients on buprenorphine for waivered clinicians, and screening for common comorbid conditions. The primary study outcome is, of patients at high risk for OUD, the percentage receiving an OUD diagnosis within 30 days of index visit. Additional outcomes are, of patients at high risk for or with a diagnosis of OUD, (a) the percentage receiving a naloxone prescription, or (b) the percentage receiving a medication for OUD (MOUD) prescription or referral to specialty care within 30 days of an index visit, and (c) total days covered by a MOUD prescription within 90 days of an index visit.. The intervention started in April 2021 and continues through December 2023. PCCs and patients in 90 clinics are included; study results are expected in 2024.. This protocol paper describes the design of a multi-site trial to help PCCs recognize and treat OUD. If effective, this OUD-SDM intervention could improve screening of at-risk patients and rates of OUD treatment for people with OUD.

Topics: Analgesics, Opioid; Buprenorphine; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Primary Health Care

This study aimed to evaluate the effectiveness of flexible take-home dosing of buprenorphine/naloxone (BUP/NX) and methadone standard model of care in reducing depressive symptoms in people with prescription-type opioid use disorder (POUD). This trial also evaluated whether improvements in depressive symptoms were mediated by opioid use.. Analyzed data came from the OPTIMA study (clinicaltrials.gov identifier: NCT03033732), a pragmatic randomised controlled trial comparing flexible take-home dosing of BUP/NX and methadone standard model of care for reducing opioid use in people with POUD. A total of 272 participants were recruited in four Canadian provinces. Participants were randomised 1:1 to BUP/NX or methadone. After treatment induction, past two-week opioid use was measured using the Timeline Followback every two weeks for a total of 24 weeks. Depressive symptoms were measured with the Beck Depression Inventory at baseline, weeks 12 and 24.. BUP/NX and methadone showed similar effectiveness in decreasing comorbid depressive symptoms in people with POUD. This effect was partially explained by a reduction in opioid use. As both treatments seem equally effective, clinicians are encouraged to tailor the selection of OAT to patients' needs and characteristics.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Canada; Depression; Humans; Methadone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Prescriptions

Chronic pain and opioid use disorder (OUD) individually represent a risk to health and well-being. Concerningly, there is evidence that they are frequently co-morbid. While few treatments exist that simultaneously target both conditions, preliminary work has supported the feasibility of an integrated behavioral treatment targeting pain interference and opioid misuse. This treatment combined Acceptance and Commitment Therapy (ACT) and Mindfulness-Based Relapse Prevention (ACT+MBRP). This paper describes the protocol for the adequately powered efficacy study of this integrated treatment.. A multisite randomized controlled trial will examine the efficacy of ACT+MBRP in comparison to a parallel education control condition, focusing on opioid safety and pain education. Participants include veterans (n = 160; 21-75 years old) recruited from three Veterans Administration (VA) Healthcare Systems with chronic pain who are on a stable dose of buprenorphine. Both conditions include twelve weekly 90 min group sessions delivered via telehealth. Primary outcomes include pain interference (Patient Reported Outcome Measurement Information System - Pain Interference) and hazardous opioid use (Current Opioid Misuse Measure), which will be examined at the end of the active treatment phase and through 12 months post-intervention. Secondary analyses will evaluate outcomes including pain intensity, depression, pain-related fear, and substance use, as well as treatment mechanisms.. This study will determine the efficacy of an integrated behavioral treatment program for pain interference and hazardous opioid use among veterans with chronic pain and OUD who are prescribed buprenorphine, addressing a critical need for more integrated treatments for chronic pain and OUD.. ClinicalTrials.gov Identifier: NCT04648228.

Topics: Acceptance and Commitment Therapy; Adult; Aged; Analgesics, Opioid; Buprenorphine; Chronic Pain; Humans; Middle Aged; Opioid-Related Disorders; Veterans; Young Adult

There is an unmet need for therapeutics with greater efficacy and tolerability for the treatment of opioid use disorder (OUD). ASP8062 is a novel compound with positive allosteric modulator activity on the γ-aminobutyric acid type B receptor under development for use with standard-of-care treatment for patients with OUD.. To investigate the safety, tolerability, interaction potential, and pharmacokinetics (PK) of ASP8062 in combination with buprenorphine/naloxone (B/N; Suboxone. In this phase 1, randomized, double-masked, placebo-controlled study, patients with OUD began B/N (titrated to 16/4 mg/day) treatment upon enrollment (induction, Days 1-4; maintenance, Days 5-18; downward titration, Days 19-26; and discharge, Day 27). On Day 12, patients received a single dose of ASP8062 60 mg or placebo with B/N and underwent safety and PK assessments. Primary endpoints included frequency and severity of treatment-emergent adverse events (TEAEs), clinical laboratory tests, respiratory depression, and suicidal ideation. Secondary endpoints investigated the impact of ASP8062 on B/N PK.. In this phase 1 study, ASP8062 was safe, well tolerated, and did not enhance respiratory suppression induced by buprenorphine.. Clinicaltrials.gov identifier: NCT04447287.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Double-Blind Method; Humans; Narcotic Antagonists; Opioid-Related Disorders; Respiratory Insufficiency

Many primary care clinicians (PCCs) hold stigma toward people with opioid use disorder (OUD), which may be a barrier to care. Few interventions exist to address PCC stigma toward people with OUD. This study examined whether an online training incorporating patient narratives reduced PCCs' stigma toward people with OUD (primary) and increased intentions to treat people with OUD compared to an attention-control training (secondary).. PCCs from 15 primary care clinics were invited to complete a 30 min online training for an electronic health record-embedded clinical decision support (CDS) tool that alerts PCCs to screen, diagnose, and treat people with OUD. PCCs were randomized to receive a stigma-reduction version of the training with patient narrative videos or a control training without patient narratives and were blinded to group assignment. Immediately after the training, PCCs completed surveys of stigma towards people with OUD and intentions and willingness to treat OUD. CDS tool use was monitored for 6 months. Analyses included independent samples t-tests, Pearson correlations, and logistic regression.. A total of 162 PCCs were randomized; 88 PCCs (58% female; 68% white) completed the training (Stigma = 48; Control = 40) and were included in analyses. There was no significant difference between intervention and control groups for stigma (t = - 0.48, p = .64, Cohen's d = - 0.11), intention to get waivered (t = 1.11, p = .27, d = 0.26), or intention to prescribe buprenorphine if a waiver were no longer required (t = 0.90, p = 0.37, d = 0.21). PCCs who reported greater stigma reported lower intentions both to get waivered (r = - 0.25, p = 0.03) and to prescribe buprenorphine with no waiver (r = - 0.25, p = 0.03). Intervention group and self-reported stigma were not significantly related to CDS tool use.. Stigma toward people with OUD may require more robust intervention than this brief training was able to accomplish. However, stigma was related to lower intentions to treat people with OUD, suggesting stigma acts as a barrier to care. Future work should identify effective interventions to reduce stigma among PCCs.. ClinicalTrials.gov NCT04867382. Registered 30 April 2021-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04867382.

Topics: Buprenorphine; Female; Humans; Male; Opiate Substitution Treatment; Opioid-Related Disorders; Primary Health Care; Surveys and Questionnaires

Co-use of stimulants and opioids is rapidly increasing. Randomized clinical trials (RCTs) have established the efficacy of medications for opioid use disorder (MOUD), but stimulant use may decrease the likelihood of initiating MOUD treatment. Furthermore, trial participants may not represent "real-world" populations who would benefit from treatment.. We conducted a two-stage analysis. First, associations between stimulant use (time-varying urine drug screens for cocaine, methamphetamine, or amphetamines) and initiation of buprenorphine or extended-release naltrexone (XR-NTX) were estimated across two RCTs (CTN-0051 X:BOT and CTN-0067 CHOICES) using adjusted Cox regression models. Second, results were generalized to three target populations who would benefit from MOUD: Housed adults identifying the need for OUD treatment, as characterized by the National Survey on Drug Use and Health (NSDUH); adults entering OUD treatment, as characterized by Treatment Episodes Dataset (TEDS); and adults living in rural regions of the U.S. with high rates of injection drug use, as characterized by the Rural Opioids Initiative (ROI). Generalizability analyses adjusted for differences in demographic characteristics, substance use, housing status, and depression between RCT and target populations using inverse probability of selection weighting.. Analyses included 673 clinical trial participants, 139 NSDUH respondents (weighted to represent 661,650 people), 71,751 TEDS treatment episodes, and 1,933 ROI participants. The majority were aged 30-49 years, male, and non-Hispanic White. In RCTs, stimulant use reduced the likelihood of MOUD initiation by 32% (adjusted HR [aHR] = 0.68, 95% CI 0.49-0.94, p = 0.019). Stimulant use associations were slightly attenuated and non-significant among housed adults needing treatment (25% reduction, aHR = 0.75, 0.48-1.18, p = 0.215) and adults entering OUD treatment (28% reduction, aHR = 0.72, 0.51-1.01, p = 0.061). The association was more pronounced, but still non-significant among rural people injecting drugs (39% reduction, aHR = 0.61, 0.35-1.06, p = 0.081). Stimulant use had a larger negative impact on XR-NTX initiation compared to buprenorphine, especially in the rural population (76% reduction, aHR = 0.24, 0.08-0.69, p = 0.008).. Stimulant use is a barrier to buprenorphine or XR-NTX initiation in clinical trials and real-world populations that would benefit from OUD treatment. Interventions to address stimulant use among patients with OUD are urgently needed, especially among rural people injecting drugs, who already suffer from limited access to MOUD.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Delayed-Action Preparations; Humans; Male; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders

Opioid use disorder (OUD) contributes to rising morbidity and mortality. Life-saving OUD treatments can be provided in primary care but most patients with OUD don't receive treatment. Comorbid depression and other conditions complicate OUD management, especially in primary care. The MI-CARE trial is a pragmatic randomized encouragement (Zelen) trial testing whether offering collaborative care (CC) to patients with OUD and clinically-significant depressive symptoms increases OUD medication treatment with buprenorphine and improves depression outcomes compared to usual care.. Adult primary care patients with OUD and depressive symptoms (n ≥ 800) from two statewide health systems: Kaiser Permanente Washington and Indiana University Health are identified with computer algorithms from electronic Health record (EHR) data and automatically enrolled. A random sub-sample (50%) of eligible patients is offered the MI-CARE intervention: a 12-month nurse-driven CC intervention that includes motivational interviewing and behavioral activation. The remaining 50% of the study cohort comprise the usual care comparison group and is never contacted. The primary outcome is days of buprenorphine treatment provided during the intervention period. The powered secondary outcome is change in Patient Health Questionnaire (PHQ)-9 depression scores. Both outcomes are obtained from secondary electronic healthcare sources and compared in "intent-to-treat" analyses.. MI-CARE addresses the need for rigorous encouragement trials to evaluate benefits of offering CC to generalizable samples of patients with OUD and mental health conditions identified from EHRs, as they would be in practice, and comparing outcomes to usual primary care. We describe the design and implementation of the trial, currently underway.. ClinicalTrials.gov Identifier: NCT05122676. Clinical trial registration date: November 17, 2021.

Topics: Adult; Buprenorphine; Depression; Humans; Motivational Interviewing; Opioid-Related Disorders; Patient-Centered Care; Randomized Controlled Trials as Topic

Extended-release injectable naltrexone (XR-NTX) is an effective treatment for opioid use disorder (OUD), but initiation remains a barrier to implementation. Standard practice requires a 10- to 15-day inpatient admission prior to XR-NTX initiation and involves a methadone or buprenorphine taper followed by a 7- to 10-day washout, as recommended in the Prescribing Information for XR-NTX. A 5- to 7-day rapid induction approach was developed that utilizes low-dose oral naltrexone and non-opioid medications.. The CTN-0097 Surmounting Withdrawal to Initiate Fast Treatment with Naltrexone (SWIFT) study was a hybrid type I effectiveness-implementation trial that compared the effectiveness of the standard procedure (SP) to the rapid procedure (RP) for XR-NTX initiation across six community inpatient addiction treatment units, and evaluated the implementation process. Sites were randomized to RP every 14 weeks in an optimized stepped wedge design. Participants (target recruitment = 450) received the procedure (SP or RP) that the site was implementing at time of admission. The hypothesis was RP will be non-inferior to SP on proportion of inpatients who receive XR-NTX, with a shorter admission time for RP. Superiority testing of RP was planned if the null hypothesis of inferiority of RP to SP was rejected.. If RP for XR-NTX initiation is shown to be effective, the shorter inpatient stay could make XR-NTX more feasible and have an important public health impact expanding access to OUD pharmacotherapy. Further, a better understanding of facilitators and barriers to RP implementation can help with future translatability and uptake to other community programs.. NCT04762537 Registered February 21, 2021.

Topics: Buprenorphine; Delayed-Action Preparations; Humans; Injections, Intramuscular; Methadone; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders

Buprenorphine-naloxone is a medication shown to improve outcomes for individuals seeking treatment for opioid use disorder (OUD); however, outcomes are limited by low medication adherence rates. This is especially true during the early stages of treatment.. The present study proposes to utilize a sequential multiple assignment randomized trial design to compare two psychological interventions targeting buprenorphine-naloxone adherence: (1) contingency management (CM) and (2) brief motivational interviewing plus substance-free activities session plus mindfulness (BSM). Participants will be N = 280 adults who present to a university-based addictions clinic seeking treatment for OUD. Participants will be randomized to condition to receive 4 sessions of their assigned intervention (CM or BSM). Participants who are adherent, defined as attending physician appointments and having buprenorphine present in urine toxicology, will enter maintenance intervention for an additional 6 months. Those who are not adherent will be re-randomized to receive either the other intervention or both interventions. Follow-up will occur at 8 months post-randomization.. This novel design will examine the benefit of sequential treatment decisions following non-adherence. The primary outcome of this study is buprenorphine-naloxone medication adherence, as assessed by physician visit attendance and presence of buprenorphine in urine. Results will elicit the relative efficacy of CM and BSM compared to one another and whether keeping the initial treatment approach when adding the alternative approach for initially non-adherent individuals is beneficial.. ClinicalTrials.gov NCT04080180.

Topics: Adult; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Economics, Behavioral; Humans; Medication Adherence; Mindfulness; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders

Conflictual evidence exists regarding the effects of cannabis use on the outcomes of opioid agonist therapy (OAT). In this exploratory analysis, we examined the effect of recent cannabis use on opioid use, craving, and withdrawal symptoms, in individuals participating in a trial comparing flexible buprenorphine/naloxone (BUP/NX) take-home dosing model to witnessed ingestion of methadone.. We analyzed data from a multi-centric, pragmatic, 24-week, open label, randomized controlled trial in individuals with prescription-type opioid use disorder (n = 272), randomly assigned to BUP/NX (n = 138) or methadone (n = 134). The study measured last week cannabis and opioid use via timeline-follow back, recorded at baseline and every two weeks during the study. Craving symptoms were measured using the Brief Substance Craving Scale at baseline, and weeks 2, 6, 10, 14, 18 and 22. The study measured opioid withdrawal symptoms via Clinical Opiate Withdrawal Scale at treatment initiation and weeks 2, 4, and 6.. The mean maximum dose taken during the study was 17.3 mg/day (range = 0.5-32 mg/day) for BUP/NX group and 67.7 mg/day (range = 10-170 mg/day) in the methadone group. Repeated measures generalized linear mixed models demonstrated that cannabis use in the last week (mean of 2.3 days) was not significantly associated with last week opioid use (aβ ± standard error (SE) = -0.06 ± 0.04; p = 0.15), craving (aβ ± SE = -0.05 ± 0.08, p = 0.49), or withdrawal symptoms (aβ ± SE = 0.09 ± 0.1, p = 0.36). Bayes factor (BF) for each of the tested models supported the null hypothesis (BF < 0.3).. The current study did not demonstrate a statistically significant effect of cannabis use on outcomes of interest in the context of a pragmatic randomized-controlled trial. These findings replicated previous results reporting no effect of cannabis use on opioid-related outcomes.

Topics: Analgesics, Opioid; Bayes Theorem; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cannabis; Humans; Methadone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Substance Withdrawal Syndrome

Despite high co-occurrence, chronic pain is often unaddressed in treatment for opioid use disorder (OUD) and little is known about mechanisms that may underlie associations between pain and opioid use. Using an attentional bias (AB) task with both pain and opioid cues, we evaluated a cognitive bias modification (CBM) task administered during regularly scheduled medications for OUD (mOUD) dosing visits. The current study evaluated the feasibility, acceptability, and preliminary efficacy of the CBM task. Outcomes for AB tasks used traditional mean-based score and trial-level bias scores (TLBS).. In a double-blind, randomized controlled trial, 28 individuals with OUD and chronic pain engaged in mOUD were randomized to either CBM or an AB control condition and completed up to three tasks per week for four weeks. Standard AB task was completed at baseline and post-treatment. Participants completed feasibility and acceptability measures, and preliminary efficacy (i.e., change in AB) was assessed using ANOVA models.. Participants attended 83.3% of scheduled sessions and generally reported the task was enjoyable, credible, and easy to complete. Preliminary results demonstrated a condition by time interaction highlighting a reduction in AB in the CBM group but not the control group in opioid TLBS variability (F[1,26]=5.01, p = .034) and pain TLBS towards (F[1,26]=6.42, p = .018) and pain TLBS variability (F[1,26]=5.24, p = .03).. The current study supports integrating brief, computer-based tasks designed to reduce AB into mOUD clinical care. The preliminary results suggest that TLBS outcomes may be more sensitive to capture changes in AB; however, larger studies are required.

Topics: Analgesics, Opioid; Buprenorphine; Chronic Pain; Cognition; Cues; Feasibility Studies; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders

Pregnant individuals with substance use disorders face complex issues that may serve as barriers to treatment entry and retention. Several professional organizations have established recommendations on comprehensive, collaborative approaches to treatment to meet the needs of this population, but information on real-world application is lacking. Sites participating in the NIDA CTN0080 "Medication treatment for Opioid use disorder in expectant Mothers (MOMs)"-a randomized clinical trial of extended release compared to sublingual buprenorphine among pregnant and postpartum individuals (PPI)-were selected, in part, because they have a collaborative approach to treating PPI with opioid use disorder (OUD). However, organizational differences among sites and how they implement expert recommendations for collaborative care could impact study outcomes.. Prior to study launch at each of the 13 MOMs sites, investigators used the Pregnancy and Addiction Services Assessment (PAASA) to collect information about organizational factors. Input from a team of addiction, perinatal, and economic evaluation experts guided the development of the PAASA. Investigators programmed the PAASA into a web-based data system and summarized the resultant site data using descriptive statistics.. Study sites represented four US census regions. Most sites were specialty obstetrics & gynecology (OB/GYN) programs providing OUD services (n = 9, 69.2 %), were affiliated with an academic institution (n = 11, 84.6 %), and prescribed buprenorphine in an ambulatory/outpatient setting (n = 11, 84.6 %); all sites offered access to naloxone. Sites reported that their population was primarily White, utilized public insurance, and faced numerous psychosocial barriers to treatment. Although all sites offered many services recommended by expert consensus groups, they varied in how they coordinated these services.. By providing the organizational characteristics of sites participating in the MOMs study, this report assists in filling the current gap in knowledge regarding similar programs providing services to PPI with OUD. Collaborative care programs such as those participating in MOMs are uniquely positioned to participate in research to determine the most effective models of care and to determine how research can be integrated into those clinical care settings.

Topics: Buprenorphine; Female; Humans; Mothers; Opiate Substitution Treatment; Opioid-Related Disorders; Postpartum Period; Pregnancy

Medications for opioid use disorder (OUD) are known to be effective, especially in reducing the risk of overdose death. Yet, many individuals suffering from OUD are not receiving treatment. One potential barrier can be the patient's ability to access providers through their insurance plans.. We used an audit (simulated patient) study methodology to examine appointment-granting behavior by buprenorphine prescribers in 10 different US states. Trained callers posed as women with OUD and were randomly assigned Medicaid or private insurance status. Callers request an OUD treatment appointment and then asked whether they would be able to use their insurance to cover the cost of care, or alternatively, whether they would be required to pay fully out-of-pocket.. We found that Medicaid and privately insured women were often asked to pay cash for OUD treatment--40% of the time over the full study sample. Such buprenorphine provider requests happened more than 60% of the time in some states. Areas with more providers or with more generous provider payments were not obviously more willing to accept the patient's insurance benefits for OUD treatment. Rural providers were less likely to require payment in cash in order for the woman to receive care.. State-to-state variation was the most striking pattern in our field experiment data. The wide variation suggests that women of reproductive age with OUD in certain states face even greater challenges to treatment access than perhaps previously thought; however, it also reveals that some states have found ways to curtail this problem. Our findings encourage greater attention to this public health challenge and possibly opportunities for shared learning across states.

Topics: Analgesics, Opioid; Buprenorphine; Female; Humans; Medicaid; Opiate Substitution Treatment; Opioid-Related Disorders; Prevalence; United States

Our objective was to examine the cost-effectiveness of flexible take-home buprenorphine-naloxone (BNX) versus methadone alongside the OPTIMA trial in Canada.. The OPTIMA study was a pragmatic, open-label, noninferiority, two-arm randomized controlled trial, to assess the comparative effectiveness of flexible take-home BNX vs. methadone in routine clinical care for individuals with prescription-type opioid use disorder. We evaluated cost-effectiveness using a semi-Markov cohort model. Probabilities of overdose were calibrated, accounting for fentanyl prevalence and other overdose risk factors such as naloxone availability. We considered health sector and societal cost perspectives, including costs (2020 CAD) for treatment, health resource use, criminal activity, and health state-specific preference weights as outcomes to calculate incremental cost-effectiveness ratios. Six-month and lifetime (3% annual discount rate) time-horizons were explored.. Over a lifetime time horizon, individuals accumulated -0.144 [CI: -0.302, -0.025] incremental quality-adjusted life years (QALYs) in BNX compared with methadone. Incremental costs were -$2047 [CI: -$39,197, $24,250] from a societal perspective, and -$4549 [CI: -$6332, -$3001] from a health sector perspective. Over a six-month time-horizon, individuals accumulated 0.002 [credible interval (CI): -0.011, 0.016] incremental QALYs in BNX compared with methadone. Incremental costs were -$307 [CI: -$10,385, $8466] from a societal perspective and -$1111 [CI: -$1517, -$631] from a health sector perspective. BNX was dominated (costlier, less effective) in 49.7% of simulations when adopting a societal perspective over a lifetime time horizon.. Flexible take-home BNX was not cost-effective versus methadone over a lifetime time horizon, resulting from better treatment retention in methadone compared to BNX.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cost-Benefit Analysis; Humans; Methadone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Prescriptions

We hypothesized that implementation facilitation would enable us to rapidly and effectively implement emergency department (ED)-initiated buprenorphine programs in rural and urban settings with high-need, limited resources and dissimilar staffing structures.. This multicenter implementation study employed implementation facilitation using a participatory action research approach to develop, introduce, and refine site-specific clinical protocols for ED-initiated buprenorphine and referral in 3 EDs not previously initiating buprenorphine. We assessed feasibility, acceptability, and effectiveness by triangulating mixed-methods formative evaluation data (focus groups/interviews and pre/post surveys involving staff, patients, and stakeholders), patients' medical records, and 30-day outcomes from a purposive sample of 40 buprenorphine-receiving patient-participants who met research eligibility criteria (English-speaking, medically stable, locator information, nonprisoners). We estimated the primary implementation outcome (proportion receiving ED-initiated buprenorphine among candidates) and the main secondary outcome (30-day treatment engagement) using Bayesian methods.. Within 3 months of initiating the implementation facilitation activities, each site implemented buprenorphine programs. During the 6-month programmatic evaluation, there were 134 ED-buprenorphine candidates among 2,522 encounters involving opioid use. A total of 52 (41.6%) practitioners initiated buprenorphine administration to 112 (85.1%; 95% confidence interval [CI] 79.7% to 90.4%) unique patients. Among 40 enrolled patient-participants, 49.0% (35.6% to 62.5%) were engaged in addiction treatment 30 days later (confirmed); 26 (68.4%) reported attending one or more treatment visits; there was a 4-fold decrease in self-reported overdose events (odds ratio [OR] 4.03; 95% CI 1.27 to 12.75). The ED clinician readiness increased by a median of 5.02 (95% CI: 3.56 to 6.47) from 1.92/10 to 6.95/10 (n(pre)=80, n(post)=83).. The implementation facilitation enabled us to effectively implement ED-based buprenorphine programs across heterogeneous ED settings rapidly, which was associated with promising implementation and exploratory patient-level outcomes.

Topics: Adult; Buprenorphine; Clinical Protocols; Emergency Service, Hospital; Female; Humans; Male; Narcotic Antagonists; Opioid-Related Disorders

Engagement and retention in opioid agonist therapy (OAT) remains a challenge. This study evaluated the impact of initial randomized OAT allocation on subsequent switching among people with prescription-type opioid use disorder (POUD).. Secondary analysis of a 24-week Canadian multicenter, pragmatic, randomized trial conducted between 2017 and 2020 comparing flexible take-home buprenorphine/naloxone versus supervised methadone models of care for POUD. We used Cox Proportional Hazards modeling to assess for impact of treatment assignment on time to OAT switching, adjusting for important confounders. For clinical correlates, we analyzed data from baseline questionnaires on demographic, substance use, and health factors as well as urine drug screen.. Of 272 randomized participants, 210 initiated OAT within 14 days per trial protocol, of whom 103 participants were randomized to buprenorphine/naloxone and 107 to methadone. Within 24-week follow-up, 41 (20.5%) of all participants switched OAT with 25 (24.3%, median 27 days, 88.4 per 100 person-years) and 16 participants (15.0%, median 53.5 days, 46.1 per 100 person-years) switching from buprenorphine/naloxone and methadone arms, respectively. In adjusted analysis, allocation to buprenorphine/naloxone was associated with significantly higher risk of switching (aHR = 2.31, 95% CI 1.22 - 4.38).. OAT switching was common in this sample of individuals with POUD, with individuals randomly allocated to buprenorphine/naloxone being more than twice as likely to switch versus methadone. This may reflect a stepped care approach in OUD management. More research is needed to evaluate overall retention and outcomes with the different observed risks of switching between methadone and buprenorphine/naloxone.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Canada; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Prescriptions

Buprenorphine/naloxone (BUP-NX) and methadone are used to treat opioid use disorder (OUD), yet there is insufficient evidence on the impact of doses on interventions' effectiveness and safety when treating OUD attributable to other opioids than heroin.. We explored associations between methadone and BUP-NX doses and treatment outcomes using data from OPTIMA, a 24-week, pragmatic, open-label, multicenter, pan-Canadian, randomized controlled, two-arm parallel trial with participants (N = 272) with OUD who primarily use opioids other than heroin. Participants were randomized to receive flexible take-home BUP-NX (n = 138) or standard supervised methadone treatment (n = 134). We examined associations between highest BUP-NX and methadone doses, and (1) percentage of opioid-positive urine drug screens (UDS); (2) retention in the assigned treatment; and (3) adverse events (AEs).. The mean (SD) highest BUP-NX and methadone dose were 17.31 mg/day (8.59) and 67.70 mg/day (34.70). BUP-NX and methadone doses were not associated with opioid-positive UDS percentages or AEs. Methadone dose was associated with higher retention in treatment (odds ratio [OR]: 1.025; 95% confidence interval [CI]: 1.010; 1.041), while BUP-NX dose was not (OR: 1.055; 95% CI: 0.990; 1.124). Higher methadone doses (70-110 mg/day) offered higher odds of treatment retention.. Methadone dose was associated with higher retention, which may be related to its full µ-opioid receptor agonism. Future research should notably ascertain the effect of pace of titration on a wide range of outcomes.. Our results extend previous findings of high doses of methadone increasing retention to be applied in our population using opioids other than heroin, including highly potent opioids.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Canada; Heroin; Humans; Methadone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Prescriptions

Topics: Adult; Analgesics, Opioid; Buprenorphine; Female; Humans; Male; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders

Sleep disturbances are seen even in individuals on opioid agonist treatment (OAT). Established pharmacotherapy for sleep disturbances such as benzodiazepines have misuse potential and increased mortality risk in patients with OAT. No study has explored the role of trazodone on sleep disturbance in individuals maintained on buprenorphine. We aimed to assess the efficacy of trazodone in improving sleep disturbance among individuals maintained on buprenorphine.. The study was a double-blind, placebo-controlled, parallel, randomised trial. Adult males (18-60 years) stabilised on buprenorphine with Pittsburgh Sleep Quality Index (PSQI) score of above five, without other psychiatric comorbidity were randomised to receive either trazodone (50-150mg per day) or placebo. Sleep-50 questionnaire, Epworth Sleepiness Scale (ESS), Brief Pain Inventory (BPI), Clinical Opiate Withdrawal Scale (COWS), Depression, Anxiety and Stress Scale (DASS)-21, Visual Analogue Scale (VAS) for opioid craving, and PSQI were assessed at baseline and at the end of six weeks.. Fifty-one patients were allocated to trazodone arm and 49 to placebo arm. Side-effects of trazodone were minimal and well-tolerated with comparable discontiuation rates between both groups. Significantly greater proportion of patients on trazodone (82%, mean dose 101.9 mg) had PSQI scores five or less than those on placebo (16%) at the end of six weeks. Sleep improvement was in various components like sleep quality, latency, efficiency, and duration of sleep.. Trazodone is well-tolerated and effective in improving sleep disturbances in individuals with opioid dependence maintained on buprenorphine over a six-week period.

Topics: Analgesics, Opioid; Buprenorphine; Double-Blind Method; Humans; Male; Opioid-Related Disorders; Sleep; Trazodone; Treatment Outcome

Few studies have examined the cost of medication for opioid use disorder (MOUD) with counseling for the adolescent and young adult population. This study calculated the health care utilization and cost of MOUD treatment, other substance use disorder treatment, and general health care for adolescents and young adults receiving treatment for opioid use disorder.. The study randomized youth ages 15 to 21 (N = 288) equally into the two study conditions: extended-release naltrexone (XR-NTX) or treatment as usual (TAU). While participants committed to treatment based on randomization the study observed considerable nonadherence to both randomized conditions. Instead of using the randomly assigned study conditions, we present descriptive costs by the type of MOUD treatment received: XR-NTX only, buprenorphine only, any other combination of MOUD treatments, and no MOUD. Health care use was aggregated over the 6-month period for each participant, and we calculated average/participant utilization for each treatment group. To determine participant costs, we multiplied the unit costs of health care services obtained from the literature by the reported amount of health care utilization for each participant. We then calculated the mean, standard error, median and IQR for MOUD costs, other substance use disorder treatment costs and general healthcare cost from the health care sector perspective.. On average, participants in the XR-NTX only group received 2.6 doses of XR-NTX (equivalent to approximately 78 days of treatment). The buprenorphine only group had an average of 97 days of buprenorphine treatment. The XR-NTX only group had higher/patient costs compared to participants in the buprenorphine only group ($10,491 vs. $8765) and higher XR-NTX utilization would further increase costs. Participants in the any other MOUD combination group had the highest total costs ($14,627) while participants in the no MOUD group at the lowest ($3453).. Our cost analysis calculates the real-world cost of MOUD treatment and, while not generalizable, provides policy makers an estimate of costs for adolescents and young adults. We found that participants in the XR-NTX only group received fewer days of medication compared to the buprenorphine only group, but their medication costs were higher due to the cost of XR-NTX injections. While the buprenorphine only group had the highest number of days of medication utilization of all the groups, the average number of days of medication utilization was considerably shorter than the six-month treatment period.

Topics: Adolescent; Buprenorphine; Counseling; Health Care Costs; Humans; Narcotic Antagonists; Opioid-Related Disorders; Young Adult

Few studies investigate the natural history of patients on long-term treatment for opioid use disorder (OUD). We evaluated the long-term efficacy, safety, and tolerability experience of monthly extended-release buprenorphine (BUP-XR) in participants seeking treatment for OUD, via integrated analysis of phase 3 studies.. Study 1 was a 24-week randomized, double-blind, placebo-controlled trial of participants receiving monthly injections of BUP-XR (300 mg × 2, 100 mg × 4 [n = 203] or 300 mg × 6 [n = 201]) or placebo (n = 100). Study 2 was a 48-week, open-label trial enrolling 257 participants who completed study 1 and 412 de novo participants, to receive 6 and 12 BUP-XR injections, respectively. Study 3 was a 24-week, open-label extension enrolling 208 participants who completed study 2 for 6 additional injections. We assessed opioid abstinence as the proportion of urine opioid negative participants by visit and the percentage of each participant's negative opioid assessments during the first 6 months.. In total, 916 participants were treated with BUP-XR or placebo. By the end of 18 months, 92.7 % of the de novo cohort and 81.8 % of the study 1 cohort were urine negative for opioids. Among early nonresponders (percentage of abstinence ≤20 %), 73.1 % were urine negative after 18 months. The longer treatment period was well tolerated, with no new safety concerns, and a low incidence of opioid withdrawal signs and symptoms, and hepatic disorder.. Extending BUP-XR treatment beyond 6 months sustained improvement in opioid abstinence and was well tolerated, supporting clinical benefit up to 18 months.. NCT02357901 (study 1); NCT02510014 (study 2); NCT02896296 (study 3).

Topics: Analgesics, Opioid; Buprenorphine; Humans; Injections, Subcutaneous; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders

Opioid use disorder (OUD) represents a public health crisis in the United States. Medication for opioid use disorder (MOUD) with buprenorphine in primary care is a proven OUD treatment strategy. MOUD induction is when patients begin withdrawal and receive the first doses of buprenorphine. Differences between induction methods might influence short-term stabilization, long-term maintenance, and quality of life. This paper describes the protocol for a study designed to: (1) compare short-term stabilization and long-term maintenance treatment engagement in MOUD in patients receiving office, home, or telehealth induction and (2) identify clinically-relevant practice and patient characteristics associated with successful long-term treatment. The study design is a randomized, parallel group, pragmatic comparative effectiveness trial of three care models of MOUD induction in 100 primary care practices in the United States. Eligible patients are at least 16 years old, have been identified by their clinician as having opioid dependence and would benefit from MOUD. Patients will be randomized to one of three induction comparators: office, home, or telehealth induction. Primary outcomes are buprenorphine medication-taking and illicit opioid use at 30, 90, and 270 days post-induction. Secondary outcomes include quality of life and potential mediators of treatment maintenance (intentions, planning, automaticity). Potential moderators include social determinants of health, substance use history and appeal, and executive function. An intent to treat analysis will assess effects of the interventions on long-term treatment, using general/generalized linear mixed models, adjusted for covariates, for the outcomes analysis. Analysis includes practice- and patient-level random effects for hierarchical/longitudinal data. No large-scale, randomized comparative effectiveness research has compared home induction to office or telehealth MOUD induction on long-term outcomes for patients with OUD seen in primary care settings. The results of this study will offer primary care providers evidence and guidance in selecting the most beneficial induction method(s) for specific patients.

Topics: Adolescent; Buprenorphine; Humans; Opioid-Related Disorders; Primary Health Care; Quality of Life; Randomized Controlled Trials as Topic; Research Design

Although methamphetamine use is rising in the United States, its impacts on patient outcomes among persons undergoing treatment for opioid use disorder (OUD) remain unclear. This study aims to assess the association between baseline methamphetamine/amphetamine (MA/A) use and subsequent illicit opioid use among patients with OUD initiating buprenorphine in an office-based setting.. We conducted a secondary analysis of a pilot randomized controlled trial of a behavioral mobile health intervention for buprenorphine adherence conducted over a 12-week study period at two clinic sites. The study defined baseline MA/A use by a positive urine drug test (UDT) and/or self-report of use within the past 30-days. Separate Poisson regression models with robust standard errors evaluated associations between MA/A and: i) illicit opioid use measured by weekly UDT (primary) and ii) self-reported past 30-day use at end of study (secondary). Other secondary outcomes included buprenorphine positive UDTs throughout the study and retention in OUD treatment at both weeks 12 and 24 post-randomization.. At baseline, 28 (36%) of the 78 participants had MA/A use and use was associated with a statistically significant increase in risk of testing positive for illicit opioids on UDT during the study follow-up period (adjusted relative risk (aRR)=1.54; 95% CI=1.09-2.17; p=0.015), as well as an increased risk for reported past 30-day illicit opioid use at week 12 (aRR=3.86; 95% CI=1.47-10.18; P=0.006). The study found no significant associations between MA/A use and buprenorphine positive UDT or retention in OUD treatment.. In this sample of patients initiating buprenorphine, methamphetamine/amphetamine use at baseline was associated with illicit opioid use over a 12-week period. These findings demonstrate how co-use of methamphetamine can impede attainment of ideal OUD treatment outcomes.

Topics: Analgesics, Opioid; Buprenorphine; Humans; Methamphetamine; Narcotic Antagonists; Opioid-Related Disorders

People living with HIV and opioid use disorder (OUD) are disproportionally affected by adverse socio-structural exposures negatively affecting health, which have shown inconsistent associations with uptake of medications for OUD (MOUD). This study aimed to determine whether social determinants of health (SDOH) were associated with MOUD uptake and trajectories of substance use in a clinical trial of people seeking treatment.. Data are from a 2018 to 2019 randomized trial comparing the effectiveness of different MOUD to achieve viral suppression among people living with HIV and OUD. SDOH were defined by variables mapping to Healthy People 2030 domains: education (Education Access and Quality), income (Economic Stability), homelessness (Neighborhood and Built Environment), criminal justice involvement (Social and Community Context), and recent SUD care (Health Care Access and Quality). Associations between SDOH and MOUD initiation were assessed with Cox proportional hazards models, and SDOH and substance use over time with generalized estimating equation models.. Participants (N = 114) averaged 47 years old, 63% were male, 56% were Black, and 12% Hispanic. Participants reported an average of 2.3 out of 5 positive SDOH indicators (SD = 1.2). Stable housing was the most commonly reported SDOH (61%), followed by no recent criminal justice involvement (59%), having a high-school level education or greater (56%), income stability (45%), and recent SUD care (13%). Each additional favorable SDOH was associated with a 25% increase in the likelihood of MOUD initiation during the study period [adjusted HR = 1.25, 95% CI = (1.01, 1.55),. Positive social determinants of health, in aggregate, may increase the likelihood of MOUD treatment initiation among people living with HIV and OUD.

Topics: Analgesics, Opioid; Buprenorphine; Female; HIV Infections; Humans; Male; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Social Determinants of Health

First study to assess any compensatory increase in use of non-opioid illicit substances and alcohol in opioid dependent patients randomized to treatment with extended-release naltrexone (XR-NTX) or buprenorphine-naloxone (BP-NLX) and in longer term treatment with extended-release naltrexone.. A multicenter, outpatient, open-label randomized clinical trial where patients received intramuscular extended-release naltrexone hydrochloride, 380 mg/month, or daily sublingual buprenorphine-naloxone 8-24/2-6 mg for 12 weeks, and an option to continue with extended-release naltrexone for an additional 36 week follow-up. The study was conducted at five urban addiction clinics and detoxification units in Norway between November 2012, and July 2016.. Among the 143 patients, 106 men and 37 women, there were no significant differences between those randomized to XR-NTX or BP-NLX in the risk of first relapse to alcohol (HR 1.31; 0.68-2.53), amphetamines (HR 0.88; 0.43-1.80), benzodiazepines (HR 1.24; 0.74-2.09) or cannabis (HR 1.55; 0.83-2.89). Also in the 36-week (12-48 weeks) follow-up period we found no significant differences between patients continuing with XR-NTX compared to those switching to XR-NTX after the randomized period in risk of first relapse to any non-opioid substance. In both study periods, the mean time in the study were longer among those relapsing to non-opioid addictive substances than those who did not. There was no significant association between first relapse to illicit opioids and first relapse to non-opioid addictive substances.. There was no increase in the risk of relapse to non-opioid addictive substances neither in short term nor longer-term treatment with extended-release naltrexone. Trial registrationclinicaltrials.gov Identifier: NCT01717963.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Chronic Disease; Delayed-Action Preparations; Female; Humans; Injections, Intramuscular; Male; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Recurrence

Emergency department (ED) initiation of buprenorphine is safe and effective but underutilized in practice. Understanding the factors affecting adoption of this practice could inform more effective interventions.. To quantify the factors, including social contagion, associated with the adoption of the practice of ED initiation of buprenorphine for patients with opioid use disorder.. This is a secondary analysis of the EMBED (Emergency Department-Initiated Buprenorphine For Opioid Use Disorder) trial, a multicentered, cluster randomized trial of a clinical decision support intervention targeting ED initiation of buprenorphine. The trial occurred from November 2019 to May 2021. The study was conducted at ED clusters across health care systems from the northeast, southeast, and western regions of the US and included attending physicians, resident physicians, and advanced practice practitioners. Data analysis was performed from August 2022 to June 2023.. This analysis included both the intervention and nonintervention groups of the EMBED trial. Graph methods were used to construct the network of clinicians who shared in the care of patients for whom buprenorphine was initiated during the trial before initiating the practice themselves, termed exposure.. Cox proportional hazard modeling with time-dependent covariates was performed to assess the association of the number of these exposures with self-adoption of the practice of ED initiation of buprenorphine while adjusting for clinician role, health care system, and intervention site status.. A total of 1026 unique clinicians in 18 ED clusters across 5 health care systems were included. Analysis showed associations of the cumulative number of exposures to others initiating buprenorphine with the self-practice of buprenorphine initiation. This increased in a dose-dependent manner (1 exposure: hazard ratio [HR], 1.31; 95% CI, 1.16-1.48; 5 exposures: HR, 2.85; 95% CI, 1.66-4.89; 10 exposures: HR, 3.55; 95% CI, 1.47-8.58). Intervention site status was associated with practice adoption (HR, 1.50; 95% CI, 1.04-2.18). Health care system and clinician role were also associated with practice adoption.. In this secondary analysis of a multicenter, cluster randomized trial of a clinical decision support tool for buprenorphine initiation, the number of exposures to ED initiation of buprenorphine and the trial intervention were associated with uptake of ED initiation of buprenorphine. Although systems-level approaches are necessary to increase the rate of buprenorphine initiation, individual clinicians may change practice of those around them.. ClinicalTrials.gov Identifier: NCT03658642.

Topics: Buprenorphine; Emergency Service, Hospital; Humans; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders

BUP-XR (SUBLOCADE. This was a secondary analysis of a randomized, double-blind, placebo-controlled study in which adults with moderate or severe OUD received monthly injections of BUP-XR (2 × 300-mg doses, then 4 × 100-mg or 300-mg maintenance doses) or placebo for 24 weeks. Abstinence was defined as opioid-negative urine drug screens combined with negative self-reports collected weekly. Each participant's percentage abstinence was calculated after the first, second, and third maintenance doses in opioid-injecting and non-injecting participants. The proportion of participants achieving opioid abstinence in each group was also calculated weekly. Treatment retention rate following the first maintenance dose was estimated for opioid-injecting participants with Kaplan-Meier method. Risk-adjusted comparisons were made via inverse propensity weighting using propensity scores. Buprenorphine plasma concentration-time profiles were compared between injecting and non-injecting participants. The percentages of participants reporting treatment-emergent adverse events were compared between maintenance dose groups within injecting and non-injecting participants separately.. BUP-XR 100-mg and 300-mg maintenance doses were equally effective in non-injecting participants. However, in opioid-injecting participants, the 300-mg maintenance dose delivered clinically meaningful improvements over the 100-mg maintenance dose for treatment retention and opioid abstinence. Exposure-response analyses confirmed that injecting participants would require higher buprenorphine plasma concentrations compared to non-injecting opioid participants to achieve similar efficacy in terms of opioid abstinence. Importantly, both 100- and 300-mg maintenance doses had comparable safety profiles, including hepatic safety events.. These analyses show clear benefits of the 300-mg maintenance dose in injecting participants, while no additional benefit was observed in non-injecting participants relative to the 100-mg maintenance dose. This is an important finding as opioid-injecting participants represent a high-risk and difficult-to-treat population. Optimal buprenorphine dosing in this population might facilitate harm reduction by improving abstinence and treatment retention.. ClinicalTrials.gov, NCT02357901.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Delayed-Action Preparations; Humans; Narcotic Antagonists; Opioid-Related Disorders; Treatment Outcome

In Vietnam, access to medications for opioid use disorder (MOUD) for people living with HIV has rapidly expanded, but MOUD use over time remains low. We sought to assess factors associated with days of MOUD treatment exposure.. From 2015 to 2019, patients with OUD in six Northern Vietnamese HIV clinics were randomized to receive HIV clinic-based buprenorphine (BUP/NX) or referral for methadone maintenance therapy (MMT) and followed for 12 months. All MOUD doses were directly observed and abstracted from dosing logs. The primary outcome was days of MOUD treatment exposure (buprenorphine or methadone) received over 12 months. Negative binomial regression modelled associations with days of MOUD exposure.. Of 281 participants, 264 (94%) were eligible for analysis. Participants were primarily male (97%), unmarried (61%), employed (54%), and previously arrested (83%). Participants had a mean 187 (SD 150) days of MOUD exposure with 134 (51%) having at least 180 days, and 35 (13.2%) having at least 360 days of MOUD exposure. Age (IRR 1.26, 95% CI 1.02-1.55), income (IRR 0.96, 95% CI 0.93-1.001), and methadone (IRR 1.88, 95% CI 1.51-2.42) were associated with MOUD exposure in multivariate models. Multivariate models predicted 127 (95% CL 109-147) days of MOUD exposure for HIV clinic based-buprenorphine vs 243 (95% CL 205-288) for MMT.. MOUD treatment exposure was suboptimal among patients with HIV and OUD in Northern Vietnam and was influenced by several factors. Interventions to support populations at risk of lower MOUD exposure as well programs administering MOUD should be considered in countries seeking to expand access to MOUD.

Topics: Analgesics, Opioid; Buprenorphine; HIV Infections; Humans; Male; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Vietnam

Identifying effective strategies to improve access to medication treatments for opioid use disorder (MOUD) is imperative. Within the Veterans Health Administration (VHA), provision of MOUD varies significantly, requiring development and testing of implementation strategies that target facilities with low provision of MOUD.. Determine the effectiveness of external facilitation in increasing the provision of MOUD among VHA facilities with low baseline provision of MOUD compared to matched controls.. Pre-post, block randomized study designed to compare facility-level outcomes in a stratified sample of eligible facilities. Four blocks (two intervention facilities in each) were defined by median splits of both the ratio of patients with OUD receiving MOUD and number of patients with OUD not currently receiving MOUD (i.e., number of actionable patients). Intervention facilities participated in a 12-month implementation intervention.. VHA facilities in the lowest quartile of MOUD provision (35 facilities), eight of which were randomly assigned to participate in the intervention (two per block) with twenty-seven serving as matched controls by block.. External facilitation included assessment of local barriers/facilitators, formation of a local implementation team, a site visit for action planning and training/education, cross-facility quarterly calls, monthly coaching calls, and consultation.. Pre- to post-change in the facility-level ratio of patients with an OUD diagnosis receiving MOUD compared to control facilities.. Intervention facilities significantly increased the ratio of patients with OUD receiving MOUD from an average of 18% at baseline to 30% 1 year later, with an absolute difference of 12% (95% confidence interval [CI]: 6.6%, 17.0%). The difference in differences between intervention and control facilities was 3.0% (95% CI: - 0.2%. 6.7%). The impact of the intervention varied by block, with smaller, less complex facilities more likely to outperform matched controls.. Intensive external facilitation improved the adoption of MOUD in most low-performing facilities and may enhance adoption beyond other interventions less tailored to individual facility contexts.

Topics: Buprenorphine; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Veterans Health

Despite dramatic increases in opioid use disorder (OUD) and overdose deaths, the U.S. has been unable to consistently deliver OUD treatment to those who need it. Syringe services programs (SSPs) can engage an out-of-treatment population of people with OUD that has elevated overdose risk. Buprenorphine treatment is safe and effective, and US regulations allow for prescribing from diverse locations, including SSPs. This study's objective is to test buprenorphine treatment initiation at SSPs. We hypothesize that offering onsite buprenorphine treatment initiation will improve OUD treatment engagement without reducing buprenorphine treatment effectiveness or safety.. We will recruit 250 out-of-treatment SSP participants with OUD in a large urban area. Participants will be randomized to onsite buprenorphine treatment initiation or enhanced referral. Over 2 weeks, participants in the onsite treatment arm will see a buprenorphine provider twice at the SSP, receive weekly medication packs, and then their care will be transferred to a community health center for treatment continuation. In the control arm, within one week, participants will receive an appointment at the same community health center as in the intervention arm for buprenorphine initiation and continuation. Participants will be assessed with urine drug tests, questionnaires, and medical record review. The primary outcome will be engagement in buprenorphine treatment at 30 days. Secondary outcomes include buprenorphine diversion, opioid-free urine drug tests, and intervention cost-effectiveness.. Our study will contribute to the growing literature on SSPs as a conduit to OUD treatment. SSPs hold promise to deliver needed care to people with OUD.

Topics: Buprenorphine; Harm Reduction; HIV Infections; Humans; Opiate Substitution Treatment; Opioid-Related Disorders

Opioid-induced respiratory depression driven by ligand binding to mu-opioid receptors is a leading cause of opioid-related fatalities. Buprenorphine, a partial agonist, binds with high affinity to mu-opioid receptors but displays partial respiratory depression effects. The authors examined whether sustained buprenorphine plasma concentrations similar to those achieved with some extended-release injections used to treat opioid use disorder could reduce the frequency and magnitude of fentanyl-induced respiratory depression.. In this two-period crossover, single-centre study, 14 healthy volunteers (single-blind, randomized) and eight opioid-tolerant patients taking daily opioid doses ≥90 mg oral morphine equivalents (open-label) received continuous intravenous buprenorphine or placebo for 360 minutes, targeting buprenorphine plasma concentrations of 0.2 or 0.5 ng/mL in healthy volunteers and 1.0, 2.0 or 5.0 ng/mL in opioid-tolerant patients. Upon reaching target concentrations, participants received up to four escalating intravenous doses of fentanyl. The primary endpoint was change in isohypercapnic minute ventilation (VE). Additionally, occurrence of apnea was recorded.. Fentanyl-induced changes in VE were smaller at higher buprenorphine plasma concentrations. In healthy volunteers, at target buprenorphine concentration of 0.5 ng/mL, the first and second fentanyl boluses reduced VE by [LSmean (95% CI)] 26% (13-40%) and 47% (37-59%) compared to 51% (38-64%) and 79% (69-89%) during placebo infusion (p = 0.001 and < .001, respectively). Discontinuations for apnea limited treatment comparisons beyond the second fentanyl injection. In opioid-tolerant patients, fentanyl reduced VE up to 49% (21-76%) during buprenorphine infusion (all concentration groups combined) versus up to 100% (68-132%) during placebo infusion (p = 0.006). In opioid-tolerant patients, the risk of experiencing apnea requiring verbal stimulation following fentanyl boluses was lower with buprenorphine than with placebo (odds ratio: 0.07; 95% CI: 0.0 to 0.3; p = 0.001).. Results from this proof-of-principle study provide the first clinical evidence that high sustained plasma concentrations of buprenorphine may protect against respiratory depression induced by potent opioids like fentanyl.

Topics: Adult; Buprenorphine; Cross-Over Studies; Delayed-Action Preparations; Female; Fentanyl; Healthy Volunteers; Humans; Infusions, Intravenous; Male; Middle Aged; Opioid-Related Disorders; Proof of Concept Study; Respiratory Insufficiency; Single-Blind Method; Young Adult

To address the US opioid epidemic, there is an urgent clinical need to provide persons with opioid use disorder (OUD) with effective medication treatments for OUD (MOUD). Formulations of sublingual buprenorphine/naloxone (SL-BUP/NLX) are considered the standard of care for OUD including within the Veterans Healthcare Administration (VHA). However, poor retention on MOUD undermines its effectiveness. Long-acting injectable monthly buprenorphine (INJ-BUP) (e.g., Sublocade®) has the potential to improve retention and therefore reduce opioid use and overdose. Designing and conducting studies for OUD pose unique challenges. The strategies and solutions to some of these considerations in designing Cooperative Studies Program (CSP) 2014, Buprenorphine for Treating Opioid Use Disorder in Veterans (VA-BRAVE), a randomized, 20-site, clinical effectiveness trial comparing INJ-BUP to SL-BUP/NLX conducted within the VHA may provide valuable guidance for others confronted with similar investigation challenges.. This 52-week, parallel group, open-label, randomized controlled trial (RCT) evaluates the comparative effectiveness of two current FDA-approved formulations of buprenorphine: (1) daily SL-BUP/NLX vs. (2) monthly (28-day) INJ-BUP for Veterans with moderate to severe OUD (n = 952). The primary outcomes are (1) retention in MOUD and (2) opioid abstinence. Secondary outcomes include measures of other drug use, psychiatric symptoms, medical outcomes including prevalence rates of HIV, hepatitis B and C as well as social outcomes (housing instability, criminal justice involvement), service utilization and cost-effectiveness. Special considerations in conducting a comparative effectiveness trial with this population and during COVID-19 pandemic were also included.. The evaluation of the extended-release formulation of buprenorphine compared to the standard sublingual formulation in real-world VHA settings is of paramount importance in addressing the opioid epidemic. The extent to which this new treatment facilitates retention, decreases opioid use, and prevents severe sequelae of OUD has not been studied in any long-term trial to date. Positive findings in this trial could lead to widespread adoption of MOUD, and, if proven superior INJ-BUP, by clinicians throughout the VHA and beyond. This treatment has the potential to reduce opioid use among Veterans, improve medical, psychological, and social outcomes, and save lives at justifiable cost. Trial registration Registered at Clinicaltrials.gov NCT04375033.

Topics: Buprenorphine; COVID-19; Humans; Narcotic Antagonists; Opioid-Related Disorders; SARS-CoV-2; Veterans

Treatment for individuals receiving medication for opioid use disorder (MOUD) should follow an informed patient-centered approach. To better support patient autonomy in the decision-making process, clinicians should be aware of patient preferences and be prepared to educate and assist patients in transitioning from one MOUD to another, when clinically indicated. This posthoc analysis describes the characteristics of clinical trial participants (NCT02696434) with a history of opioid use disorder (OUD) seeking to transition from buprenorphine (BUP) to extended-release naltrexone (XR-NTX).. The posthoc analysis included adults with OUD currently receiving BUP (≤8 mg/day) and seeking transition to XR-NTX (N = 101) in a residential setting. Baseline participant characteristics and OUD treatment history were reviewed. All patients completed a screening questionnaire that asked about their reasons for seeking transition to XR-NTX and for choosing BUP.. The most common reasons for initiating a transition to XR-NTX were "Seeking to be opioid-free" (63.4%) and "Tired of daily pill taking" (25.7%). Positive predictors of transition included a more extensive BUP treatment history and a history of prescription opioid abuse. Most participants stated they were not aware of XR-NTX as a treatment option when initiating BUP (78.2%).. Patients' reasons for seeking XR-NTX transition, more extensive BUP treatment history, and a history of prescription opioid abuse, may positively predict outcomes.. These findings may assist clinicians in optimizing outcomes of the BUP to XR-NTX transition and supporting patients to make better informed MOUD decisions.

Topics: Adult; Buprenorphine; Delayed-Action Preparations; Humans; Injections, Intramuscular; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders

Access to the opioid antidote naloxone is a critical component of addressing the opioid crisis. Naloxone is a population-level prevention intervention associated with substantial reductions in overdose mortality and reduction of nonfatal overdose. Pharmacies' pivotal role in dispensing medications like buprenorphine for the treatment of opioid use disorder and selling nonprescription syringes places them at the crossroads of opioid access and risk mitigation methods like naloxone provision. Testing ways to optimize pharmacy-based naloxone provision will be key as the country expands the implementation of naloxone through the medical system. In the Respond to Prevent Study, we conducted a large, practical study of a pharmacy-focused intervention in a sample of Washington, Oregon, Massachusetts and New Hampshire community chain pharmacies to increase naloxone dispensing and improve opioid safety. The intervention integrated two evidence-based educational toolkits and streamlined materials to enhance the focus on naloxone policy, stigma reduction, and patient communications around naloxone, nonprescription syringes and buprenorphine access. The real-world study implemented a stepped wedge, clustered randomized trial design across 175 community chain pharmacies to evaluate the effectiveness of the Respond to Prevent intervention in increasing: (a) pharmacy based naloxone distribution rates, naloxone-related patient engagement, and pharmacist and technicians' attitudes, knowledge, perceived behavioral control and self-efficacy toward naloxone; and (b) pharmacy nonprescription syringe sales, and pharmacist and technicians' attitudes, knowledge, perceived behavioral control and self-efficacy toward dispensing buprenorphine for opioid use disorder (secondary outcomes). This commentary provides a brief narrative about the study and presents insights on the design and adaptations to our study protocol, including those adopted during the unprecedented COVID-19 pandemic further compounded by Western wildfires in 2020.

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; COVID-19; Drug Overdose; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Pandemics; Pharmacies; Pharmacists; Randomized Controlled Trials as Topic; SARS-CoV-2; Syringes

The aim of this secondary analysis was to identify prodynorphin (PDYN) genetic markers moderating the therapeutic response to treatment of cocaine dependence with buprenorphine/naloxone (Suboxone®; BUP).. Cocaine-dependent participants (N = 302) were randomly assigned to a platform of injectable, extended-release naltrexone (XR-NTX) and one of three daily medication arms: 4 mg BUP (BUP4), 16 mg BUP (BUP16), or placebo (PLB) for 8 weeks (Parent Trial Registration: Protocol ID: NIDA-CTN-0048, Clinical Trials.gov ID: NCT01402492). DNA was obtained from 277 participants. Treatment response was determined from weeks 3 to 7 over each 1-week period by the number of cocaine-positive urines per total possible urines.. In the cross-ancestry group, the PLB group had more cocaine-positive urines than the BUP16 group (P = 0.0021). The interactions of genetic variant × treatment were observed in the rs1022563 A-allele carrier group where the BUP16 group (N = 35) had fewer cocaine-positive urines (P = 0.0006) than did the PLB group (N = 26) and in the rs1997794 A-allele carrier group where the BUP16 group (N = 49) had fewer cocaine-positive urines (P = 0.0003) than did the PLB group (N = 58). No difference was observed in the rs1022563 GG or rs1997794 GG genotype groups between the BUP16 and PLB groups. In the African American-ancestry subgroup, only the rs1022563 A-allele carrier group was associated with treatment response.. These results suggest that PDYN variants may identify patients who are best suited to treatment with XR-NTX plus buprenorphine for cocaine use disorder pharmacotherapy.

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cocaine; Cocaine-Related Disorders; Delayed-Action Preparations; Enkephalins; Humans; Injections, Intramuscular; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Protein Precursors

Despite the evidence in support of the use of buprenorphine in the treatment of OUD and increasing ability of emergency medicine (EM) clinicians to prescribe it, emergency department (ED)-initiated buprenorphine is uncommon. Many EM clinicians lack training on how to manage acute opioid withdrawal or initiate treatment with buprenorphine. We developed a brief buprenorphine training program and assessed the impact of the training on subsequent buprenorphine initiation and knowledge retention.. We conducted a pilot randomized control trial enrolling EM clinicians to receive either a 30-min didactic intervention about buprenorphine (standard arm) or the didactic plus weekly messaging and a monetary inducement to administer and report buprenorphine use (enhanced arm). All participants were incentivized to complete baseline, immediate post-didactic, and 90-day knowledge and attitude assessment surveys. Our objective was to achieve first time ED buprenorphine prescribing events in clinicians who had not previously prescribed buprenorphine in the ED and to improve EM-clinician knowledge and perceptions about ED-initiated buprenorphine. We also assessed whether the incentives and reminder messaging in the enhanced arm led to more clinicians administering buprenorphine than those in the standard arm following the training; we measured changes in knowledge of and attitudes toward ED-initiated buprenorphine.. Of 104 EM clinicians enrolled, 51 were randomized to the standard arm and 53 to the enhanced arm. Clinical knowledge about buprenorphine improved for all clinicians immediately after the didactic intervention (difference 19.4%, 95% CI 14.4% to 24.5%). In the 90 days following the intervention, one-third (33%) of all participants reported administering buprenorphine for the first time. Clinicians administered buprenorphine more frequently in the enhanced arm compared to the standard arm (40% vs. 26.3%, p = 0.319), but the difference was not statistically significant. The post-session knowledge improvement was not sustained at 90 days in the enhanced (difference 9.6%, 95% CI - 0.37% to 19.5%) or in the standard arm (difference 3.7%, 95% CI - 5.8% to 13.2%). All the participants reported an increased ability to recognize patients with opioid withdrawal at 90 days (enhanced arm difference .55, 95% CI .01-1.09, standard arm difference .85 95% CI .34-1.37).. A brief educational intervention targeting EM clinicians can be utilized to achieve first-time prescribing and improve knowledge around buprenorphine and opioid withdrawal. The use of weekly messaging and gain-framed incentivization conferred no additional benefit to the educational intervention alone. In order to further expand evidence-based ED treatment of OUD, focused initiatives that improve clinician competence with buprenorphine should be explored.. ClinicalTrials.gov Identifier: NCT03821103.

Topics: Analgesics, Opioid; Buprenorphine; Emergency Service, Hospital; Humans; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Substance Withdrawal Syndrome

Topics: Buprenorphine; Central Nervous System Stimulants; Cocaine; Humans; Nitrosamines; Opiate Substitution Treatment; Opioid-Related Disorders; Substance-Related Disorders

Methamphetamine use is increasing among persons with opioid use disorder (OUD). The study aims were to describe methamphetamine/amphetamine (MA/A) use among patients treated for OUD with buprenorphine/naloxone (BUP-NX) or extended-release naltrexone (XR-NTX), and to explore associations between treatment arm and MA/A use.. Secondary analysis of data from a multi-site, open-label, randomized controlled trial of XR-NTX versus BUP-NX for 24 weeks. The outcome variable was MA/A use defined by either positive urine drug toxicology or self-report. The main predictor was treatment assignment (BUP-NX v. XR-NTX). Longitudinal mixed-effects logistic regression models were fit to model the odds of MA/A use during the study. Additional predictors included study visit and baseline MA/A use.. Among the sample of 570 participants with OUD, baseline use of MA/A was observed in 105 (18.4%). There was no significant treatment effect over the study period, though BUP-NX subjects, on average, had about half the odds of MA/A use compared to XR-NTX subjects (OR=0.50; p = 0.051). In the same model, baseline MA/A use and study visit were both significantly associated with MA/A use over time.. In this sample of treated OUD patients, nearly a fifth of participants had MA/A use at baseline and the frequency of use did not decline over time: in fact, the odds of use slightly increased for each later visit. These secondary analyses found no significant difference in MA/A use between BUP-NX and XR-NTX treatment arms, however, the observation of less MA/A in the buprenorphine arm merits further investigation.. ClinicalTrials.gov (NCT02032433).

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Delayed-Action Preparations; Humans; Injections, Intramuscular; Methamphetamine; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders

Extensive exposure to prescription-type opioids has resulted in major harm worldwide, calling for better-adapted approaches to opioid agonist therapy. The authors aimed to determine whether flexible take-home buprenorphine/naloxone is as effective as supervised methadone in reducing opioid use in prescription-type opioid consumers with opioid use disorder.. This seven-site, pan-Canadian, 24-week, pragmatic, open-label, noninferiority, two-arm parallel randomized controlled trial involved treatment-seeking adults with prescription-type opioid use disorder. Participants were randomized in a 1:1 ratio to treatment with sublingual buprenorphine/naloxone (target dosage, 8 mg/2 mg to 24 mg/6 mg per day; flexible take-home dosing) or oral methadone (≈60-120 mg/day; closely supervised). The primary outcome was the proportion of opioid-free urine drug screens over 24 weeks (noninferiority margin, 15%). All randomized participants were analyzed, excluding one who died shortly after randomization, for the primary analysis (modified intention-to-treat analysis).. Of 272 participants recruited (mean age, 39 years [SD=11]; 34.2% female), 138 were randomized to buprenorphine/naloxone and 134 to methadone. The mean proportion of opioid-free urine drug screens was 24.0% (SD=34.4) in the buprenorphine/naloxone group and 18.5% (SD=30.5) in the methadone group, with a 5.6% adjusted mean difference (95% CI=-0.3, +∞). Participants in the buprenorphine/naloxone group had 0.47 times the odds (95% CI=0.24, 0.90) of being retained in the assigned treatment compared with those in the methadone group. Overall, 24 drug-related adverse events were reported (12 in the buprenorphine/naloxone group [N=8/138; 5.7%] and 12 in the methadone group [N=12/134; 9.0%]) and mostly included withdrawal, hypogonadism, and overdose.. The buprenorphine/naloxone flexible model of care was safe and noninferior to methadone in reducing opioid use among people with prescription-type opioid use disorder. This flexibility could help expand access to opioid agonist therapy and reduce harms in the context of the opioid overdose crisis.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Canada; Drug Overdose; Female; Humans; Male; Methadone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Prescriptions

Fentanyl is primarily responsible for the current phase of the overdose epidemic in North America. Despite the benefits of treatment with medications for opioid use disorder (MOUD), there are limited data on the association between fentanyl, MOUD type and treatment engagement. The objectives of this analysis were to measure the impact of baseline fentanyl exposure on initiation and discontinuation of MOUD among individuals with prescription-type opioid use disorder (POUD).. Secondary analysis of a Canadian multi-site randomized pragmatic trial conducted between 2017 and 2020. Of the 269 randomized participants, 65.4% were male, 67.3% self-identified as white and 55.4% had a positive fentanyl urine drug test (UDT) at baseline. Fentanyl-exposed participants were more likely to be younger, to self-identify as non-white, to be unemployed or homeless and to be currently using stimulants than non-fentanyl-exposed participants.. Flexible take-home dosing buprenorphine/naloxone or supervised methadone models of care for 24 weeks.. Outcomes were (1) MOUD initiation and (2) time to (a) assigned and (b) overall MOUD discontinuation. Independent variables were baseline fentanyl UDT (predictor) and assigned MOUD (effect modifier).. Overall, 209 participants (77.7%) initiated MOUD. In unadjusted analyses, fentanyl exposure was associated with reduced likelihood of treatment initiation [odds ratio (OR) = 0.18, 95% confidence interval (CI) = 0.08-0.36] and shorter median times in assigned [20 versus 168 days, hazard ratio (HR) = 3.61, 95% CI = 2.52-5.17] and any MOUD (27 versus 168 days, HR = 3.32, 95% CI = 2.30-4.80). The negative effects were no longer statistically significant in adjusted models, and no interaction between fentanyl and MOUD was observed for any of the outcomes (all P > 0.05).. Both buprenorphine/naloxone and methadone may be appropriate treatment options for people with prescription-type opioid use disorder regardless of fentanyl exposure. Other characteristics of fentanyl-exposed individuals appear to be driving the association with poorer treatment outcomes.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Canada; Female; Fentanyl; Humans; Male; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Prescriptions

To determine the effect of a user centered clinical decision support tool versus usual care on rates of initiation of buprenorphine in the routine emergency care of individuals with opioid use disorder.. Pragmatic cluster randomized controlled trial (EMBED).. 18 emergency department clusters across five healthcare systems in five states representing the north east, south east, and western regions of the US, ranging from community hospitals to tertiary care centers, using either the Epic or Cerner electronic health record platform.. 599 attending emergency physicians caring for 5047 adult patients presenting with opioid use disorder.. A user centered, physician facing clinical decision support system seamlessly integrated into user workflows in the electronic health record to support initiating buprenorphine in the emergency department by helping clinicians to diagnose opioid use disorder, assess the severity of withdrawal, motivate patients to accept treatment, and complete electronic health record tasks by automating clinical and after visit documentation, order entry, prescribing, and referral.. Rate of initiation of buprenorphine (administration or prescription of buprenorphine) in the emergency department among patients with opioid use disorder. Secondary implementation outcomes were measured with the RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) framework.. 1 413 693 visits to the emergency department (775 873 in the intervention arm and 637 820 in the usual care arm) from November 2019 to May 2021 were assessed for eligibility, resulting in 5047 patients with opioid use disorder (2787 intervention arm, 2260 usual care arm) under the care of 599 attending physicians (340 intervention arm, 259 usual care arm) for analysis. Buprenorphine was initiated in 347 (12.5%) patients in the intervention arm and in 271 (12.0%) patients in the usual care arm (adjusted generalized estimating equations odds ratio 1.22, 95% confidence interval 0.61 to 2.43, P=0.58). Buprenorphine was initiated at least once by 151 (44.4%) physicians in the intervention arm and by 88 (34.0%) in the usual care arm (1.83, 1.16 to 2.89, P=0.01).. User centered clinical decision support did not increase patient level rates of initiating buprenorphine in the emergency department. Although streamlining and automating electronic health record workflows can potentially increase adoption of complex, unfamiliar evidence based practices, more interventions are needed to look at other barriers to the treatment of addiction and increase the rate of initiating buprenorphine in the emergency department in patients with opioid use disorder.. ClinicalTrials.gov NCT03658642.

Topics: Adult; Buprenorphine; Decision Support Systems, Clinical; Emergency Service, Hospital; Humans; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders

Stigma has corrosive effects on all aspects of care and can undermine individual and population health outcomes. Addiction-related stigma has implications for opiate agonist treatment (OAT) and the people who receive, provide and fund it. It is important to understand how stigma is made in OAT and the political purposes that it serves, in order to change the relations of stigma and avoid the reproduction of stigma in the delivery of new treatment formulations, such as extended release buprenorphine (BUP-XR).. Semi-structured qualitative interviews were conducted at two time points with participants in a prospective single-arm, multicentre, open-label trial of monthly BUP-XR. Thirty-six participants (25 men, 11 women) were interviewed, and of these 32 participated in a second interview to explore their experience of transition from other treatment to BUP-XR.. Participants were highly aware of the of the social and material effects of stigma through the negative stereotypes attached to OAT and those who receive it. Participants narrated examples of how stigma governed as a biopower in the relations and practices of OAT provision at numerous levels: structural (such as in public discourse about OAT and the people who receive it, in media, in perceptions about the decisions of investment in medical technologies); organisational (policies about legitimate access to OAT); interpersonal (with health workers) and individual (self-identities). BUP-XR allowed greater freedom and normalcy for clients. The experience of BUP-XR drew attention to the stigmatising potential of time, place and things associated with other OAT requiring daily (or frequent) dosing, accentuating how stigma comes to be materialised as a relational effect of everyday practices.. Receiving BUP-XR allowed participants to avoid some of the everyday biopolitical powers of other forms of OAT and to reshape self-identities. The altering of relations between time, place and things associated with other forms of OAT allowed participants to feel as though they "pass as normal" . However, the negative public discourse and stigma of OAT is a potential threat to BUP-XR to realise its potential for individual and population benefits.

Topics: Analgesics, Opioid; Buprenorphine; Delayed-Action Preparations; Female; Humans; Male; Narcotic Antagonists; Opioid-Related Disorders; Prospective Studies

People with opioid use disorder experience high burden of disease from medical comorbidities and are increasingly hospitalized with medical complications. Medications for opioid use disorder are an effective, life-saving treatment, but patients with an opioid use disorder admitted to the hospital seldom initiate medication for their disorder while in the hospital, nor are they linked with outpatient treatment after discharge. The inpatient stay, when patients may be more receptive to improving their health and reducing substance use, offers an opportunity to discuss opioid use disorder and facilitate medication initiation and linkage to treatment after discharge. An addiction-focus consultative team that uses evidence-based tools and resources could address barriers, such as the need for the primary medical team to focus on the primary health problem and lack of time and expertise, that prevent primary medical teams from addressing substance use.. This study is a pragmatic randomized controlled trial that will evaluate whether a consultative team, called the Substance Use Treatment and Recovery Team (START), increases initiation of any US Food and Drug Administration approved medication for opioid use disorder (buprenorphine, methadone, naltrexone) during the hospital stay and increases linkage to treatment after discharge compared to patients receiving usual care. The study is being conducted at three geographically distinct academic hospitals. Patients are randomly assigned within each hospital to receive the START intervention or usual care. Primary study outcomes are initiation of medication for opioid use disorder in the hospital and linkage to medication or other opioid use disorder treatment after discharge. Outcomes are assessed through participant interviews at baseline and 1 month after discharge and data from hospital and outpatient medical records.. The START intervention offers a compelling model to improve care for hospitalized patients with opioid use disorder. The study could also advance translational science by identifying an effective and generalizable approach to treating not only opioid use disorder, but also other substance use disorders and behavioral health conditions.. Clinicaltrials.gov: NCT05086796, Registered on 10/21/2021. https://www.. gov/ct2/results?recrs=ab&cond=&term=NCT05086796&cntry=&state=&city=&dist  = .

Topics: Aftercare; Buprenorphine; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Discharge; Randomized Controlled Trials as Topic

Fatal and nonfatal opioid overdoses are at record levels, and emergency department (ED) visits may be an opportune time to intervene. Peer-led models of care are increasingly common; however, little is known about their effectiveness.. To evaluate the effect of a peer-led behavioral intervention compared with the standard behavioral intervention delivered in the ED on engagement in substance use disorder (SUD) treatment within 30 days after the ED encounter.. This randomized clinical trial recruited 648 patients from 2 EDs from November 15, 2018, to May 31, 2021. Patients were eligible to participate if they were in the ED for an opioid overdose, receiving treatment related to an opioid use disorder, or identified as having had a recent opioid overdose.. Participants were randomly assigned to receive a behavioral intervention from a certified peer recovery specialist (n = 323) or a standard intervention delivered by a hospital-employed licensed clinical social worker (n = 325). A certified peer recovery specialist was someone with at least 2 years of recovery who completed a 45-hour training program and had 500 hours of supervised work experience. After the ED intervention, the certified peer recovery specialists offered continued contact with participants for up to 90 days.. The primary outcome was receipt of SUD treatment within 30 days of enrollment, assessed with deterministic linkage of statewide administrative databases. Treatment engagement was defined as admission to a formal, publicly licensed SUD treatment program or receipt of office-based medication for opioid use disorder within 30 days of the initial ED visit.. Among the 648 participants, the mean (SD) age was 36.9 (10.8) years, and most were male (442 [68.2%]) and White (444 [68.5%]). Receipt of SUD treatment occurred for 103 of 323 participants (32%) in the intervention group vs 98 of 325 participants (30%) in the usual care group within 30 days of the ED visit. Among all participants, the most accessed treatments were outpatient medication for opioid use disorder (buprenorphine, 119 [18.4%]; methadone, 44 [6.8%]) and residential treatment (44 [6.8%]).. Overall, this study found that a substantial proportion of participants in both groups engaged in SUD treatment within 30 days of the ED visit. An ED-based behavioral intervention is likely effective in promoting treatment engagement, but who delivers the intervention may be less influential on short-term outcomes. Further study is required to determine the effects on longer-term engagement in SUD care and other health outcomes (eg, recurrent overdose).. ClinicalTrials.gov Identifier: NCT03684681.

Topics: Adult; Buprenorphine; Drug Overdose; Emergency Service, Hospital; Female; Humans; Male; Opiate Overdose; Opioid-Related Disorders

Opioid craving is suggested to correlate with the rate of reduction in buprenorphine (BUP) plasma levels. No studies explored Buprenorphine elimination rate constant (BUP EL.R) as a predictor of opioid use or retention in BUP treatment.. Analysis was performed using data from a randomized controlled trial of 141 adults with opioid use disorder (OUD) randomized to Incentivized Adherence and Abstinence monitoring (I-AAM; experimental (n = 70) and treatment-as-usual; control (n = 71). In the I-AAM, structured access to unsupervised BUP doses was provided up to 28 days contingent of adherence measured by Therapeutic Drug Monitoring and abstinence by Urinary Drug Screens (UDS). In contrast, the treatment-as-usual (control) provided unstructured access to unsupervised doses was provided for up to 14 days considering UDS results. The primary outcome was percentage negative UDS. The secondary outcome, retention in treatment, was continuous enrollment in the study and analysis was via intention-to-treat. Significant bivariate correlations with the outcomes were adjusted for group allocation.. A significant negative correlation between BUP EL.R and percentage negative opioid screens (Pearson correlation coefficient - 0.57, p < 0.01) was found. After adjusting for trial group, BUP EL.R was shown to be an independent predictor of percentage negative opioid screens (Standardized Beta Coefficient - 0.57, 95% CI - 221.57 to - 97.44, R. BUP EL.R predicted 32.2% of the variation in percentage negative opioid UDS and may serve as a potential promising tool in precision medicine of BUP treatment. Higher buprenorphine elimination is associated with higher positive opioid urine screens during treatment.. ISRCTN41645723 retrospectively registered on 15/11/2015.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Humans; Narcotic Antagonists; Opioid-Related Disorders; Treatment Outcome

Topics: Analgesics, Opioid; Buprenorphine; Delayed-Action Preparations; Humans; Injections, Intramuscular; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders

Sublingual tablet buprenorphine (BUP-SL) and oral liquid methadone (MET) are the daily, standard-of-care (SOC) opioid agonist treatment medications for opioid use disorder (OUD). A sizable proportion of the OUD treatment population is not exposed to sufficient treatment to attain the desired clinical benefit. Two promising therapeutic technologies address this deficit: long-acting injectable buprenorphine and personalised psychosocial interventions (PSI). This study will determine (A) the effectiveness and cost-effectiveness - monthly injectable, extended-release (BUP-XR) in a head-to-head comparison with BUP-SL and MET, and (B) the effectiveness of BUP-XR with adjunctive PSI versus BUP-SL and MET with PSI. Safety, retention, craving, substance use, quality-adjusted life years, social functioning, and subjective recovery from OUD will be also evaluated.. This is a pragmatic, multi-centre, open-label, parallel-group, superiority RCT, with a qualitative (mixed-methods) evaluation. The study population is adults. The setting is five National Health Service community treatment centres in England and Scotland. At each centre, participants will be randomly allocated (1:1) to BUP-XR or SOC. At the London study co-ordinating centre, there will also be allocation of participants to BUP-XR with PSI or SOC with PSI. With 24 weeks of study treatment, the primary outcome is days of abstinence from non-medical opioids during study weeks 2-24 combined with up to 12 urine drug screen tests for opioids. For 90% power (alpha, 5%; 15% inflation for attrition), 304 participants are needed for the BUP-XR versus SOC comparison. With the same planning parameters, 300 participants are needed for the BUP-XR and PSI versus SOC and PSI comparison. Statistical and health economic analysis plans will be published before data-lock on the Open Science Framework. Findings will be reported in accordance with the Consolidated Standards of Reporting Trials and Consolidated Health Economic Evaluation Reporting Standards.. This pragmatic randomised controlled trial is the first evaluation of injectable BUP-XR versus the SOC medications BUP-SL and MET, with personalised PSI. If there is evidence for the superiority of BUP-XR over SOC medication, study findings will have substantial implications for OUD clinical practice and treatment policy in the UK and elsewhere.. EU Clinical Trials register 2018-004460-63.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Cost-Benefit Analysis; Delayed-Action Preparations; Humans; Methadone; Multicenter Studies as Topic; Narcotic Antagonists; Opioid-Related Disorders; Pragmatic Clinical Trials as Topic; Randomized Controlled Trials as Topic; State Medicine; Tablets

Opioid use disorder (OUD) and injection drug use (IDU) place justice-involved individuals at increased risk for acquiring or transmitting HIV or hepatitis C virus (HCV). Methadone and buprenorphine have been associated with reduced opioid IDU; however, the effect of extended-release naltrexone (XR-NTX) on this behavior is incompletely studied.. This study examined injection opioid use and shared injection equipment behavior from a completed double-blind placebo-controlled trial of XR-NTX among 88 justice-involved participants with HIV and OUD. Changes in participants' self-reported daily injection opioid use and shared injection equipment was evaluated pre-incarceration, during incarceration, and monthly post-release for 6 months. The study also assessed differences in time to first opioid injection post-release. The research team performed intention to treat and "as treated" (high treatment versus low treatment) analyses.. Fifty-eight of 88 participants (69.5 %) endorsed IDU and 26 (29.5 %) reported sharing injection equipment in the 30 days pre-incarceration; 2 participants (2.2 %) reported IDU during incarceration; 19 (21.6 %) reported IDU one month post-release from prison or jail. Fifty-four (61.4 %) participants had an HIV RNA below 200 copies/mL and 62 (70.5 %) were baseline HCV antibody positive. The 6-month follow-up rate was 49.5 % and 50.5 % for those who received XR-NTX and placebo, respectively, which was not significantly different (p = 0.822). Participants in the XR-NTX and placebo groups had similar low mean opioid injection use post-release and time to first injection opioid use in the Intention-to-treat analysis. In the as-treated analysis, participants in the high treatment group had significantly lower mean proportion of days injecting opioids (13.8 % high treatment versus 22.8 % low treatment, p = 0.02) by month 1, which persisted up to 5 months post-release (0 % high treatment vs 24.3 % low treatment, p < 0.001) and experienced a longer time to first opioid injection post-release (143.8 days high treatment vs 67.4 days low treatment, p < 0.001).. Injection opioid use was low during incarceration and remained low post-release in this justice-involved population. Retention on XR-NTX was associated with reduced intravenous opioid use, which has important implications for reducing transmission of HIV and HCV.

Topics: Analgesics, Opioid; Buprenorphine; Delayed-Action Preparations; Hepatitis C; HIV Infections; Humans; Injections, Intramuscular; Methadone; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; RNA; Social Justice

Craving reduction is an important target in the treatment of prescription-type opioid use disorder (POUD). In this exploratory analysis, we compared the effectiveness of BUP/NX flexible model of care relative to methadone for craving reduction in individuals with POUD.. We analyzed data from a multicentric, pragmatic, 24-week open-label randomized controlled trial conducted in participants with POUD (N = 272) who were randomly assigned to BUP/NX model of care with flexible take-home dosing (n = 138) or the standard model of care with closely supervised methadone (n = 134). Treatments were prescribed and administered according to local guidelines, in diverse clinical settings. Craving was measured using the Brief Substance Craving Scale at baseline, week 2, 6, 10, 14, 18 and 22.. Cravings decreased in both treatment groups over 22 weeks (BUP/NX adjusted mean difference = -5.52, 95% CI = -6.91 to -4.13; methadone adjusted mean difference = -3.95, 95% CI = -5.28 to -2.63; p < 0.001), and were overall lower in the BUP/NX group (adjusted mean = 4.04, 95% CI = 3.43-4.64) than the methadone group (adjusted mean = 5.13, 95% CI = 4.51-5.74; p < 0.001). The time by treatment group interaction (favoring BUP/NX) was statistically significant at week 2 (adjusted mean difference = -1.58, 95% CI = -3.13 to -0.03; p = 0.041).. Compared to the standard methadone model of care, flexible take-home dosing of BUP/NX was associated with lower craving in individuals with POUD. These findings can contribute to guiding shared decision-making regarding OAT treatment in this population.

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Craving; Humans; Methadone; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Prescriptions

Opioids are effective in pain-management, but long-term opioid users can develop prescription opioid use disorder (OUD). One treatment strategy in patients with OUD is rotating from a short-acting opioid to a long-acting opioid (buprenorphine/naloxone (BuNa) or methadone). Both BuNa and methadone have been shown to be effective strategies in patients with OUD reducing opioid misuse, however data on head-to-head comparison in patients with chronic non-malignant pain and prescription OUD are limited.. This two-armed open-label, randomized controlled trial aims to compare effectiveness between BuNa and methadone in patients with chronic non-malignant with prescription OUD (n = 100). Participants receive inpatient rotation to either BuNa or methadone with a flexible dosing regimen. The primary outcome is opioid misuse 2 months after rotation. Secondary outcomes include treatment compliance, side effects, analgesia, opioid craving, quality of life, mood symptoms, cognitive and physical functioning over 2- and 6 months follow-up. Linear mixed model analysis will be used to evaluate change in outcome parameters over time between the treatment arms.. This is one of the first studies comparing buprenorphine/naloxone and methadone for treating prescription OUD in a broad patient group with chronic non-malignant pain. Results may guide future treatment for patients with chronic pain and prescription OUD. Trial registration https://www.trialregister.nl/ , NL9781.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Chronic Pain; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Prescriptions; Quality of Life; Randomized Controlled Trials as Topic

Opioid use disorder (OUD) is a debilitating and persistent disorder. The standard-of-care treatment is daily maintenance dosing of sublingual buprenorphine (BUP-SL) or oral methadone (MET). Monthly, extended-release, subcutaneous injectable buprenorphine (BUP-XR) has been developed to enhance treatment effectiveness. This study aims to investigate the experiences of participants who have been offered BUP-XR (evaluation 1), health-related quality-of-life among participants who have opted to receive BUP-XR longer term (evaluation 2) and the experiences of participants allocated to receive BUP-XR or BUP-SL or MET with the offer of adjunctive personalised psychosocial intervention (evaluation 3).. Three qualitative-quantitative (mixed-methods) evaluations embedded in a five-centre, head-to-head, randomised controlled trial of BUP-XR versus BUP-SL and MET in the UK. Evaluation 1 is a four-centre interview anchored on an OUD-related topic guide and conducted after the 24-week trial endpoint. Evaluation 2 is a two-centre interview anchored on medications for opioid use disorder-specific quality-of-life topic guide conducted among participants after 12-24 months. Evaluation 3: single-centre interview after the 24-week trial endpoint. All evaluations include selected trial clinical measures, with evaluation 2 incorporating additional questionnaires. Target participant recruitment for evaluations 1 and 2 is 15 participants per centre (n=60 and n=30, respectively). Recruitment for evaluation 3 is 15 participants per treatment arm (n=30). Each evaluation will be underpinned by theory, drawing on constructs from the behavioural model for health service use or the health-related quality-of-life model. Qualitative data analysis will be by iterative categorisation.. Study protocol, consent materials and questionnaires were approved by the London-Brighton and Sussex research ethics committee (reference: 19/LO/0483) and the Health Research Authority (IRAS project number 255522). Participants will be provided with information sheets and informed written consent will be obtained for each evaluation. Study findings will be disseminated through peer-reviewed scientific journals.. 2018-004460-63.

Topics: Buprenorphine; Humans; Methadone; Narcotic Antagonists; Opioid-Related Disorders; Randomized Controlled Trials as Topic; Tablets

An increasing number of individuals are taking buprenorphine for management of opioid use disorder (OUD). Pain control can be challenging when these patients develop acute pain requiring supplemental analgesia. Buprenorphine's pharmacokinetic profile can render supplemental opioid-based analgesia ineffective. There is limited guidance on the optimal management of buprenorphine when acute pain is anticipated. Although there is growing acceptance that the risk of OUD relapse with buprenorphine discontinuation overshadows the risks of increased opioid utilization and difficult pain control with buprenorphine continuation, perioperative courses comparing buprenorphine dose reduction and full dose buprenorphine continuation have yet to be investigated. Here, we describe the protocol for our randomized controlled, prospective trial investigating the effect of buprenorphine continuation compared to buprenorphine dose reduction on pain control, post-operative opioid use, and OUD symptom management in patients on buprenorphine scheduled for elective surgery.. This is a single institution, randomized trial that aims to enroll 80 adults using 12 mg buprenorphine or greater for treatment of OUD, scheduled for elective surgery. Participants will be randomly assigned to receive 8mg of buprenorphine on the day of surgery onwards until postsurgical pain subsides or to have their buprenorphine formulation continued at full dose perioperatively. Primary outcome will be a clinically significant difference in pain scores 24 hours following surgery. Secondary outcomes will be opioid consumption at 24, 48, and 72 hours postoperatively, opioid dispensing up to 30 days following surgery, changes in mood and withdrawal symptoms, opioid cravings, relapse of opioid misuse, and continued use of buprenorphine treatment postoperatively.

Topics: Acute Pain; Adult; Analgesics, Opioid; Buprenorphine; Drug Tapering; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Pain, Postoperative; Prospective Studies

Family interventions in substance use disorders (SUD) treatment is limited despite the evidence for benefits. Providing family interventions is hampered by patient resistance, social stigma, logistics and factors related to the capacity of the treatment programmes.. The purpose of the study was to examine the association between family engagement in treatment, and opioid use defined by percentage negative opioid screen and rate retention in treatment defined by completion of study period.. Data from a 16-week outpatient randomised controlled trial (RCT) of 141 adults with opioid use disorder (OUD) receiving Opioid Assisted Treatment (OAT) using buprenorphine/naloxone film (BUP/NX-F) was, used to examine the association between family engagement in and opioid use and rate of retention in treatment. Multiple logistic regression was, applied to examine the independent prediction of family engagement on opioid use and rate retention in treatment.. Family engagement was significantly associated with retention in treatment (Spearman's rho 0.25,. Family engagement in treatment is an independent predictor of retention in treatment but not opioid use in adults receiving OAT. It is, recommended that SUD treatment programmes integrate family related interventions in mainstream treatment. Delivering a personalised multicomponent family programme using digitised virtual communications that has been increasingly utilised during the Covid-19 pandemic is highly suggested.

Topics: Adult; Analgesics, Opioid; Buprenorphine; COVID-19; Humans; Narcotic Antagonists; Opioid-Related Disorders; SARS-CoV-2

To investigate whether reduction in opioid use differs when treated by either buprenorphine-naloxone (BUP) or methadone (MET) among adults with comorbid opioid use disorder (OUD) and mental disorders.. In a randomized controlled trial, adults with OUD were randomized to 24 weeks of either BUP or MET treatment and were followed up in 3-yearly assessments. The present secondary analyses were based on 597 participants who completed all assessments.. The outcome measure was the number of days of using opioids per month during the follow-up period. The Mini-International Neuropsychiatric Interview (MINI) was used to classify participants into three groups: life-time mood disorder (n = 302), life-time mental disorder other than mood disorder (n = 114) and no mental disorder (n = 181). Medication treatment (BUP, MET, no treatment) during the follow-up period was a time-varying predictor.. Based on zero-inflated Poisson (ZIP) mixed regression analysis, it was found that relative to no treatment, opioid use during the follow-up was significantly reduced by BUP [odds ratio (OR) = 0.12, 95% confidence interval (CI) = 0.07-0.21 for any use; risk ratio (RR) = 0.77, 95% CI =0.66-0.89 for days of use] and by MET [OR = 0.33, 95% CI = 0.25-0.45 for any use; RR = 0.78, 95% CI = 0.72-0.84 for days of use]. Relative to MET, BUP was associated with a lower likelihood of any opioid use among participants with mood disorders (OR = 0.52, 95% CI = 0.36-0.74) and for participants without mental disorder (OR = 0.37, 95% CI = 0.21-0.66) and fewer number of days using opioids (RR = 0.37, 95% CI = 0.25-0.56) among participants with other mental disorders.. Among adults with comorbid opioid use disorder and mental disorders, treatment with buprenorphine-naloxone produced greater reductions in opioid use than treatment with methadone.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Follow-Up Studies; Humans; Methadone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders

Recent studies indicate that sex-based differences exist in co-occurring psychiatric symptoms and disorders among individuals with opioid use disorders (OUD). Whether these associations are present in adolescent samples and change during OUD treatment is poorly understood.. In the current study, we examined sex-based differences in psychiatric symptoms and relationships among sex, psychiatric symptoms, and opioid use outcomes in youth with OUD receiving buprenorphine/naloxone (Bup/Nal) and psychosocial treatment.. The study randomly assigned one hundred and fifty-two youth (15-21 years old) diagnosed with OUD to either 12 weeks of treatment with Bup/Nal or up to 2 weeks of Bup/Nal detoxification with both treatment arms receiving weekly drug counseling as part of a multisite clinical trial (NIDA-CTN-0010). We compared psychiatric symptoms, assessed via the Youth Self Report (YSR) at baseline and week 12, across male and female OUD participants. The study used logistic regression models to identify sex and psychiatric symptom variables that were predictors of opioid positive urine (OPU) at week 12.. Compared to males, females with OUD had higher mean psychiatric symptom scores at baseline across broad-band and narrow-band symptom domains. The study observed significant reductions in psychiatric symptom scores in both males and females during treatment, and by week 12, females only differed from males on anxious-depressive symptom scores. Females, in general, and youth of both sexes presenting to treatment with higher anxious depression scores were less likely to have a week-12 OPU.. Clinically significant sex-based differences in psychiatric symptoms are present at baseline among youth with OUD receiving Bup/Nal-assisted treatment and mostly resolve during treatment.

Topics: Adolescent; Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Female; Humans; Male; Narcotic Antagonists; Opioid-Related Disorders; Young Adult

Dynamic, adaptive pharmacologic treatment for opioid use disorder (OUD) has been previously recommended over static dosing to prevent relapse, and is aligned with personalized medicine. However, there has been no quantitative evidence demonstrating its advantage. Our objective was to estimate the extent to which a hypothetical intervention that increased buprenorphine dose in response to opioid use would affect risk of relapse over 24 weeks of follow-up.. A secondary analysis of the buprenorphine arm of an open-label randomized controlled 24-week comparative effectiveness trial, 2014-17.. Eight community addiction treatment programs in the United States.. English-speaking adults with DSM-5 OUD, recruited during inpatient admission (n = 270). Participants were mainly white (65%) and male (72%).. Participants were treated with daily sublingual buprenorphine-naloxone (BUP-NX), with dose based on clinical indication, determined by the provider. We examined a hypothetical intervention of increasing dose in response to opioid use.. Outcome was relapse to regular opioid use during the 24 weeks of outpatient treatment, assessed in a survival framework. We estimated the relapse-free survival curves of participants under a hypothetical (i.e. counterfactual) intervention in which their BUP-NX dosage would be increased following their own subject-specific opioid use during the first 12 weeks of treatment versus a hypothetical intervention in which dose would remain constant.. We estimated that increasing BUP-NX dose in response to recent opioid use would lower risk of relapse by 19.17 percentage points [95% confidence interval (CI) = -32.17, -6.18) (additive risk)] and 32% (0.68, 95% CI = 0.49, 0.86) (relative risk). The number-needed-to-treat with this intervention to prevent a single relapse is 6.. In people with opioid use disorder, a hypothetical intervention that increases sublingual buprenorphine-naloxone dose in response to opioid use during the first 12 weeks of treatment appears to reduce risk of relapse over 24 weeks, compared with holding the dose constant after week 2.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Delayed-Action Preparations; Female; Humans; Male; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Recurrence; United States

Extended-release buprenorphine (XRB), a monthly injectable long-acting opioid use disorder (OUD) treatment, has not been studied for use in corrections facilities.. To compare treatment retention following release from jail among adults receiving daily sublingual buprenorphine-naloxone (SLB) vs those receiving XRB.. This open-label, randomized comparative effectiveness study included 52 incarcerated adults in New York City observed for 8 weeks postrelease between June 2019 and May 2020. Participants were soon-to-be-released volunteers from 1 men's and 1 women's jail facility who had OUDs already treated with SLB. Follow-up treatment was received at a primary care clinic in Manhattan. Data were analyzed between June 2020 and December 2020.. XRB treatment was offered prior to release and continued monthly through 8 weeks after release. SLB participants continued to receive daily directly observed in-jail SLB administration, were provided a 7-day SLB supply at jail release, and followed up at a designated clinic (or other preferred clinics).. Buprenorphine treatment retention at 8 weeks postrelease.. A total of 52 participants were randomized 1:1 to XRB (26 participants) and SLB (26 participants). Participants had a mean (SD) age of 42.6 (10.0) years; 45 participants (87%) were men; and 40 (77%) primarily used heroin prior to incarceration. Most participants (30 [58%]) reported prior buprenorphine use; 18 (35%) reported active community buprenorphine treatment prior to jail admission. Twenty-one of 26 assigned to XRB received 1 or more XRB injection prior to release; 3 initiated XRB postrelease; and 2 did not receive XRB. Patients in the XRB arm had fewer jail medical visits compared with daily SLB medication administration (mean [SD] visits per day: XRB, 0.11 [0.03] vs SLB, 1.06 [0.08]). Community buprenorphine treatment retention at week 8 postrelease was 18 participants in the XRB group (69.2%) vs 9 in the SLB group (34.6%), and rates of opioid-negative urine tests were 72 of 130 tests in the XRB group (55.3%) and 50 of 130 tests in the SLB group (38.4%). There were no differences in rates of serious adverse events, no overdoses, and no deaths.. XRB was acceptable among patients currently receiving SLB, and patients had fewer in-jail clinic visits and increased community buprenorphine treatment retention when compared with standard daily SLB treatment. These results support wider use and further study of XRB as correctional and reentry OUD treatment.. ClinicalTrials.gov Identifier: NCT03604159.

Topics: Administration, Sublingual; Adult; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Delayed-Action Preparations; Female; Humans; Male; Medication Adherence; Opioid-Related Disorders; Pilot Projects; Prisoners; Treatment Outcome

Relapse rates during opioid use disorder (OUD) treatment remain unacceptably high. It is possible that optimally matching patients with medication type would reduce risk of relapse. Our objective was to learn a rule by which to assign type of medication for OUD to reduce risk of relapse, and to estimate the extent to which risk of relapse would be reduced if such a rule were used.. This was a secondary analysis of an open-label randomized controlled, 24-week comparative effectiveness trial of injection extended-release naltrexone (XR-NTX), delivered approximately every 28 days, or daily sublingual buprenorphine-naloxone (BUP-NX) for treating OUD, 2014-2017 (N = 570). Outcome was a binary indicator of relapse to regular opioid use during the 24 weeks of outpatient treatment.. We found that applying an estimated individualized treatment rule-i.e., a rule that assigns patients with OUD to either XR-NTX or BUP-NX based on their individual characteristics in such a way that risk of relapse is minimized-would reduce risk of relapse by 24 weeks by 12% compared to randomly assigned treatment.. The number-needed-to-treat with the estimated treatment rule to prevent a single relapse is 14. A simpler, alternative estimated rule in which homeless participants would be treated with XR-NTX and stably housed participants would be treated with BUP-NX performed similarly. These results provide an estimate of the amount by which a relatively simple change in clinical practice could be expected to improve prevention of OUD relapse.

Topics: Buprenorphine; Delayed-Action Preparations; Humans; Injections, Intramuscular; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders

Burden of opioid use disorder (OUD) is expressed in economic values or health metrics like Disability Adjusted Life Years (DALYs). Disability Weight (DW), a component of DALYs is estimated using economic methods or psychometric tools. Estimating DW at patient level using psychometric tools is an alternative to non-population specific DW overestimated by economic methods. Providing Medication Assisted Treatment (MAT) using buprenorphine/naloxone film (BUP/NX-F) for OUD is limited by financial constraints.. To estimate the burden of OUD at patient level and explore the cost-benefit of two buprenorphine treatment interventions.. The present study was conducted alongside a randomized controlled trial of 141 adults with OUD stabilized on BUP/NX-F and randomized to BUP/NX-F with Incentivized Abstinence and Adherence Monitoring (experimental, n=70) and BUP/NX-F in usual care (control, n=71). The cost of illness was estimated applying a societal perspective. The Impairment Weight (IW) was estimated over a '0' to '1' scale, where '0' represents no impairment and '1' full impairment using the Work and Social Adjustment Scale (WSAS).. Median (interquartile range) annual cost of OUD per participant was AED 498,171.1 (413,499.0 -635,725.3) and AED 538,694.4 (4,211,398.0 - 659,949.0) in the experimental and control groups, respectively (p=0.33). Illicit drug purchase represented 60 % of the annual cost of illness. At baseline, the mean Impairment Weight (IW) was 0.55 (SD 0.26) and 0.62 (SD 0.24) in the experimental and control groups, respectively. At end of the study, the IW was 0.26 (SD 0.28) representing 51% reduction in the experimental group compared to 0.42 (SD 0.33) in the control group representing a 27% reduction. Excluding imprisonment, the cost-benefit of treatment was not realized. In contrast, accounting for imprisonment, cost benefit expressed as a return-on-investment was established at 1.55 and 1.29 in the experimental and control groups, respectively.. Cost benefit analysis can serve as a simple and practical tool to evaluate the cost benefit of treatment interventions. Demonstrating the cost benefit of buprenorphine treatment has the potential to facilitate public funding and accessibility to opioid assisted treatment.

Topics: Adult; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cost-Benefit Analysis; Humans; Narcotic Antagonists; Opioid-Related Disorders

Individuals treated for opioid use disorder (OUD) have high rates of psychiatric disorders potentially diminishing treatment outcomes. We examined long-term treatment experiences and outcomes by type of psychiatric disorder among participants who participated in the Starting Treatment with Agonist Replacement Therapies (START) study and its follow-up study.. We categorized the 593 participants who completed the Mini-International Neuropsychiatric Interview (MINI) during the START follow-up study into four mutually exclusive groups to indicate current psychiatric diagnosis: 1) bipolar disorder (BPD; n = 51), 2) major depressive disorder (MDD; n = 85), 3) anxiety disorder (AXD; n = 121), and 4) no comorbid mental disorder (NMD; n = 336). We compared participants' baseline characteristics and treatment outcomes.. Groups with mental disorders had worse substance use outcomes and poorer psychosocial functioning than the NMD group. Participants with BPD had significantly more self-reported days using opioids (Mean: 8.6 for BPD vs. 3.4 days for NMD, p < 0.01) and heroin (Mean: 6.4 for BPD vs. 2.0 for MDD, 3.1 days for NMD, p < 0.05) in the 30 days prior to the final interview. Compared to patients without mental disorders, patients with MDD spent more time engaged with OUD pharmacotherapy during the ∼16-month period between MINI and final interview (mean: 71.6 % vs. 50.6 %; p < 0.001).. Our results show that treatment outcomes in individuals with OUD vary by psychiatric comorbidity groups, which supports the need for mental health assessment and treatment for psychiatric conditions in the context of pharmacotherapy for patients with OUD.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Comorbidity; Depressive Disorder, Major; Follow-Up Studies; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Treatment Outcome

Posttraumatic stress disorder (PTSD) and opioid use disorder (OUD) may be associated with poor outcomes in rural areas where access to mental health services and opioid agonist treatment (OAT) is limited. This study examined the characteristics associated with a history of PTSD among a sample of individuals seeking buprenorphine treatment for OUD in Vermont, the second-most rural state in the US. Participants were 89 adults with OUD who participated in one of two ongoing randomized clinical trials examining the efficacy of an interim buprenorphine dosing protocol for reducing illicit opioid use during waitlist delays to OAT. Thirty-one percent of participants reported a history of PTSD. Those who did (PTSD+; n = 28) and did not (PTSD-; n = 61) report a history of PTSD were similar on sociodemographic and drug use characteristics. However, the PTSD+ group was less likely to have received prior OUD treatment compared to the PTSD- group (p = .02) despite being more likely to have a primary care physician (p = .009) and medical insurance (p = .002). PTSD+ individuals also reported greater mental health service utilization, more severe psychiatric, medical and drug use consequences, and greater pain severity and interference vs. PTSD- individuals (ps < 0.05). These findings indicate that a history of PTSD is prevalent and associated with worse outcomes among individuals seeking treatment for OUD in Vermont. Dissemination of screening measures and targeted interventions may help address the psychiatric and medical needs of rural individuals with OUD and a history of PTSD.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Humans; Longitudinal Studies; Opiate Substitution Treatment; Opioid-Related Disorders; Stress Disorders, Post-Traumatic; Vermont

Associations between fentanyl use and initiation and retention on medications for opioid use disorder (MOUD) are poorly understood.. Data were from a multisite clinical trial comparing extended-release naltrexone (XR-NTX) with treatment as usual (TAU; buprenorphine or methadone) to achieve HIV viral suppression among people with OUD and uncontrolled HIV disease. The exposure of interest was fentanyl use, as measured by urine drug screening. Outcomes were time to MOUD initiation, defined as date of first injection of XR-NTX, buprenorphine prescription, or methadone administration; MOUD persistence, the total number of injections, prescriptions, or administrations received over 24 weeks; and MOUD retention, having an injection, prescription, or administration during weeks 20-24.. Participants (N = 111) averaged 47 years old and 62% were male. Just over half (57%) were Black and 13% were Hispanic. Sixty-four percent of participants tested positive for fentanyl at baseline. Participants with baseline fentanyl positivity were 11 times less likely to initiate XR-NTX than those negative for fentanyl (aHR = 0.09, 95% CI 0.03-0.24, p < .001), but there was no evidence that fentanyl use impacted the likelihood of TAU initiation (aHR = 1.50, 0.67-3.36, p = .323). Baseline fentanyl use was not associated with persistence or retention on any MOUD.. Fentanyl use was a substantial barrier to XR-NTX initiation for the treatment of OUD in persons with uncontrolled HIV infection. There was no evidence that fentanyl use impacted partial/full agonist initiation and, once initiated, retention on any MOUD.

Topics: Buprenorphine; Delayed-Action Preparations; Fentanyl; HIV Infections; Humans; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders

Large randomized trials have found that behavioral therapy for opioid use disorder (e.g., Individual Drug Counseling, Cognitive Behavioral Therapy for Opioid Use Disorder) does not improve buprenorphine maintenance outcomes, on average, for individuals with opioid use disorder. However, recent studies indicate that certain subgroups of patients may benefit from the addition of behavioral therapy to buprenorphine. In particular, people with more complex and severe psychosocial needs may benefit from the addition of behavioral therapy for opioid use disorder.. In this study, we conducted a secondary analysis of a large, multi-site randomized trial (N = 357) of buprenorphine maintenance with and without individual Opioid Drug Counseling (ODC) for the treatment of opioid use disorder. We hypothesized that participants with posttraumatic stress disorder (PTSD) would benefit from the addition of ODC.. Logistic regression models indicated a significant PTSD by treatment condition interaction. Specifically, 67% of those with PTSD had a successful opioid use disorder treatment outcome when they were assigned to receive both ODC and buprenorphine, compared to a 36% response rate among those who received buprenorphine alone.. Although these results require replication, our findings provide initial indication that ODC is an important complement to buprenorphine maintenance treatment for people with co-occurring PTSD and opioid use disorder.

Topics: Analgesics, Opioid; Buprenorphine; Counseling; Humans; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Pharmaceutical Preparations; Stress Disorders, Post-Traumatic

Expanding access to medications for opioid use disorder (MOUD), such as buprenorphine and extended release (XR) naltrexone, is critical to addressing the US opioid epidemic, but little is known about prescriber satisfaction with delivering these two types of MOUD. The current study describes the satisfaction of prescribers delivering buprenorphine and XR-naltrexone while examining whether satisfaction is associated with current patient census and organizational environment.. As part of a cluster randomized clinical trial (RCT) focused on expanding access to medication for opioid use disorder, 41 MOUD prescribers in Florida, Ohio, and Wisconsin completed a web-based survey. The survey included measures of prescriber satisfaction with delivering buprenorphine treatment and XR-naltrexone. In addition, the survey measured several prescriber characteristics and their perceptions of the organizational environment.. Prescribers were generally satisfied with their work in delivering these two types of MOUD. Prescribers reporting a greater number of patients (r = .46, p = .006), those who would recommend the center to others (r = .56, p < .001), and those reporting positive relationships with staff (r = .56, p < .001) reported significantly greater overall satisfaction with delivering buprenorphine treatment. Prescribers who more strongly endorsed feeling overburdened reported lower overall buprenorphine satisfaction (r = -.37, p = .02). None of the prescriber characteristics or perceptions of the organizational environment were significantly associated with overall satisfaction with delivering XR-naltrexone treatment.. The generally high levels of satisfaction with both types of MOUD is notable given that prescriber dissatisfaction can lead to turnover and impact intentions to leave the profession. Future research should continue to explore the prescriber characteristics and organizational factors associated with satisfaction in providing different types of MOUD.. ClinicalTrials.gov. NCT02926482. Date of registration: September 9, 2016. https://clinicaltrials.gov/ct2/show/NCT02926482 .

Topics: Analgesics, Opioid; Buprenorphine; Humans; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Personal Satisfaction

Patients with substance use disorders are overrepresented among general hospital inpatients, and their admissions are associated with longer lengths of stay and increased readmission rates. Amid the national opioid crisis, increased attention has been given to the integration of addiction with routine medical care in order to better engage such patients and minimize fragmentation of care. General hospital addiction consultation services and transitional, hospital-based "bridge" clinics have emerged as potential solutions. We designed the Bridging Recovery Initiative Despite Gaps in Entry (BRIDGE) trial to determine if these clinics are superior to usual care for these patients.. This single-center, pragmatic, randomized controlled clinical trial is enrolling hospitalized patients with opioid use disorder (OUD) who are initiating medication for OUD (MOUD) in consultation with the addiction consult service. Patients are randomized for referral to a co-located, transitional, multidisciplinary bridge clinic or to usual care, with the assignment probability being determined by clinic capacity. The primary endpoint is hospital length of stay. Secondary endpoints include quality of life, linkage to care, self-reported buprenorphine or naltrexone fills, rate of known recurrent opioid use, readmission rates, and costs. Implementation endpoints include willingness to be referred to the bridge clinic, attendance rates among those referred, and reasons why patients were not eligible for referral. The main analysis will use an intent-to-treat approach with full covariate adjustment.. This ongoing pragmatic trial will provide evidence on the effectiveness of proactive linkage to a bridge clinic intervention for hospitalized patients with OUD initiating evidence-based pharmacotherapy in consultation with the addiction consult service.. ClinicalTrials.gov NCT04084392 . Registered on 10 September 2019. The study has been approved by the Vanderbilt Institutional Review Board. The current approved protocol is dated version May 12, 2021.

Topics: Buprenorphine; Humans; Naltrexone; Opioid-Related Disorders; Quality of Life; Randomized Controlled Trials as Topic; Referral and Consultation

Buprenorphine treatment is not equally effective in all patients with opioid use disorder (OUD). Two retrospective studies showed that, among African Americans (AAs), rs678849, a polymorphism in the delta-opioid receptor gene, moderated the therapeutic effect of sublingual buprenorphine.. We examined rs678849 as a moderator of the response to an extended-release subcutaneous buprenorphine formulation (BUP-XR) in a 24-week OUD treatment study of 127 AAs and 327 European Americans (EAs). Participants were randomly assigned to receive: (1) BUP-XR as 2 monthly injections of 300 mg followed by either 300 mg monthly or 100 mg monthly for 4 months, or (2) monthly volume-matched placebo injections. Generalized estimating equations logistic regression analyses tested, per population group, the main and interaction effects of treatment (BUP-XR vs placebo) and genotype group (rs678849*CC vs CT/TT) on weekly urine drug screens (UDS).. Among AAs, the placebo group had higher rates of opioid-positive UDS than the BUP-XR group (log odds ratio = 1.67, 95% CI = 0.36, 2.98), but no genotype by treatment effect (P = .80). Among EAs, the placebo group also showed higher rates of opioid-positive UDS than the BUP-XR group (log odds ratio = 1.97, 95% CI = 1.14, 2.79) but a significant genotype by treatment interaction (χ 2(1) = 4.33, P = .04).. We found a moderating effect of rs678849 on the response to buprenorphine treatment of OUD in EAs, but not AAs. These findings require replication in well-powered, prospective studies of both AA and EA OUD patients treated with BUP-XR and stratified on rs678849 genotype.

Topics: Adult; Black or African American; Buprenorphine; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Male; Middle Aged; Narcotics; Opioid-Related Disorders; Pharmacogenomic Testing; Polymorphism, Single Nucleotide; Receptors, Opioid, delta; White People

BUP-XR (a.k.a. RBP-6000 or SUBLOCADE™) is an extended-release subcutaneous buprenorphine formulation for the treatment of opioid use disorder. BUP-XR was designed to provide sustained buprenorphine exposure throughout the monthly dosing interval, at concentrations sufficient to control all aspects of the disease (withdrawal, craving, and blockade of opioid subjective effects).. To characterize the population pharmacokinetics of BUP-XR based on phase II and phase III data and to evaluate whether target therapeutic concentrations were reached with the dosing regimens evaluated in the phase III program.. The population pharmacokinetic analysis included 570 subjects with opioid use disorder who received up to 12 monthly BUP-XR injections following induction with sublingual buprenorphine.. In phase III studies, target therapeutic concentrations of buprenorphine were achieved from the first injection and maintained over the entire treatment duration. Buprenorphine plasma concentration-time profiles were well described by a two-compartment model, with first-order absorption for sublingual buprenorphine and a dual absorption submodel for BUP-XR. A covariate analysis evaluated the effects of subjects' demographic characteristics, laboratory data, and genetic status regarding buprenorphine-metabolizing enzymes. Only two covariates, body mass index and body weight, were retained in the final model. Overall, their effects were not of sufficient magnitude to justify a dose adjustment. Finally, pharmacokinetic simulations showed that buprenorphine plasma concentrations decreased slowly after discontinuation of treatment and that a 2-week occasional delay in dosing would not impact efficacy, which translated into labeling claims.. In conclusion, the present analysis led to the development of a robust population pharmacokinetic model and confirms the ability of BUP-XR to deliver and maintain therapeutic plasma concentrations over the entire treatment duration.

Topics: Analgesics, Opioid; Buprenorphine; Delayed-Action Preparations; Humans; Narcotic Antagonists; Opioid-Related Disorders

To evaluate patient engagement and usage of a prescription digital therapeutic (PDT) and associated outcomes of opioid use and treatment retention in a large real-world dataset of patients with opioid use disorder (OUD) treated with buprenorphine medication for opioid use disorder (MOUD). PDTs are software-based disease treatments evaluated for safety and effectiveness in randomized clinical trials (RCTs), and authorized by the U.S. Food and Drug Administration (FDA) to treat disease with approved directions for use (label).. A real-world observational evaluation of an all-comer population of patients who redeemed a 12-week prescription for the reSET-O PDT. Engagement and therapeutic use data were collected and analysed on a population level. Substance use was evaluated as a composite of self-reports recorded with reSET-O and urine drug screens (UDS).. Data from 3144 individuals with OUD were evaluated. 45.5% were between ages 30 and 39 years. 80% completed at least 8 of the 67 possible therapeutic modules, 66% completed half of all modules, and 49% completed all modules. Abstinence during the last 4 weeks of treatment was calculated with two imputation methodologies: 66% abstinent using "missing data excluded (patients with no data as positive)", and 91% abstinent with "missing data removed (patients with no data excluded)". 91% of patients met the responder definition of ≥80% of self-report or UDS negative. 74.2% of patients were retained through the last 4 weeks of treatment. Subgroup analysis of patients using reSET-O appropriately (4 or more modules per week for the first 4 weeks) showed 88.1% abstinence using "missing data excluded (patients with no data as positive)", and retention at weeks 9-12 of 85.8%.. Results demonstrate that reSET-O is readily and broadly used by patients with OUD and that high real-world engagement with the therapeutic is positively associated with abstinence and retention in treatment. ReSET-O is a potentially valuable adjunct to buprenorphine MOUD therapy for patients with OUD.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Combined Modality Therapy; Humans; Male; Methadone; Opioid-Related Disorders; Prescriptions

To evaluate the safety and efficacy of a digital therapeutic in treatment-seeking individuals with opioid use disorder (OUD) in an analysis of randomized clinical trial (RCT) data (ClinicalTrials.gov identifier: NCT00929253).. Secondary analysis of an RCT including 170 adults meeting DSM-IV criteria for OUD. Participants were randomized to 12-weeks of treatment-as-usual (TAU) or TAU plus a digital therapeutic providing 67 digital, interactive educational modules based on the Community Reinforcement Approach. TAU consisted of buprenorphine maintenance therapy, 30 min biweekly clinician interaction, and abstinence-based contingency management. Primary endpoints were treatment retention and abstinence (negative urine drug screen) during weeks 9-12 of treatment. Safety was assessed by evaluating adverse events.. Participants randomized to TAU plus a digital therapeutic had significantly greater odds of opioid abstinence during weeks 9-12 compared to TAU: 77.3 versus 62.1%, respectively (. A prescription digital therapeutic (PDT) in combination with buprenorphine therapy improves clinically significant patient outcomes including abstinence from illicit opioids and retention in treatment compared with treatment as usual.

Topics: Adult; Buprenorphine; Drug Administration Schedule; Humans; Male; Opioid-Related Disorders; Prescriptions; Safety

This study is a randomized, open label, controlled trial of extended-release buprenorphine (XR-B; BRIXADI™ formulation) versus extended-release naltrexone (XR-NTX) in Maryland jails. A 7-site, open-label, equivalence design will randomly assign 240 adults with a history of opioid use disorder (OUD), stratified by gender and jail, who are nearing release to one of two treatment arms: 1) XR-B in jail or 2) XR-NTX in jail, both followed by 6 monthly injections postrelease at a community treatment program. The primary aim is to determine the rate of pharmacotherapy adherence (number of monthly injections received) of XR-B compared to XR-NTX. The proposed study is innovative because it will be the first randomized clinical trial in the U.S. assessing the effectiveness of receiving XR-B vs. XR-NTX in county jails. The public health impact of the study will be highly significant and far-reaching because most individuals with OUD do not receive treatment while incarcerated, thereby substantially raising their likelihood of relapse to drug use, overdose death, and re-incarceration. Understanding how to expand acceptance of medications for OUD in jails, particularly extended-release medications, and supporting treatment engagement and medication adherence in transition to the community, has far-reaching implications for improving treatment access and success in this population.

Topics: Adult; Buprenorphine; Clinical Protocols; Delayed-Action Preparations; Humans; Injections, Intramuscular; Jails; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Randomized Controlled Trials as Topic

Buprenorphine (BUP) maintenance treatment for opioid use disorder (OUD) begins with supervised daily dosing. We estimated the clinical effectiveness of a novel incentivised medication adherence and abstinence monitoring protocol in BUP maintenance to enable contingent access to increasing take-home medication supplies.. Two-arm, single-centre, pragmatic, randomised controlled trial of outpatient BUP maintenance, with during-treatment follow-ups at 4 weeks, 8 weeks, 12 weeks and 16 weeks.. Inpatient and outpatient addictions treatment centre in the United Arab Emirates.. Adults with OUD, voluntarily seeking treatment.. The experimental condition was 16 weeks BUP maintenance with incentivised adherence and abstinence monitoring (I-AAM) giving contingent access to 7-day, then 14-day, then 21-day and 28-day medication supply. The control, treatment-as-usual (TAU) was 16 weeks BUP maintenance, with contingent access to 7-day then 14-day supply.. The primary outcome was number of negative urine drug screens (UDS) for opioids, with non-attendance or otherwise missed UDS, imputed as positive for opioids. The secondary outcome was retention in treatment (continuous enrolment to the 16-week endpoint).. Of 182 patients screened, 171 were enrolled and 141 were randomly assigned to I-AAM (70 [49.6%]) and to TAU (71 [50.4%]. Follow-up rates at 4 weeks, 8 weeks, 12 weeks and 16 weeks were 91.4%, 85.7%, 71.0%, 60.0% respectively in I-AAM and 84.5%, 83.1%, 69.0%, 56.3% in TAU. By intention-to-treat, the absolute difference in percentage negative UDS for opioids was 76.7% (SD = 25.0%) in I-AAM versus 63.5% (SD = 34.7%) in TAU (mean difference = 13.3%; 95% CI = 3.2%-23.3%; Cohen's d = 0.44; 95% CI = 0.10-0.87). In I-AAM, 40 participants (57.1%) were retained versus 33 (46.4%) in TAU (odds ratio = 1.54; 95% CI = 0.79-2.98).. Buprenorphine maintenance with incentivised therapeutic drug monitoring to enable contingent access to increasing take-home medication supplies increased abstinence from opioids compared with buprenorphine maintenance treatment-as-usual, but it did not appear to increase treatment retention.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Humans; Medication Adherence; Narcotic Antagonists; Opioid-Related Disorders; Treatment Outcome

Opioid Use Disorder (OUD) is a significant public health problem associated with severe morbidity and mortality. While effective pharmacotherapies are available, limitations exist with each. Induction onto extended-release naltrexone (XR-NTX) is more difficult than initiation of buprenorphine or methadone, even in inpatient settings, as it is recommended that patients remain abstinent for at least 7 days prior to initiating XR-NTX. The purpose of this trial was to determine if lorcaserin, a 5HT2c agonist, improves outpatient XR-NTX induction rates.. An 8-week trial beginning with a brief detoxification period and induction onto XR-NTX. Sixty participants with OUD were enrolled in the trial, with 49 participants at the initiation of detoxification randomized to lorcaserin or placebo for 39 days. Additionally, ancillary medications were provided. The primary outcome was the proportion of participants inducted onto the first XR-NTX injection. Secondary outcomes were withdrawal severity (measured by COWS and SOWS) prior to the first injection and the proportion of participants receiving the second XR-NTX injection.. The proportion of participants inducted onto the first (lorcaserin: 36 %; placebo: 44 %; p = .67) and the second XR-NTX injection (lorcaserin: 27 %; placebo: 31 %; p = .77) was not significantly different between treatment arms. Prior to the first injection, withdrawal scores did not significantly differ between treatment arms over time (treatment*time interaction COWS: p = .11; SOWS: p = .39).. Lorcaserin failed to improve outpatient XR-NTX induction rates. Although this study is small, the findings do not support the use of lorcaserin in promoting induction onto XR-NTX or in mitigating withdrawal symptoms.

Topics: Adult; Animals; Benzazepines; Buprenorphine; Delayed-Action Preparations; Female; Humans; Injections; Male; Methadone; Middle Aged; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Outpatients; Substance Withdrawal Syndrome; Swine

Physician and pharmacist collaboration may help address the shortage of buprenorphine-waivered physicians and improve care for patients with opioid use disorder (OUD). This study investigated the feasibility and acceptability of a new collaborative care model involving buprenorphine-waivered physicians and community pharmacists.. Nonrandomized, single-arm, open-label feasibility trial.. Three office-based buprenorphine treatment (OBBT) clinics and three community pharmacies in the United States.. Six physicians, six pharmacists, and 71 patients aged ≥18 years with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) OUD on buprenorphine maintenance.. After screening, eligible patients' buprenorphine care was transferred from their OBBT physician to a community pharmacist for 6 months.. Primary outcomes included recruitment, treatment retention and adherence, and opioid use. Secondary outcomes were intervention fidelity, pharmacists' use of prescription drug monitoring program (PDMP), participant safety, and satisfaction with treatment delivery.. A high proportion (93.4%, 71/76) of eligible participants enrolled into the study. There were high rates of treatment retention (88.7%) and adherence (95.3%) at the end of the study. The proportion of opioid-positive urine drug screens (UDSs) among complete cases (i.e. those with all six UDSs collected during 6 months) at month 6 was (4.9%, 3/61). Intervention fidelity was excellent. Pharmacists used PDMP at 96.8% of visits. There were no opioid-related safety events. Over 90% of patients endorsed that they were "very satisfied with their experience and the quality of treatment offered," that "treatment transfer from physician's office to the pharmacy was not difficult at all," and that "holding buprenorphine visits at the same place the medication is dispensed was very or extremely useful/convenient." Similarly, positive ratings of satisfaction were found among physicians/pharmacists.. A collaborative care model for people with opioid use disorder that involves buprenorphine-waivered physicians and community pharmacists appears to be feasible to operate in the United States and have high acceptability to patients.

Topics: Buprenorphine; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Pharmacists; Physicians; United States

The effectiveness of opioid agonist treatment for opioid use disorder (OUD) is well established, and delays to treatment are still common, particularly in rural geographic areas. In a randomized 12-week pilot study, we demonstrated initial efficacy of a technology-assisted Interim Buprenorphine Treatment (IBT) vs. continued waitlist control (WLC) for reducing illicit opioid use and other risk behaviors during waitlist delays. Upon completion of that parent trial, WLC participants were given the opportunity to receive 12 weeks of IBT, permitting an additional within-subject examination of IBT effects.. Sixteen WLC participants crossed over to receive IBT, involving buprenorphine maintenance with bi-monthly visits, medication administration at home via a computerized device, daily monitoring calls using an Interactive Voice Response (IVR) phone system, and IVR-generated random call-backs. Biochemically-verified illicit opioid abstinence, changes in psychosocial functioning, and HIV + HCV knowledge were examined among participants originally randomized to the WLC phase and who subsequently crossed over to IBT (IBTc).. Participants submitted a higher percentage of illicit opioid negative specimens at Weeks 4, 8, and 12 during IBT (75 %, 63 %, and 50 %) vs. WLC (0%, 0%, and 0%), respectively (p's<.01). Participants also demonstrated improvements in anxiety, depression, and HIV and HCV knowledge (p's<.01). Medication administration, daily IVR call and random call-back adherence and treatment satisfaction were also favorable.. This within-subject evaluation provides additional support for interim buprenorphine's efficacy in reducing illicit opioid use and improving health outcomes during waitlist delays for more comprehensive treatment.

Topics: Adult; Analgesics, Opioid; Anxiety; Buprenorphine; Humans; Male; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Pilot Projects; Risk-Taking; Waiting Lists; Young Adult

Most people with opioid use disorder (OUD) never receive treatment. Medication treatment of OUD in primary care is recommended as an approach to increase access to care. The PRimary Care Opioid Use Disorders treatment (PROUD) trial tests whether implementation of a collaborative care model (Massachusetts Model) using a nurse care manager (NCM) to support medication treatment of OUD in primary care increases OUD treatment and improves outcomes. Specifically, it tests whether implementation of collaborative care, compared to usual primary care, increases the number of days of medication for OUD (implementation objective) and reduces acute health care utilization (effectiveness objective). The protocol for the PROUD trial is presented here.. PROUD is a hybrid type III cluster-randomized implementation trial in six health care systems. The intervention consists of three implementation strategies: salary for a full-time NCM, training and technical assistance for the NCM, and requiring that three primary care providers have DEA waivers to prescribe buprenorphine. Within each health system, two primary care clinics are randomized: one to the intervention and one to Usual Primary Care. The sample includes all patients age 16-90 who visited the randomized primary care clinics from 3 years before to 2 years after randomization (anticipated to be > 170,000). Quantitative data are derived from existing health system administrative data, electronic medical records, and/or health insurance claims ("electronic health records," [EHRs]). Anonymous staff surveys, stakeholder debriefs, and observations from site visits, trainings and technical assistance provide qualitative data to assess barriers and facilitators to implementation. The outcome for the implementation objective (primary outcome) is a clinic-level measure of the number of patient days of medication treatment of OUD over the 2 years post-randomization. The patient-level outcome for the effectiveness objective (secondary outcome) is days of acute care utilization [e.g. urgent care, emergency department (ED) and/or hospitalizations] over 2 years post-randomization among patients with documented OUD prior to randomization.. The PROUD trial provides information for clinical leaders and policy makers regarding potential benefits for patients and health systems of a collaborative care model for management of OUD in primary care, tested in real-world diverse primary care settings. Trial registration # NCT03407638 (February 28, 2018); CTN-0074 https://clinicaltrials.gov/ct2/show/NCT03407638?term=CTN-0074&draw=2&rank=1.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Buprenorphine; Facilities and Services Utilization; Female; Humans; Male; Middle Aged; Multicenter Studies as Topic; Nurse Administrators; Opiate Substitution Treatment; Opioid-Related Disorders; Pragmatic Clinical Trials as Topic; Primary Health Care; Research Design; Treatment Adherence and Compliance; United States

UNAIDS recommends integrating methadone or buprenorphine treatment of opioid use disorder with HIV care to improve HIV outcomes, but buprenorphine adoption remains limited in many countries. We aimed to assess whether HIV clinic-based buprenorphine plus naloxone treatment for opioid use disorder was non-inferior to referral for methadone maintenance therapy in achieving HIV viral suppression in Vietnam.. In an open-label, non-inferiority trial (BRAVO), we randomly assigned people with HIV and opioid use disorder (1:1) by computer-generated random number sequence, in blocks of ten and stratified by site, to receive HIV clinic-based buprenorphine plus naloxone treatment or referral for methadone maintenance therapy in six HIV clinics in Vietnam. The primary outcome was HIV viral suppression at 12 months (HIV-1 RNA ≤200 copies per mL on PCR) by intention to treat (absolute risk difference [RD] margin ≤13%), compared by use of generalised estimating equations. Research staff actively queried treatment-emergent adverse events during quarterly study visits and passively collected adverse events reported during HIV clinic visits. This study is registered with ClinicalTrials.gov, NCT01936857, and is completed.. Between July 27, 2015, and Feb 12, 2018, we enrolled 281 patients. At baseline, 272 (97%) participants were male, mean age was 38·3 years (SD 6·1), and mean CD4 count was 405 cells per μL (SD 224). Viral suppression improved between baseline and 12 months for both HIV clinic-based buprenorphine plus naloxone (from 97 [69%] of 140 patients to 74 [81%] of 91 patients) and referral for methadone maintenance therapy (from 92 [66%] of 140 to 99 [93%] of 107). Buprenorphine plus naloxone did not demonstrate non-inferiority to methadone maintenance therapy in achieving viral suppression at 12 months (RD -0·11, 95% CI -0·20 to -0·02). Retention on medication at 12 months was lower for buprenorphine plus naloxone than for methadone maintenance therapy (40% vs 65%; RD -0·53, 95% CI -0·75 to -0·31). Participants assigned to buprenorphine plus naloxone more frequently experienced serious adverse events (ten [7%] of 141 vs four of 140 [3%] assigned to methadone maintenance therapy) and deaths (seven of 141 [5%] vs three of 141 [2%]). Serious adverse events and deaths typically occurred in people no longer taking ART or opioid use disorder medications.. Although integrated buprenorphine and HIV care may potentially increase access to treatment for opioid use disorder, scale-up in middle-income countries might require enhanced support for buprenorphine adherence to improve HIV viral suppression. The strength of our study as a multisite randomised trial was offset by low retention of patients on buprenorphine.. National Institute on Drug Abuse (US National Institutes of Health).

Topics: Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Buprenorphine; CD4 Lymphocyte Count; Drug Therapy, Combination; Female; HIV Infections; Humans; Male; Methadone; Middle Aged; Naloxone; Narcotic Antagonists; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Compliance; Random Allocation; RNA, Viral; Treatment Outcome; Vietnam; Viral Load

People with opioid use disorder (OUD) often have a co-occurring psychiatric disorder, which elevates the risk of morbidity and mortality. Promising evidence supports the use of collaborative care for treating people with OUD in primary care. Whether collaborative care interventions that treat both OUD and psychiatric disorders will result in better outcomes is presently unknown.. The Whole Health Study is a 3-arm randomized controlled trial designed to test collaborative care treatment for OUD and the psychiatric disorders that commonly accompany OUD. Approximately 1200 primary care patients aged ≥18 years with OUD and depression, anxiety, or PTSD will be randomized to one of three conditions: (1) Augmented Usual Care, which consists of a primary care physician (PCP) waivered to prescribe buprenorphine and an addiction psychiatrist to consult on medication-assisted treatment; (2) Collaborative Care, which consists of a waivered PCP, a mental health care manager trained in psychosocial treatments for OUD and psychiatric disorders, and an addiction psychiatrist who provides consultation for OUD and mental health; or (3) Collaborative Care Plus, which consists of all the elements of the Collaborative Care arm plus a Certified Recovery Specialist to help with treatment engagement and retention. Primary outcomes are six-month rates of opioid use and six-month rates of remission of co-occurring psychiatric disorders.. The Whole Health Study will investigate whether collaborative care models that address OUD and co-occurring depression, anxiety, or PTSD will result in better patient outcomes. The results will inform clinical care delivery during the current opioid crisis.. www.clinicaltrials.gov registration: NCT04245423.

Topics: Buprenorphine; Humans; Mental Health; Opiate Substitution Treatment; Opioid-Related Disorders; Primary Health Care; Randomized Controlled Trials as Topic

ED-INNOVATION (Emergency Department-INitiated bupreNOrphine VAlidaTION) is a Hybrid Type-1 Implementation-Effectiveness multisite emergency department (ED) study funded through The Helping to End Addiction Long-term

Topics: Buprenorphine; Delayed-Action Preparations; Emergency Service, Hospital; Humans; Narcotic Antagonists; Opioid-Related Disorders

Hospitalization with co-occurring opioid use disorder (OUD) and infections presents a critical time to intervene to improve outcomes for these intertwined epidemics that are typically managed separately. A surge in life-threatening infectious diseases associated with injection drug use, including bacterial and fungal infections, HIV, and HCV accounts for substantial healthcare utilization, morbidity, and mortality. Infectious Disease (ID) specialists manage severe infections that require hospitalization and are a logical resource to engage patients in medication treatment for OUD (MOUD). An injectable long-acting monthly formulation of buprenorphine (LAB) has a potential advantage for initiating MOUD within hospital settings and bridging to treatment after discharge.. A randomized multi-site trial tests a new model of care (ID/LAB) in which OUD and infections are managed by ID specialists and hospitalists using LAB coupled with referrals to community resources for long-term MOUD. A sample of 200 adults admitted to three U.S. hospitals for OUD and infections are randomly assigned 1:1 to ID/LAB or treatment as usual (TAU). The primary outcome measure is the proportion of patients enrolled in effective MOUD at 12 weeks after randomization. Secondary outcomes include relapse to opioid use, adherence to infectious disease treatment, infection morbidity and mortality, and drug overdose.. We describe the design, procedures, statistical analysis, and early implementation issues of this randomized trial.. Study findings will provide insight into the feasibility and effectiveness of integrated treatment of OUD and serious infections and have the potential to reduce morbidity and mortality in this vulnerable population.

Topics: Adult; Buprenorphine; Delivery of Health Care, Integrated; Humans; Neoplasm Recurrence, Local; Opiate Substitution Treatment; Opioid-Related Disorders

The EXIT-CJS (N = 1005) multisite open-label randomized controlled trial will compare retention and effectiveness of extended-release buprenorphine (XR-B) vs. extended-release naltrexone (XR-NTX) to treat opioid use disorder (OUD) among criminal justice system (CJS)-involved adults in six U.S. locales (New Jersey, New York City, Delaware, Oregon, Connecticut, and New Hampshire). With a pragmatic, noninferiority design, this study hypothesizes that XR-B (n = 335) will be noninferior to XR-NTX (n = 335) in retention-in-study-medication treatment (the primary outcome), self-reported opioid use, opioid-positive urine samples, opioid overdose events, and CJS recidivism. In addition, persons with OUD not eligible or interested in the RCT will be recruited into an enhanced treatment as usual arm (n = 335) to examine usual care outcomes in a quasi-experimental observational cohort.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Delayed-Action Preparations; Humans; Injections, Intramuscular; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders

Patient-reported outcomes in the treatment of opioid dependence may differ between subcutaneously administered depot buprenorphine and daily sublingual buprenorphine.. To compare patient satisfaction between depot buprenorphine and sublingual buprenorphine in adult outpatients with opioid dependence.. This open-label, randomized clinical trial was conducted among adult patients with opioid dependence at 6 outpatient clinical sites in Australia from October 2018 to September 2019. Data analysis was conducted from October 2019 to May 2020.. Participants were randomized to receive treatment with weekly or monthly depot buprenorphine or daily sublingual buprenorphine over 24 weeks.. The primary end point was the difference in global treatment satisfaction, assessed by the Treatment Satisfaction Questionnaire for Medication (TSQM) version 1.4 (range, 0-100; higher score indicates greater satisfaction) at week 24. Secondary end points included other patient-reported outcomes, including quality of life, treatment burden, and health-related outcomes, as well as measures of opioid use, retention in treatment, and safety.. A total of 119 participants (70 [58.8%] men; mean [SD] age, 44.4 [10.5] years) were enrolled, randomized to, and received either depot buprenorphine (60 participants [50.4%]) or sublingual buprenorphine (59 participants [49.6%]). From the initial sample of 120, a participant (0.8%) in the sublingual buprenorphine group withdrew consent and did not receive study treatment. All participants were receiving sublingual buprenorphine when enrolled. The mean TSQM global satisfaction score was significantly higher for the depot group compared with the sublingual group at week 24 (mean [SE] score, 82.5 [2.3] vs 74.3 [2.3]; difference, 8.2; 95% CI, 1.7 to 14.6; P = .01). Improved outcomes were also observed for several secondary end points after treatment with depot buprenorphine (eg, mean [SE] treatment burden assessed by the Treatment Burden Questionnaire global score, on which lower scores indicate lower burden: 13.2 [2.6] vs 28.6 [2.5]; difference, -15.4; 95% CI, -22.6 to -8.2; P < .001). Thirty-nine participants (65.0%) in the depot buprenorphine group experienced 117 adverse drug reactions, mainly injection site reactions of mild intensity following subcutaneous administration, and 12 participants (20.3%) in the sublingual buprenorphine group experienced 21 adverse drug reactions. No participants withdrew from the trial medication or the trial due to adverse events.. In this study, participants receiving depot buprenorphine reported improved treatment satisfaction compared with those receiving sublingual buprenorphine. The results highlight the application of patient-reported outcomes as alternative end points to traditional markers of substance use in addiction treatment outcome studies.. anzctr.org.au Identifier: ANZCTR12618001759280.

Topics: Administration, Sublingual; Adult; Buprenorphine; Delayed-Action Preparations; Female; Humans; Injections, Subcutaneous; Male; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Reported Outcome Measures; Surveys and Questionnaires

To assess the cognitive functions in participants maintained on buprenorphine for opioid dependence at peak and trough buprenorphine levels.. This was a double-blind, randomized, experimental study. Sixty participants maintained on buprenorphine were matched for age and education and randomly allocated to "peak" group or "trough" group. The "peak" group received buprenorphine two hours before assessment, whereas the trough group received placebo. The cognitive domains of attention, learning and memory, and executive function including fluency, working memory, response inhibition and set shifting were tested.. The two groups were comparable on socio-demographic, substance use profile and opioid agonist treatment-related characteristics. Significant differences in performance of peak and trough group were observed on Wisconsin Card Sorting Test parameters of number of correct responses (U = 289.00, p = 0.03), number of errors (t = 02.26, df = 58, p = 0.03), and perseverative errors (U = 301.50, p = 0.04).. The time since buprenorphine dose has significant relation on specific cognitive tasks in patients maintained on buprenorphine for opioid dependence.

Topics: Attention; Buprenorphine; Cognition; Double-Blind Method; Humans; Memory, Short-Term; Narcotic Antagonists; Opioid-Related Disorders

Opioid overdose remains a leading cause of death. Office-based buprenorphine could expand access to treatment to the many opioid users who are not in treatment and who are at risk for opioid overdose. However, many people in need of buprenorphine treatment do not enroll in treatment. This randomized pilot trial evaluated efficacy of a remotely delivered incentive intervention in promoting engagement in buprenorphine treatment in out-of-treatment adults with opioid use disorder.. Participants (N = 41) were offered referrals to buprenorphine treatment and randomly assigned to Control or Incentive groups for 6 months. Incentive participants were offered incentives for enrolling in buprenorphine treatment, verified by providing documentation showing that they received a buprenorphine prescription, and providing videos taking daily buprenorphine doses. Participants used a smartphone application to record and submit a video of their buprenorphine prescription and daily buprenorphine administration. Incentive earnings were added remotely to reloadable credit cards.. Incentive participants were significantly more likely to enroll in treatment compared to control participants (71.4 % versus 30.0 % of participants; OR [95 % CI]: 6.24 [1.46-26.72], p = .014). Few participants in either group adhered to buprenorphine treatment, and the two groups continued to use opioids, including fentanyl at high and comparable rates. The two groups did not differ in the percentage of urine samples that were positive for buprenorphine, opiates, fentanyl, or methadone at monthly assessments conducted during the 6-month intervention.. Remotely delivered incentives can connect out-of-treatment adults with opioid use disorder to treatment, but additional supports are needed to promote buprenorphine adherence.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Humans; Methadone; Motivation; Opiate Substitution Treatment; Opioid-Related Disorders

High rates of unintended pregnancy occur among women with opioid use disorder (OUD). OUD treatment settings may provide an ideal opportunity to address the family planning needs of patients. However, few studies have rigorously evaluated interventions designed to address family planning needs in the OUD treatment setting. This study assessed the feasibility, acceptability, and preliminary efficacy of a peer-led navigation intervention designed to educate and link women receiving medications for OUD to family planning services.. The study recruited women from four OUD treatment programs in Denver, Colorado, to participate in a pilot randomized controlled trial from March 2018 to February 2019. Eligible participants were English-speaking adult females who were neither pregnant nor desiring a pregnancy and who were not using a long-acting reversible contraceptive (LARC) method. Participants completed a baseline survey, and the study randomized them to receive a two-session, peer-led family planning navigation intervention or usual care. The study assessed feasibility by participant engagement in the intervention. The study used follow-up self-report surveys and electronic health record data to assess intervention acceptability and intervention efficacy for the primary outcomes of a family planning visit and use of a LARC method.. The study enrolled 119 women who were randomized to the Sexual Health Initiative for Navigation and Empowerment (SHINE) peer-led navigation intervention (n = 56) or usual care (n = 63). The average age was 32 (SD = 6.4); 76% were receiving methadone, 24% were receiving buprenorphine and 19% reported a treatment provider had ever discussed family planning with them. Most had a previous pregnancy (82%) and of these, 93% reported an unplanned pregnancy. Among intervention participants, 93% completed the first navigation session, 90% felt that intervention topics were important, 76% indicated that the information was new, and 82% found working with a peer helpful. At six months postbaseline, significantly more (p = 0.01) intervention participants (36%) received a family planning visit compared to control participants (14%). There was no between-group difference on use of LARC methods.. A peer-led family planning navigation intervention was feasible to implement, acceptable to participants, and showed evidence of preliminary efficacy. This model may be an effective and potentially sustainable approach to support the family planning needs of women in treatment for OUD.

Topics: Adult; Buprenorphine; Contraception; Family Planning Services; Female; Humans; Opioid-Related Disorders; Pilot Projects; Pregnancy

Smoking prevalence in individuals with opioid use disorder (OUD) is over 80%. Research suggests that opioid use significantly increases smoking, which could account for the strikingly low smoking-cessation rates observed in both methadone- and buprenorphine-maintained patients, even with the use of first-line smoking-cessation interventions. If opioids present a barrier to smoking-cessation, then better smoking outcomes should be observed in OUD patients treated with extended-release naltrexone (XR-NTX, an opioid antagonist) compared to those receiving buprenorphine (BUP-NX, a partial opioid agonist).. The current study is a secondary analysis of a 24-week, multi-site, open-label, randomized clinical trial conducted within the National Drug Abuse Treatment Clinical Trials Network comparing the effectiveness of XR-NTX vs. BUP-NX for adults with OUD. Longitudinal mixed effects models were used to determine if there was a significant reduction in cigarette use among daily smokers successfully inducted to treatment (n = 373) and a subset of those who completed treatment (n = 169).. Among daily smokers inducted onto OUD medication, those in the XR-NTX group smoked fewer cigarettes per day (M = 11.36, SE = 0.62) relative to smokers in the BUP-NX group (M = 13.33, SE = 0.58) across all study visits, (b (SE) = -1.97 (0.55), p < .01). Results were similar for the treatment completers.. OUD patients treated with XR-NTX reduced cigarette use more than those treated with BUP-NX, suggesting that XR-NTX in combination with other smoking cessation interventions might be a better choice for OUD smokers interested in reducing their tobacco use.

Topics: Adult; Buprenorphine; Delayed-Action Preparations; Humans; Injections, Intramuscular; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Tobacco Use

We conducted a pilot study to assess feasibility of using video directly-observed therapy (DOT) for patients initiating buprenorphine to evaluate whether it is associated with better opioid use disorder (OUD) outcomes when compared to treatment-as-usual (TAU).. Pilot randomized controlled trial of adult patients with OUD initiating buprenorphine treatment (n = 78) at two sites (Seattle, WA and Boston, MA) from January 2019 to May 2020. Intervention was video DOT using a HIPAA-compliant smartphone application to record taking daily buprenorphine. Study smartphones, text reminders to upload a video, and calendar summaries of video DOT adherence were provided. Main outcomes were 1) percentage of 12 weekly urine drug tests (UDT) negative for illicit opioids and 2) engagement in treatment at week 12 (i.e., having an active prescription for buprenorphine within the last 7 days).. Of 78 enrolled, 20 (26 %) were female; 29 (37 %) non-white; and 31 (40 %) homeless. The mean (standard deviation) percentage of doses confirmed by video was 31 % (34 %). In intention-to-treat analysis, the average percentage of weekly opioid negative UDT was 50 % (95 % CI: 40-63 %) in the intervention arm versus 64 % (95 % CI: 55-74 %) among controls; RR = 0.78 (95 % CI: 0.60-1.02, p = 0.07). Engagement at week 12 was 69 % (95 % CI: 56-86 %) v. 82 % (95 % CI: 71-95 %) in the intervention vs. TAU arms, respectively; RR = 0.84 (95 % CI: 0.65-1.10, p = 0.20).. The video DOT intervention did not result in improvements in illicit opioid use and treatment engagement compared to TAU. The study was limited by low rates of intervention use.. ClinicalTrails.gov, NCT03779997, Registered on December 19, 2018.

Topics: Adult; Buprenorphine; Directly Observed Therapy; Female; Humans; Male; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Pilot Projects

The effectiveness of linking people from short-term in-patient managed withdrawal programs ('detoxification') to long-term, primary care-based buprenorphine is unknown. We tested whether buprenorphine initiation during an opioid withdrawal program and linkage to office-based buprenorphine (LINK) after discharge would increase engagement with office-based buprenorphine and decrease illicit opioid use during the ensuing 6 months compared with standard withdrawal management (WM).. Single-site randomized controlled trial.. Short-term in-patient detoxification program in Massachusetts, USA.. People with opioid use disorder (n = 115) who averaged 32.4 years of age, 68.2% male, 79.1% white, using illicit opioids on 27.3 of the last 30 days, were randomly assigned to WM (n = 59) versus LINK (n = 56).. Intervention was buprenorphine induction, in-patient dose stabilization and post-discharge transition to maintenance buprenorphine at an affiliated primary care clinic (LINK). Comparator was 5-day buprenorphine managed withdrawal protocol (WM).. Mean 30-day rate of use of illicit opioids (primary aim) and prescribed buprenorphine (secondary aim) at 1, 3 and 6 months.. Compared with WM, participants in the LINK condition had lower illicit opioid use rates at days 12 [b = -6.81, 95% confidence interval (CI) = -9.69; -3.92, P < 0.001], 35 (b = -8.55, 95% CI - 11.63; -5.47, P < 0.001), 95 (b = -7.34, 95% CI = -10.59; -4.11, P < 0.001) and 185 (b = -3.52, 95% CI = -7.07; 0.27, P = 0.052). The LINK arm had higher prescription buprenorphine use rates (P < 0.001) at all assessments.. Among people with opioid use disorder, initiation of, and linkage to, office-based buprenorphine treatment post-discharge reduced illicit opioid use and increased days of buprenorphine treatment for up to 6 months post-discharge compared with an in-patient detoxification protocol.

Topics: Adult; Aftercare; Buprenorphine; Female; Humans; Inpatients; Male; Massachusetts; Opiate Substitution Treatment; Opioid-Related Disorders; Recurrence; Referral and Consultation

The study objective was to identify the analgesic efficacy of three different pharmacological strategies in patients receiving methadone or buprenorphine as opioid agonist treatment (OAT). The three pharmacological approaches, a) increasing maintenance methadone/buprenorphine dose by 30%, b) adding oxycodone, or c) adding a single dose of gabapentin, were compared with a control condition of the participant's usual OAT dose.. A randomized, controlled, double-blinded, double-dummy, within-subject crossover study.. Nine participants on stable doses of methadone and eight participants on stable doses of buprenorphine were recruited.. An outpatient opioid treatment clinic in inner city Sydney, Australia.. The cold pressor tolerance test was used to examine experimental pain threshold and tolerance. Ratings of subjective drug effects and safety measures (physiological and cognitive) were assessed.. There was no difference in the primary outcome measures of pain thresholds or tolerance between the conditions examined. Interindividual variability was evident. Differences in some subjective measures were identified, including lower pain recall, lower "bad effects," and higher global satisfaction in the additional methadone condition. In the buprenorphine arm, increased drug liking and "bad effects" were detected with oxycodone administration, while increased subjective intoxication was identified with gabapentin.. There was no evidence of an objective improvement in analgesia with any condition compared with control. Further research is required to optimize pain management strategies in this population.

Topics: Analgesics, Opioid; Australia; Buprenorphine; Cross-Over Studies; Double-Blind Method; Gabapentin; Humans; Methadone; Opioid-Related Disorders; Pilot Projects

The U.S. experienced nearly 48,000 opioid overdose deaths in 2017. Treatment of opioid use disorder (OUD) with buprenorphine is a recommended part of primary care, yet little is known about current U.S. practices in this setting. This observational study reports the prevalence of documented OUD and OUD treatment with buprenorphine among primary care patients in six large health systems.. Adults with ≥2 primary care visits during a three-year period (10/1/2013-9/30/2016) in six health systems were included. Data were obtained from electronic health record and claims data, with measures, assessed over the three-year period, including indicators for documented OUD from ICD 9 and 10 codes and OUD treatment with buprenorphine. The prevalence of OUD treatment was adjusted for age, gender, race/ethnicity, and health system.. Among 1,368,604 primary care patients, 13,942 (1.0 %) had documented OUD, and among these, 21.0 % had OUD treatment with buprenorphine. For those with documented OUD, the adjusted prevalence of OUD treatment with buprenorphine varied across demographic and clinical subgroups. OUD treatment was lower among patients who were older, women, Black/African American and Hispanic (compared to white), non-commercially insured, and those with non-cancer pain, mental health disorders, greater comorbidity, and more opioid prescriptions, emergency department visits or hospitalizations.. Among primary care patients in six health systems, one in five with an OUD were treated with buprenorphine, with disparities across demographic and clinical characteristics. Less buprenorphine treatment among those with greater acute care utilization highlights an opportunity for systems-level changes to increase OUD treatment.

Topics: Adolescent; Adult; Aged; Analgesics, Opioid; Buprenorphine; Cohort Studies; Cross-Sectional Studies; Delivery of Health Care; Female; Humans; Male; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Pilot Projects; Prevalence; Primary Health Care; Treatment Outcome; United States; Young Adult

We aimed to evaluate and compare the effect of different intravenous doses of naloxone on reinforcing effect of intravenous buprenorphine (2 mg) in patients stabilised on sublingual buprenorphine.. This is a double-blind, within-subject, randomised, crossover study. Opioid-dependent patients, with history of intravenous drug use, stabilised on buprenorphine maintenance treatment were included after informed consent (n = 14). We administered and assessed the reinforcing effects of six test conditions: buprenorphine and naloxone co-formulation (BNX) in 4:1, 2:1 and 1:1 dose ratio (i.e. buprenorphine 2 mg + naloxone 0.5, 1 and 2 mg, respectively), buprenorphine alone (2 mg), pheniramine maleate (45.5 mg) and saline at 24 hourly intervals.. No significant opioid withdrawals were precipitated during any test conditions. Compared to buprenorphine alone, 4:1 BNX had comparable euphoria, drug recognition, subjective opiate sensations and drug liking (P > 0.05); 2:1 BNX condition had significantly different subjective euphoria (P = 0.001), opioid recognition (P = 0.002), subjective opioid sensations at 60 min (P = 0.027) and drug liking (P < 0.001), while 1:1 BNX had significantly different objective euphoria (P = 0.002), opioid recognition (P = 0.030), subjective opioid sensations (P < 0.001) and drug liking (P < 0.001). No significant difference was noted on sedation scores between buprenorphine alone and all three combinations of BNX.. The 4:1 BNX condition did not impact the reinforcing agonist effects of buprenorphine. None of the intravenous BNX combination ratios precipitated opioid withdrawals. Findings emphasise the need for exploring more abuse deterrent mechanisms.

Topics: Administration, Intravenous; Adolescent; Adult; Analgesics, Opioid; Buprenorphine; Cross-Over Studies; Double-Blind Method; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Treatment Outcome; Young Adult

Opioid withdrawal symptoms are widely understood to contribute to health risk but have rarely been measured in community samples of opioid using people who inject drugs (PWID).. Using targeted sampling methods, 814 PWID who reported regular opioid use (at least 12 uses in the last 30 days) were recruited and interviewed about demographics, drug use, health risk, and withdrawal symptoms, frequency, and pain. Multivariable regression models were developed to examine factors associated with any opioid withdrawal, withdrawal frequency, pain severity, and two important health risks (receptive syringe sharing and non-fatal overdose).. Opioid withdrawal symptoms were reported by 85 % of participants in the last 6 months, with 29 % reporting at least monthly withdrawal symptoms and 35 % reporting at least weekly withdrawal symptoms. Very or extremely painful symptoms were reported by 57 %. In separate models, we found any opioid withdrawal (adjusted odds ratio [AOR] = 2.75, 95 % confidence interval [CI] = 1.52, 5.00) and weekly or more opioid withdrawal frequency (AOR = 1.94; 95 % CI = 1.26, 3.00) (as compared to less than monthly) to be independently associated with receptive syringe sharing while controlling for confounders. Any opioid withdrawal (AOR = 1.71; 95 % CI = 1.04, 2.81) was independently associated with nonfatal overdose while controlling for confounders. In a separate model, weekly or more withdrawal frequency (AOR = 1.69; 95 % CI = 1.12, 2.55) and extreme or very painful withdrawal symptoms (AOR = 1.53; 95 % CI = 1.08, 2.16) were associated with nonfatal overdose as well.. Withdrawal symptoms among PWID increase health risk. Treatment of withdrawal symptoms is urgently needed and should include buprenorphine dispensing.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Cross-Sectional Studies; Drug Overdose; Female; Health Status; Humans; Male; Middle Aged; Needle Sharing; Opioid-Related Disorders; Pain; Risk Factors; Substance Abuse, Intravenous; Substance Withdrawal Syndrome

The National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN), an entity aimed at bridging researchers and community-based substance abuse treatment providers to develop new treatment approaches, has taken an interest in the dissemination of findings from a randomized clinical trial by D'Onofrio demonstrating that initiating buprenorphine in the emergency department (ED) enhances linkage to treatment [JAMA 2015; 313 (16): 1636-1644]. In the Southern Consortium Node of the CTN, the authors have taken an implementation science approach to expand on the D'Onofrio study by implementing an ED-based buprenorphine initiation program in three diverse South Carolina EDs utilizing a predominantly peer recovery coach model. The aim of this pilot program was to foundationally integrate universal screening, brief interventions and referral to treatment (SBIRT) in hospital EDs to identify patients with at-risk substance use. Through brief interventions, patient navigators assessed readiness to change and motivation for treatment of patients. Patients willing to engage in treatment were referred to appropriate community resources. Patients identified to have opioid use disorder (OUD) and willing to engage in treatment were eligible for ED-initiated buprenorphine and peer recovery coaches assisted in arranging next day follow up with a community treatment program or other local provider for ongoing treatment.. Hospital partner sites included a large academic medical center, a large private hospital, and a small community hospital. Prior to implementing this quality improvement initiative, the authors completed an ED workflow analysis at each site, developed internal planning committees including identification of a "hospital champion," facilitated electronic health record modifications, educated more than 200 ED nurses and providers, and identified a network of local community "fast-track" providers able to accept patients for next-day appointments.. Within 14 months, all three sites were fully operationalized and project staff in 3 ED sites screened 6523 patients for substance misuse with 33.0% screened positive for at-risk substance use. Positive screening results were as follows by substance: 907 alcohol, 100 cocaine, 40 methamphetamine, 7 amphetamines, 96 marijuana, 12 benzodiazepines, 3 Ecstasy/MDMA/Molly, 10 other/unknown substance, 274 heroin, 90 prescription opioids, 32 other/unknown opioid, 254 undetermined polysubstance use without opioids, and 331 polysubstance use with opioids. Of the 727 positive screened patients for non-medical opioid use, 70.0% were determined potentially eligible to receive buprenorphine initiation. Two-hundred thirty-one patients were initiated with one dose of 8 mg sublingual buprenorphine or 8-2 mg sublingual buprenorphine/naloxone; 76.6% of those initiated arrived to next-day appointments for continued medications for opioid use disorder (MOUD); and 59.9% of those patients were retained in treatment at 30 days. Of referred patients, payor at time of ED visit were as follows: 71.1% uninsured, 21.4% state Medicaid, 1.6% Medicare, and 5.9% private health insurance.. With adequate resources and institutional support, implementation of evidence-based quality improvement initiatives focused on OUDs are feasible and enhance linkage to evidence-based treatment in a rural Southern state. Lessons learned from this implementation study can be used to guide future CTN studies focused on ED settings.. Financially supported by South Carolina Department of Health and Human Services with consultation and guidance from Mosaic Group and South Carolina Department of Alcohol and Other Drug Services.

Topics: Aged; Buprenorphine; Emergency Service, Hospital; Humans; Medicare; Narcotic Antagonists; Opioid-Related Disorders; United States

When patients seek to discontinue buprenorphine (BUP) treatment, monthly injectable extended-release naltrexone (XR-NTX) may help them avoid relapse. The efficacy of low ascending doses of oral NTX vs placebo for patients transitioning from BUP to XR-NTX is evaluated in this study.. In a phase 3, hybrid residential/outpatient study, clinically stable participants with opioid use disorder (N = 101), receiving BUP for more than or equal to 3 months and seeking antagonist treatment, were randomized (1:1) to 7 residential days of descending doses of BUP and low ascending doses of oral NTX (NTX/BUP, n = 50) or placebo (PBO-N/BUP, n = 51). Both groups received standing ancillary medications and psychoeducational counseling. Following negative naloxone challenge, participants received XR-NTX (day 8). The primary endpoint was the proportion of participants who received and tolerated XR-NTX.. There was no statistical difference between groups for participants receiving a first dose of XR-NTX: 68.6% (NTX/BUP) vs 76.0% (PBO-N/BUP; P = .407). The mean number of days with peak Clinical Opiate Withdrawal Scale (COWS) score less than or equal to 12 during the treatment period (days 1-7) was similar for NTX/BUP and PBO-N/BUP groups (5.8 vs 6.3; P = .511). Opioid withdrawal symptoms during XR-NTX induction and post-XR-NTX observation period (days 8-11) were mild and similar between groups (mean peak COWS score: NTX/BUP, 5.1 vs PBO-N/BUP, 5.4; P = .464). Adverse events were mostly mild/moderate.. Low ascending doses of oral NTX did not increase induction rates onto XR-NTX compared with placebo. The overall rate of successful induction across treatment groups supports a brief BUP taper with standing ancillary medications as a well-tolerated approach for patients seeking transition from BUP to XR-NTX. (Am J Addict 2020;00:00-00).

Topics: Adult; Buprenorphine; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Monitoring; Drug Substitution; Female; Humans; Male; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Substance Withdrawal Syndrome; Treatment Outcome

Opioid use disorder (OUD) in pregnant women has increased significantly in recent years. Maintaining these women on sublingual (SL) buprenorphine (BUP) is an evidence-based practice but BUP-SL is associated with several disadvantages that an extended-release (XR) BUP formulation could eliminate. The National Drug Abuse Treatment Clinical Trials Network (CTN) is conducting an intent-to-treat, two-arm, open-label, pragmatic randomized controlled trial, Medication treatment for Opioid-dependent expectant Mothers (MOMs), to compare mother and infant outcomes of pregnant women with OUD treated with BUP-XR, relative to BUP-SL. A second aim is to determine the relative economic value of utilizing BUP-XR. Approximately 300 pregnant women with an estimated gestational age (EGA) of 6-30 weeks, recruited from 12 sites, will be randomized in a 1:1 ratio to BUP-XR or BUP-SL, balancing on site, EGA, and BUP-SL status (taking/not taking) at the time of randomization. Participants will be provided with study medication and attend weekly medication visits through 12 months postpartum. Participants will be invited to participate in two sub-studies to evaluate the: 1) mechanisms by which BUP-XR may improve mother and infant outcomes; and 2) effects of prenatal exposure to BUP-XR versus BUP-SL on infant neurodevelopment. This paper describes the key design decisions for the main trial made during protocol development. This Investigational New Drug (IND) trial uniquely uses pragmatic features where feasible in order to maximize external validity, hence increasing the potential to inform clinical practice guidelines and address multiple knowledge gaps for treatment of this patient population.

Topics: Administration, Sublingual; Buprenorphine; Delayed-Action Preparations; Female; Humans; Narcotic Antagonists; Opioid-Related Disorders; Pregnancy; Research Design

Office-based buprenorphine treatment of opioid use disorder (OUD) does not typically include in-person directly observed therapy (DOT), potentially leading to non-adherence. Video DOT technologies may safeguard against this issue and thus enhance likelihood of treatment success. We describe the rationale and protocol for the Trial of Adherence Application for Buprenorphine treatment (TAAB) study, a pilot randomized controlled trial (RCT) to evaluate the effects of video DOT delivered via a smartphone app on office-based buprenorphine treatment outcomes, namely illicit opioid use and retention.. Participants will be recruited from office-based opioid addiction treatment programs in outpatient clinics at two urban medical centers and randomized to either video DOT (intervention) delivered via a HIPAA-compliant, asynchronous, mobile health (mHealth) technology platform, or treatment-as-usual (control). Eligibility criteria are: 18 years or older, prescribed sublingual buprenorphine for a cumulative total of 28 days or less from the office-based opioid treatment program, and able to read and understand English. Patients will be considered ineligible if they are unable or unwilling to use the intervention, provide consent, or complete weekly study visits. All participants will complete 13 in-person weekly visits and be followed via electronic health record data capture at 12- and 24-weeks post-randomization. Data gathered include the following: demographics; current and previous treatment for OUD; self-reported diversion of prescribed buprenorphine; status of their mental and physical health; and self-reported lifetime and past 30-day illicit substance use. Participants provide urine samples at each weekly visit to test for illicit drugs and buprenorphine. The primary outcome is percentage of weekly urines that are negative for opioids over the 12-weeks. The secondary outcome is engagement in treatment at week 12.. Video DOT delivered through mHealth technology platform offers possibility of improving patients' buprenorphine adherence by providing additional structure and accountability. The TAAB study will provide important preliminary estimates of the impact of this mHealth technology for patients initiating buprenorphine, as well as the feasibility of study procedures, thus paving the way for further research to assess feasibility and generate preliminary data for design of a future Phase III trial. Trial Registration ClinicalTrails.gov, NCT03779997, Registered on December 19, 2018.

Topics: Adult; Buprenorphine; Directly Observed Therapy; Female; Humans; Male; Medication Adherence; Mobile Applications; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Pilot Projects; Self Report; Telemedicine; Treatment Outcome

Opioid use disorder (OUD) is associated with cognitive dysfunction. Understanding how pharmacotherapy may affect cognition is an important treatment consideration.. This was a hybrid residential-outpatient, randomized trial assessing transition regimens (naltrexone/buprenorphine [NTX/BUP] vs placebo-NTX/buprenorphine [PBO-N]/BUP) to extended-release naltrexone (XR-NTX) in patients with OUD seeking BUP discontinuation. Cognition was assessed at baseline, Day 22 (XR-NTX Day 14), and Day 36 (XR-NTX Day 28) using a range of measures (Brief Assessment of Cognition Symbol Coding test, Controlled Oral Word Association Task, Wechsler Memory Scale-III Spatial Span test, Continuous Performance Test, and Test of Attentional Performance). Pre-specified exploratory analyses compared treatment groups. Post hoc analyses were treatment-arm-independent analyses overall and by baseline BUP dose (<8 mg/day [low-dose] or 8 mg/day [higher-dose]).. Baseline cognitive measures were similar between NTX/BUP and PBO-N/BUP groups and between BUP low-dose and higher-dose groups. There were improvements in several cognitive outcomes at Day 22 and Day 36 relative to baseline for the overall population, but no differences between NTX/BUP and PBO-N/BUP treatment groups were observed. Participants entering the study on low-dose BUP showed improvements at Day 36 relative to baseline in 5 of 7 cognitive outcomes; participants entering the study on higher-dose BUP generally did not show improvements in cognitive outcomes.. Improvements in most cognitive domains were associated with the transition from BUP to XR-NTX, particularly in participants entering the study on low-dose (<8 mg/day) BUP. These improvements may be due to the discontinuation of BUP, the treatment with XR-NTX, or both.

Topics: Buprenorphine; Cognition; Delayed-Action Preparations; Humans; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders

Topics: Adult; Analgesics, Opioid; Buprenorphine; Delayed-Action Preparations; Female; Humans; Lactation; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Acceptance of Health Care; Postpartum Period; Pregnancy; Pregnancy Complications; Prospective Studies; Treatment Outcome; Young Adult

Opioid use disorder (OUD) is a public health crisis. Differences in opioid withdrawal severity that predict treatment outcome could facilitate the process of matching patients to treatments. This is a secondary analysis of a randomized controlled trial (RCT) that enrolled treatment seeking heroin-users (N = 89, males = 78) into a residential study. Participants maintained on morphine (30 mg, subcutaneous, four-times daily) underwent a naloxone (0.4 mg, IM = intramuscular) challenge session to precipitate withdrawal. Area-under-the-curve (AUC) values from self-reported withdrawal ratings during the challenge session were analyzed using K-means clustering, revealing two phenotype groups. Withdrawal and retention from the subsequent 14-day double-blind, double-dummy RCT comparing three study medications (clonidine, tramadol-ER, and buprenorphine) were evaluated as a function of phenotype. Cluster analyses suggested HIGH (N = 37; mean [SD] subjective opiate withdrawal scale [SOWS]-AUC 123.7 [65.8]) and LOW (N = 52; SOWS-AUC 68.0 [47.7]) withdrawal phenotype groups. HIGH participants were significantly more female and had lower body mass indices than LOW participants; no drug-use variables were significant. Regarding RCT outcomes, HIGH phenotype participants were less likely to be retained in the study (P = 0.02) and had higher mean self-reported withdrawal (P = 0.05) than LOW phenotype participants. A significant interaction in RCT retention was observed between phenotype (P = 0.02) and study medication (P < 0.01). Self-reported withdrawal was significant for phenotype (P = 0.02); study medication trended towards significance (P = 0.07). Results suggest patients have meaningfully different experiences of opioid withdrawal that may predict differential response to opioid pharmacotherapies during supervised withdrawal. Additional prospective research to replicate and more thoroughly evaluate withdrawal phenotype correlates and sex differences is warranted.

Topics: Adult; Analgesics; Buprenorphine; Clonidine; Cluster Analysis; Double-Blind Method; Female; Humans; Male; Morphine; Naloxone; Narcotic Antagonists; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Phenotype; Severity of Illness Index; Substance Withdrawal Syndrome; Tramadol; Treatment Outcome

The purpose of this study was to pilot-test a mind-body intervention called Mindful Awareness in Body-oriented Therapy (MABT) as an adjunct to buprenorphine for individuals with opioid use disorder (OUD). MABT, a manualized 8 week protocol, teaches interoceptive awareness skills to promote self-care and emotion regulation. A small study was designed to assess MABT recruitment and retention feasibility, and intervention acceptability, among this population. Individuals were recruited from two office-based programs providing buprenorphine treatment within a large urban community medical center. Participants were randomized to receive either treatment as usual (TAU), or TAU plus MABT. Assessments administered at baseline and 10-week follow-up included validated self-report health questionnaires and a process measure, the Multidimensional Assessment of Interoceptive Awareness, to examine interoceptive awareness skills. An additional survey and exit interview for those in the MABT study arm were administered to assess intervention satisfaction. Results showed the ability to recruit and enroll 10 participants within two-weeks, and no loss to follow-up. The MABT study group showed an increase in interoceptive awareness skills from baseline to follow-up, whereas the control group did not. Responses to the satisfaction questionnaire and exit interview were positive, indicating skills learned, satisfaction with the interventionists, and overall perceived benefit of the intervention. In summary, study results demonstrated recruitment and retention feasibility, and high intervention acceptability. This pilot study suggests preliminary feasibility of successfully implementing a larger study of MABT as an adjunct to office-based medication treatment for opioid use disorder.

Topics: Adult; Analgesics, Opioid; Awareness; Buprenorphine; Female; Humans; Male; Mind-Body Therapies; Mindfulness; Opioid-Related Disorders; Patient Satisfaction; Pilot Projects; Self Report; Surveys and Questionnaires

In a pilot randomized trial in persons with opioid use disorder hospitalized with injection-related infections, an innovative care model combining outpatient parenteral antimicrobial therapy with buprenorphine treatment had similar clinical and drug use outcomes to usual care (inpatient intravenous antibiotic completion) and shortened hospital length of stay by 23.5 days.. NCT03048643.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Buprenorphine; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Outpatients

The purpose of this project was to assess the feasibility and acceptability of a hatha yoga program designed to target chronic pain in people receiving opioid agonist therapy for opioid use disorder. We conducted a pilot randomized trial in which people with chronic pain who were receiving either methadone maintenance therapy (n = 20) or buprenorphine (n = 20) were randomly assigned to weekly hatha yoga or health education (HE) classes for 3 months. We demonstrated feasibility in many domains, including recruitment of participants (58% female, mean age 43), retention for follow-up assessments, and ability of teachers to provide interventions with high fidelity to the manuals. Fifty percent of participants in yoga (95% CI: 0.28-0.72) and 65% of participants in HE (95% CI: 0.44-0.87) attended at least 6 of 12 possible classes (p = 0.62). Sixty-one percent in the yoga group reported practicing yoga at home, with a mean number of times practicing per week of 2.67 (SD = 2.37). Participant mood improved pre-class to post-class, with greater decreases in anxiety and pain for those in the yoga group (p < 0.05). In conclusion, yoga can be delivered on-site at opioid agonist treatment programs with home practice taken up by the majority of participants. Future research may explore ways of increasing the yoga "dosage" received. This may involve testing strategies for increasing either class attendance or the amount of home practice or both.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Chronic Pain; Feasibility Studies; Female; Health Education; Humans; Male; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pilot Projects; Yoga

Buprenorphine is a critically important treatment for addressing the opioid epidemic, but there are virtually no studies of physicians' job satisfaction with providing buprenorphine. Physicians' job satisfaction has been linked to burnout and turnover as well as patients' adherence to treatment recommendations, so it is important to understand how physicians' satisfaction with providing buprenorphine treatment compares to their overall job satisfaction.. As part of a cluster randomized clinical trial (RCT) focused on expanding access to medication for opioid use disorder, 55 physicians working in 38 organizations in Florida, Ohio, and Wisconsin completed a baseline web-based survey. Study measures included global job satisfaction, career satisfaction, and specialty satisfaction. Physicians who were waivered to prescribe buprenorphine were asked to rate their satisfaction with their current buprenorphine practice.. Overall, physicians were generally satisfied with their jobs, their careers, and their specialties. When waivered physicians (n = 40) were compared to non-waivered physicians (n = 15) on 13 satisfaction items, there were no statistically significant differences. Among waivered physicians, ratings for buprenorphine work were significantly lower than ratings for general medical practice for finding such work personally rewarding, being pleased with such work, and overall satisfaction.. Although waivered and non-waivered physicians both reported high global job satisfaction, these data suggest that some waivered physicians may view their buprenorphine work as somewhat less satisfying than their global medical practice. Given that job dissatisfaction is a risk factor for turnover and burnout, managers of treatment organizations should consider whether strategies may be able to mitigate some sources of lower satisfaction in the context of buprenorphine treatment. Trial registration ClinicalTrials.gov. NCT02926482. Date of registration: September 9, 2016. https://clinicaltrials.gov/ct2/show/NCT02926482.

Topics: Adult; Aged; Buprenorphine; Female; Humans; Job Satisfaction; Male; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Physicians; Practice Patterns, Physicians'

Sleep problems are commonly reported during opioid agonist treatment (OAT) for opioid use disorders. Inpatient studies have found both sleep disturbances and improved sleep during OAT. Illicit opioids can also disrupt sleep, but it is unclear how they affect sleep in outpatients receiving OAT. Therefore, we used electronic diary entries and actigraphy to measure sleep duration and timing in opioid-dependent participants (n = 37) treated with methadone (n = 15) or buprenorphine (n = 22). For 16 weeks, participants were assigned to attend our clinic under different operating hours in a crossover design: Early hours (07:00-09:00) vs. Late hours (12:00-13:00) for 4 weeks each in randomized order, followed for all participants by our Standard clinic hours (07:00-11:30) for 8 weeks. Throughout, participants made daily electronic diary self-reports of their sleep upon waking; they also wore a wrist actigraph for 6 nights in each of the three clinic-hour conditions. Drug use was assessed by thrice-weekly urinalysis. In linear mixed models controlling for other sleep-relevant factors, sleep duration and timing differed by drug use and by clinic hours. Compared to when non-using, participants slept less, went to bed later, and woke later when using illicit opioids and/or both illicit opioids and cocaine. Participants slept less and woke earlier when assigned to the Early hours. These findings highlight the role OAT clinic schedules can play in structuring the sleep/wake cycles of OAT patients and clarify some of the circumstances under which OAT patients experience sleep disruption in daily life.

Topics: Actigraphy; Adult; Ambulatory Care Facilities; Appointments and Schedules; Buprenorphine; Cross-Over Studies; Diaries as Topic; Female; Humans; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Sleep; Sleep Wake Disorders; Time Factors

Managing acute pain in buprenorphine-maintained individuals in emergency or perioperative settings is a significant challenge. This study compared analgesic and abuse liability effects of adjunct hydromorphone and buprenorphine using quantitative sensory testing, a model of acute clinical pain, in persons maintained on 12 to 16 mg sublingual buprenorphine/naloxone.. Participants (N = 13) were enrolled in a randomized within-subject, double-blind, placebo-controlled three-session experiment. Each session used a cumulative dosing design with four IV injections (4, 4, 8, and 16 mg of hydromorphone or 4, 4, 8, and 16 mg of buprenorphine); quantitative sensory testing and abuse liability assessments were measured at baseline and after each injection. The primary analgesia outcome was change from baseline cold pressor testing; secondary outcomes included thermal and pressure pain testing, as well as subjective drug effects and adverse events.. A significant two-way interaction between study drug condition and dose was exhibited in cold pressor threshold (F10,110 = 2.14, P = 0.027) and tolerance (F10,110 = 2.69, P = 0.006). Compared to after placebo, participants displayed increased cold pressor threshold from baseline after cumulative doses of 32 mg of IV hydromorphone (means ± SD) (10 ± 14 s, P = 0.035) and 32 mg of buprenorphine (3 ± 5 s, P = 0.0.39) and in cold pressor tolerance after cumulative doses of 16 mg (18 ± 24 s, P = 0.018) and 32 mg (48 ± 73 s, P = 0.041) IV hydromorphone; cold pressor tolerance scores were not significant for 16 mg (1 ± 15 s, P = 0.619) or 32 mg (7 ± 16 s, P = 0.066) buprenorphine. Hydromorphone and buprenorphine compared with placebo showed greater ratings on subjective measures of high, any drug effects, good effects, and drug liking. Adverse events were more frequent during the hydromorphone compared with buprenorphine and placebo conditions for nausea, pruritus, sedation, and vomiting.. In this acute clinical pain model, high doses of IV hydromorphone (16 to 32 mg) were most effective in achieving analgesia but also displayed higher abuse liability and more frequent adverse events. Cold pressor testing was the most consistent measure of opioid-related analgesia.

Topics: Adult; Analgesia; Analgesics, Opioid; Buprenorphine; Double-Blind Method; Female; Humans; Hydromorphone; Male; Opioid-Related Disorders; Pain; Treatment Outcome

Not enough evidence exists to compare buprenorphine-naloxone with extended-release naltrexone for treating opioid use disorder.. To evaluate the cost-effectiveness of buprenorphine-naloxone versus extended-release naltrexone.. Cost-effectiveness analysis alongside a previously reported randomized clinical trial of 570 adults in 8 U.S. inpatient or residential treatment programs.. Study instruments.. Adults with opioid use disorder.. 24-week intervention with an additional 12 weeks of observation.. Health care sector and societal.. Buprenorphine-naloxone and extended-release naltrexone.. Incremental costs combined with incremental quality-adjusted life-years (QALYs) and incremental time abstinent from opioids.. Use of the health care sector perspective and a willingness-to-pay threshold of $100 000 per QALY showed buprenorphine-naloxone to be preferable to extended-release naltrexone in 97% of bootstrap replications at 24 weeks and in 85% at 36 weeks. Similar results were obtained with incremental time abstinent from opioids as an outcome and with use of the societal perspective.. The base-case results were sensitive to the cost of the 2 treatments and the success of randomized treatment initiation.. Relatively short follow-up for a chronic condition, substantial missing data, no information on patient out-of-pocket and social service costs.. Buprenorphine-naloxone is preferred to extended-release naltrexone as first-line treatment when both options are clinically appropriate and patients require detoxification before initiating extended-release naltrexone.. National Institute on Drug Abuse, National Institutes of Health.

Topics: Adult; Buprenorphine; Cost-Benefit Analysis; Delayed-Action Preparations; Drug Therapy, Combination; Female; Health Care Costs; Humans; Male; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Treatment Outcome

Topics: Adult; Ambulatory Care; Analgesics, Opioid; Buprenorphine; Cognitive Behavioral Therapy; Combined Modality Therapy; Female; Humans; Internet-Based Intervention; Male; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Pilot Projects; Retention in Care; Treatment Outcome

RBP-6000, referred to as BUP-XR (extended-release buprenorphine), is a subcutaneously injected, monthly buprenorphine treatment for opioid use disorder. BUP-XR provides sustained buprenorphine plasma concentrations to block drug-liking of abused opioids over the entire monthly dosing period, while controlling withdrawal and craving symptoms. Administration of BUP-XR in a health-care setting also mitigates abuse, misuse, diversion, and unintentional exposure. We aimed to investigate the efficacy of different BUP-XR dosing regimens in participants with opioid use disorder.. This randomised, double-blind, placebo-controlled, phase 3 trial was done at 36 treatment centres in the USA. Treatment-seeking adults aged 18-65 years who had moderate or severe opioid use disorder (as defined by the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders) entered an open-label run-in phase of up to 2 weeks' treatment with buprenorphine-naloxone sublingual film. Eligible participants were then randomly assigned (4:4:1:1) with an interactive voice/web-response system to receive BUP-XR 300 mg/300 mg (six injections of 300 mg), BUP-XR 300 mg/100 mg (two injections of 300 mg plus four injections of 100 mg), or volume-matched placebo every 28 days, and received weekly individual drug counselling. No supplemental buprenorphine was allowed. The primary efficacy endpoint was participants' percentage abstinence from opioid use, defined as the percentage of each participant's negative urine samples and self-reports of illicit opioid use from week 5 to week 24, analysed in the full analysis set. Safety was assessed in all participants who received at least one dose of BUP-XR or placebo. This study is registered with ClinicalTrials.gov, number NCT02357901.. From Jan 28, 2015, to Nov 12, 2015, 1187 potential participants were screened, 665 entered run-in, and 504 received BUP-XR 300 mg/300 mg (n=201), BUP-XR 300 mg/100 mg (n=203), or placebo (n=100). Mean participants' percentage abstinence was 41·3% (SD 39·7) for BUP-XR 300 mg/300 mg and 42·7% (38·5) for 300 mg/100 mg, compared with 5·0% (17·0) for placebo (p<0·0001 for both BUP-XR regimens). No compensatory non-opioid drug use was observed during BUP-XR treatment. The most common adverse events were headache (17 [8%] participants in the BUP-XR 300 mg/300 mg group vs 19 [9%] participants in the BUP-XR 300 mg/100 mg group vs six [6%] participants in the placebo group), constipation (16 [8%] vs 19 [9%] vs 0), nausea (16 [8%] vs 18 [9%] vs five [5%]), and injection-site pruritis (19 [9%] vs 13 [6%] vs four [4%]). The BUP-XR safety profile was consistent with other buprenorphine products for treatment of opioid use disorder, except for injection-site reactions, which were reported in more than 5% of all participants who received BUP-XR, but were mostly mild and not treatment-limiting.. Participants' percentage abstinence was significantly higher in both BUP-XR groups than in the placebo group. Treatment with BUP-XR was also well tolerated. The availability of this monthly formulation, delivered by health-care providers, represents an advance in treatment for opioid use disorder that enhances the benefits of buprenorphine by delivering sustained, optimal exposure, while reducing risks of current buprenorphine products.. Indivior.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Injections; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Patient Compliance; Patient Satisfaction; United States

Buprenorphine can be effective in a variety of community substance use treatment settings outside of methadone programs, including outpatient programs and medical practices. In these settings, it has been found to be effective in reducing opioid use and retaining patients in treatment. Despite its effectiveness and safety, it is rarely provided to individuals with opioid use disorders in probation and parole settings.. Male and female individuals under probation or parole supervision (N = 320) with histories of opioid use disorder will be enrolled in this randomized controlled trial. Participants will be randomized to one of two study arms: Buprenorphine Bridge Treatment (BBT): Participants will begin buprenorphine using the MedicaSafe dispensing device immediately after an on-site intake at a community supervision office and continue such treatment until they are transitioned to a community program; or Treatment as Usual (TAU): Participants will receive a referral to buprenorphine pharmacotherapy treatment in the community. Treatment outcomes will be: (a) illicit opioid oral saliva drug test results; and (b) treatment adherence (i. entered community based treatment; ii. number of days receiving opioid treatment).. We describe the background and rationale for the study, its aims, hypotheses, and study design.. If shown to increase compliance rates with conditions of probation and parole, buprenorphine treatment co-located at community supervision field offices could have a major impact on delivery of buprenorphine treatment to the criminal justice population. The public health impact of the proposed study would be widespread because this intervention could be implemented throughout areas of the US.

Topics: Adolescent; Adult; Aged; Buprenorphine; Continuity of Patient Care; Criminals; Female; Humans; Male; Medication Adherence; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Research Design; Young Adult

To assess the long-term safety of subcutaneous buprenorphine (CAM2038) weekly and monthly depots.. Phase 3, open-label, observational, multi-centre 48-week trial (ClinicalTrials.gov NCT02672111).. Twenty-six out-patient sites (United States, United Kingdom, Hungary, Denmark, Sweden, Germany, Australia) between 14 December 2015 and 12 April 2017.. Two hundred and twenty-eight adults with opioid use disorder; 227 received CAM2038 (37 initiated onto CAM2038 and 190 converted from sublingual buprenorphine).. CAM2038 weekly (8, 16, 24 or 32 mg) or monthly (64, 96, 128 or 160 mg) with flexible dosing and individualized titration utilizing multiple CAM2038 weekly and monthly doses.. Safety variables, urine toxicology samples and self-reported illicit opioid use were collected at each visit. Participants were administered a patient satisfaction survey at months 6 and 12, completed by 162 of 227 (71.4%) participants.. The study treatment period was completed by 167 of 227 (73.6%) participants. At least one treatment-emergent adverse event (TEAE) was reported by 143 of 227 (63.0%) participants, of whom 60 of 227 (26.4%) reported as being drug-related. Most of the TEAEs, reported by 128 of 227 (56.4%) of participants, were mild or moderate in intensity. Injection-site reactions were reported by 46 of 227 (20.3%) participants, with most [45 of 46 (97.8%)] reported as mild to moderate. Five participants (2.2%) discontinued the study drug due to a TEAE, two cases (0.9%) of which were injection-site-related. No serious adverse events were attributed to the study drug. Among those remaining in the study, the percentage of opioid-negative urine tests combined with self-reports was 63.0% (17 of 27) in new-to-treatment participants and 82.8% (111 of 134) for those converted from sublingual buprenorphine. Participants reported high levels of satisfaction with CAM2038.. Subcutaneous buprenorphine delivered weekly or monthly (CAM2038) was well tolerated, with a systemic safety profile consistent with the known profile of sublingual buprenorphine. CAM2038 weekly and monthly was associated with high retention rates and low levels of illicit opioid use throughout this study.

Topics: Adult; Aged; Analgesics, Opioid; Australia; Buprenorphine; Delayed-Action Preparations; Denmark; Drug Monitoring; Female; Germany; Humans; Hungary; Injections, Subcutaneous; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Outpatients; Patient Safety; Patient Satisfaction; Sweden; United Kingdom; United States

To compare buprenorphine to clonidine for the treatment of opioid withdrawal in the emergency department (ED) and to study the effect assigned treatment medication had on longer-term addiction treatment outcomes.. Randomized controlled trial.. Toronto, Ont.. Twenty-six patients presenting to the ED while in opioid withdrawal or soon to be in opioid withdrawal.. Patients were randomized to receive either clonidine or buprenorphine treatment. Both groups also received a corresponding discharge prescription and information on how to follow up in the addictions rapid access clinic (RAC) within a few days. Participants were followed for 1 month with respect to attendance at the RAC and to opioid agonist treatment status. Outcome measures included attendance at the RAC within 5 days of the initial ED visit and opioid agonist treatment status at 1 month (as determined by clinic attendance or self-report during a follow-up telephone interview).. Participants who received buprenorphine in the ED were more likely to be receiving opioid agonist treatment at the 1-month mark compared with those participants who received clonidine to treat their withdrawal (. When opioid withdrawal is treated with buprenorphine in the ED, patients are more likely to be receiving opioid agonist treatment and connected with addiction treatment 1 month later.. NCT03174067 (ClinicalTrials.gov).

Topics: Adult; Buprenorphine; Clonidine; Emergency Service, Hospital; Female; Humans; Male; Narcotic Antagonists; Ontario; Opiate Substitution Treatment; Opioid-Related Disorders; Prospective Studies; Substance Withdrawal Syndrome; Treatment Outcome

The goal of this trial is to determine whether implementation of a user-centred clinical decision support (CDS) system can increase adoption of initiation of buprenorphine (BUP) into the routine emergency care of individuals with opioid use disorder (OUD).. A pragmatic cluster randomised trial is planned to be carried out in 20 emergency departments (EDs) across five healthcare systems over 18 months. The intervention consists of a user-centred CDS integrated into ED clinician electronic workflow and available for guidance to: (1) determine whether patients presenting to the ED meet criteria for OUD, (2) assess withdrawal symptoms and (3) ascertain and motivate patient willingness to initiate treatment. The CDS guides the ED clinician to initiate BUP and facilitate follow-up. The primary outcome is the rate of BUP initiated in the ED. Secondary outcomes are: (1) rates of receiving a referral, (2) fidelity with the CDS and (3) rates of clinicians providing any ED-initiated BUP, referral for ongoing treatment and receiving Drug Addiction Act of 2000 training. Primary and secondary outcomes will be analysed using generalised linear mixed models, with fixed effects for intervention status (CDS vs usual care), prespecified site and patient characteristics, and random effects for study site.. The protocol has been approved by the Western Institutional Review Board. No identifiable private information will be collected from patients. A waiver of informed consent was obtained for the collection of data for clinician prescribing and other activities. As a minimal risk implementation study of established best practices, an Independent Study Monitor will be utilised in place of a Data Safety Monitoring Board. Results will be reported in ClinicalTrials.gov and published in open-access, peer-reviewed journals, presented at national meetings and shared with the clinicians at participating sites via a broadcast email notification of publications.. NCT03658642; Pre-results.

Topics: Adult; Buprenorphine; Cluster Analysis; Decision Support Systems, Clinical; Emergency Service, Hospital; Female; Humans; Male; Middle Aged; Multicenter Studies as Topic; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Pragmatic Clinical Trials as Topic; Randomized Controlled Trials as Topic; United States; Young Adult

County, State, and Federal agencies are addressing the public health opioid crisis. Ohio's 51 county-based Alcohol, Drug Addiction and Mental Health Services (ADAMHS) Boards finance and regulate opioid treatment services within their jurisdictions. This three-year comparative trial collaborated with ADAMHS Boards (n = 14) to test the Advancing Recovery Framework, a suite of organizational and system change strategies designed to promote use of buprenorphine for opioid agonist therapy.. A multi-level intervention directed payers and treatment agencies to leverage their roles in increasing the use of buprenorphine. Half of the boards partnered with local substance use disorder treatment providers using the partnership strategies recommended by the Advancing Recovery (AR) framework. The comparison boards did not use the partnership strategies.. A logistic regression analysis detected increases in the number of patients receiving buprenorphine in both conditions. Buprenorphine use, as a percentage of patients with an opioid use disorder diagnosis, was significantly greater among the boards using the Advancing Recovery strategies during the three-year experimental period (odds ratio (OR) 1.63, 95% CI, 1.50 to 1.76, p < .001) and a one-year maintenance period (OR 2.13, 95% CI, 1.85 to 2.46, p < .001). Boards in both groups provided similar levels of financial support to implement and maintain buprenorphine prescribing. Strategy differences between the study conditions existed in use of a committee that facilitated payer-provider partnering and the ADAMHS boards setting expectations for using buprenorphine. Payer-provider partnerships achieved greater improvements and maximized the effectiveness of funding in increasing access to buprenorphine.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Female; Health Personnel; Humans; Implementation Science; Insurance, Health, Reimbursement; Male; Opiate Substitution Treatment; Opioid Epidemic; Opioid-Related Disorders

Two phase I studies assessed the pharmacokinetics of buprenorphine, its metabolite norbuprenorphine, and naloxone following administration of buprenorphine/naloxone sublingual tablets in Chinese participants.. In the first phase I, open-label, single ascending-dose (SAD) study, 82 opioid-naïve volunteers received a single buprenorphine/naloxone dose ranging from 2 mg/0.5 mg to 24 mg/6 mg while under naltrexone block. In a second phase I, open-label, multiple ascending-dose (MAD) study, 27 patients with opioid dependence in withdrawal received buprenorphine/naloxone doses of either 16 mg/4 mg or 24 mg/6 mg for 9 consecutive days. Serial blood samples were collected after a single dose (SAD study) and at steady-state (MAD study). Pharmacokinetic parameters were calculated using non-compartmental analysis. Safety assessments included adverse events monitoring and laboratory tests.. The pharmacokinetic profiles of buprenorphine and naloxone were consistent between single- and multiple-dose studies. Peak plasma concentrations (C. The present data suggest that buprenorphine/naloxone pharmacokinetic profiles in Chinese participants are consistent, overall, with those in Western populations, supporting no differences in dosing.. The protocols were registered on the official website of the China Food and Drug Administration (CFDA): http://www.chinadrugtrials.org.cn/ ; Registration numbers CTR20132963 (RB-CN-10-0012), CTR20140153 (RB-CN-10-0015).

Topics: Administration, Sublingual; Adult; Analgesics, Opioid; Area Under Curve; Asian People; Biological Availability; Buprenorphine; Female; Humans; Male; Naloxone; Opioid-Related Disorders; Tablets

Buprenorphine is widely used in the treatment of opioid use disorder and pain management. Little is known about the analgesic effects of high-dose sublingual buprenorphine, particularly in doses of >8 mg. The aim of this study was to examine the effect of ascending doses of buprenorphine upon acute pain measures in patients stabilized on buprenorphine as treatment for opioid dependence.. The pilot study (n = 7) was a randomised, controlled, double-blind, double-dummy, within-subject crossover study examining cold-pressor threshold and tolerance testing under different buprenorphine dose conditions. Each participant attended three sessions to test the analgesic effect of buprenorphine in their usual dose (100%), 150% and 200% of their usual daily dose.. No significant effects of increased dose were seen on experimental pain measures. Expected physiological effects on pupil size and pulse were observed with increasing dose. No effect of buprenorphine condition was seen on subjective ratings of drug strength, or self-reported sedation, though lower ratings drug liking were seen with 150% and 200% conditions, and lower ratings of 'bad effects' and intoxication were reported with the 200% buprenorphine dose condition. No safety concerns with the 150 and 200% buprenorphine dose condition were observed.. This pilot study suggests that a ceiling effect on analgesia may be observed in people maintained on buprenorphine, though larger studies may confirm this finding. Clinical Trial Number: ACTRN12614001038684.

Topics: Acute Pain; Administration, Sublingual; Adult; Analgesics, Opioid; Buprenorphine; Cross-Over Studies; Double-Blind Method; Female; Humans; Male; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Pain Measurement; Pilot Projects

Patients receiving medication assisted therapy (MAT) for opioid use disorder have high cigarette smoking rates. Cigarette smoking interventions have had limited success. We evaluated an intervention to increase cigarette abstinence rates in patients receiving buprenorphine-assisted therapy.. Cigarette smokers (N = 175; 78% male; 69% Caucasian; 20% Hispanic), recruited from a buprenorphine clinic were randomly assigned to either an extended innovative system intervention (E-ISI) or to Standard Treatment Control (STC). The E-ISI combined motivational intervention with extended treatment (long-term nicotine replacement therapy , varenicline, and extended cognitive behavioral therapy). STC received written information about quit-lines, medication, and resources. Assessments were held at baseline and 3, 6, 12, and 18 months. Seven-day biochemically verified point-prevalence cigarette abstinence was the primary outcome measure.. Fifty-four percent of E-ISI participants entered the extended treatment intervention; E-ISI and STC differed at 3 months on abstinence status but not at months 6, 12, and 18. E-ISI participants were more likely to attempt to quit, to have a goal of complete abstinence, and to be in a more advanced stage of change than STC participants. A higher number of cigarettes smoked and the use of cannabis in the previous 30 days predicted continued smoking.. The E-ISI was successful in increasing motivation to quit smoking but did not result in long-term abstinence. The failure of treatments that have been efficacious in the general population to produce abstinence in patients receiving MAT of opioid use disorder suggests that harm reduction and other innovative interventions should be explored.. This study demonstrates that an intervention combining motivational interviewing with an extended treatment protocol can increase cigarette quit attempts, enhance cigarette abstinence goals, and further movement through stages of change about quitting smoking in patients receiving MAT for opioid use disorder who smoke cigarettes. The intervention did not increase abstinence rates over those observed in a standard treatment control, however. The latter finding supports those of earlier investigators who also failed to find efficacy for smoking cessation in this population and who also used interventions effective in the general population. This pattern of findings suggests that patients with opioid use disorder can be motivated to change smoking behavior, but alternative and innovative approaches to cigarette smoking treatment should be studied.

Topics: Buprenorphine; Cognitive Behavioral Therapy; Humans; Narcotic Antagonists; Opioid-Related Disorders; Smoking; Smoking Cessation; Tobacco Use Cessation Devices

To examine the impact of different doses of buprenorphine on depression symptoms in opioid dependent inpatient over a three-day interval, using a randomized clinical trial design (RCT).. Patients were randomized and assigned to three groups.. Forty males who were admitted to an inpatient psychiatric unit and who fulfilled the DSM-5 criteria for both opioid dependence and major depressive disorder.. Patients randomly received 32 mg, 64 mg, or 96 mg of buprenorphine as a single high dose. Out of 40 patients, 11 (27.5%) received 32 mg, 14 (35%) received 64 mg and 15 (37.5%) received 96 mg of buprenorphine. We conducted medical precautional measures, including cardiovascular and respiratory monitoring.. Depression was measured by the Beck Depression Inventory (BDI). All patients completed the three-day treatment duration. The results showed a significant reduction in depression symptoms within each of the three groups (p = 0.00), although there was no significant difference in depression outcome across the groups (p = 0.90).. The results suggest that a single high dose of buprenorphine could provide a safe, simple and speedy means of depression improvement. A single high dose of buprenorphine can be used as medication that supplies a fast and maintained treatment for major depressive disorder in patients who are opioid dependent. Placebo-controlled trials of longer periods and larger sample sizes are needed to test ability and safety, as well as the physiological and psychological impact of extended exposure to this drug.

Topics: Adult; Buprenorphine; Depressive Disorder, Major; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Male; Narcotic Antagonists; Opioid-Related Disorders; Time Factors; Treatment Outcome; Young Adult

To investigate plasma levels of buprenorphine and norbuprenorphine and their relationship to respiratory depression.. Opioid-dependent subjects were randomized 2 : 1 to novel lyophilized rapid-disintegrating tablet ("bup-lyo") or standard sublingual buprenorphine tablet ("bup-SL"). Measurements included oximetry scores and linked plasma buprenorphine and norbuprenorphine levels.. Exploratory investigation found respiratory depression more strongly associated with norbuprenorphine than with buprenorphine. This accords with animal studies.
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Topics: Administration, Sublingual; Analgesics, Opioid; Biological Availability; Biotransformation; Buprenorphine; Drug Compounding; Freeze Drying; Humans; Lung; Opiate Substitution Treatment; Opioid-Related Disorders; Respiration; Respiratory Insufficiency; Risk Factors; Solubility; Tablets; Treatment Outcome

Methadone and buprenorphine are recommended to treat opioid use disorders during pregnancy. However, the literature on the relationship between longer-term effects of prenatal exposure to these medications and childhood development is both spare and inconsistent.. Participants were 96 children and their mothers who participated in MOTHER, a randomized controlled trial of opioid-agonist pharmacotherapy during pregnancy. The present study examined child growth parameters, cognition, language abilities, sensory processing, and temperament from 0 to 36 months of the child's life. Maternal perceptions of parenting stress, home environment, and addiction severity were also examined.. Tests of mean differences between children prenatally exposed to methadone vs. buprenorphine over the three-year period yielded 2/37 significant findings for children. Similarly, tests of mean differences between children treated for NAS relative to those not treated for NAS yielded 1/37 significant finding. Changes over time occurred for 27/37 child outcomes including expected child increases in weight, head and height, and overall gains in cognitive development, language abilities, sensory processing, and temperament. For mothers, significant changes over time in parenting stress (9/17 scales) suggested increasing difficulties with their children, notably seen in increasing parenting stress, but also an increasingly enriched home environment (4/7 scales) CONCLUSIONS: Findings strongly suggest no deleterious effects of buprenorphine relative to methadone or of treatment for NAS severity relative to not-treated for NAS on growth, cognitive development, language abilities, sensory processing, and temperament. Moreover, findings suggest that prenatal opioid agonist exposure is not deleterious to normal physical and mental development.

Topics: Adult; Buprenorphine; Child Development; Child, Preschool; Cognition; Female; Humans; Infant, Newborn; Male; Methadone; Mothers; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Parenting; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Temperament

Neonatal abstinence syndrome (NAS) is a constellation of withdrawal symptoms in infants born to mothers with chronic opioid use during pregnancy. A proportion of infants will need pharmacotherapy in addition to non-pharmacological interventions. In this article, we reviewed a clinical trial comparing the use of sublingual buprenorphine to oral morphine (the most widely used pharmacotherapy for NAS) in term infants. The primary end point was the duration of treatment, and secondary end points were the length of hospital stay, the proportion of infants who needed supplemental phenobarbital, and safety.

Topics: Administration, Oral; Administration, Sublingual; Buprenorphine; Clinical Decision-Making; Female; Humans; Infant, Newborn; Length of Stay; Male; Morphine; Narcotic Antagonists; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnancy, High-Risk; Prognosis; Risk Assessment; Severity of Illness Index; Term Birth; Time Factors; Treatment Outcome

Understanding the role of opiate dependency treatment in risky sexual behavior could help optimize interventions for people who inject drugs (PWID).. We evaluated whether long-term medication-assisted treatment (LT-MAT) of opiate dependency with buprenorphine/naloxone influenced risky sexual behavior among HIV-uninfected PWID and identified predictors of risky sexual behavior.. We used data from HPTN 058, a randomized controlled trial of LT-MAT vs. short-term medication-assisted treatment among PWID in China and Thailand. We evaluated associations between randomized opiate dependency treatment group and self-reported risky sexual behaviors within the past month: condomless sex with primary partner, condomless sex with nonprimary partner, multiple partners, and more than 3 sexual acts. We used generalized estimating equations to conduct intention-to-treat, as-treated, and exploratory analyses of these associations.. Of 1250 participants included in the analysis, 92% were male, with median age of 34 years (interquartile range 28-39). At baseline, referring to the past month, 36% of participants reported condomless sex with primary partner, 4% reported condomless sex with nonprimary partner, 6% reported multiple sex partners, and 30% reported more than 3 sexual acts. Risky sexual behaviors did not differ significantly between treatment groups at any point. Significant predictors (P < 0.05) of condomless sex with nonprimary partner were history of incarceration and noninjection drug use. Number of needle-sharing partners, noninjection drug use, and higher income were predictors for multiple sexual partners.. LT-MAT did not significantly modify risky sexual behavior among HIV-uninfected PWID. Interventions that reduce sexual risk should target PWID with history of incarceration, alcohol use, and needle sharing.

Topics: Adult; Buprenorphine; China; Female; HIV Infections; Humans; Male; Naloxone; Opioid-Related Disorders; Risk-Taking; Sexual Behavior; Thailand; Young Adult

Amphetamine type stimulants (ATS) use is highly prevalent and frequently co-occurs with opioid dependence in Malaysia and Asian countries. No medications have established efficacy for treating ATS use disorder. This study evaluated the safety, tolerability, and potential efficacy of atomoxetine for treating ATS use disorder.. Participants with opioid and ATS dependence (N = 69) were enrolled in a pilot, double-blind, placebo-controlled randomized clinical trial; all received buprenorphine/naloxone and behavioral counseling and were randomized to atomoxetine 80 mg daily (n = 33) or placebo (n = 33). The effect size of the between-group difference on the primary outcome, proportion of ATS-negative urine tests, was estimated using Cohen's d for the intention-to-treat (ITT) sample and for higher adherence subsample (≥60 days of atomoxetine or placebo ingestion).. Participants were all male with mean (SD) age 39.4 (6.8) years. The proportion of ATS-negative urine tests was higher in atomoxetine- compared to placebo-treated participants: 0.77 (0.63-0.91) vs. 0.67 (0.53-0.81, d = 0.26) in the ITT sample and 0.90 (0.75-1.00) vs. 0.64 (0.51-0.78, d = 0.56) in the higher adherence subsample. The proportion of days abstinent from ATS increased from baseline in both groups (p < 0.001) and did not differ significantly between atomoxetine- and placebo-treated participants (p = 0.42). Depressive symptoms were reduced from baseline in both groups (p < 0.02) with a greater reduction for atomoxetine- than placebo-treated participants (p < 0.02). There were no serious adverse events or adverse events leading to medication discontinuation.. The findings support clinical tolerability and safety and suggest potential efficacy of atomoxetine for treating ATS use disorder in this population.

Topics: Adrenergic Uptake Inhibitors; Adult; Amphetamine-Related Disorders; Atomoxetine Hydrochloride; Behavior Therapy; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Depression; Double-Blind Method; Humans; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Pilot Projects; Treatment Outcome; Young Adult

In a recent clinical trial (NCT00295308), we demonstrated that clonidine decreased the association between opioid craving and moderate levels of stress and affect in patients receiving buprenorphine-based opioid agonist therapy.. To examine the relationship between illicit opioid use and craving and affect during the evaluation of clonidine as an adjunct medication in buprenorphine treatment for opioid use disorder. Secondarily, to examine whether those relationships are driven by within- or between-participant factors.. This was a secondary data analysis from our original trial. Participants (N = 108, female: n = 23, male n = 85) receiving buprenorphine were randomized to receive adjunct clonidine or placebo. Participants used portable electronic devices to rate stress, mood, and craving via ecological momentary assessment (EMA) four times randomly each day. To associate the EMA data with illicit opioid use, each EMA report was linked to participants' next urine drug screen (thrice weekly). We used generalized linear mixed models to examine the interaction between treatment group and illicit opioid use, as well as to decompose the analysis into within- and between-participant effects.. Craving for opioids and cocaine was increased when participants were using illicit opioids; this effect was greater in the clonidine group. For affect, mood was poorer during periods preceding opioid-positive urines than opioid-negative urines for clonidine-treated participants, whereas there was no difference for placebo participants.. This secondary analysis provides evidence that for participants maintained on opioid agonist therapy, clonidine minimized the behavioral impact of moderate levels of negative affect and craving.

Topics: Adrenergic alpha-2 Receptor Agonists; Adult; Affect; Buprenorphine; Clonidine; Craving; Double-Blind Method; Drug Therapy, Combination; Ecological Momentary Assessment; Female; Humans; Linear Models; Male; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders

Injectable extended-release naltrexone (XR-NTX), approved to prevent relapse to opioid dependence, requires initial abstinence. This multisite outpatient clinical trial examined the efficacy and safety of low-dose oral naltrexone (NTX), combined with a brief buprenorphine (BUP) taper and standing ancillary medications, for detoxification and induction onto XR-NTX.. Patients (N = 378) were randomized, stratified by primary short-acting opioid-of-use, to one of three regimens: NTX + BUP; NTX + placebo BUP (PBO-B); placebo NTX (PBO-N) + PBO-B. Patients received 7 days of ascending NTX or placebo, concurrent with a 3-day BUP or placebo taper, and ancillary medications in an outpatient setting. Daily psychoeducational counseling was provided. On Day 8, patients passing a naloxone challenge received XR-NTX.. Rates of transition to XR-NTX were comparable across groups: NTX/BUP (46.0%) vs. NTX/PBO-B (40.5%) vs. PBO-N/PBO-B (46.0%). Thus, the study did not meet its primary endpoint. Adverse events, reported by 32.5% of all patients, were mild to moderate in severity and consistent with opioid withdrawal. A first, second, and third XR-NTX injection was received by 44.4%, 29.9%, and 22.5% of patients, respectively. Compared with the PBO-N/PBO-B group, the NTX/BUP group demonstrated higher opioid abstinence during the transition and lower post-XR-NTX subjective opioid withdrawal scores.. A 7-day detoxification protocol with NTX alone or NTX + BUP provided similar rates of induction to XR-NTX as placebo. For those inducted onto XR-NTX, management of opioid withdrawal symptoms prior to induction was achieved in a structured outpatient setting using a well-tolerated, fixed-dose ancillary medication regimen common to all three groups.

Topics: Adult; Ambulatory Care; Buprenorphine; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Outpatients; Patient Transfer; Substance Withdrawal Syndrome

This secondary analysis of a randomized trial examines the association between initiation of buprenorphine treatment prior to, versus post-release, and rearrests during the 12-months following release.. Official rearrest data (N = 199) for the 12-months post-release were examined. Four outcomes were measured: (1) rearrested (yes/no), (2) time to rearrest, (3) number of rearrests, and (4) severity of charges (less severe vs. severe).. A minority (43.1%) of the sample were rearrested (N = 91). There were no significant differences between study conditions in the proportion of rearrested participants [P = 0.28] nor in the mean number of arrests [P  = 0.15]. Likewise, the condition was not a significant predictor of the hazard of rearrest [p = 0.10]. The mean number of days until rearrest for the in prison vs. post-release buprenorphine conditions were not significantly different (205.8 days (SD  = 104.6) vs. 170.8 days (SD  = 113.1), respectively; P  = 0.13]. Treatment condition was not a significant predictor of the likelihood of rearrest for a severe crime compared to a less severe crime [P  = 0.09].. Despite the parent study finding of higher rates of post-release drug treatment entry in the group assigned to start buprenorphine treatment prior to, compared to post-release, there were no significant differences in the proportion of individuals arrested, the mean number of arrests, the time to first arrest, or the severity of their charges.

Topics: Adult; Buprenorphine; Crime; Female; Humans; Law Enforcement; Male; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Prisoners; Time Factors

Buprenorphine treatment for opioid use disorder may be improved by sustained-release formulations.. To determine whether treatment involving novel weekly and monthly subcutaneous (SC) buprenorphine depot formulations is noninferior to a daily sublingual (SL) combination of buprenorphine hydrochloride and naloxone hydrochloride in the treatment of opioid use disorder.. This outpatient, double-blind, double-dummy randomized clinical trial was conducted at 35 sites in the United States from December 29, 2015, through October 19, 2016. Participants were treatment-seeking adults with moderate-to-severe opioid use disorder.. Randomization to daily SL placebo and weekly (first 12 weeks; phase 1) and monthly (last 12 weeks; phase 2) SC buprenorphine (SC-BPN group) or to daily SL buprenorphine with naloxone (24 weeks) with matched weekly and monthly SC placebo injections (SL-BPN/NX group).. Primary end points tested for noninferiority were response rate (10% margin) and the mean proportion of opioid-negative urine samples for 24 weeks (11% margin). Responder status was defined as having no evidence of illicit opioid use for at least 8 of 10 prespecified points during weeks 9 to 24, with 2 of these at week 12 and during month 6 (weeks 21-24). The mean proportion of samples with no evidence of illicit opioid use (weeks 4-24) evaluated by a cumulative distribution function (CDF) was an a priori secondary outcome with planned superiority testing if the response rate demonstrated noninferiority.. A total of 428 participants (263 men [61.4%] and 165 women [38.6%]; mean [SD] age, 38.4 [11.0] years) were randomized to the SL-BPN/NX group (n = 215) or the SC-BPN group (n = 213). The response rates were 31 of 215 (14.4%) for the SL-BPN/NX group and 37 of 213 (17.4%) for the SC-BPN group, a 3.0% difference (95% CI, -4.0% to 9.9%; P < .001). The proportion of opioid-negative urine samples was 1099 of 3870 (28.4%) for the SL-BPN/NX group and 1347 of 3834 (35.1%) for the SC-BPN group, a 6.7% difference (95% CI, -0.1% to 13.6%; P < .001). The CDF for the SC-BPN group (26.7%) was statistically superior to the CDF for the SL-BPN/NX group (0; P = .004). Injection site adverse events (none severe) occurred in 48 participants (22.3%) in the SL-BPN/NX group and 40 (18.8%) in the SC-BPN group.. Compared with SL buprenorphine, depot buprenorphine did not result in an inferior likelihood of being a responder or having urine test results negative for opioids and produced superior results on the CDF of no illicit opioid use. These data suggest that depot buprenorphine is efficacious and may have advantages.. ClinicalTrials.gov Identifier: NCT02651584.

Topics: Administration, Sublingual; Adult; Buprenorphine; Double-Blind Method; Female; Humans; Injections, Subcutaneous; Male; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Treatment Outcome

There are approximately 256,000 heroin and other opiate users in England of whom 155,000 are in treatment for heroin (or opiate) addiction. The majority of people in treatment receive opiate substitution treatment (OST) (methadone and buprenorphine). However, OST suffers from high attrition and persistent heroin use even whilst in treatment. Contingency management (CM) is a psychological intervention based on the principles of operant conditioning. It is delivered as an adjunct to existing evidence based treatments to amplify patient benefit and involves the systematic application of positive reinforcement (financial or material incentives) to promote behaviours consistent with treatment goals. With an international evidence base for CM, NICE recommended that CM be implemented in UK drug treatment settings alongside OST to target attendance and the reduction of illicit drug use. While there was a growing evidence base for CM, there had been no examination of its delivery in UK NHS addiction services. The PRAISe trial evaluates the feasibility, acceptability, clinical and cost effectiveness of CM in UK addiction services. It is a cluster randomised controlled effectiveness trial of CM (praise and financial incentives) targeted at either abstinence from opiates or attendance at treatment sessions versus no CM among individuals receiving OST. The trial includes an economic evaluation which explores the relative costs and cost effectiveness of the two CM intervention strategies compared to TAU and an embedded process evaluation to identify contextual factors and causal mechanisms associated with variations in outcome. This study will inform UK drug treatment policy and practice. Trial registration ISRCTN 01591254.

Topics: Adult; Behavior Therapy; Buprenorphine; Cluster Analysis; Drug Misuse; Female; Heroin Dependence; Humans; Male; Medication Therapy Management; Mental Health Services; Methadone; Narcotic Antagonists; Opioid-Related Disorders; Quality Improvement; Reinforcement, Psychology; United Kingdom

Prevalence of depression, anxiety, and mood disorders among individuals with opioid use disorder far exceeds that of the general population. While psychiatric symptoms often improve upon entry into opioid treatment, this has typically been seen with treatments involving psychosocial counseling. In this secondary analysis, we examined changes in psychiatric symptoms during a randomized clinical trial evaluating an interim buprenorphine treatment without counseling among individuals awaiting entry into comprehensive treatment. Waitlisted adults with opioid use disorder (

Topics: Adult; Anxiety; Buprenorphine; Counseling; Depression; Female; Follow-Up Studies; Humans; Male; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Young Adult

Long acting naltrexone has improved the therapy of opioid use disorder (OUD), and safe and effective withdrawal management during naltrexone induction may help advance treatment. Despite the uncertain role of opioid withdrawal in predicting successful outcomes, early symptom control may favor detoxification completion.. We explored withdrawal severity and early response to treatment, safety, and clinical measures in 35 adult patients with DSM-5 OUD during a 7-day office-based buprenorphine-naltrexone and ancillary medications transition to extended-release naltrexone (XR-NTX).. Subjective and objective measures of withdrawal intensity improved consistently throughout treatment in the whole sample. Participants who went on to receive XR-NTX (n = 27, 77%) reported a greater attenuation of symptoms by treatment day 2 (r = .595, p = .001), and were less likely to be injection drug users (r = -.501, p = .004). Adverse events (AEs) were recorded in 20% of participants: the majority (n = 6, 85.7%) consisted of single episodes of increased withdrawal which were well controlled using ancillary medications. One serious AE was unrelated to treatment.. Early opioid withdrawal changes may be a useful indicator of treatment response, helping adjust the transition protocol to the individual patients' need and gather valuable information for a better understanding of the relationship between initiating and remaining in treatment. (Am J Addict 2018;27:471-476).

Topics: Adult; Buprenorphine; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Monitoring; Female; Humans; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Outcome Assessment, Health Care; Outpatients; Severity of Illness Index; Substance Withdrawal Syndrome; Symptom Assessment

There is a critical need to reduce infectious disease transmission among individuals with opioid use disorder (OUD). Here we examine the ability of a novel, automated educational intervention, delivered via iPad in a single visit, to improve human immunodeficiency virus (HIV) and Hepatitis C (HCV) knowledge among adults with OUD.. Participants were 25 adults enrolled in a 12-week trial evaluating the efficacy of an Interim Buprenorphine Treatment for reducing illicit opioid use and other risk behaviors during delays to opioid treatment. Participants completed baseline HIV and HCV knowledge assessments with corrective feedback. They then completed an interactive HIV flipbook and HCV video followed by a second administration of the knowledge assessments. The knowledge assessments were repeated at post-intake Weeks 4 and 12.. At baseline, participants answered 69% and 65% of items correctly on the HIV and HCV assessments, respectively. The educational intervention was associated with significant increases in knowledge (86% and 86% correct on the HIV and HCV assessments, respectively; p's<.001). These improvements persisted throughout the study, with scores at Week 4 and 12 significantly greater than baseline (p's<.001).. This HIV+Hepatitis Education intervention was associated with significant and sustained improvements in knowledge of HIV + HCV transmission and risk behaviors in this vulnerable group of individuals with OUD. Given the continuing opioid epidemic, efforts are urgently needed to reduce HIV and HCV contraction and transmission among individuals with OUD. Mobile health educational interventions may offer a time- and cost-effective approach for addressing these risks.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Female; Health Knowledge, Attitudes, Practice; Hepatitis C; HIV Infections; Humans; Male; Middle Aged; Opioid-Related Disorders; Patient Education as Topic; Pilot Projects; Risk-Taking; Telemedicine

Preliminary evidence suggested that the PPARγ agonist pioglitazone reduces opioid-withdrawal symptoms, possibly by inhibiting increases in proinflammatory cytokines.. A randomized, placebo-controlled clinical trial was conducted utilizing two different study designs (entirely outpatient, and a combination of inpatient and outpatient) to evaluate the safety and efficacy of pioglitazone as an adjunct medication for people with opioid physical dependence undergoing a buprenorphine taper. Participants were stabilized on buprenorphine/naloxone (sublingual, up to 16/4 mg/day), then randomized to receive oral pioglitazone (up to 45 mg/day) or placebo before, during, and after buprenorphine taper. Outcome measures included the Subjective Opiate Withdrawal Scale (SOWS) and Clinical Opiate Withdrawal Scale, use of rescue medications to alleviate opioid withdrawal symptoms, and opioid-positive urine specimens. Cerebrospinal fluid (CSF) and plasma were collected during the taper in a subset of participants for measurement of proinflammatory cytokines.. The clinical trial was prematurely terminated due to slow enrollment; 40 participants per group were required for adequate statistical power to test study hypotheses. Twenty-four participants enrolled; 17 received at least one dose of study medication (6 pioglitazone, 11 placebo). SOWS scores were higher in the pioglitazone arm than in the placebo arm after adjusting for use of rescue medications; participants in the pioglitazone arm needed more rescue medications than the placebo arm during the post-taper phase. SOWS scores were positively correlated with monocyte chemoattractant protein-1 (MCP-1) in CSF (r = 0.70, p = 0.038) and plasma (r = 0.77, p = 0.015). Participants having higher levels of plasma MCP-1 reported higher SOWS, most notably after the buprenorphine taper ended.. Results from this study provide no evidence that pioglitazone reduces opioid withdrawal symptoms during buprenorphine taper. High correlations between MCP-1 and opioid withdrawal symptoms support a role of proinflammatory processes in opioid withdrawal.. clinicaltrials.gov identifier: NCT01517165.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Cytokines; Double-Blind Method; Female; Humans; Male; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Pioglitazone; Substance Withdrawal Syndrome

We investigated gender differences in individuals with opioid use disorder (OUD) receiving inpatient services and entering a randomized controlled trial comparing extended-release naltrexone to buprenorphine.. Participants (N = 570) provided demographic, substance use, and psychiatric information.. Women were significantly younger, more likely to identify as bisexual, live with a sexual partner, be financially dependent, and less likely employed. Women reported significantly greater psychiatric comorbidity and risk behaviors, shorter duration but similar age of onset of opioid use.. Findings underscore economic, psychiatric, and infection vulnerability among women with OUD.. Interventions targeting these disparities should be explored, as women may face complicated treatment initiation, retention, and recovery. (Am J Addict 2018;27:465-470).

Topics: Adult; Buprenorphine; Comorbidity; Demography; Diagnosis, Dual (Psychiatry); Female; Humans; Male; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Risk-Taking; Sex Factors

Buprenorphine is usually administered to treat opioid use disorder and pain syndromes. This research presents the first study regarding the effectiveness of different singly administered high doses of buprenorphine (a partial opioid agonist (of μ-opioid receptors), a potent opioid antagonist (of κ-receptors) and a partial agonist of nociception receptors) in reducing suicidal ideation in acutely depressed people with co-morbid opiate dependence. It follows small studies that suggest that ultra-low-dose buprenorphine may be useful in reducing suicidal ideation. The goal of this study was to describe the outcome of different doses of buprenorphine on suicidal opioid-dependent patients over a 3-day interval, by conducting a randomized clinical trial.. Fifty-one suicidal male inpatients who fulfilled the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for both opioid dependence and major depressive disorder were randomized to three groups (n = 17 per group) to receive a single, sublingual dose of buprenorphine (32 mg, 64 mg, or 96 mg). Out of 51 participants, there were 47 patients; 16 (34.04%) received 32 mg, 17 (36.17%) received 64 mg, and 14 (29.78%) received 96 mg of sublingual buprenorphine. They were evaluated by using psychometric assessment of the Beck Scale for Suicidal Ideation (BSSI) and interviews based on DSM-5 criteria. A placebo group was not included because of the high probability of severe withdrawal without active pharmacological treatment. The study was conducted with appropriate precautions and monitoring of respiratory and cardiovascular measures. The medication was administered while the patients were in moderate opiate withdrawal, as indicated by the presence of four to five withdrawal symptoms. A structured clinical interview was conducted, and urine toxicology testing was performed.. Patients completed the 3-day trial course. The outcomes illustrated a significant reduction in BSSI scores within each of the three groups, p < 0.01., but no difference in results between the groups, p = 0.408.. The results suggest that a single high dose of buprenorphine could rapidly treat suicidal ideations. A single high dose of buprenorphine may be a main-mechanism medication that gives a rapid treatment for suicidal opioid-dependent patients. Placebo-controlled trials are required to measure the safety and the physiological and psychological effects of this medication.

Topics: Administration, Sublingual; Adult; Analgesics, Opioid; Antidepressive Agents; Buprenorphine; Comorbidity; Depressive Disorder, Major; Double-Blind Method; Humans; Iran; Male; Opioid-Related Disorders; Substance Withdrawal Syndrome; Suicidal Ideation; Time Factors; Treatment Outcome

Opioid use disorder is one of the most prevalent addiction problems worldwide. Buprenorphine is used as a medication to treat this disorder, but in countries where buprenorphine is unavailable in combination with naloxone, diversion can be a problem if the medication is given outside a hospital setting.. The objective of this research is to evaluate the effect of a single, high dose of buprenorphine on craving in opioid-dependent patients over 5 days of abstinence from use of other opioids. The primary goal was to determine the safety and efficacy of buprenorphine during withdrawal in a hospital setting.. Ninety men who used opium, heroin, or prescribed opioids and met DSM-5 criteria for opioid use disorder (severe form) were randomized to three groups (n = 30 per group) to receive a single, sublingual dose of buprenorphine (32, 64, or 96 mg). The study was conducted in an inpatient psychiatric ward, with appropriate precautions and monitoring of respiratory and cardiovascular measures. Buprenorphine was administered when the patients were in moderate opiate withdrawal, as indicated by the presence of four to five symptoms. A structured clinical interview was conducted, and urine toxicology testing was performed at baseline. Self-reports of craving were obtained at baseline and on each of the 5 days after buprenorphine administration.. Craving decreased from baseline in each of the three groups (p < 0.0001), with a significant interaction between group and time (p < 0.038), indicating that groups with higher doses of buprenorphine had greater reduction.. A single, high dose of buprenorphine can reduce craving during opioid withdrawal; additional studies with follow-up are warranted to evaluate safety.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Craving; Double-Blind Method; Humans; Inpatients; Iran; Male; Opiate Substitution Treatment; Opioid-Related Disorders; Substance Withdrawal Syndrome; Time Factors; Treatment Outcome

In the US, emergency room visits and overdoses related to prescription opioids have soared and the rates of illicit opioid use, including heroin and fentanyl, are increasing. Opioid use disorder (OUD) is associated with higher morbidity and mortality, higher HIV and HCV infection rates, and criminal behavior. Opioid agonist therapy (OAT; methadone and buprenorphine) is proven to be effective in treating OUD and decreasing its negative consequences. While the efficacy of OAT has been established, too few providers prescribe OAT to patients with OUD due to patient, provider, or system factors. While the Veterans Health Administration (VHA) has made great strides in OAT implementation, national treatment rates remain low (35% of patients with OUD) and several facilities continue to have much lower prescribing rates.. Eight VA sites with low baseline prescribing rates (lowest quartile, < 21%) were randomly selected from the 35 low prescribing sites to receive an intensive external facilitation implementation intervention to increase OAT prescribing rates. The intervention includes a site-specific developmental evaluation, a kick-off site visit, and 12 months of ongoing facilitation. The developmental evaluation includes qualitative interviews with patients, substance use disorders clinic staff, and primary care and general mental health leadership to assess site-level barriers. The site visit includes: (1) a review of site-specific barriers and potential implementation strategies; (2) instruction on using available dashboards to track prescribing rates and identify actionable patients; and (3) education on OAT, including, if requested, buprenorphine certification training for prescribers. On-going facilitation consists of monthly conference calls with individual site teams and expert clinical consultation. The primary outcomes is the proportion of Veterans with OUD initiating and sustaining OAT, with intervention sites expected to have larger increases in prescribing compared to control sites. Final qualitative interviews and a cost assessment will inform future implementation efforts.. This project will examine and respond to barriers encountered in low prescribing VHA clinics allowing refinement of an intervention to enhance access to medication treatment for OUD in additional facilities.

Topics: Buprenorphine; Humans; Inservice Training; Opiate Substitution Treatment; Opioid-Related Disorders; Practice Patterns, Physicians'; Program Development; Quality of Health Care; United States; United States Department of Veterans Affairs; Veterans

Few studies have explored predictors of entry into and retention in buprenorphine treatment following linkage from an acute medical hospitalization.. This secondary analysis of a completed clinical trial focuses on medically hospitalized, opioid-dependent patients (n = 72) who were randomized to an intervention including buprenorphine induction and dose stabilization during hospitalization followed by post-discharge transition to office-based buprenorphine treatment (OBOT). Predictors included demographics, days hospitalized, prior buprenorphine/methadone treatment, PTSD symptoms, social support, and readiness for drug use cessation. Outcome variables were treatment entry and retention (number of days in OBOT).. Previous buprenorphine treatment, more days hospitalized, and higher PTSD symptoms predicted OBOT entry. Prior treatment, older age, and non-minority status were associated with a higher mean number of days in OBOT.. OBOT may appeal to patients who have tried buprenorphine in other settings. Linking hospitalized patients to OBOT may improve utilization of addiction treatment.. Prior substance treatment, longer hospital stay, and mental health should be examined in future linkage studies. (Am J Addict 2017;26:667-672).

Topics: Adult; Buprenorphine; Continuity of Patient Care; Female; Hospitalization; Humans; Male; Methadone; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Discharge; Patient Dropouts; Risk Factors; Treatment Outcome

Sublingual buprenorphine is effective for opioid dependence treatment but associated with misuse, abuse, and diversion. The present Phase I/II study evaluated a novel buprenorphine subcutaneous depot formulation for once-weekly dosing (CAM2038 q1w) in patients receiving maintenance treatment for opioid use disorder with daily sublingual buprenorphine.. After discontinuation of buprenorphine for 48h, patients received a single CAM2038 q1w dose based on their pre-study daily sublingual maintenance dose. CAM2038 q1w doses of 7.5, 15, 22.5, and 30mg were administered in a sequential dose-escalating design. The following assessments were performed: pharmacokinetics of buprenorphine and norbuprenorphine, pharmacodynamics (evaluated using the Subjective and Clinical Opiate Withdrawal Scales), and time to intake of rescue sublingual buprenorphine medication.. Single doses of CAM2038 q1w indicated dose-proportional buprenorphine pharmacokinetics (C. Pharmacokinetics and pharmacodynamics of a novel buprenorphine subcutaneous depot formulation for once-weekly dosing was evaluated, suggesting utility in maintenance treatment of patients with opioid use disorder.

Topics: Adult; Buprenorphine; Drug Administration Schedule; Female; Humans; Injections, Subcutaneous; Male; Narcotic Antagonists; Opioid-Related Disorders

Buprenorphine is an efficacious, widely used treatment for opioid use disorder (OUD). Daily oral transmucosal formulations can be associated with misuse, diversion, and nonadherence; these limitations may be obviated by a sustained release formulation.. To evaluate the ability of a novel, weekly, subcutaneous buprenorphine depot formulation, CAM2038, to block euphorigenic opioid effects and suppress opioid withdrawal in non-treatment-seeking individuals with OUD.. This multisite, double-blind, randomized within-patient study was conducted at 3 controlled inpatient research facilities. It involved 47 adults with DSM-V moderate-to-severe OUD. The study was conducted from October 12, 2015 (first patient enrolled), to April 21, 2016 (last patient visit).. A total of five 3-day test sessions evaluated the response to hydromorphone (0, 6, and 18 mg intramuscular in random order; 1 dose/session/day). After the first 3-day session (ie, qualification phase), participants were randomized to either CAM2038 weekly at 24 mg (n = 22) or 32 mg (n = 25); the assigned CAM2038 dose was given twice, 1 week apart (day 0 and 7). Four sets of sessions were conducted after randomization (days 1-3, 4-6, 8-10, and 11-13).. The primary end point was maximum rating on the visual analog scale for drug liking. Secondary end points included other visual analog scale (eg, high and desire to use), opioid withdrawal scales, and physiological and pharmacokinetic outcomes.. A total of 46 of 47 randomized participants (mean [SD] age, 35.5 [9] years; 76% male [n = 35]) completed the study. Both weekly CAM2038 doses produced immediate and sustained blockade of hydromorphone effects (liking maximum effect, CAM2038, 24 mg: effect size, 0.813; P < .001, and CAM2038, 32 mg: effect size, 0.753; P < .001) and suppression of withdrawal (Clinical Opiate Withdrawal Scale, CAM2038, 24 mg: effect size, 0.617; P < .001, and CAM2038, 32 mg: effect size, 0.751; P < .001). CAM2038 produces a rapid initial rise of buprenorphine in plasma with maximum concentration around 24 hours, with an apparent half-life of 4 to 5 days and approximately 50% accumulation of trough concentration from first to second dose (trough concentration = 0.822 and 1.23 ng/mL for weeks 1 and 2, respectively, with 24 mg; trough concentration = 0.993 and 1.47 ng/mL for weeks 1 and 2, respectively, with 32 mg).. CAM2038 weekly, 24 and 32 mg, was safely tolerated and produced immediate and sustained opioid blockade and withdrawal suppression. The results support the use of this depot formulation for treatment initiation and stabilization of patients with OUD, with the further benefit of obviating the risk for misuse and diversion of daily buprenorphine while retaining its therapeutic benefits.. Clinicaltrials.gov Identifier: NCT02611752.

Topics: Adolescent; Adult; Analgesics, Opioid; Buprenorphine; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Hydromorphone; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Substance Withdrawal Syndrome; Treatment Outcome; Young Adult

Opioid use disorder (OUD) is a significant public health problem. Supervised withdrawal (ie, detoxification) from opioids using clonidine or buprenorphine hydrochloride is a widely used treatment.. To evaluate whether tramadol hydrochloride extended-release (ER), an approved analgesic with opioid and nonopioid mechanisms of action and low abuse potential, is effective for use in supervised withdrawal settings.. A randomized clinical trial was conducted in a residential research setting with 103 participants with OUD. Participants' treatment was stabilized with morphine, 30 mg, administered subcutaneously 4 times daily. A 7-day taper using clonidine (n = 36), tramadol ER (n = 36), or buprenorphine (n = 31) was then instituted, and patients were crossed-over to double-blind placebo during a post-taper period. The study was conducted from October 25, 2010, to June 23, 2015.. Retention, withdrawal symptom management, concomitant medication utilization, and naltrexone induction. Results were analyzed over time and using area under the curve for the intention-to-treat and completer groups.. Of the 103 participants, 88 (85.4%) were men and 43 (41.7%) were white; mean (SD) age was 28.9 (10.4) years. Buprenorphine participants (28 [90.3%]) were significantly more likely to be retained at the end of the taper compared with clonidine participants (22 [61.1%]); tramadol ER retention was intermediate and did not differ significantly from that of the other groups (26 [72.2%]; χ2 = 8.5, P = .01). Time-course analyses of withdrawal revealed significant effects of phase (taper, post taper) for the Clinical Opiate Withdrawal Scale (COWS) score (taper mean, 5.19 [SE, .26]; post-taper mean, 3.97 [SE, .23]; F2,170 = 3.6, P = .03) and Subjective Opiate Withdrawal Scale (SOWS) score (taper mean,8.81 [SE, .40]; post-taper mean, 4.14 [SE, .30]; F2,170 = 15.7, P < .001), but no group effects or group × phase interactions. Analyses of area under the curve of SOWS total scores showed significant reductions (F2,159 = 17.7, P < .001) in withdrawal severity between the taper and post-taper periods for clonidine (taper mean, 13.1; post-taper mean, 3.2; P < .001) and tramadol ER (taper mean, 7.4; post-taper mean, 2.8; P = .03), but not buprenorphine (taper mean, 6.4; post-taper mean, 7.4). Use of concomitant medication increased significantly (F2,159 = 30.7,  P < .001) from stabilization to taper in the clonidine (stabilization mean, 0.64 [SE, .05]; taper mean, 1.54 [SE, .10]; P < .001) and tramadol ER (stabilization mean, 0.53 [SE, .05]; taper mean, 1.19 [SE, .09]; P = .003) groups and from stabilization to post taper in the buprenorphine group (stabilization mean, 0.46 [SE, .05] post-taper mean, 1.17 [SE, .09]; P = .006), suggesting higher withdrawal for those groups during those periods. Naltrexone initiation was voluntary and the percentage of participants choosing naltrexone therapy within the clonidine (8 [22.2%]), tramadol ER (7 [19.4%]), or buprenorphine (3 [9.7%]) groups did not differ significantly (χ2 = 2.5, P = .29).. The results of this trial suggest that tramadol ER is more effective than clonidine and comparable to buprenorphine in reducing opioid withdrawal symptoms during a residential tapering program. Data support further examination of tramadol ER as a method to manage opioid withdrawal symptoms.. Clinicaltrials.gov Identifier: NCT01188421.

Topics: Adult; Analgesics; Analgesics, Opioid; Buprenorphine; Clonidine; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Male; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Substance Withdrawal Syndrome; Tramadol; Treatment Outcome; Young Adult

The combination of glecaprevir (formerly ABT-493), a nonstructural protein 3/4A (NS3/4A) protease inhibitor, and pibrentasvir (formerly ABT-530), an NS5A protein inhibitor, is being developed as treatment for HCV genotype 1 to 6 infection. The pharmacokinetics, pharmacodynamics, safety, and tolerability of methadone or buprenorphine-naloxone when coadministered with the glecaprevir-pibrentasvir combination in HCV-negative subjects on stable opioid maintenance therapy were investigated in a phase 1, single-center, two-arm, multiple-dose, open-label sequential study. Subjects received methadone (arm 1) or buprenorphine-naloxone (arm 2) once daily (QD) per their existing individual prescriptions alone (days 1 to 9) and then in combination with glecaprevir at 300 mg QD and pibrentasvir at 120 mg QD (days 10 to 16) each morning. Dose-normalized exposures were similar with and without glecaprevir and pibrentasvir for (

Topics: Adult; Aminoisobutyric Acids; Antiviral Agents; Benzimidazoles; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cyclopropanes; Drug Interactions; Female; Hepacivirus; Hepatitis C, Chronic; Humans; Lactams, Macrocyclic; Leucine; Male; Methadone; Middle Aged; Naloxone; Opiate Substitution Treatment; Opioid-Related Disorders; Proline; Protease Inhibitors; Pyrrolidines; Quinoxalines; Sulfonamides; Surveys and Questionnaires; Young Adult

In a recent randomized trial, patients with opioid dependence receiving brief intervention, emergency department (ED)-initiated buprenorphine and ongoing follow-up in primary care with buprenorphine (buprenorphine) were twice as likely to be engaged in addiction treatment compared with referral to community-based treatment (referral) or brief intervention and referral (brief intervention). Our aim was to evaluate the relative cost-effectiveness of these three methods of intervening on opioid dependence in the ED.. Measured health-care use was converted to dollar values. We considered a health-care system perspective and constructed cost-effectiveness acceptability curves that indicate the probability each treatment is cost-effective under different thresholds of willingness-to-pay for outcomes studied.. An urban ED in the United States.. Opioid-dependent patients aged 18 years or older.. Self-reported 30-day assessment data were used to construct cost-effectiveness acceptability curves for patient engagement in formal addiction treatment at 30 days and the number of days illicit opioid-free in the past week.. Considering only health-care system costs, cost-effectiveness acceptability curves indicate that at all positive willingness-to-pay values, ED-initiated buprenorphine treatment was more cost-effective than brief intervention or referral. For example, at a willingness-to-pay threshold of $1000 for 30-day treatment engagement, we are 79% certain ED-initiated buprenorphine is most cost-effective compared with other studied treatments. Similar results were found for days illicit opioid-free in the past week. Results were robust to secondary analyses that included patients with missing cost data, included crime and patient time costs in the numerator, and to changes in unit price estimates.. In the United States, emergency department-initiated buprenorphine intervention for patients with opioid dependence provides high value compared with referral to community-based treatment or combined brief intervention and referral.

Topics: Aftercare; Analgesics, Opioid; Buprenorphine; Cost-Benefit Analysis; Emergency Service, Hospital; Health Services; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Participation; Primary Health Care; Referral and Consultation; United States

Overdoses due to non-medical use of prescription opioids and other opiates have become the leading cause of accidental deaths in the USA. Buprenorphine and extended-release naltrexone are key evidence-based pharmacotherapies available to addiction treatment providers to address opioid use disorder (OUD) and prevent overdose deaths. Treatment organizations' efforts to provide these pharmacotherapies have, however, been stymied by limited success in recruiting providers (physicians, nurse practitioners, and physician assistants) to prescribe these medications. Historically, the addiction treatment field has not attracted physicians, and many barriers to implementing OUD pharmacotherapy exist, ranging from lack of confidence in treating OUD patients to concerns regarding reimbursement. Throughout the USA, the prevalence of OUD far exceeds the capacity of the OUD pharmacotherapy treatment system. Poor access to OUD pharmacotherapy prescribers has become a workforce development need for the addiction treatment field and a significant health issue.. This cluster randomized controlled trial (RCT) is designed to increase buprenorphine and extended-release naltrexone treatment capacity for OUD. The implementation intervention to be tested is a bundle of OUD pharmacotherapy capacity building practices called the Prescriber Recruitment Bundle (PRB), which was developed and piloted in a previous statewide buprenorphine implementation study. For this cluster RCT, organizational sites will be recruited and then randomized into one of two arms: (1) control, with treatment as usual and access to a website with PRB resources, or (2) intervention, with organizations implementing the PRB using the Network for the Improvement of Addiction Treatment organizational change model over a 24-month intervention period and a 10-month sustainability period. The primary treatment outcomes for each organizational site are self-reported monthly counts of buprenorphine slots, extended-release naltrexone capacity, number of buprenorphine patients, and number of extended-release naltrexone patients. This trial will be conducted in Florida, Ohio, and Wisconsin, resulting in 35 sites in each arm, for a total sample size of 70 organizations.. This study addresses three issues of substantial public health significance: (1) the pressing opioid misuse epidemic, (2) the low uptake of OUD treatment pharmacotherapies, and (3) the need to increase prescriber participation in the addiction treatment workforce.. ClinicalTrials.gov NCT02926482.

Topics: Buprenorphine; Capacity Building; Family Practice; Health Personnel; Humans; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Organizational Innovation; Psychiatry; Research Design; Staff Development; Telemedicine; United States; Workflow

Opioid use disorder (OUD) is a debilitating and relapsing psychiatric disorder; opioid agonist therapy (OAT) is the front-line, evidence-supported treatment. A substantial number of patients relapse or continue to use heroin or other illicit drugs during OAT. There is considerable heterogeneity in the OAT-resistant sub-population, with many behavioural moderators of treatment response. We have developed a personalised psychosocial intervention (PSI) targeting these individuals. A formulation-guided assessment is linked to a toolkit of motivational, cognitive/behavioural and social support techniques. Change methods have been adapted from evidence-supported psychological therapies and are idiosyncratically tailored to the need and response.. In this single-centre, 18-week, parallel group, pragmatic randomised clinical trial, we will determine the clinical and cost-effectiveness of the PSI as an adjunctive intervention during OAT, in comparison to opioid agonist treatment-as-usual. We plan to recruit 368 adults. The primary outcome measure is the proportion of participants categorised as 'responders' at the end of the intervention (defined as self-reported abstinence from heroin and cocaine with no positive biological drug tests during the 28days prior to the endpoint). Secondary outcomes include: percentage of days abstinent from heroin and cocaine in the 28days before follow-up; treatment retention; therapy compliance; health and social functioning; exploratory genetic biomarkers; and analyses of treatment moderation and mediation.. This pragmatic controlled trial determines the effectiveness and cost-effectiveness of a personalised PSI for non-responding patients during OAT. Our intervention applies motivational, cognitive/behavioural and social support techniques adapted from evidence-based therapies. Findings will inform stratified delivery of OAT.

Topics: Adaptation, Psychological; Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cognitive Behavioral Therapy; Combined Modality Therapy; Humans; Methadone; Motivation; Opiate Substitution Treatment; Opioid-Related Disorders; Social Support; United Kingdom

At present there is no established optimal approach for transitioning opioid-dependent adults to extended-release injection naltrexone (XR-naltrexone) while preventing relapse. The authors conducted a trial examining the efficacy of two methods of outpatient opioid detoxification for induction to XR-naltrexone.. Participants were 150 opioid-dependent adults randomly assigned 2:1 to one of two outpatient detoxification regimens, naltrexone-assisted detoxification or buprenorphine-assisted detoxification, followed by an injection of XR-naltrexone. Naltrexone-assisted detoxification lasted 7 days and included a single day of buprenorphine followed by ascending doses of oral naltrexone along with clonidine and other adjunctive medications. Buprenorphine-assisted detoxification included a 7-day buprenorphine taper followed by a week-long delay before administration of XR-naltrexone, consistent with official prescribing information for XR-naltrexone. Participants from both groups received behavioral therapy focused on medication adherence and a second dose of XR-naltrexone.. Compared with participants in the buprenorphine-assisted detoxification condition, participants assigned to naltrexone-assisted detoxification were significantly more likely to be successfully inducted to XR-naltrexone (56.1% compared with 32.7%) and to receive the second injection at week 5 (50.0% compared with 26.9%). Both models adjusted for primary type of opioid use, route of opioid administration, and morphine equivalents at baseline.. These results demonstrate the safety, efficacy, and tolerability of low-dose naltrexone, in conjunction with single-day buprenorphine dosing and adjunctive nonopioid medications, for initiating adults with opioid dependence to XR-naltrexone. This strategy offers a promising alternative to the high rates of attrition and relapse currently observed with agonist tapers in both inpatient and outpatient settings.

Topics: Administration, Oral; Adolescent; Adult; Ambulatory Care; Behavior Therapy; Buprenorphine; Clonidine; Combined Modality Therapy; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Naltrexone; Opioid-Related Disorders; Remission Induction; Secondary Prevention; Young Adult

Healthy volunteers were randomized to five treatment groups. All received a single intravenous dose of buprenorphine 600 µg, followed post-washout by a single dose of CAM2038 q4w 96 mg, a single dose of CAM2038 q4w 192 mg, or sublingual buprenorphine 8, 16, or 24 mg daily for 7 days, followed post-washout by a single dose of CAM2038 q4w 64 or 128 mg or four repeated weekly doses of CAM2038 q1w 16 mg. All subjects received daily naltrexone.. Eighty-seven subjects were randomized. Median buprenorphine t. The pharmacokinetic profiles of CAM2038 q1w and q4w versus sublingual buprenorphine support expected treatment efficacy with once-weekly and once-monthly dosing, respectively. CAM2038 formulations were safe and showed good local tolerability.. ISRCTN24987553.. Camurus AB.

Topics: Administration, Sublingual; Adult; Biological Availability; Buprenorphine; Delayed-Action Preparations; Drug Monitoring; Female; Healthy Volunteers; Humans; Injections, Subcutaneous; Male; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Treatment Outcome

This study examined whether starting buprenorphine treatment prior to prison and after release from prison would be associated with better drug treatment outcomes and whether males and females responded differently to the combination of in-prison treatment and post-release service setting.. Study design was a 2 (In-Prison Treatment: Condition: Buprenorphine Treatment: vs. Counseling Only)×2 [Post-Release Service Setting Condition: Opioid Treatment: Program (OTP) vs. Community Health Center (CHC)]×2 (Gender) factorial design. The trial was conducted between September 2008 and July 2012. Follow-up assessments were completed in 2014. Participants were recruited from two Baltimore pre-release prisons (one for men and one for women). Adult pre-release prisoners who were heroin-dependent during the year prior to incarceration were eligible. Post-release assessments were conducted at 1, 3, 6, and 12-month following prison release.. Participants (N=211) in the in-prison treatment condition effect had a higher mean number of days of community buprenorphine treatment compared to the condition in which participants initiated medication after release (P=0.005). However, there were no statistically significant hypothesized effects for the in-prison treatment condition in terms of: days of heroin use and crime, and opioid and cocaine positive urine screening test results (all Ps>0.14) and no statistically significant hypothesized gender effects (all Ps>0.18).. Although initiating buprenorphine treatment in prison compared to after-release was associated with more days receiving buprenorphine treatment in the designated community treatment program during the 12-months post-release assessment, it was not associated with superior outcomes in terms of heroin and cocaine use and criminal behavior.

Topics: Adult; Buprenorphine; Cocaine-Related Disorders; Counseling; Crime; Female; Follow-Up Studies; Heroin Dependence; Humans; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Prisoners; Recurrence; Sex Characteristics; Treatment Outcome; Young Adult

Methadone maintenance treatment (MMT) is the gold standard for pregnant women with opioid use disorders. Still, low birth-weights were reported, in particular of mothers who became pregnant before admission to MMT. We studied whether an escalating incentive contingency-management approach may contribute to better newborn birth-weights.. A nationwide controlled randomized trial among all Israeli methadone/buprenorphine maintenance treatment (MBMT), newly or already in treatment pregnant women was performed. A modified contingency-management protocol with coupons of escalating value depending upon reduction of drug use, cigarette smoking, and alcohol consumption was compared to standard care arm. Drugs in urine, smoking (Fagerstrom score), alcohol use, and depression were monitored.. Thirty-five women had 46 pregnancies. In their first pregnancy, 19 from the contingency-management and 16 from the standard care arms were studied. Contingency-management group as compared to the standard care arm included more newly admitted women (36.8% vs. 6.3%, p = .05), with benzodiazepine and cannabis onset at a younger age, and higher proportion of any drug abuse while pregnant (100% vs. 68.8%, p = .01). Fifteen of the contingency-management and 14 of the control arm gave birth (78.9% vs. 87.5%, p = .3) with similar proportions of normal (>2,500 g) birth-weight (71.4% vs. 61.5%, p = .8).. Newborns' birth-weight was comparable among the two study arms indicating no contribution of the contingency-management approach. Small sample and baseline differences between arms might have influenced results. Intensive intervention should be evaluated on a larger scale of participants. (Am J Addict 2017;26:167-175).

Topics: Adult; Age of Onset; Alcohol Drinking; Birth Weight; Buprenorphine; Cigarette Smoking; Female; Humans; Infant, Low Birth Weight; Infant, Newborn; Israel; Methadone; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Care Management; Pregnancy; Pregnancy Complications

Emergency department (ED)-initiated buprenorphine/naloxone with continuation in primary care was found to increase engagement in addiction treatment and reduce illicit opioid use at 30 days compared to referral only or a brief intervention with referral.. To evaluate the long-term outcomes at 2, 6 and 12 months following ED interventions.. Evaluation of treatment engagement, drug use, and HIV risk among a cohort of patients from a randomized trial who completed at least one long-term follow-up assessment.. A total of 290/329 patients (88% of the randomized sample) were included. The followed cohort did not differ significantly from the randomized sample.. ED-initiated buprenorphine with 10-week continuation in primary care, referral, or brief intervention were provided in the ED at study entry.. Self-reported engagement in formal addiction treatment, days of illicit opioid use, and HIV risk (2, 6, 12 months); urine toxicology (2, 6 months).. A greater number of patients in the buprenorphine group were engaged in addiction treatment at 2 months [68/92 (74%), 95% CI 65-83] compared with referral [42/79 (53%), 95% CI 42-64] and brief intervention [39/83 (47%), 95% CI 37-58; p < 0.001]. The differences were not significant at 6 months [51/92 (55%), 95% CI 45-65; 46/70 (66%) 95% CI 54-76; 43/76 (57%) 95% CI 45-67; p = 0.37] or 12 months [42/86 (49%) 95% CI 39-59; 37/73 (51%) 95% CI 39-62; 49/78 (63%) 95% CI 52-73; p = 0.16]. At 2 months, the buprenorphine group reported fewer days of illicit opioid use [1.1 (95% CI 0.6-1.6)] versus referral [1.8 (95% CI 1.2-2.3)] and brief intervention [2.0 (95% CI 1.5-2.6), p = 0.04]. No significant differences in illicit opioid use were observed at 6 or 12 months. There were no significant differences in HIV risk or rates of opioid-negative urine results at any time.. ED-initiated buprenorphine was associated with increased engagement in addiction treatment and reduced illicit opioid use during the 2-month interval when buprenorphine was continued in primary care. Outcomes at 6 and 12 months were comparable across all groups.

Topics: Adult; Buprenorphine; Emergency Service, Hospital; Female; Follow-Up Studies; Humans; Male; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Outcome Assessment, Health Care; Primary Health Care; Referral and Consultation; Self Report; Young Adult

To test the safety of new buprenorphine oral lyophilisate wafer ("bup-lyo") versus standard sub-lingual buprenorphine ("bup-SL").. Randomised (2:1) open-label study; opioid-dependent subjects; subsequent partial cross-over.. Specialised clinical trials facility and addictions treatment facility.. Opioid-dependent subjects (n = 36) commencing buprenorphine maintenance (personalised dose-titration) including patients co-using alcohol, cocaine and benzodiazepines (below thresholds).. Respiratory function (respiratory rate, pulse-oximetry); medication hold and dose adequacy; opiate withdrawal signs and symptoms; tablet disintegration times; treatment retention. Pharmacokinetics (PK) for plasma buprenorphine and norbuprenorphine (n = 11).. Oral lyophilised buprenorphine ("bup-lyo") completely dissolved within 2 min for 58 vs. 5% for "bup-SL." Dose titration resulted in similar maintenance dosing (10.8 vs. 9.6 mg). There were no significant between-group differences in opiate-withdrawal phenomena, craving, adequacy of "hold," respiratory function. No serious adverse events (AEs), nor "severe" AEs, although more AEs and Treatment-Emergent AEs with "bup-lyo" (mostly "mild"). PK found greater bioavailability of buprenorphine with "bup-lyo" (but not norbuprenorphine).. Orally disintegrating buprenorphine oral lyophilisate wafer disintegrated rapidly. No increased respiratory depression was found and clinically no difference between medications was observed. PK found substantially increased bioavailability of buprenorphine (but not of nor-buprenorphine) with "bup-lyo" relative to "bup-SL." In supervised dosing contexts, rapidly disintegrating formulations may enable wider buprenorphine prescribing.

Topics: Analgesics, Opioid; Buprenorphine; Drug Administration Routes; Female; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Tablets

RBP-6000 is a novel sustained-release formulation of buprenorphine for the treatment of opioid use disorder, which has been designed for once-monthly (28 days) subcutaneous (SC) injections. A population pharmacokinetic (PK) model was developed to describe the time course of buprenorphine plasma concentrations after repeated SC injections of RBP-6000 at 50 mg, 100 mg, 200 mg, or 300 mg in treatment-seeking opioid-dependent subjects previously on sublingual buprenorphine (Subutex(®) ) treatment. The μ-opioid receptor occupancy was predicted using a previously developed PK/PD Emax model. The results of the population PK analysis jointly with the predicted level of μ-opioid receptor occupancy provided quantitative criteria for clinical dose selection for RBP-6000: the dose of 300 mg every 28 days seems appropriate for immediately achieving an effective exposure after the first SC injection and to maintain effective levels of exposure during chronic treatment. Furthermore, simulations conducted to evaluate the potential impact of a holiday in drug intake indicated that in the unexpected event of a 2-week holiday, levels of μ-opioid receptor occupancy remained consistently above 70% with no significant loss of drug efficacy. This analysis indicated that RBP-6000 has the potential for becoming an effective treatment for opioid-dependent subjects by addressing compliance issues associated with the current once-a-day treatments.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Compounding; Female; Humans; Injections, Subcutaneous; Male; Middle Aged; Models, Biological; Opioid-Related Disorders; Receptors, Opioid, mu; Young Adult

A major goal for the treatment of opioid use disorder is to reduce or eliminate the use of illicit opioids. Buprenorphine, a μ-opioid receptor partial agonist and kappa opioid receptor antagonist, is now being developed as a monthly, sustained-release formulation (RBP-6000). The objective of this study was to demonstrate that RBP-6000 blocks the subjective effects and reinforcing efficacy of the μ-opioid receptor agonist hydromorphone (intramuscularly administered) in subjects with moderate or severe opioid use disorder. Subjects were first inducted and dose stabilized on sublingual buprenorphine/naloxone (8-24 mg daily; dose expressed as the buprenorphine component), then received two subcutaneous injections of RBP-6000 (300 mg) on Day 1 and Day 29. Hydromorphone challenges (6 mg, 18 mg or placebo administered in randomized order) occurred on 3 consecutive days of each study week before and after receiving RBP-6000. Subjects reported their responses to each challenge on various 100-mm Visual Analogue Scales (VAS). Subjects also completed a choice task to assess the reinforcing efficacy of each hydromorphone dose relative to money. At baseline, mean "drug liking" VAS scores for hydromorphone 18 mg and 6 mg versus placebo were 61 mm (95% confidence interval, 52.3-68.9) and 45 mm (95% confidence interval, 37.2-53.6), respectively. After 300 mg RBP-6000 was administered, mean VAS score differences from placebo were less than 10 mm through week 12. The reinforcing efficacy of hydromorphone decreased in a parallel manner. This study demonstrated that RBP-6000 at a 300 mg dose provides durable and potent blockade of the subjective effects and reinforcing efficacy of hydromorphone in subjects with moderate or severe opioid use disorder.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Delayed-Action Preparations; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Hydromorphone; Injections, Intramuscular; Injections, Subcutaneous; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Young Adult

Few randomized controlled trials have evaluated buprenorphine treatment interventions for opioid-dependent youth. Consequently, optimal administration strategies for this cohort are unclear. Our aim was to evaluate the relative efficacy of two different buprenorphine taper lengths in promoting abstinence from illicit opioids and treatment retention among opioid-dependent youth.. A double-blind, placebo controlled, multicenter randomized controlled trial.. Two hospital-based research clinics (Manhattan and Brooklyn) in New York City, USA from 2005 to 2010.. Volunteer sample of 53 primarily Caucasian participants between the ages of 16 and 24 (n = 11 under age 18) who met DSM-IV opioid dependence criteria.. Participants were assigned randomly to either a 28-day buprenorphine taper (n = 28) or 56-day buprenorphine taper (n = 25) via a parallel-groups design during a 63-day period. Both groups received behavioral counseling and opioid abstinence incentives. Both taper conditions had a minimum of 1 week of placebo dosing at the end of the taper.. The primary outcome was opioid abstinence measured as a percentage of scheduled urine toxicology tests documented to be negative for opioids. The secondary outcome was treatment retention, measured as number of days attended scheduled visits.. Intent-to-treat analyses revealed that participants who received a 56-day buprenorphine taper had a significantly higher percentage of opioid-negative scheduled urine tests compared with participants who received a 28-day buprenorphine taper [35 versus 17%, P = 0.039; Cohen's d = 0.57, 95% confidence interval (CI) = 0.02, 1.13]. Participants who received a 56-day buprenorphine taper were retained in treatment significantly longer than participants who received a 28-day buprenorphine taper (37.5 versus 26.4 days, P = 0.027; Cohen's d = 0.63, 95% CI = 0.06, 1.19). Daily attendance requirement was associated with decreased abstinence and shorter retention compared with a two to three times weekly attendance requirement, independent of taper duration. Follow-up data were insufficient to report.. Longer (56-day) buprenorphine taper produces better opioid abstinence and retention outcomes than shorter (28-day) buprenorphine taper for opioid-dependent youth.

Topics: Adolescent; Analgesics, Opioid; Buprenorphine; Counseling; Double-Blind Method; Female; Humans; Male; Motivation; New York City; Opioid-Related Disorders; Time Factors; Young Adult

In addiction care, urine drug screening tests are recommended to assess psychoactive substances use. While intrinsic diagnostic value of these tests is demonstrated, the consequences of carrying out these tests on opiate maintenance treatment (OMT) have not been established. The main objective will be to assess the impact of on-site urine drug screening tests (OS-UDS) in general practice compared to routine medical care on OMT retention at 6 months in opioid-dependent patients initiating buprenorphine.. The ESUB-MG study uses a pragmatic, cluster randomized controlled trial design. General Practitioners (GPs) regularly managing patients treated with buprenorphine and consenting for participating will be invited to participate. GPs will be randomly assigned to one of two groups for 6 to 24 months: (a) control group (usual care: standard medical strategy for assessing drug use); (b) interventional group (including 1/ a training session on practice and interpretation of OS-UDS; 2/ the supply of OS-UDS at GPs' medical offices; 3/ performing an OS-UDS before the first prescription of buprénorphine). GPs will have to include 1 to 10 patients aged 18 years-old or more, consulting for starting treatment by buprenorphine, not opposed to participate. The primary outcome will be OMT retention at 6 months.. This randomized interventional trial should bring sufficient level of evidence to assess effectiveness of performing OS-UDS in general practice for patients treated by buprenorphine. Training GPs to drug tests and supplying them in their office should lead to an improvement of opioid-addicted patients' care through helping decision.. NCT02345655 (first registration May 14, 2014).

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Buprenorphine; Clinical Protocols; Female; General Practice; Humans; Male; Medication Adherence; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Substance Abuse Detection; Young Adult

Buprenorphine can be abused by the intranasal route. This study sought to examine the relative abuse liability and reinforcing efficacy of intranasal buprenorphine compared to intranasal buprenorphine/naloxone in opioid-dependent individuals.. Eleven healthy male and female volunteers physically dependent on short-acting opioids resided as inpatients during participation in this double blind, within subject, placebo-controlled study. Participants were maintained on oxycodone (30 mg/q.i.d., p.o.) throughout the 6-week study. Eight pairs of experimental sessions were conducted at ≥48 h intervals to examine the pharmacodynamic profile (Sample) and reinforcing efficacy (Self-administration the following day) of intranasal placebo, oxycodone (60 mg), buprenorphine (2, 8 & 16 mg) and buprenorphine/naloxone (2/0.5, 8/2 & 16/4 mg). Subjective, observer-rated and physiological measures were collected to assess the magnitude of opioid agonist and antagonist effects. A progressive ratio self-administration procedure assessed choices for drug versus money.. All active doses produced opioid agonist-like effects (e.g., increased ratings of "liking," and miosis) compared to placebo. The effects of buprenorphine and buprenorphine/naloxone were not reliably dose-dependent. Intranasal buprenorphine/naloxone elicited modest and transient opioid withdrawal-like effects in the first hour post-drug administration, while simultaneously blunting or blocking the early onset of agonist effects seen with buprenorphine alone. All active doses of buprenorphine were self-administered more than placebo, but buprenorphine/naloxone doses were not.. These data confirm that intranasal buprenorphine/naloxone has deterrent properties related to transient withdrawal effects that likely decrease its desirability for misuse compared to buprenorphine in opioid-dependent individuals maintained on short-acting opioids.

Topics: Administration, Intranasal; Adolescent; Adult; Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Oxycodone; Reinforcement, Psychology; Self Administration; Substance Withdrawal Syndrome; Young Adult

The present study examined the psychometric characteristics of the Neonatal Abstinence Scoring System (NASS; "Finnegan Scale") and the MOTHER NAS Scale (MNS).. Secondary analysis of data from 131 neonates from the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study, a randomized trial in opioid-dependent pregnant women administered buprenorphine or methadone.. Both the NASS and MNS demonstrated poor psychometric properties, with internal consistency (Cronbach's αs) failing to exceed .62 at first administration, peak NAS score, and NAS treatment initiation.. Findings support the need for development of a NAS measure based on sound psychometric principles.. This study found that two frequently used measures of neonatal abstinence syndrome suffer inadequacies in regard to their basic measurement characteristics. (Am J Addict 2016;25:370-373).

Topics: Adult; Analgesics, Opioid; Buprenorphine; Female; Humans; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Neonatal Screening; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Psychometrics; Reproducibility of Results

Buprenorphine has established effectiveness for outpatient treatment of opioid use disorder. Our previously published STOP (Suboxone Transition to Opiate Program) trial showed that buprenorphine induction, stabilization, and linkage to outpatient treatment in opioid-dependent inpatients (injection and non-injection drug users) decreased illicit opioid use over 6months. The present study was a planned subgroup analysis of injection opiate users from STOP.. To determine if inpatient buprenorphine initiation and linkage to outpatient buprenorphine reduce injection opiate users' frequency of injection opiate use (IOU).. Inpatient injection opiate users at a safety-net hospital were randomized to buprenorphine linkage (induction, stabilization, bridge prescription, and facilitated referral to outpatient treatment) or detoxification (5-day inpatient buprenorphine taper). Conditional fixed-effects Poisson regression was used to estimate the effects of intervention on 30-day (self-report) at 1, 3, and 6months, measured using 30-day timeline follow-back. The secondary outcome was linkage effectiveness, measured as % presenting to initial outpatient buprenorphine visits after hospital discharge.. Analysis was limited to persons (n=62 randomized to detoxification and n=51 to linkage) with baseline IOU. There were no significant differences in age, ethnicity, or baseline IOU frequency. At follow-up, linkage patients (70.6%) were significantly more likely (p<0.001) to present to initial buprenorphine visits than detoxification patients (9.7%). However, there was no significant between group difference in the rate of IOU at 1- (IRR=0.73, p=0.32), 3- (IRR=1.20, p=0.54), or 6-month (IRR=0.73, p=0.23) follow-ups. Using person-day analysis, participants self-reported IOU on 5.8% of follow-up days in which they used prescription buprenorphine and 37.5% of non-buprenorphine days. Using a generalized estimating equation, the estimated odds of IOU was 4.57 times higher (p<0.001) on non-buprenorphine days.. Despite STOP's success in linking patients who inject opiates to outpatient buprenorphine, the intervention did not significantly decrease their IOU frequency. Injection opiate users will require a more intensive protocol to sustain outpatient buprenorphine treatment and decrease injection with its attendant risks.

Topics: Adult; Ambulatory Care; Buprenorphine; Female; Follow-Up Studies; Hospitalization; Humans; Male; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Transfer; Referral and Consultation; Safety-net Providers; Substance Abuse, Intravenous; Time Factors; Treatment Outcome

The effectiveness of buprenorphine treatment of opioid dependence is limited by suboptimal medication adherence, abuse, and diversion.. To determine whether 6-month buprenorphine implants are noninferior to daily sublingual buprenorphine as maintenance treatment for opioid-dependent patients with stable abstinence.. Outpatient, randomized, active-controlled, 24-week, double-blind, double-dummy study conducted at 21 US sites from June 26, 2014, through May 18, 2015. Outpatients were prescribed daily sublingual buprenorphine for 6 months or more, were abstinent while taking 8 mg/d or less of sublingual buprenorphine for 90 days or longer, and were determined to be clinically stable by their physician.. Participants were randomized to receive sublingual buprenorphine plus 4 placebo implants or sublingual placebo plus four 80-mg buprenorphine hydrochloride implants (expected efficacy, 24 weeks).. The primary end point was between-group difference in proportion of responders (≥4 of 6 months without opioid-positive urine test result [monthly and 4 times randomly] and self-report). The noninferiority established for the lower bound of the 95% confidence interval was greater than -0.20 (P < .025). Secondary end points included cumulative percentage of negative opioid urine results, abstinence, and time to first illicit opioid use. Safety was assessed by adverse event reporting.. Of 177 participants (mean age, 39 years; 40.9% female), 90 were randomized to sublingual buprenorphine with placebo implants and 87 to buprenorphine implants with sublingual placebo; 165 of 177 (93.2%) completed the trial. Eighty-one of 84 (96.4%) receiving buprenorphine implants and 78 of 89 (87.6%) receiving sublingual buprenorphine were responders, an 8.8% difference (1-sided 97.5% CI, 0.009 to ∞; P < .001 for noninferiority). Over 6 months, 72 of 84 (85.7%) receiving buprenorphine implants and 64 of 89 (71.9%) receiving sublingual buprenorphine maintained opioid abstinence (hazard ratio, 13.8; 95% CI, 0.018-0.258; P = .03). Non-implant-related and implant-related adverse events occurred in 48.3% and 23% of the buprenorphine implant group and in 52.8% and 13.5% of participants in the sublingual buprenorphine group, respectively.. Among adults with opioid dependence maintaining abstinence with a stable dose of sublingual buprenorphine, the use of buprenorphine implants compared with continued sublingual buprenorphine did not result in an inferior likelihood of remaining a responder. However, the study population had an exceptionally high response rate in the control group, and further studies are needed in broader populations to assess the efficacy in other settings.. clinicaltrials.gov Identifier: NCT02180659.

Topics: Administration, Sublingual; Adult; Analgesics, Opioid; Buprenorphine; Double-Blind Method; Drug Administration Schedule; Drug Implants; Female; Humans; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Self Report

Hepatitis C virus (HCV) infection is common in persons who inject drugs (PWID).. To evaluate elbasvir-grazoprevir in treating HCV infection in PWID.. Randomized, placebo-controlled, double-blind trial. (ClinicalTrials.gov: NCT02105688).. Australia, Canada, France, Germany, Israel, the Netherlands, New Zealand, Norway, Spain, Taiwan, the United Kingdom, and the United States.. 301 treatment-naive patients with chronic HCV genotype 1, 4, or 6 infection who were at least 80% adherent to visits for opioid agonist therapy (OAT).. The immediate-treatment group (ITG) received elbasvir-grazoprevir for 12 weeks; the deferred-treatment group (DTG) received placebo for 12 weeks, no treatment for 4 weeks, then open-label elbasvir-grazoprevir for 12 weeks.. The primary outcome was sustained virologic response at 12 weeks (SVR12), evaluated separately in the ITG and DTG. Other outcomes included SVR24, viral recurrence or reinfection, and adverse events.. The SVR12 was 91.5% (95% CI, 86.8% to 95.0%) in the ITG and 89.5% (95% CI, 81.5% to 94.8%) in the active phase of the DTG. Drug use at baseline and during treatment did not affect SVR12 or adherence to HCV therapy. Among 18 patients with posttreatment viral recurrence through 24-week follow-up, 6 had probable reinfection. If the probable reinfections were assumed to be responses, SVR12 was 94.0% (CI, 89.8% to 96.9%) in the ITG. One patient in the ITG (1 of 201) and 1 in the placebo-phase DTG (1 of 100) discontinued treatment because of an adverse event.. These findings may not be generalizable to PWID who are not receiving OAT, nor do they apply to persons with genotype 3 infection, a common strain in PWID.. Patients with HCV infection who were receiving OAT and treated with elbasvir-grazoprevir had high rates of SVR12, regardless of ongoing drug use. These results support the removal of drug use as a barrier to interferon-free HCV treatment for patients receiving OAT.. Merck & Co.

Topics: Adolescent; Adult; Aged; Antiviral Agents; Benzofurans; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Double-Blind Method; Drug Combinations; Drug Resistance, Viral; Female; Genotype; Hepatitis C, Chronic; Humans; Imidazoles; Male; Medication Adherence; Methadone; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Quinoxalines; Recurrence; Substance Abuse, Intravenous; Young Adult

To determine whether treatment outcomes differed for prescription opioid and heroin use disorder patients, we conducted a secondary analysis of a 24-week (N=140) randomized trial of physician management (PM) or PM plus cognitive behavioral therapy (CBT) in primary care buprenorphine/naloxone treatment. Self-reported opioid use and urine toxicology analyses were obtained weekly. We examined baseline demographic differences between primary prescription opioid use patients (n=49) and primary heroin use patients (n=91) and evaluated whether treatment response differed by assigned condition. Compared to primary heroin use patients, primary prescription opioid use patients had marginally fewer years of opioid use, were less likely to have had a previous drug treatment or detoxification, and were less likely to report injection drug use. Although opioid abstinence only, and treatment retention did not differ by opioid use group, opioid category moderated the effect of CBT on urine samples negative for all drugs. Primary prescription opioid use patients assigned to PM-CBT had more than twice the mean number of weeks of abstinence for all drugs (7.6) than those assigned to PM only (3.6; p=.02), while primary heroin use patients did not differ by treatment. Findings suggest that examination of other factors that may predict response to behavioral interventions is warranted.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Cognitive Behavioral Therapy; Combined Modality Therapy; Female; Humans; Male; Opiate Substitution Treatment; Opioid-Related Disorders; Outcome Assessment, Health Care; Substance-Related Disorders; Young Adult

Opioid dependence has devastating and increasingly widespread consequences and costs, and the most common outcome of treatment is early relapse. People who inject opioids are also at disproportionate risk for contracting the human immunodeficiency virus (HIV) and hepatitis C virus (HCV). This study tests an approach that has been shown to improve recovery rates: medication along with other supportive services (medication-assisted treatment, or MAT) against MAT combined with a smartphone innovation called A-CHESS (MAT + A-CHESS).. This unblinded study will randomly assign 440 patients to receive MAT + A-CHESS or MAT alone. Eligible patients will meet criteria for having an opioid use disorder of at least moderate severity and will be taking methadone, injectable naltrexone, or buprenorphine. Patients with A-CHESS will have smartphones for 16 months; all patients will be followed for 24 months. The primary outcome is the difference between patients in the two arms in percentage of days using illicit opioids during the 24-month intervention. Secondary outcomes are differences between patients receiving MAT + A-CHESS versus MAT in other substance use, quality of life, retention in treatment, health service use, and, related to HIV and HCV, screening and testing rates, medication adherence, risk behaviors, and links to care. We will also examine mediators and moderators of the effects of MAT + A-CHESS. We will measure variables at baseline and months 4, 8, 12, 16, 20, and 24. At each point, patients will respond to a 20- to 30-min phone survey; urine screens will be collected at baseline and up to twice a month thereafter. We will use mixed-effects to evaluate the primary and secondary outcomes, with baseline scores functioning as covariates, treatment condition as a between-subject factor, and the outcomes reflecting scores for a given assessment at the six time points. Separate analyses will be conducted for each outcome.. A-CHESS has been shown to improve recovery for people with alcohol dependence. It offers an adaptive and extensive menu of services and can attend to patients nearly as constantly as addiction does. This suggests the possibility of increasing both the effectiveness of, and access to, treatment for opioid dependence.. ClinicalTrials.gov, NCT02712034 . Registered on 14 March 2016.

Topics: Adaptation, Psychological; Analgesics, Opioid; Buprenorphine; Clinical Protocols; Combined Modality Therapy; Drug Users; Health Services Accessibility; Humans; Methadone; Mobile Applications; Naltrexone; Opiate Substitution Treatment; Opioid-Related Disorders; Quality of Life; Recurrence; Research Design; Smartphone; Telemedicine; Time Factors; Treatment Outcome; Wisconsin

Topics: Buprenorphine; Humans; Narcotic Antagonists; Opioid-Related Disorders; Pilot Projects; Waiting Lists

In spite of the clinical utility of buprenorphine, parenteral abuse of this medication has been reported in several laboratory investigations and in the real world. Studies have demonstrated lower abuse liability of the buprenorphine/naloxone combination relative to buprenorphine alone. However, clinical research has not yet examined the utility of the combined formulation to deter intranasal use in a buprenorphine-maintained population. Heroin-using volunteers (n = 12) lived in the hospital for 8-9 weeks and were maintained on each of three sublingual buprenorphine doses (2, 8, 24 mg). Under each maintenance dose, participants completed laboratory sessions during which the reinforcing and subjective effects of intranasal doses of buprenorphine (8, 16 mg), buprenorphine/naloxone (8/2, 8/8, 8/16, 16/4 mg) and controls (placebo, heroin 100 mg, naloxone 4 mg) were assessed. Intranasal buprenorphine alone typically produced increases in positive subjective effects and the 8 mg dose was self-administered above the level of placebo. The addition of naloxone dose dependently reduced positive subjective effects and increased aversive effects. No buprenorphine/naloxone combination dose was self-administered significantly more than placebo. These data suggest that within a buprenorphine-dependent population, intranasal buprenorphine/naloxone has reduced abuse potential in comparison to buprenorphine alone. These data strongly argue in favor of buprenorphine/naloxone rather than buprenorphine alone as the more reasonable option for managing the risk of buprenorphine misuse.

Topics: Administration, Intranasal; Administration, Sublingual; Adult; Analysis of Variance; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Dose-Response Relationship, Drug; Double-Blind Method; Female; Heroin Dependence; Humans; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Psychomotor Performance; Reinforcement, Psychology; Self Administration; Surveys and Questionnaires; Treatment Outcome; Young Adult

Most research examining buprenorphine has been conducted with heroin users. Few studies have examined buprenorphine pharmacotherapy for prescription opioid users. Data were from a randomized controlled trial of behavioral treatment provided for 16weeks on a platform of buprenorphine pharmacotherapy and medication management. We compared heroin (H, n=54), prescription opioid (PO, n=54) and combination heroin+prescription opioid (POH, n=71) users to test the hypothesis that PO users will have better treatment outcomes compared with heroin users. The PO group provided more opioid-negative urine drug screens over the combined treatment period (PO:70%, POH:40%, H:38%, p<0.001) and at the end of the combined treatment period (PO:65%, POH:31%, H:33%, p<0.001). Retention was lowest in the H group (PO:80%, POH:65%, H:57%, p=0.039). There was no significant difference in buprenorphine dose between the groups. PO users appear to have better outcomes in buprenorphine pharmacotherapy compared to those reporting any heroin use, confirming that buprenorphine pharmacotherapy is effective in PO users.

Topics: Adult; Analgesics, Opioid; Behavior Therapy; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Female; Heroin Dependence; Humans; Male; Middle Aged; Naloxone; Opiate Substitution Treatment; Opioid-Related Disorders; Prescription Drug Misuse; Treatment Outcome

Despite the high prevalence of prescription opioid dependence in the U.S., little is known about the course of this disorder and long-term response to treatment. We therefore examined 18-month post-randomization outcomes of participants in the Prescription Opioid Addiction Treatment Study, a multi-site, randomized controlled trial examining varying durations of buprenorphine-naloxone treatment and different intensities of counseling for prescription opioid dependence. Thus the current follow-up study provides a unique contribution to the field by reporting longer-term outcomes of a well-characterized population of treatment-seeking prescription opioid dependent patients. Participants from the treatment trial (N=252/653) completed an 18-month follow-up telephone assessment. Multivariable analyses examined associations between participant characteristics and key indicators of month-18 status: opioid abstinence, DSM-IV opioid dependence, and opioid agonist treatment. Overall, participants showed improvement from baseline to month 18: 49.6% were abstinent in the previous 30 days, with only 16.3% opioid-dependent. Some participants, however, had initiated past-year heroin use (n=9) or opioid injection (n=17). Most participants (65.9%) engaged in substance use disorder treatment during the past year, most commonly opioid agonist therapy (48.8%). Of particular interest in this population, multivariable analysis showed that greater pain severity at baseline was associated with opioid dependence at 18 months. In conclusion, although opioid use outcomes during the treatment trial were poor immediately following a buprenorphine-naloxone taper compared to those during 12 weeks of buprenorphine-naloxone stabilization, opioid use outcomes at 18-month follow-up showed substantial improvement over baseline and were comparable to the rate of successful outcomes during buprenorphine-naloxone stabilization in the treatment trial.

Topics: Adult; Buprenorphine; Counseling; Female; Follow-Up Studies; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Outcome Assessment, Health Care; Prescription Drug Misuse; Time Factors

Most patients relapse to opioids within one month of opioid agonist detoxification, making the antecedents and parallel processes of first use critical for investigation. Craving and withdrawal are often studied in relationship to opioid outcomes, and a novel analytic strategy applied to these two phenomena may indicate targeted intervention strategies.. Specifically, this secondary data analysis of the Prescription Opioid Addiction Treatment Study used a discrete-time mixture analysis with time-to-first opioid use (survival) simultaneously predicted by craving and withdrawal growth trajectories. This analysis characterized heterogeneity among prescription opioid-dependent individuals (N=653) into latent classes (i.e., latent class analysis [LCA]) during and after buprenorphine/naloxone stabilization and taper.. A 4-latent class solution was selected for overall model fit and clinical parsimony. In order of shortest to longest time-to-first use, the 4 classes were characterized as 1) high craving and withdrawal, 2) intermediate craving and withdrawal, 3) high initial craving with low craving and withdrawal trajectories and 4) a low initial craving with low craving and withdrawal trajectories. Odds ratio calculations showed statistically significant differences in time-to-first use across classes.. Generally, participants with lower baseline levels and greater decreases in craving and withdrawal during stabilization combined with slower craving and withdrawal rebound during buprenorphine taper remained opioid-free longer. This exploratory work expanded on the importance of monitoring craving and withdrawal during buprenorphine induction, stabilization, and taper. Future research may allow individually tailored and timely interventions to be developed to extend time-to-first opioid use.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Craving; Disease-Free Survival; Female; Humans; Male; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Outpatients; Recurrence; Substance Withdrawal Syndrome; Treatment Outcome

The aim of this study is to assess the prevalence of non-opioid drug use among opioid-addicted, buprenorphine injecting individuals in Georgia, during and after a 12-week course of buprenorphine-naloxone (Suboxone®) or methadone.. Randomized controlled trial with daily observed Suboxone® or methadone and weekly counseling, urine tests and timeline followback (TLFB) in weeks 0-12 and 20, and the Addiction Severity Index (ASI) at weeks 0, 4, 8, 12, 20.. Of the 80 patients (40/group, 4 women), 68 (85%) completed the 12-weeks of study treatment and 66 (82.5%) completed the 20-week follow-up. At baseline, injecting more than one drug in the last 30 days was reported by 68.4% of patients in the methadone and 72.5% in the Suboxone® groups. Drug use was markedly reduced in both treatment conditions but there were significant differences in the prevalence of specific drugs with more opioid (1.5 vs. 0.2%; p=0.03), less amphetamine (0.2 vs. 2.8%; p<0.001) and less marijuana (1.7 vs. 10.2%; p<0.001) positive urine tests in the methadone vs. Suboxone® groups. At the 20-week follow-up, TLFB results on the 34 that continued methadone or the 3 on Suboxone® showed less opioid (5.6 vs. 27.6%; p<0.001), illicit buprenorphine (2.7 vs. 13.8%; p=0.005), benzodiazepine (13.5 vs. 34.5%; p<0.001), and marijuana (2.8 vs. 20.7%; p<0.001) use than the 29 who did not continue opioid substitution therapy.. Despite small but significant differences in opioid and other drug use, both treatments were highly effective in reducing opioid and non-opioid drug use.

Topics: Adult; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Counseling; Drug Users; Female; Georgia (Republic); Humans; Methadone; Middle Aged; Naloxone; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Substance Abuse, Intravenous; Treatment Outcome

While research suggests primary prescription opioid (PO) abusers may exhibit less severe demographic and drug use characteristics than primary heroin abusers, less is known about whether a lifetime history of heroin use confers greater severity among PO abusers.. In this secondary analysis, we examined demographic and drug use characteristics as a function of lifetime heroin use among 89 PO-dependent adults screened for a trial evaluating the relative efficacy of buprenorphine taper durations. Exploratory analyses also examined contribution of lifetime heroin use to treatment response among a subset of participants who received a uniform set of study procedures.. Baseline characteristics were compared between participants reporting lifetime heroin use ≥5 (H(+); n=41) vs. <5 (H(-); n=48) times. Treatment response (i.e., illicit opioid abstinence and treatment retention at end of study) was examined in the subset of H(+) and H(-) participants randomized to receive the 4-week taper condition (N=22).. H(+) participants were significantly older and more likely to be male. They reported longer durations of illicit opioid use, greater alcohol-related problems, more past-month cocaine use, greater lifetime IV drug use, and greater lifetime use of cigarettes, amphetamines and hallucinogens. H(+) participants also had lower scores on the Positive Symptom Distress and Depression subscales of the Brief Symptom Inventory. Finally, there was a trend toward poorer treatment outcomes among H(+) participants.. A lifetime history of heroin use may be associated with elevated drug severity and unique treatment needs among treatment-seeking PO abusers.

Topics: Adult; Behavior Therapy; Buprenorphine; Chronic Disease; Double-Blind Method; Drug Therapy, Combination; Female; Heroin Dependence; Humans; Male; Naltrexone; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Prescription Drug Misuse

The prevalence of hepatitis-C-virus (HCV) infections is high among opioid-dependent individuals. Prior research on the simultaneous treatment of both conditions has primarily assessed success as it pertains to HCV. However, it has been noted that favorable substance use therapy outcomes may improve the likelihood of HCV-treatment initiation and success. Therefore, current guidelines for the treatment of HCV among illicit drug users suggest that treatment for addiction be given the highest priority.. To determine whether opioid-dependent participants in a clinical trial of buprenorphine-treatment tapering regimens, who tested positive for the HCV antibody, experienced significantly different levels of opioid abstinence than those not infected.. Data came from the National Drug Abuse Treatment Clinical Trial Network study 0003. 516 eligible opioid-dependent participants were randomized to either a 7-day or 28-day buprenorphine tapering schedule following a 4-week buprenorphine stabilization period. Generalized estimating equations were used to test the research question.. Participants with the HCV antibody were significantly less likely to submit opioid-negative urine analyses during and/or immediately following active treatment [OR = 0.69; CI = 0.51-0.93], indicating a higher rate of opioid use among this group.. Individualized opioid-dependence treatment strategies may be required for opioid-dependent individuals who test positive for the HCV antibody in order to ensure resources for both opioid-dependence and HCV therapies are used efficiently.

Topics: Adolescent; Adult; Buprenorphine; Drug Administration Schedule; Female; Hepacivirus; Hepatitis Antibodies; Hepatitis C; Humans; Longitudinal Studies; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Treatment Outcome

Buprenorphine opioid agonist treatment (OAT) has established efficacy for treating opioid dependency but early relapse rates are high and are often associated with withdrawal-related or emotional distress.. To determine whether a novel distress tolerance (DT) intervention during buprenorphine initiation decreases opioid relapse, we conducted a preliminary randomized controlled trial with opioid-dependent outpatients. Participants received buprenorphine-naloxone induction and 3-months of maintenance buprenorphine plus seven, 50-min manualized, individual sessions (DT vs. health education (HE) control) over a 28-day period, linked to clinician medication dosing visits, and beginning 2 days prior to buprenorphine induction. Primary outcomes included use of illicit opioids (positive defined as any self-reported use in the prior 28 days or detected by urine toxicology) and treatment drop out.. Among 49 participants, the mean age was 41 years, 65.3% were male. Persons randomized to DT had lower rates of opioid use at all three monthly assessments, and at 3-months, 72% of HE participants were opioid positive compared with 62.5% of DT participants. Rates of dropout were 24% and 25% in the HE and DT arms, respectively.. This distress tolerance treatment produced a small, but not statistically significant reduction in opioid use during the first three months of treatment although no differences were found in drop-out rates between conditions. If replicated in a larger study, DT could offer clinicians a useful behavioral treatment to complement the effects of buprenorphine.

Topics: Acceptance and Commitment Therapy; Adult; Ambulatory Care; Buprenorphine; Combined Modality Therapy; Female; Humans; Implosive Therapy; Male; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Outpatients; Recurrence; Treatment Outcome

Initial medication response has been shown to predict treatment outcome across a variety of substance use disorders, but no studies have examined the predictive power of initial response to buprenorphine-naloxone in the treatment of prescription opioid dependence. We therefore conducted a secondary analysis of data from the Prescription Opioid Addiction Treatment Study to determine whether initial response to buprenorphine-naloxone predicted 12-week treatment outcome in a prescription opioid-dependent population.. Using data from a multisite, randomized controlled trial of buprenorphine-naloxone plus counseling for DSM-IV prescription opioid dependence (June 2006-July 2009), we conducted a secondary analysis to investigate the relationship between initial medication response and 12-week treatment outcome to establish how soon the efficacy of buprenorphine-naloxone could be predicted (N = 360). Outcomes were determined from the Substance Use Report, a self-report measure of substance use, and confirmatory urinalysis. Predictive values were calculated to determine the importance of abstinence versus use at various time points within the first month of treatment (week 1, weeks 1-2, 1-3, or 1-4) in predicting successful versus unsuccessful treatment outcome (based on abstinence or near-abstinence from opioids) in the last 4 weeks of buprenorphine-naloxone treatment (weeks 9-12).. Outcome was best predicted by medication response after 2 weeks of treatment. Two weeks of initial abstinence was moderately predictive of treatment success (positive predictive value = 71%), while opioid use in both of the first 2 weeks was strongly predictive of unsuccessful treatment outcome (negative predictive value [NPV] = 84%), especially when successful outcome was defined as total abstinence from opioids in weeks 9-12 (NPV = 94%).. Evaluating prescription opioid-dependent patients after 2 weeks of buprenorphine-naloxone treatment may help determine the likelihood of successful outcome at completion of the current treatment regimen.. ClinicalTrials.gov identifier: NCT00316277.

Topics: Adolescent; Adult; Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Combined Modality Therapy; Counseling; Female; Follow-Up Studies; Humans; Male; Middle Aged; Naloxone; Opioid-Related Disorders; Prescription Drug Misuse; Recurrence; Temperance; United States; Young Adult

Research grounded in behavioral economics has previously linked addictive behavior to disrupted decision-making and reward-processing, but these principles have not been examined in prescription opioid addiction, which is currently a major public health problem. This study examined whether pre-treatment drug reinforcement value predicted opioid use during outpatient treatment of prescription opioid addiction.. Secondary analyses examined participants with prescription opioid dependence who received 12 weeks of buprenorphine-naloxone and counseling in a multi-site clinical trial (N=353). Baseline measures assessed opioid source and indices of drug reinforcement value, including the total amount and proportion of income spent on drugs. Weekly urine drug screens measured opioid use.. Obtaining opioids from doctors was associated with lower pre-treatment drug spending, while obtaining opioids from dealers/patients was associated with greater spending. Controlling for demographics, opioid use history, and opioid source frequency, patients who spent a greater total amount (OR=1.30, p<.001) and a greater proportion of their income on drugs (OR=1.31, p<.001) were more likely to use opioids during treatment.. Individual differences in drug reinforcement value, as indicated by pre-treatment allocation of economic resources to drugs, reflects propensity for continued opioid use during treatment among individuals with prescription opioid addiction. Future studies should examine disrupted decision-making and reward-processing in prescription opioid users more directly and test whether reinforcer pathology can be remediated in this population.

Topics: Adult; Aged; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Economics, Behavioral; Female; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Predictive Value of Tests; Prescription Drug Misuse; Treatment Outcome

The authors tested whether clonidine blocks stress-induced seeking of heroin and cocaine. The study was also intended to confirm translational findings from a rat model of drug relapse by using ecological momentary assessment of patients' stress to test hypotheses about clonidine's behavioral mechanism of action.. The authors conducted a randomized double-blind placebo-controlled clinical trial with 208 opioid-dependent patients at an outpatient buprenorphine clinic. The 118 participants (57%) who maintained abstinence during weeks 5-6 were continued on buprenorphine and randomly assigned to receive clonidine (N=61) or placebo (N=57) for 14 weeks. Urine was tested thrice weekly. Lapse was defined as any opioid-positive or missed urine test, and relapse as two or more consecutive lapses. Time to lapse and relapse were examined with Cox regressions; longest period of abstinence was examined with a t test, and ecological momentary assessment data were examined with generalized linear mixed models.. In an intent-to-treat analysis, clonidine produced the longest duration (in consecutive days) of abstinence from opioids during the intervention phase (34.8 days [SD=3.7] compared with 25.5 days [SD=2.7]; Cohen's d=0.38). There was no group difference in time to relapse, but the clonidine group took longer to lapse (hazard ratio=0.67, 95% CI=0.45-1.00). Ecological momentary assessment showed that daily-life stress was partly decoupled from opioid craving in the clonidine group, supporting the authors' hypothesized mechanism for clonidine's benefits.. Clonidine, a readily available medication, is useful in opioid dependence not just for reduction of withdrawal signs, but also as an adjunctive maintenance treatment that increases duration of abstinence. Even in the absence of physical withdrawal, it decouples stress from craving in everyday life.

Topics: Adult; Analgesics; Buprenorphine; Clonidine; Craving; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Maintenance Chemotherapy; Male; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Proportional Hazards Models; Substance Withdrawal Syndrome; Treatment Outcome

Buprenorphine is an effective and popular treatment for opioid dependence. It remains unclear, however, when or how to transition stable buprenorphine-maintained individuals to complete abstinence. This trial investigates the feasibility of using naltrexone to facilitate buprenorphine discontinuation in stable individuals who had tolerated a taper to 2mg or less but were unable to terminate entirely due to withdrawal-related distress.. The sample consisted of 6 buprenorphine-maintained individuals in sustained full remission, and who had tolerated a taper but were unable to discontinue altogether. A rapid induction procedure was performed, which included supervised buprenorphine discontinuation, oral naltrexone titration with a starting dose of 6.25mg, and administration of long-acting injectable naltrexone. Participants were followed weekly for 5weeks after the injection, with telephone follow-up occurring at 6months.. The rapid induction procedure was well tolerated. There was no observed or reported clinical worsening over the course of study participation. Notably, no participants experienced an increase in Subjective Opioid Withdrawal Scale (SOWS) scores after the first oral dose of NTX as compared to day 1 (24hours after last dose of buprenorphine); instead, SOWS scores decreased between days 1 and 7 (p=0.043). All participants were able to discontinue buprenorphine and to remain opioid free during the trial and at follow-up.. This preliminary trial represented for all participants the first successful attempt at buprenorphine discontinuation. Further research is needed to better understand if naltrexone is effective at facilitating buprenorphine discontinuation, as well as the feasibility of a sequential approach (buprenorphine stabilization to naltrexone) for opioid use disorders.

Topics: Administration, Oral; Adult; Buprenorphine; Drug Administration Schedule; Feasibility Studies; Female; Humans; Injections; Male; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Substance Withdrawal Syndrome; Treatment Outcome

Prescription opioid (PO) abuse has become an urgent public health issue in the United States. Detoxification is one important treatment option, yet relatively little is known about the time course and severity of opioid withdrawal during buprenorphine detoxification.. This is a secondary analysis of data from a randomized, placebo-controlled, double-blind evaluation of 1, 2, and 4-week outpatient buprenorphine tapers among primary prescription opioid (PO) abusers. The aim is to characterize the time course and severity of buprenorphine withdrawal under rigorous, double-blind conditions, across multiple taper durations, and using multiple withdrawal-related measures (i.e., self-report and observer ratings, pupil diameter, ancillary medication utilization). Participants were PO-dependent adults undergoing buprenorphine detoxification and biochemically-verified to be continuously abstinent from opioids during their taper (N = 28).. Participants randomly assigned to the 4-week taper regimen experienced a relatively mild and stable course of withdrawal, with few peaks in severity. In contrast, the 1- and 2-week taper groups experienced stark increases in withdrawal severity during the week following the last buprenorphine dose, followed by declines in withdrawal severity thereafter. The 4-week taper group also reported significantly fewer disruptions in sleep compared to the other experimental groups. When predictors of withdrawal were examined, baseline ratings of "Expected Withdrawal Severity" was the most robust predictor of withdrawal experienced during the taper.. Data from this trial may inform clinicians about the expected time course, magnitude, and pattern of buprenorphine withdrawal and aid efforts to identify patients who may need additional clinical support during outpatient buprenorphine detoxification.

Topics: Adult; Buprenorphine; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Acuity; Prescription Drug Misuse; Substance Withdrawal Syndrome; Treatment Outcome; United States

Attentional bias (AB) is implicated in the development and maintenance of substance dependence and in treatment outcome. We assessed the effects of attentional bias modification (ABM), and the relationship between AB and treatment adherence in opiate dependent patients.. An independent groups design was used to compare 23 opiate dependent patients with 21 healthy controls. Participants completed an AB task before either a control or an ABM task designed to train attention away from substance-related stimuli. Pre- and post-ABM AB and craving were assessed to determine any changes. Relationships between treatment adherence ('using on top' of prescribed opiates or not) and AB, craving and psychopathology were also examined.. There was no baseline difference in AB between patients and controls, and no significant effect of ABM on AB or substance craving. However, treatment adherent patients who did not use illicit opiates on top of their prescribed opiates had statistically significantly greater AB away from substance-related stimuli than both participants using on top and controls, and reported significantly lower levels of craving than non-treatment adherent patients.. Whilst we did not find any significant effects of ABM on AB or craving, patients who were treatment adherent differed from both those who were not and from controls in their attentional functioning and substance craving. These findings are the first to suggest that AB may be a within-treatment factor predictive of adherence to pharmacological treatment and potentially of recovery in opiate users.

Topics: Analysis of Variance; Attention; Buprenorphine; Craving; Female; Humans; Impulsive Behavior; Male; Medication Adherence; Methadone; Middle Aged; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Psychotherapy; Surveys and Questionnaires

Hepatitis C virus (HCV)-infected patients with a history of injection drug use have low rates of initiation and completion of interferon-based therapies. This study evaluated efficacy, safety, and pharmacokinetics of a 12-week all-oral regimen of ombitasvir/paritaprevir/ritonavir and dasabuvir+ribavirin in HCV genotype 1-infected patients on stable opioid replacement therapy.. This was a phase II, multicenter, open-label, single-arm study in treatment-naïve or peginterferon/ribavirin treatment-experienced HCV genotype 1-infected patients on methadone or buprenorphine±naloxone. Patients received 12weeks of co-formulated ombitasvir/paritaprevir/ritonavir (25mg/150mg/100mg once daily) and dasabuvir (250mg twice daily)+weight-based ribavirin. The primary efficacy endpoint was sustained virologic response 12 weeks post-treatment.. Thirty-eight non-cirrhotic patients on chronic methadone (n=19) or buprenorphine (n=19) were enrolled. A total of 37 patients (97.4%) had a sustained virologic response 12 weeks post-treatment. No patient had a viral breakthrough or relapse. One patient discontinued due to serious adverse events unrelated to study drug (cerebrovascular accident and sarcoma). The most frequent adverse events were nausea, fatigue, and headache. Eight patients had on-treatment hemoglobin concentrations <10g/dl. Pharmacokinetic analyses indicated no clinically meaningful impact of methadone or buprenorphine on ombitasvir, paritaprevir, ritonavir, dasabuvir, or dasabuvir M1 metabolite exposures. No dose adjustments of methadone or buprenorphine were required.. The interferon-free regimen of ombitasvir/paritaprevir/ritonavir and dasabuvir+ribavirin for 12weeks was well tolerated and achieved sustained virologic response in 97.4% of patients on opioid substitution therapy in this study. This all-oral regimen may provide an effective alternative to interferon-based therapies for HCV-infected patients with a history of injection drug use.

Topics: 2-Naphthylamine; Adolescent; Adult; Aged; Analgesics, Opioid; Anilides; Antiviral Agents; Buprenorphine; Carbamates; Cyclopropanes; DNA, Viral; Drug Therapy, Combination; Female; Follow-Up Studies; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Lactams, Macrocyclic; Macrocyclic Compounds; Male; Methadone; Middle Aged; Opioid-Related Disorders; Proline; Retrospective Studies; Ribavirin; Sulfonamides; Uracil; Valine; Young Adult

Extended-release (XR) injection naltrexone has proved promising in the treatment of opioid dependence. Induction onto naltrexone is often accomplished with a procedure known as rapid naltrexone induction. The purpose of this study was to evaluate pre-treatment patient characteristics as predictors of successful completion of a rapid naltrexone induction procedure prior to XR naltrexone treatment.. A chart review of 150 consecutive research participants (N = 84 completers and N = 66 non-completers) undergoing a rapid naltrexone induction with the buprenorphone-clonidine procedure were compared on a number of baseline demographic, clinical and psychosocial factors. Logistic regression was used to identify client characteristics that may predict successful initiation of naltrexone after a rapid induction-detoxification.. Patients who failed to successfully initiate naltrexone were younger (AOR: 1.040, CI: 1.006, 1.075), and using 10 or more bags of heroin (or equivalent) per day (AOR: 0.881, CI: 0.820, 0.946). Drug use other than opioids was also predictive of failure to initiate naltrexone in simple bivariate analyses, but was no longer significant when controlling for age and opioid use level.. Younger age, and indicators of greater substance dependence severity (more current opioid use, other substance use) predict difficulty completing a rapid naltrexone induction procedure. Such patients might require a longer period of stabilization and/or more gradual detoxification prior to initiating naltrexone.. Our study findings identify specific characteristics of patients who responded positively to rapid naltrexone induction.

Topics: Administration, Oral; Adult; Buprenorphine; Clonidine; Delayed-Action Preparations; Drug Therapy, Combination; Female; Heroin Dependence; Humans; Injections, Intramuscular; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Patient Selection; Prognosis

Opioid-dependent patients often use the emergency department (ED) for medical care.. To test the efficacy of 3 interventions for opioid dependence: (1) screening and referral to treatment (referral); (2) screening, brief intervention, and facilitated referral to community-based treatment services (brief intervention); and (3) screening, brief intervention, ED-initiated treatment with buprenorphine/naloxone, and referral to primary care for 10-week follow-up (buprenorphine).. A randomized clinical trial involving 329 opioid-dependent patients who were treated at an urban teaching hospital ED from April 7, 2009, through June 25, 2013.. After screening, 104 patients were randomized to the referral group, 111 to the brief intervention group, and 114 to the buprenorphine treatment group.. Enrollment in and receiving addiction treatment 30 days after randomization was the primary outcome. Self-reported days of illicit opioid use, urine testing for illicit opioids, human immunodeficiency virus (HIV) risk, and use of addiction treatment services were the secondary outcomes.. Seventy-eight percent of patients in the buprenorphine group (89 of 114 [95% CI, 70%-85%]) vs 37% in the referral group (38 of 102 [95% CI, 28%-47%]) and 45% in the brief intervention group (50 of 111 [95% CI, 36%-54%]) were engaged in addiction treatment on the 30th day after randomization (P < .001). The buprenorphine group reduced the number of days of illicit opioid use per week from 5.4 days (95% CI, 5.1-5.7) to 0.9 days (95% CI, 0.5-1.3) vs a reduction from 5.4 days (95% CI, 5.1-5.7) to 2.3 days (95% CI, 1.7-3.0) in the referral group and from 5.6 days (95% CI, 5.3-5.9) to 2.4 days (95% CI, 1.8-3.0) in the brief intervention group (P < .001 for both time and intervention effects; P = .02 for the interaction effect). The rates of urine samples that tested negative for opioids did not differ statistically across groups, with 53.8% (95% CI, 42%-65%) in the referral group, 42.9% (95% CI, 31%-55%) in the brief intervention group, and 57.6% (95% CI, 47%-68%) in the buprenorphine group (P = .17). There were no statistically significant differences in HIV risk across groups (P = .66). Eleven percent of patients in the buprenorphine group (95% CI, 6%-19%) used inpatient addiction treatment services, whereas 37% in the referral group (95% CI, 27%-48%) and 35% in the brief intervention group (95% CI, 25%-37%) used inpatient addiction treatment services (P < .001).. Among opioid-dependent patients, ED-initiated buprenorphine treatment vs brief intervention and referral significantly increased engagement in addiction treatment, reduced self-reported illicit opioid use, and decreased use of inpatient addiction treatment services but did not significantly decrease the rates of urine samples that tested positive for opioids or of HIV risk. These findings require replication in other centers before widespread adoption.. clinicaltrials.gov Identifier: NCT00913770.

Topics: Adult; Buprenorphine; Emergency Service, Hospital; Female; Health Services; HIV Infections; Hospitals, Teaching; Hospitals, Urban; Humans; Male; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Referral and Consultation; Risk; Young Adult

To examine patient and medication characteristics associated with retention and continued illicit opioid use in methadone (MET) versus buprenorphine/naloxone (BUP) treatment for opioid dependence.. This secondary analysis included 1267 opioid-dependent individuals participating in nine opioid treatment programs between 2006 and 2009 and randomized to receive open-label BUP or MET for 24 weeks.. The analyses included measures of patient characteristics at baseline (demographics; use of alcohol, cigarettes and illicit drugs; self-rated mental and physical health), medication dose and urine drug screens during treatment, and treatment completion and days in treatment during the 24-week trial.. The treatment completion rate was 74% for MET versus 46% for BUP (P < 0.01); the rate among MET participants increased to 80% when the maximum MET dose reached or exceeded 60 mg/day. With BUP, the completion rate increased linearly with higher doses, reaching 60% with doses of 30-32 mg/day. Of those remaining in treatment, positive opioid urine results were significantly lower [odds ratio (OR) = 0.63, 95% confidence interval (CI) = 0.52-0.76, P < 0.01] among BUP relative to MET participants during the first 9 weeks of treatment. Higher medication dose was related to lower opiate use, more so among BUP patients. A Cox proportional hazards model revealed factors associated with dropout: (i) BUP [versus MET, hazard ratio (HR) = 1.61, CI = 1.20-2.15], (ii) lower medication dose (<16 mg for BUP, <60 mg for MET; HR = 3.09, CI = 2.19-4.37), (iii) the interaction of dose and treatment condition (those with higher BUP dose were 1.04 times more likely to drop out than those with lower MET dose, and (iv) being younger, Hispanic and using heroin or other substances during treatment.. Provision of methadone appears to be associated with better retention in treatment for opioid dependence than buprenorphine, as does use of provision of higher doses of both medications. Provision of buprenorphine is associated with lower continued use of illicit opioids.

Topics: Adolescent; Adult; Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Female; Humans; Male; Medication Adherence; Methadone; Middle Aged; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Treatment Outcome; Young Adult

The adjective rating scale for withdrawal (ARSW) is commonly used to assess opiate withdrawal in clinical practice and research. The aims of this study were to examine the factor structure of the ARSW, test measurement invariance across gender and treatment groups, and assess longitudinal measurement invariance across the clinical trial. Secondary data analysis of the National Drug Abuse Treatment Clinical Trials Network 000-3, a randomized clinical trial comparing two tapering strategies, was performed. The ARSW was analyzed at baseline, end of taper and 1-month follow-up (N=515 opioid-dependent individuals). A 1-factor model of the ARSW fit the data and demonstrated acceptable reliability. Measurement invariance was supported across gender and taper groups. Longitudinal measurement invariance was not found across the course of the trial, with baseline assessment contributing to the lack of invariance. If change over time is of interest, change from post-treatment through follow-up may offer the most valid comparison.

Topics: Adult; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Female; Follow-Up Studies; Humans; Longitudinal Studies; Male; Middle Aged; Naloxone; Opioid-Related Disorders; Psychiatric Status Rating Scales; Psychometrics; Reproducibility of Results; Sex Factors; Substance Withdrawal Syndrome; Time Factors

Given the growing prevalence of prescription opioid dependence and the considerable rates of additional psychopathology in drug dependence, we examined the association between the presence of a co-occurring Axis I psychiatric disorder and sociodemographic and clinical characteristics in this secondary analysis of patients entering a treatment study for dependence on prescription opioids. Treatment outcomes were also compared.. Patients dependent on prescription opioids participated in a multi-site, two-phase, randomized, controlled trial to assess different lengths of buprenorphine-naloxone pharmacotherapy and different intensities of counseling (Clinicaltrials.gov identifier: NCT00316277). Among the 653 participants entering the first phase of the trial, 360 entered the second phase, receiving 12 weeks of buprenorphine-naloxone treatment; they are reported here. Half of those participants (180/360) had a current co-occurring psychiatric disorder in addition to substance dependence.. Sociodemographic characteristics were similar overall between those with and without a co-occurring psychiatric disorder, but women were 1.6 times more likely than men to have a co-occurring disorder. On several clinical indicators at baseline, participants with a co-occurring disorder had greater impairment. However, they had better opioid use outcomes at the conclusion of 12 weeks of buprenorphine-naloxone stabilization than did participants without a co-occurring disorder.. Prescription opioid-dependent patients with a co-occurring psychiatric disorder had a better response to buprenorphine-naloxone treatment despite demonstrating greater impairment at baseline. Additional research is needed to determine the mechanism of this finding and to adapt treatments to address this population.

Topics: Adult; Buprenorphine; Diagnosis, Dual (Psychiatry); Drug Therapy, Combination; Female; Humans; Male; Mental Disorders; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Prescription Drugs; Treatment Outcome; Young Adult

Preliminary evidence suggests that there is minimal withdrawal after the cessation of chronically administered buprenorphine and that opioid withdrawal symptoms are delayed compared with those of other opioids. The present study compared the time course and magnitude of buprenorphine withdrawal with a prototypical μ-opioid agonist, morphine. Healthy, out-of-treatment opioid-dependent residential volunteers (N = 7) were stabilized on either buprenorphine (32 mg/day i.m.) or morphine (120 mg/day i.m.) administered in four divided doses for 9 days. They then underwent an 18-day period of spontaneous withdrawal, during which four double-blind i.m. placebo injections were administered daily. Stabilization and spontaneous withdrawal were assessed for the second opioid using the same time course. Opioid withdrawal measures were collected eight times daily. Morphine withdrawal symptoms were significantly (P < 0.05) greater than those of buprenorphine withdrawal as measured by mean peak ratings of Clinical Opiate Withdrawal Scale (COWS), Subjective Opiate Withdrawal Scale (SOWS), all subscales of the Profile of Mood States (POMS), sick and pain (0-100) Visual Analog Scales, systolic and diastolic blood pressure, heart rate, respiratory rate, and pupil dilation. Peak ratings on COWS and SOWS occurred on day 2 of morphine withdrawal and were significantly greater than on day 2 of buprenorphine withdrawal. Subjective reports of morphine withdrawal resolved on average by day 7. There was minimal evidence of buprenorphine withdrawal on any measure. In conclusion, spontaneous withdrawal from high-dose buprenorphine appears subjectively and objectively milder compared with that of morphine for at least 18 days after drug cessation.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Humans; Injections, Intramuscular; Male; Middle Aged; Morphine; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Dropouts; Psychiatric Status Rating Scales; Receptors, Opioid, mu; Remission, Spontaneous; Residential Treatment; Severity of Illness Index; Time Factors

Many opioid-dependent patients leave treatment prematurely. This study is a planned secondary analysis from a randomized trial of counseling for African Americans (N=297) entering buprenorphine treatment at one of two outpatient programs. This study examines: (1) whether patients' initial treatment duration intentions prospectively predict retention; and (2) patients' reasons for leaving treatment. Participants were queried about their treatment duration intentions at treatment entry, and their reasons for leaving treatment at 6-month follow-up. At baseline, 28.0% reported wanting to stay in buprenorphine treatment less than 6 months, while 42.1% actually left buprenorphine treatment within 6 months. However, participants intending short-term buprenorphine at the outset were not at elevated risk of early treatment discontinuation (OR=1.15; p=.65). Participants attributed treatment cessation predominantly to conflicts with staff, involuntary discharge, and perceived inflexibility of the program. Future research should examine patient-centered models of buprenorphine treatment that could improve retention.

Topics: Adult; Analgesics, Opioid; Black or African American; Buprenorphine; Counseling; Female; Humans; Male; Middle Aged; Opioid-Related Disorders; Patient Dropouts

Supervised consumption of opiate substitution treatment is standard practice in the UK yet little is known about the patient experience of this treatment modality. This study aimed to assess the patient experience of receiving supervised compared with unsupervised consumption of methadone or buprenorphine.. A qualitative study utilising a grounded theory approach to analysis. Participants (29) were theoretically sampled from 293 opioid-dependent patients entering a randomised controlled trial of opiate substitution treatment across four urban and community drug treatment services in England. Multidisciplinary staff were recruited for interviews and focus groups (55).. Supervised consumption was accepted by patients, despite causing practical limitations and raising issues of privacy and stigma. Patients recognised that establishing a daily routine away from illicit drugs was useful early in treatment. However, having flexibility to move away from supervision was important. Unsupervised patients reported that they ultimately preferred this treatment approach and appreciated the trust and sense of reward that unsupervised treatment bought. Clinicians expressed confidence in supervised prescribing and reduced risk for their patients, but also concern that a minority of individuals may remain inappropriately supervised for lengthy time periods.. This study provides an important patient perspective and is the first in-depth qualitative investigation directly comparing supervision with unsupervised treatment to consider both patient and professional perspectives. Overall, our qualitative findings suggest that flexibly timed discontinuation of supervision may have positive benefits.

Topics: Attitude of Health Personnel; Buprenorphine; Directly Observed Therapy; Female; Focus Groups; Humans; Interviews as Topic; Male; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Satisfaction; Self Administration

Buprenorphine pharmacotherapy for opioid-dependent pregnant women is associated with maternal and neonatal outcomes superior to untreated opioid dependence. However, the literature is inconsistent regarding the possible existence of a dose-response relationship between maternal buprenorphine dose and neonatal clinical outcomes.. The present secondary analysis study (1) examined the relationship between maternal buprenorphine dose at delivery and neonatal abstinence syndrome (NAS) peak score, estimated gestational age at delivery, Apgar scores at 1 and 5 min, neonatal head circumference, length, and weight at birth, amount of morphine needed to treat NAS, duration of NAS treatment, and duration of neonatal hospital stay and (2) compared neonates who required pharmacotherapy for NAS to neonates who did not require such pharmacotherapy on these same outcomes, in 58 opioid-dependent pregnant women receiving buprenorphine as participants in a randomized clinical trial.. (1) Analyses failed to provide evidence of a relationship between maternal buprenorphine dose at delivery and any of the 10 outcomes (all p-values>.48) and (2) significant mean differences between the untreated (n=31) and treated (n=27) for NAS groups were found for duration of neonatal hospital stay and NAS peak score (both p-values<.001).. (1) Findings failed to support the existence of a dose-response relationship between maternal buprenorphine dose at delivery and any of 10 neonatal clinical outcomes, including NAS severity and (2) that infants treated for NAS had a higher mean NAS peak score and, spent a longer time in the hospital than did the group not treated for NAS is unsurprising.

Topics: Buprenorphine; Double-Blind Method; Female; Humans; Infant, Newborn; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prenatal Exposure Delayed Effects

Supervised consumption of opioid maintenance treatment (OMT) is standard in many drug centres reducing drug diversion, but is costly. We aimed to determine whether supervised consumption of OMT improved retention and other measures of drug use.. Pragmatic randomized controlled trial comparing 3 months of daily supervised consumption of OMT with 1 month or less of daily supervised OMT, then daily unsupervised consumption.. Four community drug services in the United Kingdom.. A total of 293 opioid-dependent patients entering OMT.. retention in treatment at 12 weeks. Secondary: retention at 6 months; illicit drug use [Maudsley Addiction Profile (MAP)]; quality of life (SF-12 and MAP); criminality (MAP); and social functioning.. No significant between-group difference was observed for the primary outcome: 69% (100 of 145) supervised and 74% (109 of 148) unsupervised were retained [odds ratio (OR) = 0.74, 95% confidence interval (CI) = 0.43-1.27]. Per protocol survival analysis suggested that supervised patients were less well retained (hazard ratio for retention = 0.71, 95% CI = 0.51-1.00). Illicit opioid use reduced in both groups and, while not statistically significant by intention-to-treat analysis, favoured unsupervised patients in per protocol analysis (odds of positive opioid screen for supervised versus unsupervised = 2.07, 95% CI = 1.05-4.06). Data on criminal activity also favoured unsupervised patients with 21% supervised patients committing crime versus 9% unsupervised (OR = 3.37, 95% CI = 1.28-8.86).. There was no evidence of a difference in treatment retention or opioid use rates between patients whose consumption of opioid maintenance treatment was supervised for 3 months daily (except Saturdays) compared with supervision for 1 month. There was some evidence that longer periods of supervised consumption were associated with higher levels of criminality.

Topics: Adult; Buprenorphine; Crime; Female; Humans; Maintenance Chemotherapy; Male; Medication Adherence; Methadone; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Proportional Hazards Models; Quality of Life; Treatment Outcome; United Kingdom

Disulfiram may be efficacious for treating cocaine dependence or abuse, possibly through inhibiting dopamine β-hydroxylase (DβH). Consequently, this randomized, placebo-controlled clinical trial of disulfiram during buprenorphine maintenance treatment evaluated the study hypothesis that disulfiram is superior to placebo and explored whether disulfiram response is greatest for participants with a single nucleotide polymorphism coding for genetically low DβH (T-allele carriers).. We randomized 177 buprenorphine-treated opioid dependent participants with cocaine dependence or abuse to 12 weeks of double-blind treatment with disulfiram 250mg daily (n=91) or placebo (n=86). Of 155 participants genotyped, 84 were CC-homozygous, and 71 CT or TT genotypes. Primary outcomes included days per week cocaine use, number of cocaine-negative urine tests, and maximum consecutive weeks of cocaine abstinence. We analyzed an intention-to-treat comparison between disulfiram and placebo. We also explored potential pharmacogenetic interactions and examined treatment responses of four participant groups based on medication (disulfiram or placebo) by genotype (CC-homozygous or T-allele carrier) classification.. Disulfiram participants reported significantly less frequent cocaine use; the differences in cocaine-negative urine tests or consecutive weeks abstinence were not significant. Frequency of cocaine use was lowest in disulfiram-treated T-allele carriers; differences in cocaine-negative urine tests or consecutive weeks abstinence were not significant among the four medication-genotype groups.. The findings provide limited support for the efficacy of disulfiram for reducing cocaine use and suggest that its mechanism of action may involve inhibition of DβH. Further studies of its efficacy, mechanism of action, and pharmacogenetics of response are warranted.

Topics: Adolescent; Adult; Alcohol Deterrents; Alcoholism; Alleles; Buprenorphine; Cocaine-Related Disorders; Data Interpretation, Statistical; Disulfiram; DNA; Double-Blind Method; Drug Therapy, Combination; Female; Genotype; Humans; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Pharmacogenetics; Polymerase Chain Reaction; Sample Size; Treatment Outcome; Young Adult

Few studies have assessed associations between craving and subsequent opioid use. We prospectively evaluated the relative utility of two craving questionnaires to predict opioid use among opioid-dependent patients in outpatient treatment.. Opioid-dependent patients (n = 147) initiating buprenorphine treatment were assessed every two weeks for 3 months. Craving was measured using the: (1) Desires for Drug Questionnaire (DDQ) and (2) Penn Alcohol-Craving Scale adapted for opioid craving (PCS). Multi-level logistic regression models estimated the effects of craving on the likelihood of opioid use. Craving assessed at time t was entered as a time-varying predictor of opioid use at time t + 1.. Craving scores plateaued at approximately 2 weeks after initiation of buprenorphine. In adjusted regression models, a 1-point increase in PCS scores (on a 7-point scale) was associated with a significant increase in the odds of opioid use at the subsequent assessment (OR = 1.27, 95% CI 1.08; 1.49, p < 0.01). The odds of opioid use at the subsequent follow-up assessment increased significantly as DDQ desire and intention scores increased (OR = 1.25, 95%CI 1.03; 1.51, p < 0.05), but was not significantly associated with DDQ negative reinforcement (OR = 1.01, 95%CI 0.88; 1.17, p > 0.05) or DDQ control (OR = 0.97, 95%CI 0.85; 1.11, p > 0.05) scores.. Self-reported craving for opioids was modestly associated with subsequent relapse to opioid use among a cohort of patients treated with buprenorphine. Assessment of craving may provide clinical utility in predicting relapse among treated opioid-dependent patients.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Female; Humans; Longitudinal Studies; Male; Middle Aged; Motivation; Narcotic Antagonists; Opioid-Related Disorders; Recurrence; Surveys and Questionnaires

The approval of extended release injectable naltrexone (XR-NTX; Vivitrol(®)) has introduced a new option for treating opioid addiction, but studies are needed to identify its place within the spectrum of available therapies. The absence of physiological opioid dependence is a necessary and challenging first step for starting XR-NTX. Outpatient detoxification gives poor results and inpatient detoxification is either unavailable or too brief for the physiological effects of opioids to resolve. Here we present findings from an open label study that tested whether the transition from opioid addiction to XR-NTX can be safely and effectively performed in an outpatient setting using very low dose naltrexone and buprenorphine.. Twenty treatment seeking opioid addicted individuals were given increasing doses of naltrexone starting at 0.25mg with decreasing doses of buprenorphine starting at 4 mg during a 7-day outpatient XR-NTX induction procedure. Withdrawal discomfort, craving, drug use, and adverse events were assessed daily until the XR-NTX injection, then weekly over the next month.. Fourteen of the 20 participants received XR-NTX and 13 completed weekly assessments. Withdrawal, craving, and opioid or other drug use were significantly lower during induction and after XR-NTX administration compared with baseline, and no serious adverse events were recorded.. Outpatient transition to XR-NTX combining upward titration of very low dose naltrexone with downward titration of low dose buprenorphine was safe, well tolerated, and completed by most participants. Further studies with larger numbers of subjects are needed to see if this approach is useful for naltrexone induction.

Topics: Adult; Buprenorphine; Craving; Delayed-Action Preparations; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Outpatients; Substance Withdrawal Syndrome; Young Adult

Detoxification with psychosocial counseling remains a standard opioid-use disorder treatment practice but is associated with poor outcomes. This study tested the efficacy of a newly developed psychosocial intervention, Community Reinforcement Approach and Family Training for Treatment Retention (CRAFT-T), relative to psychosocial treatment as usual (TAU), for improving treatment outcomes.. A randomized, 14-week trial with follow-up visits at 6 and 9 months post-randomization conducted at two substance use disorder (SUD) treatment programs. Opioid-dependent adults (i.e., identified patient - IP) enrolled in a residential buprenorphine-detoxification program and their identified concerned significant other (CSO) was randomized to CRAFT-T (n=28 dyads) or TAU (n=24 dyads). CRAFT-T consisted of two sessions with the IP and CSO together and 10 with the CSO alone, over 14 weeks. TAU for the CSOs was primarily educational and referral to self-help. All IPs received treatment as usually provided by the SUD program in which they were enrolled. The primary outcome was time to first IP drop from treatment lasting 30 days or more. Opioid and other drug use were key secondary outcomes.. CRAFT-T resulted in a moderate but non-significant effect on treatment retention (p=0.058, hazard ratio=0.57). When the CSO was parental family, CRAFT-T had a large and significant effect on treatment retention (p<0.01, hazard ratio=.040). CRAFT-T had a significant positive effect on IP opioid and other drug use (p<0.0001).. CRAFT-T is a promising treatment for opioid use disorder but replication is needed to confirm these results.

Topics: Adult; Buprenorphine; Combined Modality Therapy; Female; Humans; Male; Narcotic Antagonists; Opioid-Related Disorders; Patient Compliance; Pilot Projects; Psychotherapy; Young Adult

Compare HIV injecting and sex risk in patients being treated with methadone (MET) or buprenorphine-naloxone (BUP).. Secondary analysis from a study of liver enzyme changes in patients randomized to MET or BUP who completed 24 weeks of treatment and had 4 or more blood draws. The initial 1:1 randomization was changed to 2:1 (BUP:MET) after 18 months due to higher dropout in BUP. The Risk Behavior Survey measured HIV risk before 30 days at baseline and weeks 12 and 24.. Among 529 patients randomized to MET, 391 (74%) were completers; among 740 randomized to BUP, 340 (46%) were completers; 700 completed the Risk Behavior Survey. There were significant reductions in injecting risk (P < 0.0008) with no differences between groups in mean number of times reported injecting heroin, speedball, other opiates, and number of injections; or percent who shared needles; did not clean shared needles with bleach; shared cookers; or engaged in front/back loading of syringes. The percent having multiple sex partners decreased equally in both groups (P < 0.03). For males on BUP, the sex risk composite increased; for males on MET, the sex risk decreased resulting in significant group differences over time (P < 0.03). For females, there was a significant reduction in sex risk (P < 0.02) with no group differences.. Among MET and BUP patients who remained in treatment, HIV injecting risk was equally and markedly reduced; however, MET retained more patients. Sex risk was equally and significantly reduced among females in both treatment conditions, but it increased for males on BUP and decreased for males on MET.

Topics: Adult; Buprenorphine; Female; HIV Infections; Humans; Male; Methadone; Middle Aged; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Risk Reduction Behavior; Substance Abuse, Intravenous; Unsafe Sex

In the multi-site Prescription Opioid Addiction Treatment Study (POATS), conducted within the National Drug Abuse Clinical Trials Network, participants randomly assigned to receive individual drug counseling in addition to buprenorphine-naloxone and medical management did not have superior opioid use outcomes. However, research with other substance-dependent populations shows that subgroups of participants may benefit from a treatment although the entire population does not.. We conducted a secondary analysis of POATS data to determine whether a subgroup of participants benefited from drug counseling in addition to buprenorphine-naloxone and medical management, either due to greater problem severity or more exposure to counseling as a result of greater treatment adherence. Problem severity was measured by a history of heroin use, higher Addiction Severity Index drug composite score, and chronic pain. Adequate treatment adherence was defined a priori as attending at least 60% of all offered sessions.. Patients who had ever used heroin and received drug counseling were more likely to be successful (i.e., abstinent or nearly abstinent from opioids) than heroin users who received medical management alone, but only if they were adherent to treatment and thus received adequate exposure to counseling (OR=3.7, 95% CI=1.1-11.8, p=0.03). The association between severity and outcome did not vary by treatment condition for chronic pain or ASI drug severity score.. These findings emphasize the importance of treatment adherence, and suggest that patients with prescription opioid dependence are a heterogeneous group, with different optimal treatment strategies for different subgroups.

Topics: Adult; Aged; Buprenorphine; Case Management; Counseling; Female; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Patient Compliance; Prescription Drugs; Treatment Outcome

Evidence suggests a positive association between administration of psychoactive drugs and rates of cigarette smoking. Prevalence of smoking among opioid-dependent individuals, for example, is four times greater than the general population. We recently completed a randomized double-blind trial evaluating outpatient buprenorphine taper for prescription opioid (PO) abusers, which provided a unique opportunity to examine naturalistic changes in smoking among participants who detoxified without resumption of illicit opioid use.. Participants received no smoking-cessation services and were not encouraged to alter their smoking in any way. A subset of 10 opioid-dependent smokers, who were randomized to receive the same 4-week buprenorphine taper and successfully completed detoxification, were included in the present study. They provided staff-observed urine specimens thrice-weekly throughout the 12-week trial. Specimens were analyzed on-site via enzyme-multiplied immunoassay for urinary cotinine, a metabolite of nicotine that provides a sensitive biochemical measure of smoking status.. Mean cotinine levels were significantly different across study phases, with significantly lower cotinine levels during taper (1317.5 ng/ml) and post-taper (1015.8 ng/ml) vs. intake (1648.5 ng/ml) phases (p''s<.05). Overall, mean cotinine levels decreased by 38% between intake and end-of-study, reflecting a reduction of approximately eight cigarettes per day.. These data provide additional evidence that opioids influence smoking and extend prior findings to include primary PO abusers, rigorous double-blind opioid dosing conditions and urinary cotinine. These results also suggest that, while likely insufficient for complete cessation, patients who successfully taper from opioids may also experience concurrent reductions in smoking and thus may be ideal candidates for smoking cessation services.

Topics: Adult; Buprenorphine; Cotinine; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Tobacco Use Disorder; Treatment Outcome; Young Adult

Buprenorphine/naloxone (BUP/NX), an effective treatment for opioid dependence, has been implicated in hepatic toxicity. However, as persons taking BUP/NX have multiple hepatic risk factors, comparative data are needed to quantify the risk of hepatoxicity with BUP/NX.. We compared rates of alanine aminotransferase (ALT) elevation≥grade 3 (ALT≥5.1 times the upper limit of normal) and graded bilirubin elevations in HIV-negative opioid injectors randomized to long-term (52 weeks) or short-term (18 days) medication assisted treatment (LT-MAT and ST-MAT, respectively) with BUP/NX in a multisite trial conducted in China and Thailand. ALT and bilirubin were measured at baseline, 12, 26, 40 and 52 weeks, times temporally remote from BUP/NX exposure in the ST-MAT participants.. Among1036 subjects with at least one laboratory follow-up measurement, 76 (7%) participants experienced ALT elevation≥grade 3. In an intent-to-treat analysis, the risk of ALT events was similar in participants randomized to LT-MAT compared with ST-MAT (adjusted hazard ratio 1.25, 95% confidence interval 0.79 to 1.98). This finding was supported by an as-treated analysis, in which actual exposure to BUP/NX was considered. Hepatitis C seroconversion during follow-up was strongly associated with ALT events. Bilirubin elevations≥grade 2 occurred in 2% of subjects, with no significant difference between arms.. Over 52-week follow-up, the risk of hepatotoxicity was similar in opioid injectors receiving brief and prolonged treatment with BUP/NX. These data suggest that most hepatotoxic events observed during treatment with BUP/NX are due to other factors.

Topics: Adult; Alanine Transaminase; Analgesics, Opioid; Bilirubin; Buprenorphine; Chemical and Drug Induced Liver Injury; China; Female; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Thailand; Treatment Outcome

This study implemented pharmacokinetic/pharmacodynamic modelling to support the clinical development of RBP-6000, a new, long-acting, sustained-release formulation of buprenorphine for the treatment of opioid dependence. Such a formulation could offer advantages over existing buprenorphine pharmacotherapy by improving patient compliance and reducing the diversion of the product.. A population pharmacokinetic model was developed using 36 opioid-dependent subjects who received single subcutaneous doses of RBP-6000. Another pharmacokinetic/pharmacodynamic model was developed using μ-opioid receptor occupancy (µORO) data to predict efficacy of RBP-6000 after repeated doses. It was also assessed how buprenorphine plasma concentrations were correlated with opioid withdrawal symptoms and hydromorphone agonist blockade data from 15 heroin-dependent subjects.. The resulting pharmacokinetic model accurately described buprenorphine and norbuprenorphine plasma concentrations. A saturable maximum effect (E max) model with 0.67 ng/mL effective concentration at 50 % of maximum (EC50) and 91 % E max best described µORO versus buprenorphine plasma concentrations. Linear relationships were found among µORO, withdrawal symptoms and blockade of agonist effects.. Previously published findings have demonstrated µORO ≥70 % is needed to achieve withdrawal suppression and blockade of opioid agonist subjective effects. Model simulations indicated that a 200 mg RBP-6000 dose should achieve 2–3 ng/mL buprenorphine average concentrations and desired efficacy.

Topics: Adult; Buprenorphine; Delayed-Action Preparations; Female; Humans; Injections; Injections, Subcutaneous; Male; Models, Biological; Opioid-Related Disorders; Receptors, Opioid, mu

To examine the benefit of adding an Internet-delivered behavior therapy to a buprenorphine medication program and voucher-based motivational incentives.. A block-randomized, unblinded, parallel, 12-week treatment trial was conducted with 170 opioid-dependent adult patients (mean age = 34.3 years; 54.1% male; 95.3% White). Participants received an Internet-based community reinforcement approach intervention plus contingency management (CRA+) and buprenorphine or contingency management alone (CM-alone) plus buprenorphine. The primary outcomes, measured over the course of treatment, were longest continuous abstinence, total abstinence, and days retained in treatment.. Compared to those receiving CM-alone, CRA+ recipients exhibited, on average, 9.7 total days more of abstinence (95% confidence interval [CI = 2.3, 17.2]) and had a reduced hazard of dropping out of treatment (hazard ratio = 0.47; 95% CI [0.26, 0.85]). Prior treatment for opioid dependence significantly moderated the additional improvement of CRA+ for longest continuous days of abstinence.. These results provide further evidence that an Internet-based CRA+ treatment is efficacious and adds clinical benefits to a contingency management/medication based program for opioid dependence.

Topics: Adult; Aged; Analgesics, Opioid; Buprenorphine; Cognitive Behavioral Therapy; Combined Modality Therapy; Female; Humans; Internet; Male; Middle Aged; Motivation; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Reinforcement, Psychology; Residence Characteristics; Treatment Outcome

Buprenorphine opioid agonist treatment (OAT) has established efficacy for treating opioid dependency among persons seeking addiction treatment. However, effectiveness for out-of-treatment, hospitalized patients is not known.. To determine whether buprenorphine administration during medical hospitalization and linkage to office-based buprenorphine OAT after discharge increase entry into office-based OAT, increase sustained engagement in OAT, and decrease illicit opioid use at 6 months after hospitalization.. From August 1, 2009, through October 31, 2012, a total of 663 hospitalized, opioid-dependent patients in a general medical hospital were identified. Of these, 369 did not meet eligibility criteria. A total of 145 eligible patients consented to participation in the randomized clinical trial. Of these, 139 completed the baseline interview and were assigned to the detoxification (n = 67) or linkage (n = 72) group.. Five-day buprenorphine detoxification protocol or buprenorphine induction, intrahospital dose stabilization, and postdischarge transition to maintenance buprenorphine OAT affiliated with the hospital's primary care clinic (linkage).. Entry and sustained engagement with buprenorphine OAT at 1, 3, and 6 months (medical record verified) and prior 30-day use of illicit opioids (self-report).. During follow-up, linkage participants were more likely to enter buprenorphine OAT than those in the detoxification group (52 [72.2%] vs 8 [11.9%], P < .001). At 6 months, 12 linkage participants (16.7%) and 2 detoxification participants (3.0%) were receiving buprenorphine OAT (P = .007). Compared with those in the detoxification group, participants randomized to the linkage group reported less illicit opioid use in the 30 days before the 6-month interview (incidence rate ratio, 0.60; 95% CI, 0.46-0.73; P < .01) in an intent-to-treat analysis.. Compared with an inpatient detoxification protocol, initiation of and linkage to buprenorphine treatment is an effective means for engaging medically hospitalized patients who are not seeking addiction treatment and reduces illicit opioid use 6 months after hospitalization. However, maintaining engagement in treatment remains a challenge.. clinicaltrials.gov Identifier: NCT00987961.

Topics: Adult; Ambulatory Care; Buprenorphine; Female; Hospitalization; Humans; Male; Middle Aged; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Discharge; Treatment Outcome

In recent years, the U.S. has experienced a significant increase in the prevalence of pregnant opioid-dependent women and of neonatal abstinence syndrome (NAS), which is caused by withdrawal from in-utero drug exposure. While methadone-maintenance currently is the standard of care for opioid dependence during pregnancy, research suggests that buprenorphine-maintenance may be associated with shorter infant hospital lengths of stay (LOS) relative to methadone-maintenance. There is no "gold standard" treatment for NAS but there is evidence that buprenorphine, relative to morphine or methadone, treatment may reduce LOS and length of treatment.. Point-of-care clinical trial (POCCT) designs, maximizing external validity while reducing cost and complexity associated with classic randomized clinical trials, were selected for two planned trials to compare methadone to buprenorphine treatment for opioid dependence during pregnancy and for NAS. This paper describes design considerations for the Medication-assisted treatment for Opioid-dependent expecting Mothers (MOMs; estimated N = 370) and Investigation of Narcotics for Ameliorating Neonatal abstinence syndrome on Time in hospital (INFANTs; estimated N = 284) POCCTs, both of which are randomized, intent-to-treat, two-group trials. Outcomes would be obtained from participants' electronic health record at three participating hospitals. Additionally, a subset of infants in the INFANTs POCCT would be from mothers in the MOMs POCCT and, thus, potential interaction between medication treatment of mother and infant could be evaluated.. This pair of planned POCCTs would evaluate the comparative effectiveness of treatments for opioid dependence during pregnancy and for NAS. The results could have a significant impact on practice.

Topics: Adult; Birth Weight; Buprenorphine; Female; Humans; Infant, Newborn; Length of Stay; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Research Design

The present analysis describes the longitudinal change in buprenorphine treatment outcome. It also examines several participant characteristics to predict response to buprenorphine.. Participants (n=501, age>15 years) received buprenorphine/naloxone treatment for 4 weeks, and then were randomly assigned to undergo dose tapering over either 7 days or 28 days. An empirical model was developed to describe the longitudinal changes in treatment outcome. Several patient characteristics were also examined as possible factors influencing treatment outcome.. We have developed a model that captures the general behavior of the longitudinal change in the probability of having an opioid-negative urine sample following buprenorphine treatment. The model captures both the initial increase (i. e., initial response) and the subsequent decrease (i. e., relapse to opioid) in the likelihood of providing an opioid-negative urine sample. Characteristics associated with successful buprenorphine treatment outcome include: having a negative urine test for drugs, having alcohol problems [assessed using alcohol domain of addiction severity index (ASI-alcohol)] at screening, being older, and receiving low cumulative buprenorphine dose. However, ASI-alcohol values were generally low which make the application of the proposed alcohol effect for patients with more severe alcohol problems questionable.. A novel approach for analyzing buprenorphine treatment outcome is presented in this manuscript. This approach describes the longitudinal change in the probability of providing an opioid-free urine sample instead of considering opioid use outcome at a single time point. Additionally, this model successfully describes relapse to opioid. Finally, several patient characteristics are identified as predictors of treatment outcome.

Topics: Adolescent; Adult; Age Factors; Aged; Alcoholism; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Longitudinal Studies; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Severity of Illness Index; Substance Abuse Detection; Treatment Outcome; Young Adult

Prescription opioid dependence is increasing and creates a significant public health burden, but primary care physicians lack evidence-based guidelines to decide between tapering doses followed by discontinuation of buprenorphine hydrochloride and naloxone hydrochloride therapy (hereinafter referred to as buprenorphine therapy) or ongoing maintenance therapy.. To determine the efficacy of buprenorphine taper vs ongoing maintenance therapy in primary care-based treatment for prescription opioid dependence.. We conducted a 14-week randomized clinical trial that enrolled 113 patients with prescription opioid dependence from February 17, 2009, through February 1, 2013, in a single primary care site.. Patients were randomized to buprenorphine taper (taper condition) or ongoing buprenorphine maintenance therapy (maintenance condition). The buprenorphine taper was initiated after 6 weeks of stabilization, lasted for 3 weeks, and included medications for opioid withdrawal, after which patients were offered naltrexone treatment. The maintenance group received ongoing buprenorphine therapy. All patients received physician and nurse support and drug counseling.. Illicit opioid use via results of urinanalysis and patient report, treatment retention, and reinitiation of buprenorphine therapy (taper group only).. During the trial, the mean percentage of urine samples negative for opioids was lower for patients in the taper group (35.2% [95% CI, 26.2%-44.2%]) compared with those in the maintenance group (53.2% [95% CI, 44.3%-62.0%]). Patients in the taper group reported more days per week of illicit opioid use than those in the maintenance group once they were no longer receiving buprenorphine (mean use, 1.27 [95% CI, 0.60-1.94] vs 0.47 [95% CI, 0.19-0.74] days). Patients in the taper group had fewer maximum consecutive weeks of opioid abstinence compared with those in the maintenance group (mean abstinence, 2.70 [95% CI, 1.72-3.75] vs 5.20 [95% CI, 4.16-6.20] weeks). Patients in the taper group were less likely to complete the trial (6 of 57 [11%] vs 37 of 56 [66%]; P < .001). Sixteen patients in the taper group reinitiated buprenorphine treatment after the taper owing to relapse.. Tapering is less efficacious than ongoing maintenance treatment in patients with prescription opioid dependence who receive buprenorphine therapy in primary care.. clinicaltrials.gov Identifier: NCT00555425.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Drug Administration Schedule; Female; Humans; Male; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Prescription Drugs; Primary Health Care; Recurrence; Substance Withdrawal Syndrome; Treatment Outcome; Urinalysis

We aim to examine predictors of opiate abstinence status 3 months after the end of buprenorphine/naloxone treatment for opioid-dependent participants.. Participants (n= 516, age > 15 years) received buprenorphine/ naloxone treatment for 4 weeks and then randomly assigned to undergo dose tapering over either 7 days or 28 days. Bivariate analysis was performed to identify possible predictors of successful opiate abstinence outome (p-value < 0.10). Logistic regression analysis with backward stepwise selection was, then, performed to produce final model containing independent predictors at p-value < 0.05.. Bivariate analysis identified several possible predictors including: opioid and drug urine tests result at the end taper; employment status, family problems, and alcohol use domains of addiction severity index (ASI) score; and clinical opiate withdrawal scale (COWS) at the end of stabilization. Final predictor list identified by logistic regression include: ASI score for family and alcohol problems, COWS at the end of stabilization and opiate urine test at the end of taper.. Participants presenting with a negative urine test for opiate, more severe alcohol, more severe family problems, or more symptoms of opiate withdrawal at the end of stabilization were more likely to have a successful opiate abstinence.

Topics: Adolescent; Adult; Aged; Analgesics, Opioid; Buprenorphine; Female; Humans; Logistic Models; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Substance Withdrawal Syndrome; Treatment Outcome; Young Adult

Providing unobserved opioid substitution treatment (OST) safely is a major challenge. This study examined whether electronic medicine dispensers (EMDs) can reduce diversion of take-home buprenorphine-naloxone (BNX) in a medium-sized Finnish city. All BNX treated OST patients in Kuopio received their take-home BNX in EMDs for 4months. EMDs' effect on diversion was investigated using questionnaires completed by patients (n=37) and treatment staff (n=19), by survey at the local needle exchange service and by systematic review of drug screen data from the Kuopio University Hospital. The majority of patients (n=21, 68%) and treatment staff (n=11, 58%) preferred to use EMDs for the safe storage of tablets. Five patients (16%) declared that EMDs had prevented them from diverting BNX. However, EMDs had no detectable effect on the availability or origin of illegal BNX or on the hospital-treated buprenorphine-related health problems. EMDs may improve the safety of storage of take-home BNX, but their ability to prevent diversion needs further research.

Topics: Adult; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Crime; Drug Storage; Equipment Design; Female; Finland; Humans; Male; Naloxone; Needle-Exchange Programs; Opiate Substitution Treatment; Opioid-Related Disorders; Substance Abuse Detection; Surveys and Questionnaires; Tablets; Treatment Outcome; Young Adult

Patients with opioid addiction who receive prescription opioids for treatment of nonmalignant chronic pain present a therapeutic challenge. Fifty-four participants with chronic pain and opioid addiction were randomized to receive methadone or buprenorphine/naloxone. At the 6-month follow-up examination, 26 (48.1%) participants who remained in the study noted a 12.75% reduction in pain (P = 0.043), and no participants in the methadone group compared to 5 in the buprenorphine group reported illicit opioid use (P = 0.039). Other differences between the two conditions were not found. Long-term, low-dose methadone or buprenorphine/naloxone treatment produced analgesia in participants with chronic pain and opioid addiction.

Topics: Administration, Sublingual; Analgesics, Opioid; Analysis of Variance; Buprenorphine; Chronic Pain; Drug Combinations; Female; Humans; Male; Methadone; Middle Aged; Naloxone; Opioid-Related Disorders; Prescription Drug Misuse; Severity of Illness Index; Substance Abuse Detection; Treatment Outcome

Cannabis use is common among opioid-dependent patients, but studies of its association with treatment outcome are mixed. In this secondary analysis, the association of cannabis use with opioid treatment outcome is assessed.. In the main study, participants (n=152) aged 15-21 years were randomized to receive psychosocial treatments and either a 12-week course of buprenorphine-naloxone with a dose taper to zero in weeks 9-12, or a 2-week detoxification with buprenorphine-naloxone. Drug use was assessed by self-report and urine drug screen at baseline and during study weeks 1-12. The association between cannabis and opioid use at weeks 4, 8, and 12 was examined using logistic regression models.. Participants reported a median of 3.0 days (range=0-30) cannabis use in the past month; half (50.3%; n=77) reported occasional use, one-third reported no use (33.1%; n=50), and one-sixth reported daily cannabis use (16.6%; n=25). Median lifetime cannabis use was 4.0 years (range=0-11) and median age of initiation of use was 15.0 years (range 9-21). Neither past cannabis use (age of initiation and use in the month prior to baseline) nor concurrent use was associated with level of opioid use.. Overall, cannabis use had no association with opioid use over 12 weeks in this sample of opioid-dependent youth. While cannabis use remains potentially harmful, it was not a predictor of poor opioid treatment outcome.

Topics: Adult; Buprenorphine; Data Interpretation, Statistical; Female; Humans; Logistic Models; Male; Marijuana Abuse; Naloxone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Substance Abuse Detection; Treatment Outcome; Young Adult

Methadone has been the most commonly used pharmacotherapy for the treatment of opioid dependence in U.S. public sector treatment, but availability of buprenorphine as an alternative medication continues to increase. Drawing data from two community-based clinical trials that were conducted nearly contemporaneously, this study examined retention in methadone versus buprenorphine treatment over 6 months among urban African Americans receiving treatment in one of four publicly-funded programs (N=478; 178 methadone; 300 buprenorphine). Adjusting for confounds related to medication selection, survival analysis revealed that buprenorphine patients are at substantially higher risk of dropout compared to methadone patients (HR=2.43; p<.001). Buprenorphine's retention disadvantage appears to be concentrated in the earlier phases of treatment (approximately the first 50 days), after which risk of subsequent dropout becomes similar for the two medications. These findings confirm a retention disparity between methadone and buprenorphine in this population, and suggest potential avenues for future research to enhance retention in buprenorphine treatment.

Topics: Adult; Black or African American; Buprenorphine; Female; Humans; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Compliance; Patient Dropouts; Substance Abuse Treatment Centers; United States; Urban Population

Psychological improvements in patients with substance use disorders have been reported after neurofeedback treatment. However, neurofeedback has not been commonly accepted as a treatment for substance dependence. This study was carried out to examine the effectiveness of this therapeutic method for opiate dependence disorder. The specific aim was to investigate whether treatment leads to any changes in mental health and substance craving. In this experimental study with a pre-post test design, 20 opiate dependent patients undergoing Methadone or Buprenorphine maintenance treatment were examined and matched and randomized into two groups. While both experimental and control groups received their usual maintenance treatment, the experimental group received 30 sessions of neurofeedback treatment in addition. The neurofeedback treatment consisted of sensory motor rhythm training on Cz, followed by an alpha-theta protocol on Pz. Data from the general health questionnaire and a heroin craving questionnaire were collected before and after treatment. Multivariate analysis of covariance showed that the experimental group achieved improvement in somatic symptoms, depression, and total score in general mental health; and in anticipation of positive outcome, desire to use opioid, and relief from withdrawal of craving in comparison with the control group. The study supports the effectiveness of neurofeedback training as a therapeutic method in opiate dependence disorder, in supplement to pharmacotherapy.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Humans; Male; Mental Health; Methadone; Middle Aged; Motivation; Neurofeedback; Opiate Substitution Treatment; Opioid-Related Disorders; Surveys and Questionnaires; Treatment Outcome

Although buprenorphine and methadone are both effective treatments for opioid dependence, their efficacy can vary significantly among patients. Genetic differences may explain some of the variability in treatment outcome. Understanding the interactions between genetic background and pharmacotherapy may result in more informed treatment decisions. This study is a pharmacogenetic analysis of the effects of genetic variants in OPRD1, the gene encoding the δ-opioid receptor, on the prevalence of opioid-positive urine tests in African-Americans (n=77) or European-Americans (n=566) undergoing treatment for opioid dependence. Patients were randomly assigned to treatment with either methadone or buprenorphine/naloxone (Suboxone) over a 24-week open-label clinical trial, in which illicit opioid use was measured by weekly urinalysis. In African-Americans, the intronic SNP rs678849 predicted treatment outcome for both medications. Methadone patients with the CC genotype were less likely to have opioid-positive urine tests than those in the combined CT and TT genotypes group (relative risk (RR)=0.52, 95% confidence interval (CI)=0.44-0.60, p=0.001). In the buprenorphine treatment group, however, individuals with the CC genotype were more likely to have positive opioid drug screens than individuals in the combined CT and TT genotypes group (RR=2.17, 95% CI=1.95-2.68, p=0.008). These findings indicate that the genotype at rs678849 predicts African-American patient response to two common treatments for opioid dependence, suggesting that matching patients to treatment type based on the genotype at this locus may improve overall treatment efficacy. This observation requires confirmation in an independent population.

Topics: Adult; Analgesics, Opioid; Black or African American; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Female; Genotype; Humans; Introns; Male; Methadone; Middle Aged; Naloxone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Polymorphism, Single Nucleotide; Receptors, Opioid, delta; Treatment Outcome; White People

More effective methods are needed to implement evidence-based findings into practice. The Advancing Recovery Framework offers a multi-level approach to evidence-based practice implementation by aligning purchasing and regulatory policies at the payer level with organizational change strategies at the organizational level.. The Advancing Recovery Buprenorphine Implementation Study is a cluster-randomized controlled trial designed to increase use of the evidence-based practice buprenorphine medication to treat opiate addiction. Ohio Alcohol, Drug Addiction, and Mental Health Services Boards (ADAMHS), who are payers, and their addiction treatment organizations were recruited for a trial to assess the effects of payer and treatment organization changes (using the Advancing Recovery Framework) versus treatment organization changes alone on the use of buprenorphine. A matched-pair randomization, based on county characteristics, was applied, resulting in seven county ADAMHS boards and twenty-five treatment organizations in each arm. Opioid dependent patients are nested within cluster (treatment organization), and treatment organization clusters are nested within ADAMHS county board. The primary outcome is the percentage of individuals with an opioid dependence diagnosis who use buprenorphine during the 24-month intervention period and the 12-month sustainability period. The trial is currently in the baseline data collection stage.. Although addiction treatment providers are under increasing pressure to implement evidence-based practices that have been proven to improve patient outcomes, adoption of these practices lags, compared to other areas of healthcare. Reasons frequently cited for the slow adoption of EBPs in addiction treatment include, regulatory issues, staff, or client resistance and lack of resources. Yet the way addiction treatment is funded, the payer's role-has not received a lot of attention in research on EBP adoption.This research is unique because it investigates the role of payers in evidence-based practice implementation using a randomized controlled design instead of case examples. The testing of the Advancing Recovery Framework is designed to broaden the understanding of the impact payers have on evidence-based practice (EBP) adoption.. http://NCT01702142 (ClinicalTrials.gov registry, USA).

Topics: Buprenorphine; Clinical Protocols; Cluster Analysis; Delivery of Health Care; Diffusion of Innovation; Evidence-Based Medicine; Humans; Narcotic Antagonists; Nurses; Ohio; Opiate Substitution Treatment; Opioid-Related Disorders; Organizational Innovation; Physicians; Reimbursement Mechanisms; Sample Size

The Controlled Substances Act requires physicians in the United States to provide or refer to behavioral treatment when treating opioid-dependent individuals with buprenorphine; however, no research has examined the combination of buprenorphine with different types of behavioral treatments. This randomized controlled trial compared the effectiveness of four behavioral treatment conditions provided with buprenorphine and medical management (MM) for the treatment of opioid dependence.. After a 2-week buprenorphine induction/stabilization phase, participants were randomized to one of four behavioral treatment conditions provided for 16 weeks: cognitive behavioral therapy (CBT = 53); contingency management (CM = 49); both CBT and CM (CBT + CM = 49); and no additional behavioral treatment (NT = 51).. Study activities occurred at an out-patient clinical research center in Los Angeles, California, USA.. Included were 202 male and female opioid-dependent participants.. Primary outcome was opioid use, measured as a proportion of opioid-negative urine results over the number of tests possible. Secondary outcomes include retention, withdrawal symptoms, craving, other drug use and adverse events.. No group differences in opioid use were found for the behavioral treatment phase (χ2  = 1.25, P = 0.75), for a second medication-only treatment phase, or at weeks 40 and 52 follow-ups. Analyses revealed no differences across groups for any secondary outcome.. There remains no clear evidence that cognitive behavioural therapy and contingency management reduce opiate use when added to buprenorphine and medical management in opiate users seeking treatment.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Cognitive Behavioral Therapy; Combined Modality Therapy; Female; Humans; Los Angeles; Male; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Outpatients; Substance Withdrawal Syndrome; Treatment Outcome; Young Adult

The objective of this secondary analysis was to explore differences in baseline clinical characteristics and opioid replacement therapy treatment outcomes by type (heroin, opioid analgesic [OA], or combined [heroin and OA]) and route (injector or non-injector) of opioid use.. A total of 1,269 participants (32.2% female) were randomized to receive one of two study medications (methadone or buprenorphine/naloxone [BUP]). Of these, 731 participants completed the 24-week active medication phase. Treatment outcomes were opioid use during the final 30 days of treatment (among treatment completers) and treatment attrition.. Non-opioid substance dependence diagnoses and injecting differentiated heroin and combined users from OA users. Non-opioid substance dependence diagnoses and greater heroin use differentiated injectors from non-injectors. Further, injectors were more likely to be using at end of treatment compared with non-injectors. OA users were more likely to complete treatment compared with heroin users and combined users. Non-injectors were more likely than injectors to complete treatment. There were no interactions between type of opioid used or injection status and treatment assignment (methadone or BUP) on either opioid use or treatment attrition.. Findings indicate that substance use severity differentiates heroin users from OA users and injectors from non-injectors. Irrespective of medication, heroin use and injecting are associated with treatment attrition and opioid misuse during treatment. These results have particular clinical interest, as there is no evidence of superiority of BUP over methadone for treating OA users versus heroin users.

Topics: Adult; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Female; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Severity of Illness Index; Substance Abuse, Intravenous; Treatment Outcome; Young Adult

Objective measures of drug use are very important in treatment outcome studies of persons with substance use disorders, but obtaining and interpreting them can be challenging and not always practical. Thus, it is important to determine if, and when, drug-use self-reports are valid. To this end we explored the relationships between urine drug screen results and self-reported substance use among adolescents and young adults with opioid dependence participating in a clinical trial of buprenorphine-naloxone. In this study, 152 individuals seeking treatment for opioid dependence were randomized to a 2-week detoxification with buprenorphine-naloxone (DETOX) or 12weeks of buprenorphine-naloxone (BUP), each with weekly individual and group drug counseling. Urine drug screens and self-reported frequency of drug use were obtained weekly, and patients were paid $5 for completing weekly assessments. At weeks 4, 8, and 12, more extensive assessments were done, and participants were reimbursed $75. Self-report data were dichotomized (positive vs. negative), and for each major drug class we computed the kappa statistic and the sensitivity, specificity, positive predictive value, and negative predictive value of self-report using urine drug screens as the "gold standard". Generalized linear mixed models were used to explore the effect of treatment group assignment, compensation amounts, and participant characteristics on self-report. In general, findings supported the validity of self-reported drug use. However, those in the BUP group were more likely to under-report cocaine and opioid use. Therefore, if used alone, self-report would have magnified the treatment effect of the BUP condition.

Topics: Adolescent; Buprenorphine; Counseling; Female; Humans; Linear Models; Male; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Research Subjects; Self Report; Sensitivity and Specificity; Substance Abuse Detection; Substance-Related Disorders; Treatment Outcome; Young Adult

This double-blind, placebo-controlled study investigated the effects of oral morphine (0, 45, 135 mg/70 kg) and oral oxycodone (0, 15, 45 mg/70 kg) on buprenorphine-maintained opioid addicts. As a 3: 1 morphine : oxycodone oral dose ratio yielded equivalent subjective and physiological effects in nondependent individuals, this ratio was used in the present study. Two self-administration laboratory procedures - that is, a drug versus money and a drug versus drug procedure - were assessed. Study participants (N=12) lived in the hospital and were maintained on 4 mg/day sublingual buprenorphine. When participants chose between drug and money, money was preferred over all drug doses; only high-dose oxycodone was self-administered more than placebo. When participants chose between drug and drug, both drugs were chosen more than placebo, high doses of each drug were chosen over low doses, and high-dose oxycodone was preferred over high-dose morphine. The subjective, performance-impairing, and miotic effects of high-dose oxycodone were generally greater than those of high-dose morphine. The study demonstrated that a 3: 1 oral dose ratio of morphine : oxycodone was not equipotent in buprenorphine-dependent individuals. Both self-administration procedures were effective for assessing the relative reinforcing effects of drugs; preference for one procedure should be driven by the specific research question of interest.

Topics: Administration, Oral; Adult; Analgesics, Opioid; Buprenorphine; Choice Behavior; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; In Vitro Techniques; Male; Middle Aged; Morphine; Narcotic Antagonists; Opioid-Related Disorders; Oxycodone; Pain Measurement; Pupil; Reward; Self Administration; Surveys and Questionnaires; Time Factors; Token Economy; Young Adult

This pilot study examined the efficacy of the N-type calcium channel blocker gabapentin to improve outcomes during a brief detoxification protocol with buprenorphine. Treatment-seeking opioid-dependent individuals were enrolled in a 5-week, double-blind, placebo-controlled trial examining the effects of gabapentin during a 10-day outpatient detoxification from buprenorphine. Participants were inducted onto buprenorphine sublingual tablets during Week 1, were randomized and inducted onto gabapentin or placebo during Week 2, underwent a 10-day buprenorphine taper during Weeks 3 and 4, and then were tapered off gabapentin/placebo during Week 5. Assessments included thrice-weekly opioid withdrawal scales, vitals, and urine drug screens. Twenty-four individuals (13 male; 17 Caucasian, 3 African American, 4 Latino; mean age 29.7 years) participated in the detoxification portion of the study (gabapentin, n = 11; placebo, n = 13). Baseline characteristics did not differ significantly between groups. Self-reported and observer-rated opioid withdrawal ratings were relatively low and did not differ between groups during the buprenorphine taper. Urine results showed a Drug × Time interaction, such that the probability of opioid-positive urines significantly decreased over time in the gabapentin versus placebo groups during Weeks 3 and 4 (OR = 0.73, p = .004). These results suggest that gabapentin reduces opioid use during a 10-day buprenorphine detoxification procedure.

Topics: Adult; Amines; Buprenorphine; Cyclohexanecarboxylic Acids; Diagnostic and Statistical Manual of Mental Disorders; Directly Observed Therapy; Double-Blind Method; Excitatory Amino Acid Antagonists; Female; Gabapentin; gamma-Aminobutyric Acid; Humans; Induction Chemotherapy; Maintenance Chemotherapy; Male; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Dropouts; Pilot Projects; Secondary Prevention; Severity of Illness Index; Substance Withdrawal Syndrome

Determine the extent to which buprenorphine injectors continue treatment with buprenorphine-naloxone or methadone, and the impact of these treatments on substance use and HIV risk in the Republic of Georgia.. Randomized controlled 12-week trial of daily-observed methadone or buprenorphine-naloxone followed by a dose taper, referral to ongoing treatment, and follow-up at week 20 at the Uranti Clinic in Tbilisi, Republic of Georgia. Eighty consenting treatment-seeking individuals (40/group) aged 25 and above who met ICD-10 criteria for opioid dependence with physiologic features and reported injecting buprenorphine 10 or more times in the past 30 days. Opioid use according to urine tests and self-reports, treatment retention, and HIV risk behavior as determined by the Risk Assessment Battery.. Mean age of participants was 33.7 (SD5.7), 4 were female, mean history of opioid injection use was 5.8 years (SD4.6), none were HIV+ at intake or at the 12-week assessment and 73.4% were HCV+. Sixty-eight participants (85%) completed the 12-week medication phase (33 from methadone and 35 from buprenorphine/naloxone group); 37 (46%) were in treatment at the 20-week follow-up (21 from methadone and 16 from the buprenorphine/naloxone group). In both study arms, treatment resulted in a marked reduction in unprescribed buprenorphine, other opioid use, and HIV injecting risk behavior with no clinically significant differences between the two treatment arms.. Daily observed methadone or buprenorphine-naloxone are effective treatments for non-medical buprenorphine and other opioid use in the Republic of Georgia and likely to be useful for preventing HIV infection.

Topics: Adult; Buprenorphine; Female; Georgia (Republic); Hepatitis C; HIV Infections; Humans; Male; Methadone; Narcotics; Needle Sharing; Opiate Substitution Treatment; Opioid-Related Disorders; Risk-Taking; Substance Abuse Detection; Substance Abuse, Intravenous; Treatment Outcome

To evaluate the safety and efficacy of buprenorphine implants (BI) versus placebo implants (PI) for the treatment of opioid dependence. A secondary aim compared BI to open-label sublingual buprenorphine/naloxone tablets (BNX).. Randomized, double-blind, placebo-controlled trial. Subjects received either four buprenorphine implants (80 mg/implant) (n = 114), four placebo implants (n = 54) or open-label BNX (12-16 mg/day) (n = 119).. Twenty addiction treatment centers.. Adult out-patients (ages 18-65) with DSM-IV-TR opioid dependence.. The primary efficacy end-point was the percentage of urine samples negative for opioids collected from weeks 1 to 24, examined as a cumulative distribution function (CDF).. The BI CDF was significantly different from placebo (P < 0.0001). Mean [95% confidence interval (CI)] proportions of urines negative for opioids were: BI = 31.2% (25.3, 37.1) and PI = 13.4% (8.3, 18.6). BI subjects had a higher study completion rate relative to placebo (64 versus 26%, P < 0.0001), lower clinician-rated (P < 0.0001) and patient-rated (P < 0.0001) withdrawal, lower patient-ratings of craving (P < 0.0001) and better subjects' (P = 0.031) and clinicians' (P = 0.022) global ratings of improvement. BI also resulted in significantly lower cocaine use (P = 0.0016). Minor implant-site reactions were comparable in the buprenorphine [27.2% (31 of 114)] and placebo groups [25.9% (14 of 54)]. BI were non-inferior to BNX on percentage of urines negative for opioids [mean (95% CI) = 33.5 (27.3, 39.6); 95% CI for the difference of proportions = (-10.7, 6.2)].. Compared with placebo, buprenorphine implants result in significantly less frequent opioid use and are non-inferior to sublingual buprenorphine/naloxone tablets.

Topics: Administration, Sublingual; Adolescent; Adult; Aged; Buprenorphine; Double-Blind Method; Drug Implants; Female; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Tablets; Treatment Outcome; Young Adult

The high rates of HIV and Hepatitis C (HCV) infection among opioid abusers is a serious public health problem, and efforts to enhance knowledge regarding risks for HIV/hepatitis infection in this population are important. Abuse of prescription opioids (POs), in particular, has increased substantially in the past decade and is associated with increasing rates of injection drug use and HCV infection.. This study describes the effects of a brief HIV/HCV educational intervention delivered in the context of a larger randomized, double-blind clinical trial evaluating the relative efficacy of 1-, 2-, and 4-week outpatient buprenorphine tapers and subsequent oral naltrexone maintenance for treating PO dependence. HIV- and HCV-related knowledge and risk behaviors were characterized pre- and post-intervention in 54 primary PO abusers.. The educational intervention was associated with significant improvements in HIV (p<.001) and HCV (p<.001) knowledge. Significant improvements (p<.001) were observed on all three domains of the HIV questionnaire (i.e., general knowledge, sexual risk behaviors, drug risk behaviors) and on 21 and 11 individual items on the HIV and HCV questionnaires, respectively. Self-reported likelihood of using a condom also increased significantly (p<.05) from pre- to post-intervention. No additional changes in self-reported risk behaviors were observed.. These results suggest that a brief, easy-to-administer intervention is associated with substantial gains in HIV and HCV knowledge among PO abusers and represents the necessary first step toward the dissemination of a structured prevention HIV and HCV intervention for PO abusers.

Topics: Adolescent; Adult; Buprenorphine; Data Interpretation, Statistical; Diagnostic and Statistical Manual of Mental Disorders; Female; Health Education; Health Knowledge, Attitudes, Practice; Hepatitis C; HIV Infections; Humans; Male; Narcotics; Opioid-Related Disorders; Prescription Drug Misuse; Risk Assessment; Risk-Taking; Sexually Transmitted Diseases; Surveys and Questionnaires; Unsafe Sex; Young Adult

Although abuse of prescription opioids (POs) is a significant public health problem, few experimental studies have investigated the treatment needs of this growing population.. To evaluate, following brief stabilization with a combination of buprenorphine hydrochloride and naloxone hydrochloride dihydrate, the relative efficacy of 1-, 2-, and 4-week buprenorphine tapering regimens and subsequent naltrexone hydrochloride therapy in PO-dependent outpatients.. A double-blind, 12-week randomized clinical trial was conducted in an outpatient research clinic. Following a brief period of buprenorphine stabilization, 70 PO-dependent adults were randomized to receive 1-, 2-, or 4-week tapers followed by naltrexone therapy.. During phase 1 (weeks 1-5 after randomization), participants visited the clinic daily; during phase 2 (weeks 6-12), visits were reduced to thrice weekly. Participants received behavioral therapy and urine toxicology testing throughout the trial.. The percentage of participants negative for illicit opioid use, retention, naltrexone ingestion, and favorable treatment response (ie, retained in treatment, opioid abstinent, and receiving naltrexone at the end of the study).. Opioid abstinence at the end of phase 1 was greater in the 4-week compared with the 2- and 1-week taper conditions (P = .02), with 63% (n = 14), 29% (n = 7), and 29% (n = 7) of participants abstinent in the 4-, 2-, and 1-week conditions, respectively. Abstinence at the end of phase 2 was also greater in the 4-week compared with the 2- and 1-week conditions (P = .03), with 50% (n = 11), 16% (n = 4), and 20% (n = 5) of participants abstinent in the 4-, 2-, and 1-week conditions, respectively. There were more treatment responders in the 4-week condition (P = .03), with 50% (n = 11), 17% (n = 4), and 21% (n = 5) of participants in the 4-, 2-, and 1-week groups considered responders at the end of treatment, respectively. Retention and naltrexone ingestion also were superior in the 4-week vs briefer tapers (both P = .04). Experimental condition (ie, taper duration) was the strongest predictor of treatment response, followed by buprenorphine stabilization dose.. This study represents a rigorous experimental evaluation of outpatient buprenorphine stabilization, brief taper, and naltrexone maintenance for treatment of PO dependence. Results suggest that a meaningful subset of PO-dependent outpatients may respond positively to a 4-week taper plus naltrexone maintenance intervention.

Topics: Adult; Buprenorphine; Cognitive Behavioral Therapy; Combined Modality Therapy; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Naloxone; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Psychiatric Status Rating Scales; Severity of Illness Index; Time Factors; Treatment Outcome; Young Adult

The focus of drug policy in the UK has shifted markedly in the past 5 years to move beyond merely emphasising drug abstinence towards maximising individuals' opportunities for recovery. The UK government continues to recognise the prescribing of narcotic medications indicated for opiate dependence as a key element of these individuals' recovery journey. This article describes a small, naturalistic comparison of the efficacy of the two most commonly prescribed opiate substitute medications in the UK--methadone hydrochloride (methadone oral solution) and Suboxone (buprenorphine-naloxone sublingual tablets)--for reducing current heroin users' (n = 34) days of heroin use, and preventing short-term abstainers (n = 37) from relapsing to regular heroin use. All patients had been prescribed either methadone or Suboxone for maintenance for 6 months prior to intake. Results showed that when controlling for a number of patient-level covariates, both methadone and Suboxone significantly reduced current users' days of heroin use between the 90 days prior to intake and at the 8-month follow-up, with Suboxone yielding a significantly larger magnitude reduction in heroin use days than methadone. Methadone and Suboxone were highly and equally effective for preventing relapse to regular heroin use, with all but 3 of 37 (91.9%) patients who were abstinent at intake reporting past 90-day point prevalence heroin abstinence at the 8-month follow-up. Overall, prescribing methadone or Suboxone for eight continuous months was highly effective for initiating abstinence from heroin use, and for converting short-term abstinence to long-term abstinence. However, the study design, which was based on a relatively small sample size and was not able randomise patients to medication and so could not control for the effects of potential prognostic factors inherent within each patient group, means that these conclusions can only be made tentatively. These positive but preliminary indications of the comparative efficacy of methadone and Suboxone for treating opiate dependence now require replication in a well-powered, randomised controlled trial.

Topics: Adult; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Female; Follow-Up Studies; Health Policy; Heroin Dependence; Humans; Male; Methadone; Naloxone; Opiate Substitution Treatment; Opioid-Related Disorders; Recurrence; Time Factors; Treatment Outcome; United Kingdom

Buprenorphine/naloxone (BUP) and methadone (MET) are efficacious treatments for opioid dependence, although concerns about a link between BUP and drug-induced hepatitis have been raised. This study compares the effects of BUP and MET on liver health in opioid-dependent participants.. This was a randomized controlled trial of 1269 opioid-dependent participants seeking treatment at 8 federally licensed opioid treatment programs and followed for up to 32 weeks between May 2006 and August 2010; 731 participants met "evaluable" criteria defined as completing 24 weeks of medication and providing at least 4 blood samples for transaminase testing. Participants were randomly assigned to receive BUP or MET for 24 weeks. Shift table analysis determined how many evaluable participants moved between categories of low and elevated transaminase levels. Predictors of moving from low to high transaminase levels were identified.. Changes in transaminase levels did not differ by medication condition. Baseline infection with hepatitis C or B was the only significant predictor of moving from low to elevated transaminase levels; 9 BUP and 15 MET participants showed extreme liver test elevations and were more likely than those without extreme elevations to have seroconverted to both hepatitis B and C during the study, or to use illicit drugs during the first 8 weeks of treatment. MET participants were retained longer in treatment than BUP participants.. This study demonstrated no evidence of liver damage during the initial 6 months of treatment in either condition. Physicians can prescribe either medication without major concern for liver injury.

Topics: Adolescent; Adult; Buprenorphine; Chemical and Drug Induced Liver Injury; Drug Combinations; Female; Humans; Liver; Male; Methadone; Middle Aged; Naloxone; Opioid-Related Disorders; Transaminases; Treatment Outcome

Buprenorphine is increasingly being used in community-based treatment programs, but little is known about the optimal level of psychosocial counseling in these settings. The aim of this study was to compare the effectiveness of OP and IOP level counseling when provided as part of buprenorphine treatment for opioid-dependent African Americans.. Participants were African American men and women starting buprenorphine treatment at one of two community-based clinics (N=300). Participants were randomly assigned to OP or IOP. Measures at baseline, 3- and 6-month included the primary outcome of DSM-IV opioid and cocaine dependence criteria, as well as additional outcomes of illicit opioid and cocaine use (urine test and self-report), criminal activity, retention in treatment, Quality of Life, Addiction Severity Index composite scores, and HIV risk behaviors.. Participants assigned to OP received, on average, 3.67 (SD=1.30)h of counseling per active week in treatment. IOP participants received an average of 5.23 (SD=1.68)h of counseling per active week (less than the anticipated 9h per week of counseling). Both groups showed substantial improvement over a 6-month period on nearly all measures considered. There were no significant differences between groups in meeting diagnostic criteria for opioid (p=.67) or cocaine dependence (p=.63). There were no significant between group differences on any of the other outcomes. A secondary analysis restricting the sample to participants meeting DSM-IV criteria for baseline cocaine dependence also revealed no significant between-group differences (all ps>.05).. Buprenorphine patients receiving OP and IOP levels of care both show short-term improvements.

Topics: Ambulatory Care; Baltimore; Black or African American; Buprenorphine; Cocaine-Related Disorders; Counseling; Female; Humans; Male; Opiate Substitution Treatment; Opioid-Related Disorders

Using buprenorphine as a medication to treat opioid dependence is becoming more prevalent as illicit opiate use increases. Identifying the characteristics of opiate dependent individuals best suited to benefit from buprenorphine would improve guidelines for its administration. This study evaluates baseline and treatment participation variables for predicting positive response to short-term stabilization with buprenorphine. Data include demographic, drug use, and other variables collected from participants undergoing stabilization over a 4-week period before being tapered off buprenorphine in a short-term detoxification process. Outcome variables include opioid use and retention. Logistic regression results indicate several characteristics associated with opioid use at the end of the stabilization period. These include being older, having no criminal history, and less opiate use. Criminal activity and opioid use in the last 30 days were significantly associated with shorter treatment stays. The benefits of identifying individual characteristics that may predict treatment response are discussed.

Topics: Age Factors; Buprenorphine; Crime; Female; Humans; Logistic Models; Male; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Psychiatric Status Rating Scales; Substance Withdrawal Syndrome; Time Factors; Treatment Outcome

Effective medications to treat cocaine dependence have not been identified. Recent pharmacotherapy trials demonstrate the potential efficacy of buprenorphine (BUP) (alone or with naltrexone) for reducing cocaine use. The National Institute on Drug Abuse Clinical Trials Network (CTN) launched the Cocaine Use Reduction with Buprenorphine (CURB) investigation to examine the safety and efficacy of sublingual BUP (as Suboxone®) in the presence of extended-release injectable naltrexone (XR-NTX, as Vivitrol®) for the treatment of cocaine dependence. This paper describes the design and rationale for this study.. This multi-site, double-blind, placebo-controlled study will randomize 300 participants across 11 sites. Participants must meet the DSM-IV criteria for cocaine dependence and past or current opioid dependence or abuse. Participants are inducted onto XR-NTX after self-reporting at least 7 days of abstinence from opioids and tolerating a naloxone challenge followed by oral naltrexone and are then randomly assigned to one of three medication conditions (4 mg BUP, 16 mg BUP, or placebo) for 8 weeks. Participants receive a second injection of XR-NTX 4 weeks after the initial injection, and follow-up visits are scheduled at 1 and 3 months post-treatment. Participants receive weekly cognitive behavioral therapy (CBT). Recruitment commenced in September, 2011. Enrollment, active medication, and follow-up phases are ongoing, and recruitment is exceeding targeted enrollment rates.. This research using 2 medications will demonstrate whether BUP, administered in the presence of XR-NTX, reduces cocaine use in adults with cocaine dependence and opioid use disorders and will demonstrate if XR-NTX prevents development of physiologic dependence on BUP.

Topics: Administration, Sublingual; Adolescent; Adult; Aged; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cocaine-Related Disorders; Cognitive Behavioral Therapy; Combined Modality Therapy; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Naloxone; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Treatment Outcome; Young Adult

Lessons learned in research and treatment of opioid dependence demonstrate the need to include pregnant women in clinical trials.. Two double-blind, double-dummy, randomized controlled trials (Pilot study, European sample(†) of MOTHER-trial) comparing buprenorphine and methadone in opioid-dependent pregnant women were conducted. In both studies, participants received voucher-based incentives for attendance and completion of study assessments. In the MOTHER trial, participants additionally received escalating voucher incentives for drug-free urine samples. Neonatal abstinence syndrome was treated with oral morphine solution based on standardized modified Finnegan scores.. After a mean treatment period of 13.79 weeks in the Pilot study (PS, n = 18) and 20.78 weeks in the MOTHER-trial (MT, n = 41), respectively (p < 0.001), PS patients delivered at mean doses of 14.00 mg buprenorphine/52.50 mg methadone and MT participants at 13.44 mg buprenorphine/63.68 mg methadone. Nonsignificant differences regarding dropout rates were found (22% in PS versus 10% in MT), but dropout was significantly earlier in the MT (p = 0.013). Significantly higher rates of concomitant consumption of opioids and benzodiazepines occurred in the PS compared with the MT (p < 0.001), however, with no significant differences in neonatal data between both settings.. Early treatment enrolment combined with contingency management contributes to reduced illicit drug use throughout pregnancy, surprisingly without influencing neonatal outcome parameters.

Topics: Adolescent; Adult; Buprenorphine; Double-Blind Method; Evidence-Based Medicine; Female; Humans; Infant, Newborn; Learning; Methadone; Opioid-Related Disorders; Pilot Projects; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Young Adult

To determine the impact of cognitive behavioral therapy on outcomes in primary care, office-based buprenorphine/naloxone treatment of opioid dependence.. We conducted a 24-week randomized clinical trial in 141 opioid-dependent patients in a primary care clinic. Patients were randomized to physician management or physician management plus cognitive behavioral therapy. Physician management was brief, manual guided, and medically focused; cognitive behavioral therapy was manual guided and provided for the first 12 weeks of treatment. The primary outcome measures were self-reported frequency of illicit opioid use and the maximum number of consecutive weeks of abstinence from illicit opioids, as documented by urine toxicology and self-report.. The 2 treatments had similar effectiveness with respect to reduction in the mean self-reported frequency of opioid use, from 5.3 days per week (95% confidence interval, 5.1-5.5) at baseline to 0.4 (95% confidence interval, 0.1-0.6) for the second half of maintenance (P<.001 for the comparisons of induction and maintenance with baseline), with no differences between the 2 groups (P=.96) or between the treatments over time (P=.44). For the maximum consecutive weeks of opioid abstinence there was a significant main effect of time (P<.001), but the interaction (P=.11) and main effect of group (P=.84) were not significant. No differences were observed on the basis of treatment assignment with respect to cocaine use or study completion.. Among patients receiving buprenorphine/naloxone in primary care for opioid dependence, the effectiveness of physician management did not differ significantly from that of physician management plus cognitive behavioral therapy.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Cognitive Behavioral Therapy; Female; Humans; Male; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Compliance; Primary Health Care; Treatment Outcome; Young Adult

Little is known about the relationship between cigarette smoking and agonist treatment in opioid-dependent pregnant patients. The objective of this study is to examine the extent to which cigarette smoking profiles differentially changed during the course of pregnancy in opioid-dependent patients receiving either double-blind methadone or buprenorphine. Patients were participants in the international, randomized controlled Maternal Opioid Treatment: Human Experimental Research (MOTHER) study.. A sample of opioid-maintained pregnant patients (18-41 years old) with available smoking data who completed a multisite, double-blind, double-dummy, randomized controlled trial of methadone (n = 67) and buprenorphine (n = 57) between 2005 and 2008. Participants were compared on smoking variables based on opioid agonist treatment condition.. Overall, 95% of the sample reported cigarette smoking at treatment entry. Participants in the two medication conditions were similar on pretreatment characteristics including smoking rates and daily cigarette amounts. Over the course of the pregnancy, no meaningful changes in cigarette smoking were observed for either medication condition. The fitted difference in change in adjusted cigarettes per day between the two conditions was small and nonsignificant (β = -0.08, SE = 0.05, p = .132).. Results support high rates of smoking with little change during pregnancy among opioid-dependent patients, regardless of the type of agonist medication received. These findings are consistent with evidence that suggests nicotine effects, and interactions may be similar for buprenorphine compared with methadone. The outcomes further highlight that aggressive efforts are needed to reduce/eliminate smoking in opioid-dependent pregnant women.

Topics: Adolescent; Adult; Buprenorphine; Female; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Smoking; Young Adult

Buprenorphine-naloxone sublingual film was introduced in 2011 in Australia as an alternative to tablets. This study compared the two formulations on subjective dose effects and equivalence, trough plasma levels, adverse events, patient satisfaction, supervised dosing time, and impact upon treatment outcomes (substance use, psychosocial function).. 92 buprenorphine-naloxone tablet patients were recruited to this outpatient multi-site double-blind double-dummy parallel group trial. Patients were randomised to either tablets or film, without dose changes, over a 31 day period.. No significant group differences were observed for subjective dose effects, trough plasma buprenorphine or norbuprenorphine levels, adverse events and treatment outcomes. Buprenorphine-naloxone film took significantly less time to dissolve than tablets (173±71 versus 242±141s, p=0.007, F=7.67).. The study demonstrated dose equivalence and comparable clinical outcomes between the buprenorphine-naloxone film and tablet preparations, whilst showing improved dispensing times and patient ratings of satisfaction with the film.

Topics: Administration, Sublingual; Adult; Buprenorphine; Chemistry, Pharmaceutical; Disease Management; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Naloxone; Opioid-Related Disorders; Tablets; Treatment Outcome

Prescription opioid dependence is a growing problem, but little research exists on its treatment, including patient characteristics that predict treatment outcome.. A secondary analysis of data from a large multisite, randomized clinical trial, the National Drug Abuse Treatment Clinical Trials Network Prescription Opioid Addiction Treatment Study (POATS) was undertaken to examine baseline patient characteristics (N=360) associated with success during 12-week buprenorphine/naloxone treatment for prescription opioid dependence. Baseline predictor variables included self-reported demographic and opioid use history information, diagnoses assessed via the Composite International Diagnostic Interview, and historical opioid use and related information from the Pain And Opiate Analgesic Use History.. In bivariate analyses, pre-treatment characteristics associated with successful opioid use outcome included older age, past-year or lifetime diagnosis of major depressive disorder, initially obtaining opioids with a medical prescription to relieve pain, having only used opioids by swallowing or sublingual administration, never having used heroin, using an opioid other than extended-release oxycodone most frequently, and no prior opioid dependence treatment. In multivariate analysis, age, lifetime major depressive disorder, having only used opioids by swallowing or sublingual administration, and receiving no prior opioid dependence treatment remained as significant predictors of successful outcome.. This is the first study to examine characteristics associated with treatment outcome in patients dependent exclusively on prescription opioids. Characteristics associated with successful outcome after 12 weeks of buprenorphine/naloxone treatment include some that have previously been found to predict heroin-dependent patients' response to methadone treatment and some specific to prescription opioid-dependent patients receiving buprenorphine/naloxone.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Drug Therapy, Combination; Female; Humans; Male; Naloxone; Opioid-Related Disorders; Prescription Drugs; Treatment Outcome; Young Adult

Heroin addicts consume large quantities of refined sugars. This study investigated the effect of opiate use and antagonism on sweet taste in opiate-maintained drug users and detoxified former chronic opiate users, using a within-subject design. Seven opiate users received methadone and seven buprenorphine maintenance. Six detoxified subjects received naltrexone. Sucrose recognition thresholds and measurements of pleasantness and intensity were determined before and four hours after 1) a single dose of methadone or buprenorphine or 2) naltrexone. Control data were taken from a cohort of healthy volunteers including smokers. All measures of sweet and salt taste perception were significantly greater in opiate users and recently detoxified subjects compared to control subjects, with the exception of sweet pleasantness, which returned to control level after detoxification. Acute methadone administration reduced salt thresholds and unpleasantness to control levels. Increased sweet thresholds and salt unpleasantness in detoxified subjects were reversed by acute opioid antagonism, returning to control levels. These results suggest that opiate use and antagonism alters taste perception. Some of the alterations reverse on detoxification (sweet pleasantness), and others can be reversed by opioid antagonism (sweet threshold, salt unpleasantness). Changes in taste perception may underlie altered consumption of refined sugars in opiate users.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Cohort Studies; Cross-Over Studies; Dietary Sucrose; Double-Blind Method; England; Female; Food Preferences; Humans; Male; Methadone; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Osmolar Concentration; Sodium Chloride, Dietary; Taste Perception; Taste Threshold; Young Adult

How best to measure the occurrence of adverse events during a randomized clinical trial is an issue that has not been adequately examined in the research literature. Focus of this study was on the examination of the relative frequency of occurrence of adverse events directly recorded during the conduct of the trial compared to an indirect determination of adverse events derived from data collected as part of the trial.. A secondary analysis of nonserious adverse events that occurred in the Maternal Opioid Treatment: Human Experimental Research (MOTHER) Study was undertaken. MOTHER was a randomized clinical trial of methadone versus buprenorphine in 175 opioid-dependent pregnant women.. The two methods of recording adverse events failed to agree on where differences in the frequency of occurrence of adverse events between the medication conditions might exist. Moreover, indirect assessment indicated all participants had experienced at least one adverse event, yet indirect coverage of adverse events was incomplete.. Findings suggest indirect examination of occurrence of adverse events should be cautiously undertaken, because indirect assessment of adverse events makes no distinction between what might be simply typical variation in behavior rather than systematic changes in behavior attributable to study condition, and lacks coverage of the full spectrum of adverse events.. Contemporaneous direct measurement of adverse events likely yield reasonably valid estimates of the rate of occurrence of the adverse events, while indirect measu-rement of adverse events may not be sufficiently reliable.

Topics: Analgesics, Opioid; Buprenorphine; Data Collection; Double-Blind Method; Female; Humans; Infant, Newborn; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications

Buprenorphine/naloxone (BUP/NX) is not licenced for use in China or Thailand and there was little clinical experience with this drug combination in these countries at the inception of HIV Prevention Trial Network (HPTN) 058, a randomized trial comparing risk reduction counselling combined with either short-term or long-term medication assisted treatment with BUP/NX to prevent HIV infection and death amongst opioid-dependent injectors.. We conducted a safety phase that included the first 50 subjects enrolled at each of the three initial study sites (N=150). Clinical and laboratory assessments were conducted at baseline and weekly for the first 4 weeks. Changes in laboratory parameters were estimated with random effects models.. BUP/NX was well tolerated by study subjects and opioid withdrawal scores decreased substantially during the 3-day induction. Two participants experienced grade 3 clinical adverse events, which were categorized as probably not related to the study drug. Grade 2 or 3 increases in alanine aminotransferase (ALT) occurred in 25 (17%) subjects. The magnitude of ALT increase over 4-week follow-up was strongly associated with baseline ALT elevation.. In Chinese and Thai opioid-dependent injectors, we found BUP/NX to be effective in reducing opioid withdrawal symptoms and safe during short-term use. ALT increases were observed over 4-week-follow-up, which are consistent with reports from Western populations. Long-term safety and efficacy evaluations are indicated.

Topics: Adult; Buprenorphine; Buprenorphine, Naloxone Drug Combination; China; Female; Follow-Up Studies; HIV Infections; HIV Seronegativity; Humans; Male; Models, Statistical; Naloxone; Opiate Substitution Treatment; Opioid-Related Disorders; Substance Abuse, Intravenous; Substance Withdrawal Syndrome; Thailand; Time Factors

Attrition in studies of substance use disorder treatment is problematic, potentially introducing bias into data analysis.. This study aimed to determine the effect of participant compensation amounts on rates of missing data and observed rates of drug use.. We performed a secondary analysis of a clinical trial of buprenorphine/naloxone among 152 treatment-seeking opioid-dependent subjects aged 15-21 during participation in a randomized trial. Subjects were randomized to a 2-week detoxification with buprenorphine/naloxone (DETOX; N = 78) or 12 weeks buprenorphine/naloxone (BUP; N = 74). Participants were compensated $5 for weekly urine drug screens and self-reported drug use information and $75 for more extensive assessments at weeks 4, 8, and 12.. Though BUP assignment decreased the likelihood of missing data, there were significantly less missing data at 4, 8, and 12 weeks than other weeks, and the effect of compensation on the probability of urine screens being positive was more pronounced in DETOX subjects.. These findings suggest that variations in the amount of compensation for completing assessments can differentially affect outcome measurements, depending on treatment group assignment.. Adequate financial compensation may minimize bias when treatment condition is associated with differential dropout and may be a cost-effective way to reduce attrition. Moreover, active users may be more likely than non-active users to drop out if compensation is inadequate, especially in control groups or in groups who are not receiving active treatment.

Topics: Adolescent; Buprenorphine; Clinical Trials as Topic; Cost-Benefit Analysis; Data Collection; Female; Humans; Male; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Patient Dropouts; Remuneration; Research Design; Research Subjects; Treatment Outcome; Young Adult

Although use of buprenorphine in the treatment of opioid dependence is expected to continue to increase, little is known about the optimal setting for providing the medical and psychosocial care required with buprenorphine pharmacotherapy.. This study compared buprenorphine therapy delivered in 3 distinct treatment settings: an opioid treatment program (OTP) offering individual counseling, a group counseling program utilizing the manualized Matrix Model (MMM) of cognitive-behavioral treatment, and a private clinic setting mirroring standard medical management for buprenorphine treatment provided specifically at a psychiatrist's private practice (primary care setting).. Participants were inducted on buprenorphine and provided with treatment over a 52-week study duration. All participants were scheduled for weekly treatment visits for the first 6 study weeks and 2 sites reduced treatment to monthly visits for dispensing of medication and psychosocial counseling. Outcomes include opioid use, participant retention in treatment, and treatment participation.. Participants presenting for treatment at the sites differed only by race/ethnicity and opioid use did not differ by site. Retention differed by treatment site, with the number of participants who stayed in the study until the end of 20 weeks significantly associated with treatment site. The mean number of minutes spent in each individual counseling session also differed by site. Although no difference in opioid use by treatment site was found, results document a significant association between opioid use and buprenorphine dose.. These results show some differences by treatment site, although the similarity and relative ease in which the sites were able to recruit participants for treatment with buprenorphine, and minor implementation problems reported suggests the feasibility of treatment with buprenorphine across various treatment settings.. Similar rates of continued opioid use across study sites and few qualitative reports of problems indicates that treatment with buprenorphine and associated psychosocial counseling are safe and relatively easy to implement in a variety of treatment settings.

Topics: Adult; Behavior Therapy; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Combined Modality Therapy; Drug Combinations; Feasibility Studies; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Education as Topic; Primary Health Care; Psychotherapy; Social Support

Prescription opioid (PO)-dependent treatment presentations are becoming increasingly common; however, most research on the treatment of opioid-dependent populations has been conducted in heroin users. The aim of this secondary data analysis was to compare the buprenorphine induction experience of 167 heroin and 61 PO users. Results demonstrate that although the groups differed on some baseline characteristics, many of the key induction experience variables were comparable between the groups. Heroin users were found to have significantly higher preinduction Clinical Opiate Withdrawal Scale (COWS) scores (p = .014) and postinduction COWS score (p = .008) compared with the PO users. No differences between groups were found for self-reported craving and withdrawal scores, mean buprenorphine dose on Day 1, or retention at the end of the first week. The findings of this study suggest that existing buprenorphine induction practices developed for heroin users appear to be equally effective with PO users.

Topics: Adult; Aged; Buprenorphine; Female; Follow-Up Studies; Heroin Dependence; Humans; Male; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Prescription Drugs; Substance Withdrawal Syndrome; Treatment Outcome

The present study examined the impact of a telephonic patient support program known as HereToHelp™ (HTH) on compliance and treatment outcomes among opioid dependent (OD) patients new to buprenorphine treatment (BUP).. A total of 1426 OD patients new to BUP were randomized to receive BUP alone (standard care) or BUP plus the HTH patient support program. All patients completed the Addiction Severity Index (ASI) at the time of enrollment, and at 12months post-enrollment.. Subjects randomized to the HTH support program who accepted at least 3 care coach intervention calls were more compliant with BUP than the standard care group at month 12 (64.4% vs. 56.1%, χ(2)=5.09, p<.025). Compared to patients who were non-compliant with BUP, compliant patients reported significantly lower scores on all 7 of the ASI composite scores, indicating lower severity on addiction-related problems.. The HTH intervention seemed to improve patient treatment outcomes indirectly by improving compliance with BUP. Supplementing BUP with a structured, telephonic compliance-enhancement program is an effective way to improve compliance with medication which then improves patient outcomes.

Topics: Adolescent; Adult; Buprenorphine; Female; Humans; Male; Medication Adherence; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Social Support; Telemedicine; Telephone; Treatment Outcome; Young Adult

Multi-center trials enable the recruitment of larger study samples, although results might be influenced by site-specific factors.. Site differences of a multi-center prospective double-blind, double-dummy randomized controlled trial (7 centers: Central Europe (Vienna)/USA (3 urban/3 rural centers)) comparing safety and efficacy of methadone and buprenorphine in pregnant opioid-dependent women and their neonates.. Urban US women had the highest rate of concomitant opioid (p = 0.050) and cocaine consumption (p = 0.003), the highest dropout rate (p = 0.001), and received the lowest voucher sums (p = 0.001). Viennese neonates had significantly higher Apgar scores 1 min (p = 0.001) and 5 min after birth (p < 0.001) and were more often born by cesarean section (p = 0.024). Rural US newborns had a significantly shorter neonatal abstinence syndrome treatment duration compared to Viennese and urban US sites (p = 0.006), in addition to other site-specific differences, suggesting a more severely affected group of women in the urban US sites.. This clinical trial represents a role model for pharmacological treatment in this unique sample of pregnant women and demonstrates the clinical importance of considering site-specific factors in research and clinical practice.

Topics: Adolescent; Adult; Buprenorphine; Double-Blind Method; Europe; Female; Humans; Infant, Newborn; Methadone; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pregnant Women; Prospective Studies; Rural Population; United States; Urban Population; Young Adult

Increased pain sensitivity and the development of opioid tolerance complicate the treatment of pain experiencedby opioid maintained pregnantwomenduring delivery and the perinatal period. Theaim of the present study was to investigate differences in pain management of opioid maintained compared to nondependent pregnant women during delivery and the postpartum period. 40 deliveries of 37 opioid dependent women enrolled in a double-blind, double-dummy randomized controlled trial (RCT) examining the safety and efficacy of methadone (mean dose at the time of delivery = 63.89 mg) and buprenorphine (mean dose at the time of delivery = 14.05 mg) during pregnancy were analyzed and participants were matched to a non-dependent comparison group of 80 pregnant women. Differences in pain management (opioid and non-opioid analgesic medication) during delivery and perinatal period were analyzed. Following cesarean delivery opioid maintained women received significantly less opioid analgesics (day of delivery p = 0.038; day 1: p = 0.02), NSAIDs were administered more frequently to opioid dependent patients than to the comparison group during cesarean section and on the third day postpartum. Significantly higher nicotine consumption in the group of opioid dependentwomenhad a strong influence onthe retrieved results, and might be considered as an independent factor of altered pain experience. Differences in pain treatment became evident when comparing opioid maintained women to healthy controls. These differences might be based on psychosocial consequences of opioid addiction along with the lack of an interdisciplinary consensus on pain treatment protocols for opioid dependent patients.

Topics: Adult; Analgesics; Buprenorphine; Cesarean Section; Delivery, Obstetric; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Infant, Newborn; Methadone; Narcotics; Opioid-Related Disorders; Pain Management; Peripartum Period; Postpartum Period; Pregnancy; Pregnancy Outcome; Smoking; Young Adult

This study compared the clinical and demographic profiles of three opioid-dependent user groups, and measured their response to 1 year of buprenorphine-medication assisted treatment. Opioid prescription, street, and combination (street + prescription) users completed the Addiction Severity Index multiple times over the course of one treatment year. Although groups differed on all measured demographics (P values <.05) and on six of seven Addiction Severity Index composite scores at induction (P values <.05), differences were ameliorated after 1 year. Findings highlight the disparities between the various opioid-dependent patient subpopulations and suggest that buprenorphine-medication assisted treatment is an effective treatment across user subtypes.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Female; Humans; Illicit Drugs; Male; Managed Care Programs; Opioid-Related Disorders; Prescription Drugs; Psychiatric Status Rating Scales; Residence Characteristics; Socioeconomic Factors; Treatment Outcome; Young Adult

Counseling and medication adherence can affect opioid agonist treatment outcomes. We investigated the impact of 2 counseling intensities and 2 medication-dispensing methods in patients receiving buprenorphine in primary care.. In a 12-week trial, patients were assigned to physician management (PM) with weekly buprenorphine dispensing (n = 28) versus PM and directly observed, thrice-weekly buprenorphine (DOT) and cognitive-behavioral therapy (CBT) (PM+DOT/CBT; n = 27) based on therapist availability. Fifteen-minute PM visits were provided at entry, after induction, and then monthly. Cognitive-behavioral therapy was weekly 45-minute sessions provided by trained therapists.. Treatment groups differed on baseline characteristics of years of opioid use, history of detoxification from opioids, and opioid negative urines during induction. Analyses adjusting for baseline characteristics showed no significant differences between groups on retention or drug use based on self-report or urines. Patient satisfaction was high across conditions, indicating acceptability of CBT counseling with observed medication. The number of CBT sessions attended was significantly associated with improved outcome, and session attendance was associated with a greater abstinence the following week.. Although the current findings were nonsignificant, DOT and individual CBT sessions were feasible and acceptable to patients. Additional research evaluating the independent effect of directly observed medication and CBT counseling is needed.

Topics: Adult; Buprenorphine; Cognitive Behavioral Therapy; Combined Modality Therapy; Directly Observed Therapy; Drug Administration Schedule; Feasibility Studies; Humans; Male; Middle Aged; Narcotics; Opioid-Related Disorders; Patient Satisfaction; Pilot Projects; Primary Health Care

In opioid dependent youth there is substantial attrition from medication-assisted treatment. If youth at risk for attrition can be identified at treatment entry or early in treatment, they can be targeted for interventions to help retain them in treatment.. Opioid dependent adolescents and young adults (n=152), aged 15-21, were randomized to 12 weeks (BUP, n=74) or 2 weeks of detoxification (DETOX, n=78) with buprenorphine/naloxone (Bup/Nal), both in combination with 12 weeks of psychosocial treatment. Baseline and early treatment related predictors of treatment attrition were identified in each group using bivariate and multivariate logistic regression.. In the DETOX group 36% left between weeks 2 and 4, at the end of the dose taper, while in the BUP group only 8% left by week 4. In the BUP group, early adherence to Bup/Nal, early opioid negative urines, use of any medications in the month prior to treatment entry, and lifetime non-heroin opioid use were associated with retention while prior 30-day hallucinogen use was associated with attrition. In the DETOX group, only use of sleep medications was associated with retention although not an independent predictor. A broad range of other pre-treatment characteristics was unrelated to attrition.. Prompt attention to those with early non-adherence to medication or an early opioid positive urine, markers available in the first 2 weeks of treatment, may improve treatment retention. Extended Bup/Nal treatment appeared effective in improving treatment retention for youth with opioid dependence across a wide range of demographics, and pre-treatment clinical characteristics.

Topics: Adolescent; Buprenorphine; Female; Humans; Male; Medication Adherence; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Risk Factors; Treatment Outcome; Young Adult

This retrospective quality improvement study was to evaluate if Suboxone therapy reduced the risk of terminating treatment against medical advice compared with the use clonidine in men aged 18--55 years.. Data were collected through chart review for all opioid-addicted male clients admitted voluntarily to a community-based treatment center between July 1, 2009, and December 30, 2009.. The chi-square test of independence between treatment completion and treatment noncompletion was found to be significant at the 5% critical level (P = .027) for Suboxone therapy.. Suboxone treatment decreased premature termination of opioid detoxification completion when compared with clonidine.

Topics: Adolescent; Adrenergic alpha-2 Receptor Agonists; Adult; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Clonidine; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Patient Dropouts; Quality Improvement; Rehabilitation Centers; Retrospective Studies; Risk; Young Adult

Lapse to opiate use after initiation of buprenorphine treatment is common and is a strong predictor of poor treatment retention and increased risk of long-term opiate use. Drug cues and situations or events associated with distress are known to provoke craving and increase risk for lapse. This study evaluated the predictive validity of a behavioral index of persistence during a stress challenge among opiate users identified as affectively vulnerable to lapse risk due to elevated depressive symptoms.. Patients from an ongoing clinical trial (n = 48) completed a stress-challenge task before receiving their first dose of buprenorphine.. After controlling for levels of craving on their induction day, persistence on the stress-challenge task before initiating buprenorphine treatment was associated with successful transition to early abstinence, and lower rates of opiate use during the initial 3 months of buprenorphine treatment across antidepressant and placebo groups.. Results from this preliminary study suggest the promise of laboratory-based behavioral paradigms in facilitating an understanding of important mechanisms of early lapse. Identifying individual behavioral responses to drug and stress cues before attempts at abstinence may facilitate delivery of adjunctive behavioral treatments to prevent early lapse.

Topics: Adult; Antidepressive Agents, Second-Generation; Buprenorphine; Citalopram; Comorbidity; Depressive Disorder; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Medication Adherence; Middle Aged; Motivation; Narcotics; Opioid-Related Disorders; Patient Dropouts; Probability; Risk Assessment; Stress, Psychological; Substance Abuse Detection; Substance Withdrawal Syndrome

Untreated opioid dependence adversely affects HIV outcomes. Integrating buprenorphine/naloxone into HIV treatment settings is feasible; however, the optimal level of counseling has not been established. We conducted a 12-week randomized clinical trial of physician management (PM) versus PM plus enhanced medical management (EMM) in 47 subjects. At 12 weeks, there were no differences between the two groups in percentage of opioid negative urines (63.6% PM vs. 69.0% PM+EMM, p=.5), maximum duration of continuous abstinence (4.9 weeks PM vs. 5.2 weeks PM+EMM, p=.8) or retention (80% PM vs. 59% PM+EMM, p=.1). The percentage of subjects with detectable HIV viral loads decreased from 58% at baseline to 40% at 12 weeks across both groups (p=.02 for time) with no between group differences (p=.84 and p=.27 for the interaction). Providing more extensive counseling beyond PM is feasible in an HIV clinic, but we are unable to detect an improvement in outcomes associated with these services.

Topics: Adult; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Counseling; Delivery of Health Care, Integrated; Feasibility Studies; Female; Follow-Up Studies; HIV Infections; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Psychotherapy, Brief; Substance Abuse Detection; Time Factors; Treatment Outcome; Viral Load

Physical pain is common among individuals seeking treatment for opioid dependence. Pain may negatively impact addiction treatment. The authors prospectively studied opioid-dependent individuals initiating office-based buprenorphine treatment, comparing buprenorphine treatment outcomes (treatment retention and opioid use) among participants with and without pain (baseline pain or persistent pain). Among 82 participants, 60% reported baseline pain and 38% reported persistent pain. Overall, treatment retention was 56% and opioid use decreased from 89% to 26% over 6 months. In multivariable analyses, the authors found no association between pain and buprenorphine treatment outcomes. Opioid-dependent individuals with and without pain can achieve similar success with buprenorphine treatment.

Topics: Buprenorphine; Female; Humans; Longitudinal Studies; Male; Medication Adherence; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Pain; Primary Health Care; Treatment Outcome

Topics: Adolescent; Adult; Buprenorphine; Female; Humans; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Treatment Outcome; Young Adult

The Maternal Opioid Treatment: Human Experimental Research (MOTHER) project, an eight-site randomized, double-blind, double-dummy, flexible-dosing, parallel-group clinical trial is described. This study is the most current--and single most comprehensive--research effort to investigate the safety and efficacy of maternal and prenatal exposure to methadone and buprenorphine.. The MOTHER study design is outlined, and its basic features are presented.. At least seven important lessons have been learned from the MOTHER study: (i) an interdisciplinary focus improves the design and methods of a randomized clinical trial; (ii) multiple sites in a clinical trial present continuing challenges to the investigative team due to variations in recruitment, patient populations and hospital practices that, in turn, differentially impact recruitment rates, treatment compliance and attrition; (iii) study design and protocols must be flexible in order to meet the unforeseen demands of both research and clinical management; (iv) staff turnover needs to be addressed with a proactive focus on both hiring and training; (v) the implementation of a protocol for the treatment of a particular disorder may identify important ancillary clinical issues worthy of investigation; (vi) timely tracking of data in a multi-site trial is both demanding and unforgiving; and (vii) complex multi-site trials pose unanticipated challenges that complicate the choice of statistical methods, thereby placing added demands on investigators to effectively communicate their results.

Topics: Buprenorphine; Double-Blind Method; Drug Administration Schedule; Female; Humans; Infant, Newborn; Narcotic Antagonists; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Selection; Pregnancy; Pregnancy Complications; Randomized Controlled Trials as Topic; Treatment Outcome; United States

To determine pre- and post-dosing effects of prenatal methadone compared to buprenorphine on fetal wellbeing.. A secondary analysis of data derived from the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study, a double-blind, double-dummy, randomized clinical trial.. Six United States sites and one European site that provided comprehensive opioid-dependence treatment to pregnant women.. Eighty-one of the 131 opioid-dependent pregnant women completing the MOTHER clinical trial, assessed between 31 and 33 weeks of gestation.. Two fetal assessments were conducted, once before and once after study medication dosing. Measures included mean fetal heart rate (FHR), number of FHR accelerations, FHR reactivity in the fetal non-stress test (NST) and biophysical profile (BPP) score.. Significant group differences were found for number of FHR accelerations, non-reactive NST and BPP scores (all Ps < 0.05). There were no significant group differences before time of dosing. Significant decreases (all Ps < 0.05) occurred from pre- to post-dose assessment for mean FHR, FHR accelerations, reactive NST and fetal movement. The decrease in accelerations and reactive NST were significant only for fetuses in the methadone group, and this resulted in a significantly lower likelihood of a reactive NST compared to fetuses in the buprenorphine group.. Buprenorphine compared with methadone appears to result in less suppression of mean fetal heart rate, fetal heart rate reactivity and the biophysical profile score after medication dosing and these findings provide support for the relative safety of buprenorphine when fetal indices are considered as part of the complete risk-benefit ratio.

Topics: Adolescent; Adult; Analgesics, Opioid; Biophysical Phenomena; Buprenorphine; Double-Blind Method; Female; Fetal Monitoring; Fetal Movement; Fetus; Gestational Age; Heart Rate, Fetal; Humans; Infant, Newborn; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Outcome Assessment, Health Care; Pregnancy; Pregnancy Complications; Young Adult

To identify factors that predict the expression of neonatal abstinence syndrome (NAS) in infants exposed to methadone or buprenorphine in utero.. Multi-site randomized clinical trial in which infants were observed for a minimum of 10 days following birth, and assessed for NAS symptoms by trained raters.. A total of 131 infants born to opioid dependent mothers, 129 of whom were available for NAS assessment.. Generalized linear modeling was performed using maternal and infant characteristics to predict: peak NAS score prior to treatment, whether an infant required NAS treatment, length of NAS treatment and total dose of morphine required for treatment of NAS symptoms.. Of the sample, 53% (68 infants) required treatment for NAS. Lower maternal weight at delivery, later estimated gestational age (EGA), maternal use of selective serotonin re-uptake inhibitors (SSRIs), vaginal delivery and higher infant birthweight predicted higher peak NAS scores. Higher infant birthweight and greater maternal nicotine use at delivery predicted receipt of NAS treatment for infants. Maternal use of SSRIs, higher nicotine use and fewer days of study medication received also predicted total dose of medication required to treat NAS symptoms. No variables predicted length of treatment for NAS.. Maternal weight at delivery, estimated gestational age, infant birthweight, delivery type, maternal nicotine use and days of maternal study medication received and the use of psychotropic medications in pregnancy may play a role in the expression of neonatal abstinence syndrome severity in infants exposed to either methadone or buprenorphine.

Topics: Adolescent; Adult; Analgesics, Opioid; Birth Weight; Buprenorphine; Dose-Response Relationship, Drug; Female; Humans; Infant, Newborn; Length of Stay; Linear Models; Methadone; Morphine; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Risk Factors; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index; Smoking; Young Adult

To compare the profile of signs of neonatal abstinence syndrome (NAS) in methadone- versus buprenorphine-exposed infants.. Secondary analysis of NAS data from a multi-site, double-blind, double-dummy, flexible-dosing, randomized clinical trial. Data from a total of 129 neonates born to opioid-dependent women who had been assigned to receive methadone or buprenorphine treatment during pregnancy were examined.. For 10 days after delivery, neonates (methadone = 72, buprenorphine = 57) were assessed regularly using a 19-item modified Finnegan scale. Data from neonates who required pharmacological treatment (methadone = 41, buprenorphine = 27) were included up to the time treatment was initiated. The incidence and mean severity of the total NAS score and each individual sign of NAS were calculated and compared between medication conditions, as was the median time until morphine treatment initiation among treated infants in each condition.. Two NAS signs (undisturbed tremors and hyperactive Moro reflex) were observed significantly more frequently in methadone-exposed neonates and three (nasal stuffiness, sneezing, loose stools) were observed more frequently in buprenorphine-exposed neonates. Mean severity scores on the total NAS score and five individual signs (disturbed and undisturbed tremors, hyperactive Moro reflex, excessive irritability, failure to thrive) were significantly higher among methadone-exposed neonates, while sneezing was higher among buprenorphine-exposed neonates. Among treated neonates, methadone-exposed infants required treatment significantly earlier than buprenorphine-exposed infants (36 versus 59 hours postnatal, respectively).. The profile of neonatal abstinence syndrome differs in methadone- versus buprenorphine-exposed neonates, with significant differences in incidence, severity and treatment initiation time. Overall, methadone-exposed neonates have a more severe neonatal abstinence syndrome.

Topics: Adult; Analgesics, Opioid; Analysis of Variance; Buprenorphine; Double-Blind Method; Female; Humans; Incidence; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Severity of Illness Index; Symptom Assessment; Time Factors; Treatment Outcome

To determine the effects of in utero exposure to methadone or buprenorphine on infant neurobehavior.. Three sites from the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study, a double-blind, double-dummy, randomized clinical trial participated in this substudy.. Medical Centers that provided comprehensive maternal care to opioid-dependent pregnant women in Baltimore, MD, Providence, RI and Vienna, Austria.. Thirty-nine full-term infants.. The Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale (NNNS) was administered to a subgroup of infants on postpartum days 3, 5, 7, 10, 14-15 and 28-30.. While neurobehavior improved for both medication conditions over time, infants exposed in utero to buprenorphine exhibited fewer stress-abstinence signs (P < 0.001), were less excitable (P < 0.001) and less over-aroused (P < 0.01), exhibited less hypertonia (P < 0.007), had better self-regulation (P < 0.04) and required less handling (P < 0.001) to maintain a quiet alert state relative to in utero methadone-exposed infants. Infants who were older when they began morphine treatment for withdrawal had higher self-regulation scores (P < 0.01), and demonstrated the least amount of excitability (P < 0.02) and hypertonia (P < 0.02) on average. Quality of movement was correlated negatively with peak NAS score (P < 0.01), number of days treated with morphine for NAS (P < 0.01) and total amount of morphine received (P < 0.03). Excitability scores were related positively to total morphine dose (P < 0.03).. While neurobehavior improves during the first month of postnatal life for in utero agonist medication-exposed neonates, buprenorphine exposure results in superior neurobehavioral scores and less severe withdrawal than does methadone exposure.

Topics: Adolescent; Adult; Analgesics, Opioid; Buprenorphine; Female; Humans; Infant Behavior; Infant, Newborn; Linear Models; Male; Methadone; Morphine; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Severity of Illness Index; Young Adult

To examine the relationship of anxiety and depression symptoms with treatment outcomes (treatment discontinuation, rates of ongoing use of illicit drugs and likelihood of preterm delivery) in opioid-dependent pregnant women and describe their use of psychotropic medications.. Secondary data analysis from a randomized clinical trial of treatment for opioid dependence during pregnancy.. A total of 175 opioid-dependent pregnant women, of whom 131 completed treatment.. Symptoms of anxiety and depression were captured with the 15-item Mini International Neuropsychiatric Interview (MINI) screen. Use of illicit drugs was measured by urine drug screening. Preterm delivery was defined as delivery prior to 37 weeks' gestation. Self-reported use of concomitant psychotropic medication at any point during the study was recorded.. Women reporting only anxiety symptoms at study entry were more likely to discontinue treatment [adjusted odds ratio (OR) = 4.56, 95% confidence interval (CI) : 1.91-13.26, P = 0.012], while those reporting only depression symptoms were less likely to discontinue treatment (adjusted OR = 0.14, 95% CI : 0.20-0.88, P = 0.036) compared to women who reported neither depression nor anxiety symptoms. No statistically significant between-group differences were observed for ongoing illicit drug use or preterm delivery. A majority (61.4%) of women reported use of concomitant psychotropic medication at some point during study participation.. Opioid agonist-treated pregnant patients with co-occurring symptoms of anxiety require additional clinical resources to prevent premature discontinuation.

Topics: Adolescent; Adult; Analgesics, Opioid; Anxiety; Buprenorphine; Comorbidity; Depression; Double-Blind Method; Female; Humans; Interview, Psychological; Logistic Models; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Compliance; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Severity of Illness Index; Treatment Outcome; Young Adult

To characterize infections and compare obstetric outcomes in opioid-dependent pregnant women who participated in a randomized clinical trial comparing agonist medications, methadone and buprenorphine.. Incidence of infections was identified as part of the screening medical assessment. As part of a planned secondary analysis, analysis of variance and polytomous logistic regressions were conducted on obstetric outcome variables using treatment randomization condition (maternal maintenance with either methadone or buprenorphine) as the predictor variable, controlling for differences between study sites.. Six United States sites and one European site that provided comprehensive treatment to opioid-dependent pregnant women.. Pregnant opioid-dependent women (n = 131) who delivered while participating in the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study.. Obstetric, infectious and other maternal medical complications captured by medical records, physical examination, blood tests and self-report. Neonatal medical complications captured by medical records.. Hepatitis C was the most common infection (32.3%), followed by hepatitis B (7.6%) and chlamydia (6.1%) among participants at study enrollment. Maternal methadone versus buprenorphine maintenance was associated with a higher incidence of preterm labor (P = 0.04) and a significantly higher percentage of signs of respiratory distress in neonates at delivery (P = 0.05). Other medical and obstetric complications were infrequent in the total sample, as well as in both methadone and buprenorphine conditions.. Buprenorphine appears to have an acceptable safety profile for use during pregnancy.

Topics: Adolescent; Adult; Analgesics, Opioid; Analysis of Variance; Buprenorphine; Communicable Diseases; Female; Humans; Incidence; Infant, Newborn; Logistic Models; Methadone; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Respiratory Distress Syndrome, Newborn; Young Adult

To examine hepatic enzyme test results throughout the course of pregnancy in women maintained on methadone or buprenorphine.. Participants were randomized to either methadone or buprenorphine maintenance. Blood chemistry tests, including liver transaminases and hepatitis C virus (HCV) status, were determined every 4 weeks and once postpartum. As part of a planned secondary analysis, generalized mixed linear models were conducted with aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) as the dependent variables.. Six US sites and one European site that provided comprehensive treatment to pregnant opioid-dependent women.. A total of 175 opioid-dependent pregnant women enrolled in the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study.. ALT, AST and GGT levels decreased for all subjects across pregnancy trimesters, rising slightly postpartum. HCV-positive subjects exhibited higher transaminases at all time-points compared to HCV-negative subjects, regardless of medication (all Ps < 0.05) condition. Both HCV-positive and negative buprenorphine-maintained participants exhibited lower GGT levels than those who were methadone-maintained (P < 0.05).. Neither methadone nor buprenorphine appear to have adverse hepatic effects in the treatment of pregnant opioid-dependent women.

Topics: Adolescent; Adult; Analgesics, Opioid; Buprenorphine; Female; gamma-Glutamyltransferase; Hepatitis C; Humans; Linear Models; Liver; Liver Function Tests; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Trimesters; Transaminases; Young Adult

A sublingual soluble-film formulation of buprenorphine/naloxone (B/N) has been approved by the US Food and Drug Administration for the treatment of opioid dependency. This preparation provides unit-dose, child-resistant packaging amenable to tracking and accountability, offers more rapid dissolution, and has a potentially preferred taste vs. tablets. This study compared the ability of buprenorphine (B) and B/N films to suppress spontaneous withdrawal in opioid-dependent volunteers. Participants were maintained on morphine and underwent challenge sessions to confirm sensitivity to naloxone-induced opioid withdrawal. Subjects were randomized to receive either B (16 mg, n = 18) or B/N (16/4 mg, n = 16) soluble films for 5 days. The primary outcome measure was the Clinical Opiate Withdrawal Scale (COWS) score. Thirty-four subjects completed induction onto soluble films. There was a significant decrease in COWS scores but no significant differences between the groups. The results support the use of B and B/N soluble films as safe and effective delivery methods for opioid induction.

Topics: Administration, Sublingual; Adult; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Double-Blind Method; Drug Approval; Drug Packaging; Female; Humans; Male; Medication Systems; Middle Aged; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Solubility; Substance Withdrawal Syndrome; Tablets; Taste; United States; United States Food and Drug Administration

Despite findings that opioid detoxification serves little more than a palliative function, few patients who enter detoxification subsequently transition to long-term treatment. The current study evaluated intensive role induction (IRI), a strategy adapted from a single-session intervention previously shown to facilitate engagement of substance-dependent patients in drug-free treatment. IRI was delivered either alone or combined with case management (IRI+CM) to determine the capacity of each condition to enhance transition and engagement in long-term treatment of detoxification patients. Study participants were 240 individuals admitted to a 30-day buprenorphine detoxification delivered at a publicly funded outpatient drug treatment clinic. Following clinic intake, participants were randomly assigned to IRI, IRI+CM, or standard clinic treatment (ST). Outcomes were assessed in terms of adherence and satisfaction with the detoxification program, detoxification completion, and transition and retention in treatment following detoxification. Participants who received IRI and IRI+CM attended more counseling sessions during detoxification than those who received ST (both ps<.001). IRI, but not IRI+CM participants, were more likely to complete detoxification (p=.017), rated their counselors more favorably (p=.01), and were retained in long-term treatment for more days following detoxification (p=.005), than ST participants. The current study demonstrated that an easily administered psychosocial intervention can be effective for enhancing patient involvement in detoxification and for enabling their engagement in long-term treatment following detoxification.

Topics: Adult; Ambulatory Care Facilities; Buprenorphine; Case Management; Certification; Counseling; Female; Humans; Male; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Satisfaction; Psychometrics; Psychotherapy; Standard of Care; Substance Withdrawal Syndrome; Tape Recording; Time Factors; Treatment Outcome

Having opioid dependence and HIV infection are associated with poor HIV-related treatment outcomes.. HIV-infected, opioid-dependent subjects (N = 295) recruited from 10 clinical sites initiated buprenorphine/naloxone (BUP/NX) and were assessed at baseline and quarterly for 12 months. Primary outcomes included receiving antiretroviral therapy (ART), HIV-1 RNA suppression, and mean changes in CD4 lymphocyte count. Analyses were stratified for the 119 subjects not on ART at baseline. Generalized estimating equations were deployed to examine time-dependent correlates for each outcome.. At baseline, subjects on ART (N = 176) were more likely than those not on ART (N = 119) to be older, heterosexual, have lower alcohol addiction severity scores, and lower HIV-1 RNA levels; they were less likely to be homeless and report sexual risk behaviors. Subjects initiating BUP/NX (N = 295) were significantly more likely to initiate or remain on ART and improve CD4 counts over time compared with baseline; however, these improvements were not significantly improved by longer retention on BUP/NX. Retention on BUP/NX for three or more quarters was, however, significantly associated with increased likelihood of initiating ART (β = 1.34 [1.18, 1.53]) and achieve viral suppression (β = 1.25 [1.10, 1.42]) for the 64 of 119 (54%) subjects not on ART at baseline compared with the 55 subjects not retained on BUP/NX. In longitudinal analyses, being on ART was positively associated with increasing time of observation from baseline and higher mental health quality of life scores (β = 1.25 [1.06, 1.46]) and negatively associated with being homo- or bisexual (β = 0.55 [0.35, 0.97]), homeless (β = 0.58 [0.34, 0.98]), and increasing levels of alcohol addiction severity (β = 0.17 [0.03, 0.88]). The strongest correlate of achieving viral suppression was being on ART (β = 10.27 [5.79, 18.23]). Female gender (β = 1.91 [1.07, 3.41]), Hispanic ethnicity (β = 2.82 [1.44, 5.49]), and increased general health quality of life (β = 1.02 [1.00,1.04]) were also independently correlated with viral suppression. Improvements in CD4 lymphocyte count were significantly associated with being on ART and increased over time.. Initiating BUP/NX in HIV clinical care settings is feasible and correlated with initiation of ART and improved CD4 lymphocyte counts. Longer retention on BPN/NX was not associated with improved prescription of ART, viral suppression, or CD4 lymphocyte counts for the overall sample in which the majority was already prescribed ART at baseline. Among those retained on BUP/NX, HIV treatment outcomes did not worsen and were sustained. Increasing time on BUP/NX, however, was especially important for improving HIV treatment outcomes for those not on ART at baseline, the group at highest risk for clinical deterioration. Retaining subjects on BUP/NX is an important goal for sustaining HIV treatment outcomes for those on ART and improving them for those who are not. Comorbid substance use disorders (especially alcohol), mental health problems, and quality-of-life indicators independently contributed to HIV treatment outcomes among HIV-infected persons with opioid dependence, suggesting the need for multidisciplinary treatment strategies for this population.

Topics: Alcoholism; Anti-HIV Agents; Buprenorphine; Buprenorphine, Naloxone Drug Combination; CD4 Lymphocyte Count; Female; HIV Infections; HIV-1; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Risk Factors; RNA, Viral; Treatment Outcome

Buprenorphine/naloxone allows the integration of opioid dependence and HIV treatment.. We conducted a prospective study in HIV-infected opioid-dependent patients to investigate the impact of buprenorphine/naloxone treatment on drug use. Self-report and chart review assessments were conducted every 3 months (quarters 1-4) for 1 year. Outcomes were buprenorphine/naloxone treatment retention, drug use, and addiction treatment processes.. Among 303 patients enrolled between July 2005 and December 2007, retention in buprenorphine/naloxone treatment was 74%, 67%, 59%, and 49% during Quarters 1, 2, 3, and 4, respectively. Past 30-day illicit opioid use decreased from 84% of patients at baseline to 42% in retained patients over the year. Patients were 52% less likely to use illicit opioids for each quarter in treatment (Odds ratio = 0.66; 95% CI: 0.61 to 0.72). Buprenorphine/naloxone doses and office visits approximated guidelines published by the United States Department of Health and Human Services. Urine toxicology monitoring was less frequent than recommended.. Buprenorphine/naloxone provided in HIV treatment settings can decrease opioid use. Strategies are needed to improve retention and address ongoing drug use in this treatment population.

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Female; HIV Infections; Humans; Male; Naloxone; Narcotic Antagonists; Odds Ratio; Opiate Substitution Treatment; Opioid-Related Disorders; Prospective Studies; Treatment Outcome

Substance abuse is associated with poor medical and quality-of-life outcomes among HIV-infected individuals. Although drug treatment may reduce these negative consequences, for many patients, options are limited. Buprenorphine/naloxone, an opioid agonist treatment that can be prescribed in the United States in office-based settings, can be used to expand treatment capacity and integrate substance abuse services into HIV care. Recognizing this potential, the US Health Resources and Services Administration funded the development and implementation of demonstration projects that integrated HIV care and buprenorphine/naloxone treatment at 10 sites across the country. An Evaluation and Technical Assistance Center provided programmatic and clinical support as well as oversight for an evaluation that examined the processes for and outcomes of integrated care. The evaluation included patient-level self-report and chart abstractions as well as provider and site level data collected through surveys and in-depth interviews. Although multisite demonstrations pose implementation and evaluation challenges, our experience demonstrates that these can, in part, be addressed through ongoing communication and technical assistance as well as a comprehensive evaluation design that incorporates multiple research methods and data sources. Although limitations to evaluation findings persist, they may be balanced by the scope and "real-world" context of the initiative.

Topics: Ambulatory Care; Buprenorphine; Buprenorphine, Naloxone Drug Combination; HIV Infections; Humans; Methadone; Multicenter Studies as Topic; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Pilot Projects; United States

Previous work suggests that opioid users have lower health-related quality of life (HRQOL) than patients with more prevalent chronic illnesses such as hypertension or diabetes. Although comparisons with population norms are informative, studies of the correlates of HRQOL for opioid users are needed to plan clinical services.. We tested a conceptual model of the pathways between physiologic factors and symptoms in relation to HRQOL among 344 opioid users in a clinical trial. Physical and mental HRQOL were measured by the Short-Form (SF)-36; withdrawal signs, symptoms, and functioning were also measured with validated instruments. Using structural equation modeling, we tested hypotheses that medical history directly predicts withdrawal signs and symptoms, and that medical history, withdrawal signs and symptoms, and functioning predict the physical and mental HRQOL latent variables of the SF-36.. Most hypothesized relationships were significant, and model fit was good. The model explained 36% of the variance in mental HRQOL and 34% of the variance in physical HRQOL.. The conceptual framework appears valid for explaining variation in the physical and mental HRQOL of opioid users undergoing medically managed withdrawal. Analysis of longitudinal data would help to evaluate more rigorously the adequacy of the model for explaining HRQOL in opioid withdrawal.

Topics: Adolescent; Adult; Analgesics, Opioid; Body Mass Index; Buprenorphine; Humans; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Quality of Life; Severity of Illness Index; Sickness Impact Profile; Substance Withdrawal Syndrome; Young Adult

Despite the fact that buprenorphine is effective, well tolerated and due to its pharmacological profile a very safe drug, the impact of long-term buprenorphine substitution therapy on complex psychomotor and cognitive function predicting driving ability is not yet clear. Therefore, a prospective comparison between patients receiving sublingual buprenorphine and a control group of untreated, healthy volunteers was performed.. Treated and untreated subjects were matched for age and sex, with three control subjects selected for every buprenorphine patient. Patients using unreported drugs were included in the intention-to-treat (ITT) analysis; the remaining patients were analysed as the per-protocol (PP) group. The test battery comprised the assessment of: performance during stress, visual orientation, concentration, attention, vigilance and reaction time. The primary endpoint was defined as the sum of the relevant scores of the tests after z-transformation of the individual scores.. 30 patients with sublingual buprenorphine treatment (7.7±3.9 mg per day) were matched to 90 controls. 19 patients were excluded from the PP-analysis because of additional unreported drug intake. Significant non-inferiority could be demonstrated for the PP-group (p<0.05) as well as for the ITT-group (p<0.001).. Patients receiving a stable dose of sublingual buprenorphine showed no significant impairment of complex psychomotor or cognitive performance as compared to healthy controls. However intake of illicit drugs as well as the lack of social reliability are major problems in this specific patients group. Despite of the absence of a relevant impact of the drug on driving ability, those patients do not seem to be qualified for getting their driving license.

Topics: Adult; Attention; Automobile Driving; Buprenorphine; Chronic Disease; Cognition; Control Groups; Female; Humans; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Prospective Studies; Psychomotor Performance; Reaction Time; Time Factors; Visual Perception

Sublingual buprenorphine and buprenorphine/naloxone are efficacious opioid dependence pharmacotherapies, but there are reports of their diversion and misuse by the intranasal route. The study objectives were to characterize and compare their intranasal pharmacodynamic and pharmacokinetic profiles.. A randomized, double-blind, placebo-controlled, cross-over study.. An in-patient research unit at the University of Kentucky.. Healthy adults (n = 10) abusing, but not physically dependent on, intranasal opioids.. Six sessions (72 hours apart) tested five intranasal doses [0/0, crushed buprenorphine (2, 8 mg), crushed buprenorphine/naloxone (2/0.5, 8/2 mg)] and one intravenous dose (0.8 mg buprenorphine/0.2 mg naloxone for bioavailability assessment). Plasma samples, physiological, subject- and observer-rated measures were collected before and for up to 72 hours after drug administration.. Both formulations produced time- and dose-dependent increases on subjective and physiological mu-opioid agonist effects (e.g. 'liking', miosis). Subjects reported higher subjective ratings and street values for 8 mg compared to 8/2 mg, but these differences were not statistically significant. No significant formulation differences in peak plasma buprenorphine concentration or time-course were observed. Buprenorphine bioavailability was 38-44% and T(max) was 35-40 minutes after all intranasal doses. Naloxone bioavailability was 24% and 30% following 2/0.5 and 8/2 mg, respectively.. It is difficult to determine if observed differences in abuse potential between intranasal buprenorphine and buprenorphine/naloxone are clinically relevant at the doses tested. Greater bioavailability and faster onset of pharmacodynamic effects compared to sublingual administration suggests a motivation for intranasal misuse in non-dependent opioid abusers. However, significant naloxone absorption from intranasal buprenorphine/naloxone administration may deter the likelihood of intranasal misuse of buprenorphine/naloxone, but not buprenorphine, in opioid-dependent individuals.

Topics: Administration, Intranasal; Adult; Analysis of Variance; Area Under Curve; Biological Availability; Buprenorphine; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Female; Humans; Injections, Intravenous; Male; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Tablets; Time Factors

Previous reports on the pharmacokinetic of tipranavir (TPV) and buprenorphine (BUP)/ naloxone found that coadministration resulted in an 80% reduction in the area under the curve AUC of the primary BUP metabolite, norBUP, without any pharmacodynamic consequences. This study was conducted to characterize how tipranivir/ritonavir effects the glucuronide metabolites of BUP and may explain the reduction in the norBUP.. HIV-seronegative subjects stabilized on at least 3 weeks of BUP/naloxone sequentially underwent baseline and steady-state pharmacokinetic evaluation of twice daily TPV 500?mg coadministered with ritonavir 200?mg (TPV/r).. Twelve subjects were enrolled and ten completed the study. The steady-state pharmacokinetics for BUP-3-glucuronide (BUP-3G) and norBUP-3-glucuronide (norBUP-3G) in the presence and absence of steady-state TPV/r were analyzed. The C(max) of BUP-3G was 8.78???5.23?ng/mL without TPV/r and increased to 12.7???11.7 after steady state of TPV/r was achieved. The AUC of BUP-3G was 31.1???19.4?(ng/mL)?(h) without TPV/r and increased to 58. 6???49.5 after steady state of TPV/r was achieved (p?=?.0966). In contrast, steady-state norBUP-3G AUC(0?24?h) (p?=?.0216) and C(max) (p?=?.0088) were significantly decreased in the presence of steady-state TPV/r.. This study further elucidates the effects of TPV/r on glucuronidation. The current evaluation of glucuronide metabolites of BUP and norBUP are suggestive of combined inhibition of Uridine diphosphate (UDP)-glucuronosyltransferase of the 1A family and cytochrome P450 3A4 that spares UGT2B7 leading to a shunting of BUP away from production of norBUP and toward BUP-3G as seen by a statistically significant increase in the AUC of BUP-3G.

Topics: Adult; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Drug Interactions; Female; HIV Seronegativity; Humans; Inactivation, Metabolic; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Pyridines; Pyrones; Ritonavir; Sulfonamides

Chronic medical conditions such as opioid dependence require evidence-based treatment recommendations. However, pregnant women are under-represented in clinical trials. We describe the first within-subject comparison of maternal and neonatal outcomes for methadone- versus buprenorphine-exposed pregnancies. Although methadone is the established treatment of pregnant opioid-dependent women, recent investigations have shown a trend for a milder neonatal abstinence syndrome (NAS) under buprenorphine. However, it is not only the choice of maintenance medication that determines the occurrence of NAS; other factors such as maternal metabolism, illicit substance abuse and nicotine consumption also influence its severity and duration and represent confounding factors in the assessment of randomized clinical trials. CASE SERIES DESCRIPTION: Three women who were part of the European cohort of a randomized, double-blind multi-center trial with a contingency management tool [the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study], each had two consecutive pregnancies and were maintained on either methadone or buprenorphine for their first and then the respective opposite, still-blinded medication for their second pregnancy. Birth measurements, the total neonatal abstinence score, the total amounts of medication used to treat NAS and the days of NAS treatment duration were assessed.. Both medications were effective and safe in reducing illicit opioid relapse and avoiding preterm labor. Methadone maintenance yielded to a significantly higher neonatal birth weight. Data patterns suggest that buprenorphine exposure was associated with lower neonatal abstinence syndrome (NAS) scores. Findings from this unique case series are consistent with earlier reports using between-group analyses.. Buprenorphine has the potential to become an established treatment alternative to methadone for pregnant opioid-dependent women. Under special consideration of ethical boundaries, psychopharmacological treatment during pregnancy must be addressed as an integral part of clinical research projects in order to optimize treatment for women and neonates.

Topics: Adult; Analgesics, Opioid; Birth Weight; Buprenorphine; Double-Blind Method; Female; Humans; Infant, Newborn; Male; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Severity of Illness Index; Smoking; Treatment Outcome; Young Adult

In order to investigate the effects of exposure to buprenorphine compared with methadone during pregnancy, a prospective multicenter study was conducted in collaboration with maternity hospitals, maintenance therapy centers, and general practitioners involved in addiction care. Ninety pregnant women exposed to buprenorphine and 45 to metadone were selected for the study.. During pregnancy, some women were exposed to illicit agents: cannabis (42% in the buprenorphine group vs. 58% in the methadone-treated group), heroin (17% vs. 44%), or cocaine (3% vs. 11%). Pregnancies ended in 85 vs. 40 live births, one vs. two stillbirths, two vs. one spontaneous abortion, two vs. one voluntary termination, and one vs. one medical termination in the buprenorphine and the methadone groups, respectively. Newborns had a birth weight of 2,892 ± 506 g (buprenorphine) vs. 2,731 ± 634 g (methadone) and a body length of 47.6 ± 2.5 cm vs. 47.1 ± 3 cm. 18.8% vs. 10% of newborns were delivered before 37 weeks of amenorrhea. Neonatal withdrawal syndrome occurred more frequently in the methadone group (62.5% vs. 41.2, p = 0.03). After adjustment for heroin exposure in late pregnancy, rates of neonatal withdrawal were no longer different between the methadone and buprenorphine groups. Twenty-one babies (84%) in the methadone group and 20 (57%) in the buprenorphine group (p = 0.03) required opiate treatment.. We did not observe more frequent malformations or cases of withdrawal syndrome in the buprenorphine group than in the methadone-treated group. Buprenorphine appears to be as safe as the currently approved substitute methadone considered to date as the reference treatment for pregnant opioid-dependent women.

Topics: Adult; Analgesics, Opioid; Birth Weight; Buprenorphine; Female; Heroin; Heroin Dependence; Humans; Infant, Newborn; Methadone; Narcotics; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prospective Studies

The purpose was to explore methadone and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) umbilical cord disposition, correlate with maternal methadone dose and neonatal outcomes, and evaluate the window of drug detection in umbilical cord of in utero illicit drug exposure.. Subjects comprised 19 opioid-dependent pregnant women from 2 clinical studies, one comparing methadone and buprenorphine pharmacotherapy for opioid-dependence treatment and the second examining monetary reinforcement schedules to maintain drug abstinence. Correlations were calculated for methadone and EDDP umbilical cord concentrations and maternal methadone dose, and neonatal outcomes. Cocaine- and opiate-positive umbilical cord concentrations were compared with those in placenta and meconium, and urine specimens collected throughout gestation.. Significant positive correlations were found for umbilical cord methadone concentrations and methadone mean daily dose, mean dose during the third trimester, and methadone cumulative daily dose. Umbilical cord EDDP concentrations and EDDP/methadone concentration ratios were positively correlated to newborn length, peak neonatal abstinence syndrome (NAS) score, and time-to-peak NAS score. Methadone concentrations and EDDP/methadone ratios in umbilical cord and placenta were positively correlated. Meconium identified many more cocaine- and opiate-positive specimens than did umbilical cord.. Umbilical cord methadone concentrations were correlated to methadone doses. Also, our results indicate that methadone and EDDP concentrations might help to predict the NAS severity. Meconium proved to be more suitable than umbilical cord to detect in utero exposure to cocaine and opiates; however, umbilical cord could be useful when meconium is unavailable due to in utero or delayed expulsion.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Cocaine; Dose-Response Relationship, Drug; Female; Humans; Infant, Newborn; Maternal-Fetal Exchange; Meconium; Methadone; Narcotics; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Placenta; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pyrrolidines; Umbilical Cord

Recent studies have demonstrated the efficacy of both methadone and buprenorphine when used with opioid dependent men transitioning from prison to the community, but no studies have been conducted with women in the criminal justice (CJ) system. The aim of this study was to determine the efficacy of buprenorphine for relapse prevention among opioid dependent women in the CJ system transitioning back to the community.. 36 women under CJ supervision were recruited from an inpatient drug treatment facility that treats CJ individuals returning back to the community. Nine were enrolled in an open label buprenorphine arm then 27 were randomized to buprenorphine (n=15) or placebo (n=12; double-blind). All women completed baseline measures and started study medication prior to release. Participants were followed weekly, provided urine drug screens (UDS), received study medication for 12 weeks, and returned for a 3-month follow-up. Intent-to-treat analyses were performed for all time points through 3 month follow-up.. The majority of participants were Caucasian (88.9%), young (M±SD=31.8±8.4 years), divorced/separated (59.2%) women with at least a high school/GED education (M±SD=12±1.7 years). GEE analyses showed that buprenorphine was efficacious in maintaining abstinence across time compared to placebo. At end of treatment, 92% of placebo and 33% of active medication participants were positive for opiates on urine drug screen (Chi-Square=10.9, df=1; p<0.001). However, by the three month follow-up point, no differences were found between the two groups, with 83% of participants at follow-up positive for opiates.. Women in the CJ system who received buprenorphine prior to release from a treatment facility had fewer opiate positive UDS through the 12 weeks of treatment compared to women receiving placebo. Initiating buprenorphine in a controlled environment prior to release appears to be a viable strategy to reduce opiate use when transitioning back to the community.

Topics: Adult; Alabama; Buprenorphine; Criminal Law; Double-Blind Method; Female; Follow-Up Studies; Humans; Longitudinal Studies; Opioid-Related Disorders; Pilot Projects; Substance Abuse Treatment Centers; Young Adult

The objective of this study is to compare maternal and neonatal outcome of opioid-dependent women maintained on buprenorphine or methadone throughout pregnancy in a randomized double-blind double-dummy clinical trial (CT) with a comparison group undergoing a structured standard protocol (SP) at the Medical University of Vienna, Austria.. One hundred and fourteen subjects were included in the analysis, with 77 in SP (n = 51 methadone, n = 26 buprenorphine), and 37 in CT (n = 19 methadone, n = 18 buprenorphine), comparing maternal concomitant consumption during third trimester, demographic birth data, duration of treatment for neonatal abstinence syndrome (NAS), morphine dose for NAS treatment and length of hospital stay (LOS).. Both study groups yielded healthy neonates with no significant demographic differences and equivalently low rates of positive maternal urine toxicologies. However, NAS parameters were significantly better in CT regarding total medication dose administered to neonates (p = 0.014) and LOS (p = 0.015). Superior results were achieved in buprenorphine compared with methadone-exposed neonates regarding gestational age at birth (p = 0.003), birth weight (p = 0.011), total morphine dose administered (p = 0.008), NAS treatment duration (p = 0.008) and LOS (p = 0.001).. Comparably favorable outcome for mothers and infants and efficacy and safety of opioid medications were shown in both treatment approaches. Neonatal care could benefit from transferring successful CT procedures into clinical practice.

Topics: Adult; Austria; Birth Weight; Buprenorphine; Double-Blind Method; Female; Gestational Age; Humans; Infant, Newborn; Length of Stay; Male; Methadone; Morphine; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pregnancy Trimester, Third; Prospective Studies; Time Factors; Young Adult

Buprenorphine and methadone are widely used for the treatment of opioid dependence, but their diversion and/or misuse are frequent. In principle, buprenorphine/naloxone combination therapy should be associated with a lower frequency of drug abuse/misuse than methadone. This study assessed the efficacy of the substitution of buprenorphine treatment with the buprenorphine/naloxone combination in opioid-dependent patients.. 3812 drug-addicted outpatients selected from 10 Italian Public Services for Addiction (Ser.T.) centres in Naples (Italy) were enrolled: 3105 (81.5%) were treated with methadone and 707 (18.5%) with buprenorphine. The buprenorphine treatment was switched to buprenorphine/naloxone (4:1), and the patients were followed for about 1 year. The number of subjects still on treatment after 1 year, their status according to social, educational and toxicologic (assessed by a urine toxicology test) parameters were assessed.. 1 year after the therapy switch, the number of patients still on treatment was similarly reduced with methadone (2883; -7.5%) and buprenorphine/naloxone (632; -10.6%; p=0.369). However, in patients treated with buprenorphine/naloxone, a significant improvement was reported in social life status (63% versus 39% of the buprenorphine/naloxone and methadone treated subjects, respectively, were married/cohabiting p<0.001), in the educational level (43% of buprenorphine/naloxone treated versus 32% of the methadone treated subjects obtained at least a high school certificate, p<0.001) and in the toxicological conditions (53% of buprenorphine/naloxone treated subject versus 30% of methadone treated individuals had opioid- and cocaine- negative urine tests, p<0.001).. These preliminary data suggest that buprenorphine/naloxone treatment of opioid dependence reduces the percentage of treated subjects similarly to methadone, and is associated with an improvement in social life, educational and toxicological conditions, compared with methadone treatment. However, we cannot exclude a selection bias, i.e. patients who were more likely to stabilize their opiate dependence switched to buprenorphine/naloxone.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Cocaine; Drug Therapy, Combination; Educational Status; Female; Humans; Longitudinal Studies; Male; Methadone; Naloxone; Opiate Substitution Treatment; Opioid-Related Disorders; Social Behavior

Accumulating evidence indicates important gender differences in substance use disorders. Little is known, however, about gender differences and opioid use disorders.. To compare demographic characteristics, substance use severity, and other associated areas of functioning (as measured by the Addiction Severity Index-Lite (ASI-Lite)) among opioid-dependent men and women participating in a multisite effectiveness trial.. Participants were 892 adults screened for the National Institute on Drug Abuse Clinical Trials Network investigation of the effectiveness of two buprenorphine tapering schedules.. The majority of men and women tested positive for oxycodone (68% and 65%, respectively) and morphine (89% each). More women than men tested positive for amphetamines (4% vs. 1%, p < .01), methamphetamine (11% vs. 4%, p < .01), and phencyclidine (8% vs. 4%, p = .02). More men than women tested positive for methadone (11% vs. 6%, p = .05) and marijuana (22% vs. 15%, p = .03). Craving for opioids was significantly higher among women (p < .01). Men evidenced higher alcohol (p < .01) and legal (p = .04) ASI composite scores, whereas women had higher drug (p < .01), employment (p < .01), family (p < .01), medical (p < .01), and psychiatric (p < .01) ASI composite scores. Women endorsed significantly more current and past medical problems.. Important gender differences in the clinical profiles of opioid-dependent individuals were observed with regard to substance use severity, craving, medical conditions, and impairment in associated areas of functioning. The findings enhance understanding of the characteristics of treatment-seeking men and women with opioid dependence, and may be useful in improving identification, prevention, and treatment efforts for this challenging and growing population.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Female; Humans; Male; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Severity of Illness Index; Sex Factors; Substance-Related Disorders; United States

Clinical parameters for determining buprenorphine dose have not been adequately examined in treatment outcome research.. This study is a secondary analysis of data collected in a recently completed comparison of buprenorphine taper schedules conducted as part of the National Institute on Drug Abuse's Clinical Trials Network to assess whether participant baseline characteristics are associated with buprenorphine dose.. After 3 weeks of flexible dosing, 516 participants were categorized by dose provided in the final dosing week (9.3% received a final week dose of 8 mg buprenorphine, 27.3% received 16 mg, and 63.4% received 24 mg).. Findings show that final week dose groups differed in baseline demographic and drug use characteristics including education, heroin use, route of drug administration, withdrawal symptoms, and craving. These groups also differed in opioid use during the four dosing weeks, with the lowest use in the 8 mg group and highest use in the 24 mg group (p < .0001). Additional analyses address withdrawal symptoms and craving.. Final week dose groups differed in demographic and drug use characteristics, and the group receiving the largest final week dose had the highest rate of continued opioid use. These findings may contribute to the development of clinical guidelines regarding buprenorphine dose in the treatment of opioid dependence; however, further investigations that include random assignment to dose by baseline characteristics are needed.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Heroin Dependence; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; National Institute on Drug Abuse (U.S.); Opiate Substitution Treatment; Opioid-Related Disorders; United States

In many but not in all neuropsychological studies buprenorphine-treated opioid-dependent patients have shown fewer cognitive deficits than patients treated with methadone. In order to examine if hypothesized cognitive advantage of buprenorphine in relation to methadone is seen in clinical patients we did a neuropsychological follow-up study in unselected sample of buprenorphine- vs. methadone-treated patients.. In part I of the study fourteen buprenorphine-treated and 12 methadone-treated patients were tested by cognitive tests within two months (T1), 6-9 months (T2), and 12-17 months (T3) from the start of opioid substitution treatment. Fourteen healthy controls were examined at similar intervals. Benzodiazepine and other psychoactive comedications were common among the patients. Test results were analyzed with repeated measures analysis of variance and planned contrasts. In part II of the study the patient sample was extended to include 36 patients at T2 and T3. Correlations between cognitive functioning and medication, substance abuse, or demographic variables were then analyzed.. In part I methadone patients were inferior to healthy controls tests in all tests measuring attention, working memory, or verbal memory. Buprenorphine patients were inferior to healthy controls in the first working memory task, the Paced Auditory Serial Addition Task and verbal memory. In the second working memory task, the Letter-Number Sequencing, their performance improved between T2 and T3. In part II only group membership (buprenorphine vs. methadone) correlated significantly with attention performance and improvement in the Letter-Number Sequencing. High frequency of substance abuse in the past month was associated with poor performance in the Letter-Number Sequencing.. The results underline the differences between non-randomized and randomized studies comparing cognitive performance in opioid substitution treated patients (fewer deficits in buprenorphine patients vs. no difference between buprenorphine and methadone patients, respectively). Possible reasons for this are discussed.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Cognition; Female; Follow-Up Studies; Humans; Male; Methadone; Neuropsychological Tests; Opiate Substitution Treatment; Opioid-Related Disorders; Psychomotor Performance; Statistics as Topic

Buprenorphine is currently under investigation as a pharmacotherapy to treat pregnant women for opioid dependence. This research evaluates buprenorphine (BUP), norbuprenophine (NBUP), buprenorphine-glucuronide (BUP-Gluc), and norbuprenorphine-glucuronide (NBUP-Gluc) pharmacokinetics after high-dose (14-20 mg) BUP sublingual tablet administration in three opioid-dependent pregnant women.. Oral fluid and sweat specimens were collected in addition to plasma specimens for 24 hours during gestation weeks 28 or 29 and 34, and 2 months after delivery. Time to maximum concentration was not affected by pregnancy; however, BUP and NBUP maximum concentration and area under the curve at 0 to 24 hours tended to be lower during pregnancy compared with postpartum levels.. Statistically significant but weak positive correlations were found for BUP plasma and OF concentrations and BUP/NBUP ratios in plasma and oral fluid. Statistically significant negative correlations were observed for times of specimen collection and BUP and NBUP oral fluid/plasma ratios. BUP-Gluc and NBUP-Gluc were detected in only 5% of oral fluid specimens. In sweat, BUP and NBUP were detected in only four of 25 (12 or 24 hours) specimens in low concentrations (less than 2.4 ng/patch).. These preliminary data describe BUP and metabolite pharmacokinetics in pregnant women and suggest that, like methadone, upward dose adjustments may be needed with advancing gestation.

Topics: Area Under Curve; Buprenorphine; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Narcotic Antagonists; Opioid-Related Disorders; Postpartum Period; Pregnancy; Saliva; Sweat

To examine predictors of opioid abstinence in buprenorphine/naloxone (Bup/Nal)-assisted psychosocial treatment for opioid-dependent youth.. Secondary analyses were performed of data from 152 youth (15-21 years old) randomly assigned to 12 weeks of extended Bup/Nal therapy or up to 2 weeks of Bup/Nal detoxification with weekly individual and group drug counseling. Logistic regression models were constructed to identify baseline and during-treatment predictors of opioid-positive urine (OPU) at week 12. Predictors were selected based on significance or trend toward significance (i.e., p < .1), and backward stepwise selection was used, controlling for treatment group, to produce final independent predictors at p ≤ .05.. Youth presenting to treatment with previous 30-day injection drug use and more active medical/psychiatric problems were less likely to have a week-12 OPU. Those with early treatment opioid abstinence (i.e., weeks 1 and 2) and those who received additional nonstudy treatments during the study were less likely to have a week-12 OPU and those not completing 12 weeks of treatment were more likely to have an OPU.. Youth with advanced illness (i.e., reporting injection drug use and additional health problems) and those receiving ancillary treatments to augment study treatment were more likely to have lower opioid use. Treatment success in the first 2 weeks and completion of 12 weeks of treatment were associated with lower rates of OPU. These findings suggest that youth with advanced illness respond well to Bup/Nal treatment and identify options for tailoring treatment for opioid-dependent youth presenting at community-based settings.. Buprenorphine/Naloxone-Facilitated Rehabilitation for Opioid Dependent Adolescents; http://www.clinicaltrials.gov; NCT00078130.

Topics: Adolescent; Adult; Buprenorphine; Combined Modality Therapy; Counseling; Female; Humans; Male; Naloxone; Narcotic Antagonists; National Institute on Drug Abuse (U.S.); Opiate Substitution Treatment; Opioid-Related Disorders; Severity of Illness Index; Substance Abuse Detection; Treatment Outcome; United States; Young Adult

No randomized trials have examined treatments for prescription opioid dependence, despite its increasing prevalence.. To evaluate the efficacy of brief and extended buprenorphine hydrochloride-naloxone hydrochloride treatment, with different counseling intensities, for patients dependent on prescription opioids.. Multisite, randomized clinical trial using a 2-phase adaptive treatment research design. Brief treatment (phase 1) included 2-week buprenorphine-naloxone stabilization, 2-week taper, and 8-week postmedication follow-up. Patients with successful opioid use outcomes exited the study; unsuccessful patients entered phase 2: extended (12-week) buprenorphine-naloxone treatment, 4-week taper, and 8-week postmedication follow-up.. Ten US sites. Patients A total of 653 treatment-seeking outpatients dependent on prescription opioids.. In both phases, patients were randomized to standard medical management (SMM) or SMM plus opioid dependence counseling; all received buprenorphine-naloxone.. Predefined "successful outcome" in each phase: composite measures indicating minimal or no opioid use based on urine test-confirmed self-reports.. During phase 1, only 6.6% (43 of 653) of patients had successful outcomes, with no difference between SMM and SMM plus opioid dependence counseling. In contrast, 49.2% (177 of 360) attained successful outcomes in phase 2 during extended buprenorphine-naloxone treatment (week 12), with no difference between counseling conditions. Success rates 8 weeks after completing the buprenorphine-naloxone taper (phase 2, week 24) dropped to 8.6% (31 of 360), again with no counseling difference. In secondary analyses, successful phase 2 outcomes were more common while taking buprenorphine-naloxone than 8 weeks after taper (49.2% [177 of 360] vs 8.6% [31 of 360], P < .001). Chronic pain did not affect opioid use outcomes; a history of ever using heroin was associated with lower phase 2 success rates while taking buprenorphine-naloxone.. Prescription opioid-dependent patients are most likely to reduce opioid use during buprenorphine-naloxone treatment; if tapered off buprenorphine-naloxone, even after 12 weeks of treatment, the likelihood of an unsuccessful outcome is high, even in patients receiving counseling in addition to SMM.

Topics: Adult; Buprenorphine; Combined Modality Therapy; Counseling; Drug Therapy, Combination; Female; Humans; Interview, Psychological; Male; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Psychiatric Status Rating Scales; Treatment Outcome

Prior studies have shown an increased vulnerability among males to adverse outcomes during the postnatal period. Most children exposed to opioids and other medications in utero develop neonatal abstinence syndrome (NAS), yet individual predisposition for NAS is poorly understood.. This investigation examined the role of neonatal sex in the postnatal period for neonates exposed to standardized opioid maintenance treatment in utero with a focus on NAS regarding severity, medication requirements, and duration.. This was a secondary analysis of data collected in a prospective randomized, double-blind, double-dummy, multicenter trial (MOTHER study) that examined the comparative safety and efficacy of methadone and buprenorphine during pregnancy. A total of 131 neonates born to opioid-dependent women randomized at 6 US sites (n = 74) and 1 European site (n = 37) were analyzed. Sex-based differences in birth weight, length, head circumference, NAS duration, NAS severity, and treatment parameters of full-term neonates were assessed.. Males had a significantly higher birth weight (P = 0.027) and head circumference (P = 0.017) compared with females, with no significant sex difference in rates of preterm delivery. No significant sex-related differences were found for NAS development, severity, or duration, or medication administered, and there were no significant differences in concomitant drug consumption during pregnancy (P = 0.959).. This unique prospective study shows similar postnatal vulnerability for both sexes, suggesting that factors other than sex are the major determinants of clinically significant NAS. ClinicalTrials.gov identifier: NCT 00271219.

Topics: Birth Weight; Buprenorphine; Double-Blind Method; Female; Humans; Infant, Newborn; Male; Methadone; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prenatal Exposure Delayed Effects; Prospective Studies; Risk Factors; Severity of Illness Index; Sex Distribution; Sex Factors

Many opiate users require prescribed medication to help them achieve abstinence, commonly taking the form of a detoxification regime. In UK prisons, drug users are nearly universally treated for their opiate use by primary care clinicians, and once released access GP services where 40% of practices now treat drug users. There is a paucity of evidence evaluating methadone and buprenorphine (the two most commonly prescribed agents in the UK) for opiate detoxification.. To evaluate whether buprenorphine or methadone help to achieve drug abstinence at completion of a reducing regimen for heroin users presenting to UK prison health care for detoxification.. Open-label, pragmatic, randomised controlled trial in three prison primary healthcare departments in the north of England.. Prisoners (n = 306) using illicit opiates were recruited and given daily sublingual buprenorphine or oral methadone, in the context of routine care, over a standard reduced regimen of not more than 20 days. The primary outcome measure was abstinence from illicit opiates at 8 days post detoxification, as indicated by urine test (self-report/clinical notes where urine sample was not feasible). Secondary outcomes were also recorded.. Abstinence was ascertained for 73.7% at 8 days post detoxification (urine sample = 52.6%, self report = 15.2%, clinical notes = 5.9%). There was no statistically significant difference in the odds of achieving abstinence between methadone and buprenorphine (odds ratio [OR] = 1.69; 95% confidence interval [CI] = 0.81 to 3.51; P = 0.163). Abstinence was associated solely with whether or not the participant was still in prison at that time (15.22 times the odds; 95% CI = 4.19 to 55.28). The strongest association for lasting abstinence was abstinence at an earlier time point.. There is equal clinical effectiveness between methadone and buprenorphine in achieving abstinence from opiates at 8 days post detoxification within prison.

Topics: Administration, Oral; Administration, Sublingual; Adult; Aged; Buprenorphine; Humans; Methadone; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Prisoners; Young Adult

This pilot study tested the effectiveness of transcutaneous electric acupoint stimulation (TEAS) as an adjunctive treatment for inpatients receiving opioid detoxification with buprenorphine-naloxone at a private psychiatric hospital. Participants (N = 48) were randomly assigned to active or sham TEAS and received three 30-minute treatments daily for 3 to 4 days. In active TEAS, current was set to maximal tolerable intensity (8-15 mA); in sham TEAS, it was set to 1 mA. By 2 weeks postdischarge, participants in active TEAS were less likely to have used any drugs (35% vs. 77%, p < .05). They also reported greater improvements in pain interference (F = 4.52, p < .05) and physical health (F = 4.84, p < .01) over time. TEAS is an acceptable, inexpensive adjunctive treatment that is feasible to implement on an inpatient unit and may be a beneficial adjunct to pharmacological treatments for opioid detoxification.

Topics: Acupuncture Points; Adolescent; Adult; Analgesics, Opioid; Analysis of Variance; Buprenorphine; Chi-Square Distribution; Combined Modality Therapy; Drug Administration Schedule; Female; Health Status; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Pain; Patient Selection; Substance Withdrawal Syndrome; Survival Analysis; Time Factors; Transcutaneous Electric Nerve Stimulation

The present investigation examines baseline patient characteristics to predict dosing of buprenorphine-naloxone, a promising treatment for opioid addiction in youths.. This study of 69 opioid-dependent youths is a secondary analysis of data collected during a National Institute on Drug Abuse (NIDA) Clinical Trials Network study. Outpatients aged 15-21 were randomized to a 12-week buprenorphine-naloxone dosing condition (including 4 weeks of taper). Predictors of dosing included sociodemographic characteristics (gender, race, age, and education), substance use (alcohol, cannabis, cocaine, and nicotine use), and clinical characteristics (pain and withdrawal severity).. Most (75.4%) reported having either "some" (n=40, 58.0%) or "extreme" (n=12, 17.4%) pain on enrollment. Maximum daily dose of buprenorphine-naloxone (19.7 mg) received by patients reporting "extreme" pain at baseline was significantly higher than the dose received by patients reporting "some" pain (15.0mg) and those without pain (12.8 mg). In the adjusted analysis, only severity of pain and withdrawal significantly predicted dose. During the dosing period, there were no significant differences in opioid use, as measured by urinalysis, by level of pain.. These data suggest that the presence of pain predicts buprenorphine-naloxone dose levels in opioid-dependent youth, and that patients with pain have comparable opioid use outcomes to those without pain, but require higher buprenorphine-naloxone doses.

Topics: Adolescent; Age Factors; Buprenorphine; Data Interpretation, Statistical; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Male; Naloxone; Narcotic Antagonists; Narcotics; National Institute on Drug Abuse (U.S.); Opioid-Related Disorders; Outpatients; Pain; Pain Measurement; Socioeconomic Factors; Substance Withdrawal Syndrome; Time Factors; Treatment Outcome; United States; Young Adult

Physician adoption of buprenorphine treatment of opioid dependence may be limited in part by concerns regarding the induction process. Although national guidelines recommend observed induction, some physicians utilize unobserved induction outside the office. The aim of this pilot randomized clinical trial was to assess preliminary safety and effectiveness of unobserved versus observed office buprenorphine/naloxone induction among patients entering a 12-week primary care maintenance study. Participants (N=20) with DSM-IV opioid dependence were randomly assigned to unobserved or office induction, stratifying by past buprenorphine use. All patients received verbal and written instructions. A withdrawal scale was used during initiation and to monitor treatment response. Clinic visits occurred weekly for 4 weeks then decreased to monthly. The primary outcome, successful induction one week after the initial clinic visit, was defined as retention in buprenorphine/naloxone treatment and being withdrawal free. Secondary outcomes included prolonged withdrawal beyond 2 days after medication initiation and stabilization at week 4, defined as being in treatment without illicit opioid use for the preceding 2 weeks. Outcome results were similar in the two groups: 6/10 (60%) successfully inducted in each group, 3/10 (30%) experienced prolonged withdrawal, and 4/10 (40%) stabilized by week 4. These pilot study results suggest comparable safety and effectiveness of unobserved and office induction and point toward utilization of non-inferiority design during future definitive protocol development. By addressing an important barrier for physician adoption, further validation of the unobserved buprenorphine induction method will hopefully lead to increased availability of effective opioid dependence treatment.

Topics: Adolescent; Adult; Aged; Ambulatory Care; Buprenorphine; Directly Observed Therapy; Female; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; New York; Opioid-Related Disorders; Pilot Projects; Practice Patterns, Physicians'; Primary Health Care; Substance Withdrawal Syndrome; Treatment Outcome; Young Adult

The National Institute on Drug Abuse Clinical Trials Network launched the Prescription Opioid Addiction Treatment Study (POATS) in response to rising rates of prescription opioid dependence and gaps in understanding the optimal course of treatment for this population. POATS employed a multi-site, two-phase adaptive, sequential treatment design to approximate clinical practice. The study took place at 10 community treatment programs around the United States. Participants included men and women age > or =18 who met Diagnostic and Statistical Manual, 4th Edition criteria for dependence upon prescription opioids, with physiologic features; those with a prominent history of heroin use (according to pre-specified criteria) were excluded. All participants received buprenorphine/naloxone (bup/nx). Phase 1 consisted of 4 weeks of bup/nx treatment, including a 14-day dose taper, with 8 weeks of follow-up. Phase 1 participants were monitored for treatment response during these 12 weeks. Those who relapsed to opioid use, as defined by pre-specified criteria, were invited to enter Phase 2; Phase 2 consisted of 12 weeks of bup/nx stabilization treatment, followed by a 4-week taper and 8 weeks of post-treatment follow-up. Participants were randomized at the beginning of Phase 1 to receive bup/nx, paired with either Standard Medical Management (SMM) or Enhanced Medical Management (EMM; defined as SMM plus individual drug counseling). Eligible participants entering Phase 2 were re-randomized to either EMM or SMM. POATS was developed to determine what benefit, if any, EMM offers over SMM in short-term and longer-term treatment paradigm. This paper describes the rationale and design of the study.

Topics: Analgesics, Opioid; Buprenorphine; Directive Counseling; Female; Health Status Indicators; Humans; Male; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Prescription Drugs; Psychometrics; Quality of Life; Research Design; United States

Buprenorphine (Subutex) is the most abused opioid in Finland. In order to curb the abuse potential of this drug, many treatment centers and prisons crush Subutex tablets before administering them to patients. To date, there are no published studies comparing the efficacy and bioavailability of crushed and whole Subutex tablets.. A total of 16 opioid-dependent patients stabilized on 24 mg of buprenorphine were enrolled in a double-blind, double-dummy, randomized cross-over study comparing crushed and whole buprenorphine tablets on a range of pharmacokinetic and pharmacodynamic variables. Buprenorphine tablets (either crushed or whole) and placebo tablets (either crushed or whole) were administered to subjects simultaneously. Buprenorphine and norbuprenorphine serum levels were measured at 30, 60, 90, 120, 180, 240 and 360 min, as well as 24 h, after tablet administration. After 1 week, the experiment was repeated in a cross-over design so that, by the end of the study, each patient had received the active drug (buprenorphine) as both crushed and whole tablets.. Pharmacokinetic parameters (mean serum levels, C(max), T(max), AUC) of buprenorphine or norbuprenorphine did not differ significantly between crushed and whole tablets, although serum levels were slightly higher after administration of the crushed tablets. There were also no significant differences in dissolution/absorption time, withdrawal signs or opiate craving.. We conclude that crushing Subutex tablets does not significantly alter serum buprenorphine or norbuprenorphine levels or the drug's clinical effect. Our results indicate that crushing Subutex tablets may be used as an alternative method to counter the risk of buprenorphine diversion.

Topics: Adult; Area Under Curve; Biological Availability; Buprenorphine; Cross-Over Studies; Double-Blind Method; Female; Humans; Male; Narcotic Antagonists; Opioid-Related Disorders; Powders; Substance Withdrawal Syndrome; Tablets; Time Factors; Young Adult

Analysis of saccadic eye movements (SEMs) has previously been used to detect drug- and sleep-deprivation-induced sedation, but never in combination. We compared the effects of sleep deprivation and opioids on 10 opioid-naive with nine opioid-tolerant participants. The naive-participant study evaluated the effects of sleep deprivation alone, morphine alone and the combination; the tolerant-participant study compared day-to-day effects of alternate-daily-dosed buprenorphine and the combination of buprenorphine on the dosing day with sleep deprivation. Psychomotor impairment was measured using SEMs, a 5-minute pupil adaptation test (PAT), pupil light reflex (PLR) and alertness visual analogue scale (AVAS). The PAT and PLR did not detect sleep deprivation, in contrast to previous studies. Whilst consistently detecting sleep deprivation, the AVAS also detected buprenorphine in the tolerant study, but not morphine in the naive study. SEMs detected morphine alone and sleep deprivation alone as well as an additive interaction in the naive study and the effect of sleep deprivation in the tolerant study. The alternate-day buprenorphine dosing did not alter SEMs. The current study revealed greater SEMs, but not AVAS impairment in tolerant versus naive participants. The current study demonstrates that objective measures provide additional information to subjective measures and thus should be used in combination.

Topics: Adult; Analgesics, Opioid; Biomarkers, Pharmacological; Buprenorphine; Deep Sedation; Drug Interactions; Drug Tolerance; Female; Humans; Male; Middle Aged; Morphine; Opioid-Related Disorders; Psychomotor Disorders; Saccades; Sleep Deprivation; Young Adult

Behaviors associated with opioid dependence often involve criminal activity, which can lead to incarceration. The impact of a history of incarceration on outcomes in primary care office-based buprenorphine/naloxone is not known.. The purpose of this study is to determine whether having a history of incarceration affects response to primary care office-based buprenorphine/naloxone treatment.. In this post hoc secondary analysis of a randomized clinical trial, we compared demographic, clinical characteristics, and treatment outcomes among 166 participants receiving primary care office-based buprenorphine/naloxone treatment stratifying on history of incarceration.. Participants with a history of incarceration have similar treatment outcomes with primary care office-based buprenorphine/naloxone than those without a history of incarceration (consecutive weeks of opioid-negative urine samples, 6.2 vs. 5.9, p = 0.43; treatment retention, 38% vs. 46%, p = 0.28).. Prior history of incarceration does not appear to impact primary care office-based treatment of opioid dependence with buprenorphine/naloxone. Community health care providers can be reassured that initiating buprenorphine/naloxone in opioid dependent individuals with a history of incarceration will have similar outcomes as those without this history.

Topics: Adult; Buprenorphine; Criminals; Female; Humans; Male; Middle Aged; Naloxone; Office Visits; Opioid-Related Disorders; Primary Health Care; Socioeconomic Factors; Treatment Outcome; Young Adult

Buprenorphine is approved as pharmacotherapy for opioid dependence in nonpregnant patients in multiple countries and is currently under investigation for pregnant women in the United States and Europe. This research evaluates the disposition of buprenorphine, opiates, cocaine, and metabolites in five term placentas from a US cohort. Placenta and matched meconium concentrations were compared, and relationships among maternal buprenorphine dose, placenta concentrations, and neonatal outcomes after controlled administration during gestation were investigated. Buprenorphine and/or metabolites were detected in all placenta specimens and were uniformly distributed across this tissue (coefficient of variation less than 27.5%, four locations), except for buprenorphine in three placentas. In two of these, buprenorphine was not detected in some locations and in the third placenta was totally absent. Median (range) concentrations were 1.6 ng/g buprenorphine (not detected to 3.2), 14.9 ng/g norbuprenorphine (6.2-24.2), 3 ng/g buprenorphine-glucuronide (1.3-5.0), and 14.7 ng/g norbuprenorphine-glucuronide (11.4-25.8). Placenta is a potential alternative matrix for detecting in utero buprenorphine exposure, but at lower concentrations (15- to 70-fold) than in meconium. Statistically significant correlations were observed for mean maternal daily dose from enrollment to delivery and placenta buprenorphine-glucuronide concentration and for norbuprenorphine-glucuronide concentrations and time to neonatal abstinence syndrome onset and duration, for norbuprenorphine/norbuprenorphine-glucuronide ratio and maximum neonatal abstinence syndrome score, and newborn length. Analysis of buprenorphine and metabolites in this alternative matrix, an abundant waste product available at the time of delivery, may be valuable for prediction of neonatal outcomes for clinicians treating newborns of buprenorphine-exposed women.

Topics: Adult; Buprenorphine; Cohort Studies; Female; Humans; Infant, Newborn; Male; Maternal-Fetal Exchange; Opioid-Related Disorders; Placenta; Pregnancy; Pregnancy Outcome; Prenatal Exposure Delayed Effects; Treatment Outcome; Young Adult

For individuals dependent on opioids, recovery efforts begin with a period of withdrawal that typically includes discomfort from symptoms, possibly precipitating a return to drug use. The study described here investigated whether the provision of ancillary medications for opioid withdrawal symptoms affected treatment outcomes in 139 participants receiving buprenorphine in a 13-day detoxification trial. Outcome measures include the number of opioid-free urine samples collected and retention in treatment. Ancillary medications were provided to 70% of participants: 59% received medication for insomnia, 45% for anxiety, 40% for bone pain, 35% for nausea, and 28% for diarrhea. Findings indicate no difference in the number of opioid-free urine samples between the group receiving ancillary medication and the group who did not, although tests of specific ancillary medications indicate that those who received diarrhea medication had fewer opioid-free urines than those who did not (P = .004). Results also indicate that participants attended fewer days of treatment if they received anxiety, nausea, or diarrhea medication compared to no medication (all P values < .05).

Topics: Adult; Analgesics, Opioid; Anxiety; Buprenorphine; Diarrhea; Female; Humans; Inactivation, Metabolic; Male; Middle Aged; Narcotics; Nausea; Opioid-Related Disorders; Pain; Receptors, Opioid, delta; Sleep Initiation and Maintenance Disorders; Substance Withdrawal Syndrome; Treatment Outcome

Opioid dependence is common in HIV clinics. Buprenorphine-naloxone (BUP) is an effective treatment of opioid dependence that may be used in routine medical settings.. To compare clinic-based treatment with BUP (clinic-based BUP) with case management and referral to an opioid treatment program (referred treatment).. Single-center, 12-month randomized trial. Participants and investigators were aware of treatment assignments. (ClinicalTrials.gov registration number: NCT00130819). HIV clinic in Baltimore, Maryland.. 93 HIV-infected, opioid-dependent participants who were not receiving opioid agonist therapy and were not dependent on alcohol or benzodiazepines.. Clinic-based BUP included BUP induction and dose titration, urine drug testing, and individual counseling. Referred treatment included case management and referral to an opioid-treatment program.. Initiation and long-term receipt of opioid agonist therapy, urine drug test results, visit attendance with primary HIV care providers, use of antiretroviral therapy, and changes in HIV RNA levels and CD4 cell counts.. The average estimated participation in opioid agonist therapy was 74% (95% CI, 61% to 84%) for clinic-based BUP and 41% (CI, 29% to 53%) for referred treatment (P < 0.001). Positive test results for opioids and cocaine were significantly less frequent in clinic-based BUP than in referred treatment, and study participants receiving clinic-based BUP attended significantly more HIV primary care visits than those receiving referred treatment. Use of antiretroviral therapy and changes in HIV RNA levels and CD4 cell counts did not differ between the 2 groups.. This was a small single-center study, follow-up was only moderate, and the study groups were unbalanced in terms of recent drug injections at baseline.. Management of HIV-infected, opioid-dependent patients with a clinic-based BUP strategy facilitates access to opioid agonist therapy and improves outcomes of substance abuse treatment.. Health Resources and Services Administration Special Projects of National Significance program.

Topics: Anti-HIV Agents; Baltimore; Buprenorphine; Community Health Services; Drug Therapy, Combination; HIV Infections; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Outcome Assessment, Health Care; Referral and Consultation; Substance Abuse Treatment Centers; Treatment Outcome

Buprenorphine is a partial mu opioid receptor agonist with clinical efficacy as a pharmacotherapy for opioid dependence. A sublingual combination formulation was developed containing buprenorphine and naloxone with the intent of decreasing abuse liability in opioid-dependent individuals. However, the addition of naloxone may not limit abuse potential of this medication when taken by individuals without opioid physical dependence.. The present study investigated the effects of buprenorphine alone and in combination with naloxone administered intramuscularly and sublingually to non-dependent opioid abusers.. In a within-subject crossover design, non-dependent opioid-experienced volunteers (N = 8) were administered acute doses of buprenorphine (4, 8, and 16 mg) and buprenorphine/naloxone (4/1, 8/2, and 16/4 mg) via both intramuscular and sublingual routes, intramuscular hydromorphone (2 and 4 mg as an opioid agonist control), and placebo, for a total of 15 drug conditions. Laboratory sessions were conducted twice per week using a double-blind, double-dummy design.. Buprenorphine and buprenorphine/naloxone engendered effects similar to hydromorphone. Intramuscular administration produced a greater magnitude of effects compared to the sublingual route at the intermediate dose of buprenorphine and at both the low and high doses of the buprenorphine/naloxone combination. The addition of naloxone did not significantly alter the effects of buprenorphine.. These results suggest that buprenorphine and buprenorphine/naloxone have similar abuse potential in non-dependent opioid abusers, and that the addition of naloxone at these doses and in this dose ratio confers no evident advantage for decreasing the abuse potential of intramuscular or sublingual buprenorphine in this population.

Topics: Administration, Sublingual; Adult; Buprenorphine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Drug Users; Female; Humans; Hydromorphone; Injections, Intramuscular; Male; Middle Aged; Naloxone; Opioid-Related Disorders; Surveys and Questionnaires

Our goal was to determine whether treatment of depressive symptoms with escitalopram during buprenorphine treatment for opioid dependence would improve treatment retention compared to placebo in a 12-week, randomized, double-blind trial. Treatment dropout was defined as missing seven consecutive buprenorphine dosing days. Participants were 76% male, 80% non-Hispanic Caucasian, and 64% heroin users. At baseline, the mean Beck Depression Inventory II (BDI-II) score was 28.4 (+/-9.7). Sixty-one percent of participants completed the 12-week buprenorphine protocol. Dropout rates were 33.3% and 44.0% among those randomized to escitalopram or placebo, respectively (p = .19). Relative to baseline, mean BDI-II scores were significantly lower at all follow-up assessments, but the Treatment x Time interaction effect was not statistically significant (p = .18). Participants randomized to escitalopram also did not have a significantly lower likelihood of testing positive for either opiates or other drugs during follow-up. Depressive symptoms often resolved with buprenorphine treatment, and the immediate initiation of escitalopram does not improve treatment retention, depression outcomes, or illicit drug use. Clinicians should determine the need for antidepressant treatment later in buprenorphine care.

Topics: Adult; Antidepressive Agents; Buprenorphine; Citalopram; Depression; Double-Blind Method; Female; Humans; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders

The objective is to estimate cost, net social cost and cost-effectiveness in a clinical trial of extended buprenorphine-naloxone (BUP) treatment versus brief detoxification treatment in opioid-dependent youth.. Economic evaluation of a clinical trial conducted at six community out-patient treatment programs from July 2003 to December 2006, who were randomized to 12 weeks of BUP or a 14-day taper (DETOX). BUP patients were prescribed up to 24 mg per day for 9 weeks and then tapered to zero at the end of week 12. DETOX patients were prescribed up to 14 mg per day and then tapered to zero on day 14. All were offered twice-weekly drug counseling.. 152 patients aged 15-21 years.. Data were collected prospectively during the 12-week treatment and at follow-up interviews at months 6, 9 and 12.. The 12-week out-patient study treatment cost was $1514 (P < 0.001) higher for BUP relative to DETOX. One-year total direct medical cost was only $83 higher for BUP (P = 0.97). The cost-effectiveness ratio of BUP relative to DETOX was $1376 in terms of 1-year direct medical cost per quality-adjusted life year (QALY) and $25,049 in terms of out-patient treatment program cost per QALY. The acceptability curve suggests that the cost-effectiveness ratio of BUP relative to DETOX has an 86% chance of being accepted as cost-effective for a threshold of $100,000 per QALY.. Extended BUP treatment relative to brief detoxification is cost effective in the US health-care system for the outpatient treatment of opioid-dependent youth.

Topics: Adolescent; Adult; Ambulatory Care; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Child; Cost of Illness; Cost-Benefit Analysis; Counseling; Drug Combinations; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Outcome Assessment, Health Care; Quality-Adjusted Life Years; Substance Abuse Detection; Substance Abuse Treatment Centers; United States; Young Adult

Opioid-dependent (OD) patients seeking treatment have multiple treatment options including abstinence-based and medication replacement therapies. A recent and growing addition to medication replacement therapy is buprenorphine medication-assisted treatment (B-MAT), which may be provided by certified physicians practicing in private offices. Research on OD treatment is often performed on samples of patients recruited from specialty treatment facilities, which may not generalize to B-MAT patients. Thus, B-MAT as a treatment approach has been understudied. The present research describes (a) new methods developed to facilitate sample recruitment and survey data collection from a national B-MAT patient sample and (b) a telephonic support program designed for new B-MAT patients. Results indicate that by using appropriate tools, it is feasible to conduct a clinical study of B-MAT patients, recruited at the point of service, and that telephonic patient support was an acceptable treatment adjunct.

Topics: Adult; Ambulatory Care; Buprenorphine; Data Collection; Feasibility Studies; Female; Follow-Up Studies; Humans; Male; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Selection; Research Design; Telephone; United States; Young Adult

This prospective patient-preference study examined the effectiveness in practice of methadone versus buprenorphine maintenance treatment and the beliefs of subjects regarding these drugs. A total of 361 opiate-dependent individuals (89% of those eligible, presenting for treatment over 2 years at a drug service in England) received rapid titration then flexible dosing with methadone or buprenorphine; 227 patients chose methadone (63%) and 134 buprenorphine (37%). Participants choosing methadone had more severe substance abuse and psychiatric and physical problems but were more likely to remain in treatment. Survival analysis indicated those prescribed methadone were over twice as likely to be retained (hazard ratio for retention was 2.08 and 95% confidence interval [CI] = 1.49-2.94 for methadone vs. buprenorphine), However, those retained on buprenorphine were more likely to suppress illicit opiate use (odds ratio = 2.136, 95% CI = 1.509-3.027, p < .001) and achieve detoxification. Buprenorphine may also recruit more individuals to treatment because 28% of those choosing buprenorphine (10% of the total sample) stated they would not have accessed treatment with methadone.

Topics: Adult; Buprenorphine; Choice Behavior; England; Female; Humans; Male; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Preference; Pilot Projects; Proportional Hazards Models; Prospective Studies; Severity of Illness Index; Treatment Outcome; Young Adult

The aim of this study was to determine whether oral sustained release d-amphetamine (SR-AMP) reduces cocaine and opioid/cocaine combination ('speedball'-like) seeking in volunteers with current opioid dependence and cocaine dependence. Following outpatient buprenorphine (BUP) 8 mg/day stabilization without SR-AMP, eight participants completed a 3-week in-patient study with continued BUP 8 mg/day maintenance and double-blind ascending SR-AMP weekly doses of 0, 30, and 60 mg/day, respectively. After 3 days (Saturday-Monday) stabilization at each SR-AMP weekly dose (0, 15, or 30 mg administered at 0700 and 1225 each day), on Tuesday-Friday mornings (0900-1200 hours), participants sampled four drug combinations in randomized, counterbalanced order under double-blind, double-dummy (intranasal cocaine and intramuscular hydromorphone) conditions: cocaine (COC 100 mg+saline); hydromorphone (COC 4 mg+HYD 24 mg); 'speedball' (COC 100 mg+HYD 24 mg); and placebo (COC 4 mg+saline). Subjective and physiological effects of these drug combinations were measured. From 1230 to 1530 hours, participants could respond on a choice, 12-trial progressive ratio schedule to earn drug units (1/12th of total morning dose) or money units (US$2). SR-AMP significantly reduced COC, but not HYD or speedball, choices and breakpoints. SR-AMP also significantly reduced COC subjective (eg, abuse-related) effects and did not potentiate COC-induced cardiovascular responses. This study shows the ability of SR-AMP to attenuate COC self-administration, as well as its selectivity, in cocaine/heroin polydrug abusers. Further research is warranted to ascertain whether SR-AMP combined with BUP could be a useful dual-agonist pharmacotherapy.

Topics: Adolescent; Adult; Buprenorphine; Choice Behavior; Cocaine; Cocaine-Related Disorders; Delayed-Action Preparations; Dextroamphetamine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Drug-Seeking Behavior; Female; Humans; Hydromorphone; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Reinforcement Schedule; Reward; Substance Withdrawal Syndrome

Limitations of existing pharmacological treatments for opioid dependence include low adherence, medication diversion, and emergence of withdrawal symptoms.. To determine the efficacy of buprenorphine implants that provide a low, steady level of buprenorphine over 6 months for the treatment of opioid dependence.. A randomized, placebo-controlled, 6-month trial conducted at 18 sites in the United States between April 2007 and June 2008. One hundred sixty-three adults, aged 18 to 65 years, diagnosed with opioid dependence. One hundred eight were randomized to receive buprenorphine implants and 55 to receive placebo implants.. After induction with sublingual buprenorphine-naloxone tablets, patients received either 4 buprenorphine implants (80 mg per implant) or 4 placebo implants. A fifth implant was available if a threshold for rescue use of sublingual buprenorphine-naloxone treatment was exceeded. Standardized individual drug counseling was provided to all patients.. The percentage of urine samples negative for illicit opioids for weeks 1 through 16 and for weeks 17 through 24.. The buprenorphine implant group had significantly more urine samples negative for illicit opioids during weeks 1 through 16 (P = .04). Patients with buprenorphine implants had a mean percentage of urine samples that tested negative for illicit opioids across weeks 1 through 16 of 40.4% (95% confidence interval [CI], 34.2%-46.7%) and a median of 40.7%; whereas those in the placebo group had a mean of 28.3% (95% CI, 20.3%-36.3%) and a median of 20.8%. A total of 71 of 108 patients (65.7%) who received buprenorphine implants completed the study vs 17 of 55 (30.9%) who received placebo implants (P < .001). Those who received buprenorphine implants also had fewer clinician-rated (P <.001) and patient-rated (P = .004) withdrawal symptoms, had lower patient ratings of craving (P <.001), and experienced a greater change on clinician global ratings of severity of opioid dependence (P<.001) and on the clinician global ratings of improvement (P < .001) than those who received placebo implants. Minor implant site reactions were the most common adverse events: 61 patients (56.5%) in the buprenorphine group and 29 (52.7%) in the placebo group.. Among persons with opioid dependence, the use of buprenorphine implants compared with placebo resulted in less opioid use over 16 weeks as assessed by urine samples.. clinicaltrials.gov Identifier: NCT00447564.

Topics: Adult; Buprenorphine; Double-Blind Method; Drug Implants; Female; Humans; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Placebos; Severity of Illness Index; Treatment Outcome

Methadone, a full mu-opioid agonist, is the recommended treatment for opioid dependence during pregnancy. However, prenatal exposure to methadone is associated with a neonatal abstinence syndrome (NAS) characterized by central nervous system hyperirritability and autonomic nervous system dysfunction, which often requires medication and extended hospitalization. Buprenorphine, a partial mu-opioid agonist, is an alternative treatment for opioid dependence but has not been extensively studied in pregnancy.. We conducted a double-blind, double-dummy, flexible-dosing, randomized, controlled study in which buprenorphine and methadone were compared for use in the comprehensive care of 175 pregnant women with opioid dependency at eight international sites. Primary outcomes were the number of neonates requiring treatment for NAS, the peak NAS score, the total amount of morphine needed to treat NAS, the length of the hospital stay for neonates, and neonatal head circumference.. Treatment was discontinued by 16 of the 89 women in the methadone group (18%) and 28 of the 86 women in the buprenorphine group (33%). A comparison of the 131 neonates whose mothers were followed to the end of pregnancy according to treatment group (with 58 exposed to buprenorphine and 73 exposed to methadone) showed that the former group required significantly less morphine (mean dose, 1.1 mg vs. 10.4 mg; P<0.0091), had a significantly shorter hospital stay (10.0 days vs. 17.5 days, P<0.0091), and had a significantly shorter duration of treatment for the neonatal abstinence syndrome (4.1 days vs. 9.9 days, P<0.003125) (P values calculated in accordance with prespecified thresholds for significance). There were no significant differences between groups in other primary or secondary outcomes or in the rates of maternal or neonatal adverse events.. These results are consistent with the use of buprenorphine as an acceptable treatment for opioid dependence in pregnant women. (Funded by the National Institute on Drug Abuse; ClinicalTrials.gov number, NCT00271219.).

Topics: Adult; Buprenorphine; Double-Blind Method; Female; Head; History, Ancient; Humans; Infant, Newborn; Length of Stay; Logistic Models; Methadone; Morphine; Narcotics; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications

The aim of this study was to compare the transfer of buprenorphine and methadone between maternal and cord blood in women under chronic dosing conditions and to determine if differences exist in the transfer of the two methadone enantiomers.. Maternal and cord blood samples were collected at delivery from women maintained on methadone (35, 25-140 mg day⁻¹) (median; range) or buprenorphine (6.00, 2-20 mg day⁻¹) during pregnancy. Plasma concentration ratios are presented as an indicator of foetal exposure relative to the mother.. Methadone was quantified in all samples, with cord : maternal plasma methadone concentration ratios (n= 15 mother-infant pairs) being significantly higher (P < 0.0001; mean difference (MD) 0.07; 95% confidence interval (CI) 0.048, 0.092) for the active (R)-methadone enantiomer (0.41; 0.19, 0.56) (median; range) compared with (S)-methadone (0.36; 0.15, 0.53). (R)- : (S)-methadone concentration ratios were also significantly higher (P < 0.0001; MD 0.24 95% CI 0.300, 0.180) for cord (1.40; 0.95, 1.67) compared with maternal plasma (1.16; 0.81, 1.38). Half the infant buprenorphine samples were below the assay lower limit of quantification (LLOQ) (0.125 ng ml⁻¹). The latter was four-fold lower than the LLOQ for methadone (0.50 ng ml⁻¹). The cord : maternal plasma buprenorphine concentration ratio (n= 9 mother-infant pairs) was 0.35; 0.14, 0.47 and for norbuprenorphine 0.49; 0.24, 0.91.. The transfer of the individual methadone enantiomers to the foetal circulation is stereoselective. Infants born to buprenorphine maintained women are not exposed to a greater proportion of the maternal dose compared with methadone and may be exposed to relatively less of the maternal dose compared with infants born to women maintained on methadone during pregnancy.

Topics: Analgesics, Opioid; Buprenorphine; Drug Administration Schedule; Female; Fetal Blood; Humans; Infant, Newborn; Maternal-Fetal Exchange; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications

Few studies in community settings have evaluated predictors, mediators, and moderators of treatment success for medically supervised opioid withdrawal treatment. This report presents new findings about these factors from a study of 344 opioid-dependent men and women prospectively randomized to either buprenorphine-naloxone or clonidine in an open-label 13-day medically supervised withdrawal study. Subjects were either inpatient or outpatient in community treatment settings; however not randomized by treatment setting. Medication type (buprenorphine-naloxone versus clonidine) was the single best predictor of treatment retention and treatment success, regardless of treatment setting. Compared to the outpatient setting, the inpatient setting was associated with higher abstinence rates but similar retention rates when adjusting for medication type. Early opioid withdrawal severity mediated the relationship between medication type and treatment outcome with buprenorphine-naloxone being superior to clonidine at relieving early withdrawal symptoms. Inpatient subjects on clonidine with lower withdrawal scores at baseline did better than those with higher withdrawal scores; inpatient subjects receiving buprenorphine-naloxone did better with higher withdrawal scores at baseline than those with lower withdrawal scores. No relationship was found between treatment outcome and age, gender, race, education, employment, marital status, legal problems, baseline depression, or length/severity of drug use. Tobacco use was associated with worse opioid treatment outcomes. Severe baseline anxiety symptoms doubled treatment success. Medication type (buprenorphine-naloxone) was the most important predictor of positive outcome; however the paper also considers other clinical and policy implications of other results, including that inpatient setting predicted better outcomes and moderated medication outcomes.

Topics: Adrenergic alpha-Agonists; Adult; Aged; Anxiety; Buprenorphine; Clonidine; Data Interpretation, Statistical; Depression; Drug Therapy, Combination; Female; Heroin Dependence; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; National Institute on Alcohol Abuse and Alcoholism (U.S.); Opioid-Related Disorders; Prognosis; Smoking; Socioeconomic Factors; Substance Abuse Detection; Substance Withdrawal Syndrome; Treatment Outcome; United States; Young Adult

Buprenorphine has rarely been administered as an opioid agonist maintenance therapy in a correctional setting. This study introduced buprenorphine maintenance in a large urban jail, Rikers Island in New York City. Heroin-dependent men not enrolled in community methadone treatment and sentenced to 10-90 days in jail (N=116) were voluntarily randomly assigned either to buprenorphine or methadone maintenance, the latter being the standard of care for eligible inmates at Rikers. Buprenorphine and methadone maintenance completion rates in jail were equally high, but the buprenorphine group reported for their designated post-release treatment in the community significantly more often than did the methadone group (48% vs. 14%, p<.001). Consistent with this result, prior to release from Rikers, buprenorphine patients stated an intention to continue treatment after release more often than did methadone patients (93% vs. 44%, p<.001). Buprenorphine patients were also less likely than methadone patients to withdraw voluntarily from medication while in jail (3% vs. 16%, p<.05). There were no post-release differences between the buprenorphine and methadone groups in self-reported relapse to illicit opioid use, self-reported re-arrests, self-reported severity of crime or re-incarceration in jail. After initiating opioid agonist treatment in jail, continuing buprenorphine maintenance in the community appears to be more acceptable to offenders than continuing methadone maintenance.

Topics: Adolescent; Adult; Aged; Buprenorphine; Diagnosis, Dual (Psychiatry); Female; Follow-Up Studies; HIV Infections; Humans; Male; Mental Disorders; Methadone; Middle Aged; Narcotics; Opioid-Related Disorders; Patient Selection; Prisons; Recurrence; Socioeconomic Factors; Treatment Outcome; Young Adult

To compare the effects of a short or long taper schedule after buprenorphine stabilization on participant outcomes as measured by opioid-free urine tests at the end of each taper period.. This multi-site study sponsored by Clinical Trials Network (CTN, a branch of the US National Institute on Drug Abuse) was conducted from 2003 to 2005 to compare two taper conditions (7 days and 28 days). Data were collected at weekly clinic visits to the end of the taper periods, and at 1-month and 3-month post-taper follow-up visits.. Eleven out-patient treatment programs in 10 US cities.. Non-blinded dosing with Suboxone during the 1-month stabilization phase included 3 weeks of flexible dosing as determined appropriate by the study physicians. A fixed dose was required for the final week before beginning the taper phase.. The percentage of participants in each taper group providing urine samples free of illicit opioids at the end of the taper and at follow-up.. At the end of the taper, 44% of the 7-day taper group (n = 255) provided opioid-free urine specimens compared to 30% of the 28-day taper group (n = 261; P = 0.0007). There were no differences at the 1-month and 3-month follow-ups (7-day = 18% and 12%; 28-day = 18% and 13%, 1 month and 3 months, respectively).. For individuals terminating buprenorphine pharmacotherapy for opioid dependence, there appears to be no advantage in prolonging the duration of taper.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Substance Abuse Detection; Substance Withdrawal Syndrome; Time Factors; United States; Young Adult

Many opiate users entering British prisons require prescribed medication to help them achieve abstinence. This commonly takes the form of a detoxification regime. Previously, a range of detoxification agents have been prescribed without a clear evidence base to recommend a drug of choice. There are few trials and very few in the prison setting. This study compares dihydrocodeine with buprenorphine.. Open label, pragmatic, randomised controlled trial in a large remand prison in the North of England. Ninety adult male prisoners requesting an opiate detoxification were randomised to receive either daily sublingual buprenorphine or daily oral dihydrocodeine, given in the context of routine care. All participants gave written, informed consent. Reducing regimens were within a standard regimen of not more than 20 days and were at the discretion of the prescribing doctor. Primary outcome was abstinence from illicit opiates as indicated by a urine test at five days post detoxification. Secondary outcomes were collected during the detoxification period and then at one, three and six months post detoxification. Analysis was undertaken using relative risk tests for categorical data and unpaired t-tests for continuous data.. 64% of those approached took part in the study. 63 men (70%) gave a urine sample at five days post detoxification. At the completion of detoxification, by intention to treat analysis, a higher proportion of people allocated to buprenorphine provided a urine sample negative for opiates (abstinent) compared with those who received dihydrocodeine (57% vs 35%, RR 1.61 CI 1.02-2.56). At the 1, 3 and 6 month follow-up points, there were no significant differences for urine samples negative for opiates between the two groups. Follow up rates were low for those participants who had subsequently been released into the community.. These findings would suggest that dihydrocodeine should not be routinely used for detoxification from opiates in the prison setting. The high relapse rate amongst those achieving abstinence would suggest the need for an increased emphasis upon opiate maintenance programmes in the prison setting.. Current Controlled Trials ISRCTN07752728.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Codeine; England; Follow-Up Studies; Humans; Inactivation, Metabolic; Male; Middle Aged; Opioid-Related Disorders; Prisoners; Prisons; Substance Abuse Detection; Treatment Outcome; Young Adult

Opioid-substitution treatment (OST) for opioid dependence (OD) has proven effective in retaining patients in treatment and reducing illegal opiate abuse and crime. Consequently, the World Health Organization (WHO) has listed the opioid agonists methadone and buprenorphine as essential drugs for OD that should be available worldwide. In many areas of the world, OD is often associated with concomitant benzodiazepine (BZD) dependence and abuse, which complicates treatment. However, possible changes in the cognitive functioning of these patients are not well-known. The present study is the first to examine longitudinal stability of memory function in OST patients with BZD use, thus providing a new tool for health policy authorities in evaluating the usefulness of OST.. Within the first two months (T1) and between 6-9 months (T2) after OST admission, we followed the working memory, immediate verbal memory, and memory consolidation of 13 methadone- and 15 buprenorphine- or buprenorphine/naloxone-treated patients with BZD dependence or abuse disorder. The results were compared to those of fifteen normal comparison participants. All participants also completed a self-reported memory complaint questionnaire on both occasions.. Both patient groups performed statistically significantly worse than normal comparison participants in working memory at time points T1 and T2. In immediate verbal memory, as measured by list learning at T1, patients scored lower than normal comparison participants. Both patient groups reported significantly more subjective memory problems than normal comparison participants. Patients with more memory complaints recalled fewer items at T2 from the verbal list they had learned at T1 than those patients with fewer memory complaints. The significance of the main analyses remained nearly the same when the statistical tests were performed without buprenorphine-only patients leaving 12 patients to buprenorphine/naloxone group.. Working memory may be persistently affected in OST patients with BZD use. A high number of memory complaints among OST patients with BZD use may indicate memory consolidation impairment. These findings show that recovery of memory function in OD patients treated along with BZDs takes time, and their memory complaints may have practical relevance.

Topics: Adult; Analgesics, Opioid; Benzodiazepines; Buprenorphine; Drug Interactions; Drug Therapy, Combination; Female; Humans; Male; Memory; Methadone; Naloxone; Opioid-Related Disorders; Substance-Related Disorders; Time Factors

In the United Kingdom (UK), there is an extensive market for the class 'A' drug heroin and many heroin users spend time in prison. People addicted to heroin often require prescribed medication when attempting to cease their drug use. The most commonly used detoxification agents in UK prisons are currently buprenorphine and methadone, both are recommended by national clinical guidelines. However, these agents have never been compared for opiate detoxification in the prison estate and there is a general paucity of research evaluating the most effective treatment for opiate detoxification in prisons. This study seeks to address this paucity by evaluating the most routinely used interventions amongst drug users within UK prisons.. This study uses randomised controlled trial methodology to compare the open use of buprenorphine and methadone for opiate detoxification, given in the context of routine care, within three UK prisons. Prisoners who are eligible and give informed consent will be entered into the trial. The primary outcome will be abstinence status eight days after detoxification, as determined by a urine test. Secondary outcomes will be recorded during the detoxification and then at one, three and six months post-detoxification.. Current Controlled Trials ISRCTN58823759.

Topics: Buprenorphine; Humans; Methadone; Narcotics; Opioid-Related Disorders; Prisoners; Prisons; Research Design; United Kingdom

During a 12-week intervention, opioid dependent participants (N = 120) maintained on thrice-a-week (M, W, F) buprenorphine plus therapist and computer-based counseling were randomized to receive: (a) medication contingencies (MC = thrice weekly dosing schedule vs. daily attendance and single-day 50% dose reduction imposed upon submission of an opioid and/or cocaine positive urine sample); (b) voucher contingency (VC = escalating schedule for opioid and/or cocaine negative samples with reset for drug-positive samples); or (c) standard care (SC), with no programmed consequences for urinalysis results. VC resulted in better 12-week retention (85%) compared to MC (58%; p = 0.009), but neither differed from SC (76% retained). After adjusting for baseline differences in employment, and compared to SC, the MC group achieved 1.5 more continuous weeks of combined opioid/cocaine abstinence (p = 0.030), while the VC group had 2 more total weeks of abstinence (p = 0.048). Drug use results suggest that both the interventions were efficacious, with effects primarily in opioid rather than cocaine test results. Findings should be interpreted in light of the greater attrition associated with medication-based contingencies versus the greater monetary costs of voucher-based contingencies.

Topics: Adolescent; Adult; Buprenorphine; Cocaine-Related Disorders; Directive Counseling; Female; Humans; Male; Middle Aged; Opioid-Related Disorders; Patient Compliance; Reward; Secondary Prevention

HIV-infected patients with opioid dependence often require opioid replacement therapy. Pharmacokinetic interactions between HIV therapy and opioid dependence treatment medications can occur. HIV-seronegative subjects stabilized on at least 3 weeks of buprenorphine/naloxone (BUP/NLX) therapy sequentially underwent baseline and steady-state pharmacokinetic evaluation of open-label, twice daily tipranavir 500 mg co-administered with ritonavir 200 mg (TPV/r). Twelve subjects were enrolled and 10 completed the study. Prior to starting TPV/r, the geometric mean BUP AUC(0-24h) and C(max) were 43.9 ng h/mL and 5.61 ng/mL, respectively. After achieving steady-state with TPV/r (> or = 7 days), these values were similar at 43.7 ng h/mL and 4.84 ng/mL, respectively. Similar analyses for norBUP, the primary metabolite of BUP, demonstrated a reduction in geometric mean for AUC(0-24h) [68.7-14.7 ng h/mL; ratio=0.21 (90% CI 0.19-0.25)] and C(max) [4.75-0.94 ng/mL; ratio=0.20 (90% CI 0.17-0.23)]. The last measurable NLX concentration (C(last)) in the concentration-time profile, never measured in previous BUP/NLX interaction studies with antiretroviral medications, was decreased by 20%. Despite these pharmacokinetic effects on BUP metabolites and NLX, no clinical opioid withdrawal symptoms were noted. TPV steady-state AUC(0-12h) and C(max) decreased 19% and 25%, respectively, and C(min) was relatively unchanged when compared to historical control subjects receiving TPV/r alone. No dosage modification of BUP/NLX is required when co-administered with TPV/r. Though mechanistically unclear, it is likely that decreased plasma RTV levels while on BUP/NLX contributed substantially to the decrease in TPV levels. BUP/NLX and TPV/r should therefore be used cautiously to avoid decreased efficacy of TPV in patients taking these agents concomitantly.

Topics: Adult; Anti-Retroviral Agents; Buprenorphine; Drug Interactions; Drug Therapy, Combination; Female; HIV Infections; HIV Seronegativity; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Pyridines; Pyrones; Ritonavir; Sulfonamides; Treatment Outcome

For the first time, relationships among maternal buprenorphine dose, meconium buprenorphine and metabolite concentrations, and neonatal outcomes are reported. Free and total buprenorphine and norbuprenorphine, nicotine, opiates, cocaine, benzodiazepines, and metabolites were quantified in meconium from 10 infants born to women who had received buprenorphine during pregnancy. Neither cumulative nor total third-trimester maternal buprenorphine dose predicted meconium concentrations or neonatal outcomes. Total buprenorphine meconium concentrations and buprenorphine/norbuprenorphine ratios were significantly related to neonatal abstinence syndrome (NAS) scores >4. As free buprenorphine concentration and percentage free buprenorphine increased, head circumference decreased. Thrice-weekly urine tests for opiates, cocaine, and benzodiazepines and self-reported smoking data from the mother were compared with data from analysis of the meconium to estimate in utero exposure. Time of last drug use and frequency of use during the third trimester were important factors associated with drug-positive meconium specimens. The results suggest that buprenorphine and metabolite concentrations in the meconium may predict the onset and frequency of NAS.

Topics: Adult; Buprenorphine; Cocaine; Double-Blind Method; Female; Humans; Infant, Newborn; Male; Maternal Behavior; Maternal-Fetal Exchange; Meconium; Methadone; Narcotic Antagonists; Neonatal Abstinence Syndrome; Nicotine; Opiate Alkaloids; Opioid-Related Disorders; Pregnancy; Smoking

In the present study, we investigated whether buprenorphine as a partial mu-opioid receptor agonist is associated with less cognitive impairment than methadone.. Neuropsychological functioning of opioid-dependent patients, previously assigned to methadone (MMP, n = 30) or buprenorphine (BMP, n = 26) maintenance treatment according to their own preference, was compared and dose effects were investigated.. MMP and BMP performed equally well on all measures of neuropsychological functioning including the trail making test, the continuous performance test, and a vigilance task. However, patients receiving a higher dose of methadone were impaired in a vigilance task.. In a free-choice administration of methadone or buprenorphine, there seems to be no difference in cognitive functioning. Possible explanations are discussed.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Cognition Disorders; Dose-Response Relationship, Drug; Female; Humans; Male; Methadone; Middle Aged; Neuropsychological Tests; Opioid-Related Disorders; Receptors, Opioid, mu; Young Adult

The usual treatment for opioid-addicted youth is detoxification and counseling. Extended medication-assisted therapy may be more helpful.. To evaluate the efficacy of continuing buprenorphine-naloxone for 12 weeks vs detoxification for opioid-addicted youth.. Clinical trial at 6 community programs from July 2003 to December 2006 including 152 patients aged 15 to 21 years who were randomized to 12 weeks of buprenorphine-naloxone or a 14-day taper (detox).. Patients in the 12-week buprenorphine-naloxone group were prescribed up to 24 mg per day for 9 weeks and then tapered to week 12; patients in the detox group were prescribed up to 14 mg per day and then tapered to day 14. All were offered weekly individual and group counseling.. Opioid-positive urine test result at weeks 4, 8, and 12.. The number of patients younger than 18 years was too small to analyze separately, but overall, patients in the detox group had higher proportions of opioid-positive urine test results at weeks 4 and 8 but not at week 12 (chi(2)(2) = 4.93, P = .09). At week 4, 59 detox patients had positive results (61%; 95% confidence interval [CI] = 47%-75%) vs 58 12-week buprenorphine-naloxone patients (26%; 95% CI = 14%-38%). At week 8, 53 detox patients had positive results (54%; 95% CI = 38%-70%) vs 52 12-week buprenorphine-naloxone patients (23%; 95% CI = 11%-35%). At week 12, 53 detox patients had positive results (51%; 95% CI = 35%-67%) vs 49 12-week buprenorphine-naloxone patients (43%; 95% CI = 29%-57%). By week 12, 16 of 78 detox patients (20.5%) remained in treatment vs 52 of 74 12-week buprenorphine-naloxone patients (70%; chi(2)(1) = 32.90, P < .001). During weeks 1 through 12, patients in the 12-week buprenorphine-naloxone group reported less opioid use (chi(2)(1) = 18.45, P < .001), less injecting (chi(2)(1) = 6.00, P = .01), and less nonstudy addiction treatment (chi(2)(1) = 25.82, P < .001). High levels of opioid use occurred in both groups at follow-up. Four of 83 patients who tested negative for hepatitis C at baseline were positive for hepatitis C at week 12.. Continuing treatment with buprenorphine-naloxone improved outcome compared with short-term detoxification. Further research is necessary to assess the efficacy and safety of longer-term treatment with buprenorphine for young individuals with opioid dependence.. clinicaltrials.gov Identifier: NCT00078130.

Topics: Adolescent; Adult; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Counseling; Female; Humans; Male; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Substance Abuse Detection

Cognitive impairment in drug-dependent patients receiving methadone (MMP) maintenance treatment has been reported previously. We assessed cognitive functioning after at least 14 days of stable substitution treatment with buprenorphine (BUP) or MMP and after 8 to 10 weeks. We performed a randomized, nonblinded clinical trial in 59 drug-dependent patients receiving either BUP or MMP maintenance treatment and healthy normal controls (n = 24) matched for sex, age, and educational level. Thirteen patients dropped out of the study before the second testing was performed (BUP, n = 22; MMP, n = 24). A neuropsychological test battery was used to measure selective attention, verbal memory, motor/cognitive speed, and cognitive flexibility. In addition, subjective perceived stress was assessed with a questionnaire. Patients in both treatment groups performed equally well in all of the cognitive domains tested. Both BUP and MMP patients showed significantly improved concentration and executive functions after 8 to 10 weeks of stable substitution treatment. The control group achieved better results than the BUP and MMP groups in most cognitive domains, indicating cognitive impairment in the patients. Perceived stress did not show any significant change after 8 to 10 weeks of treatment, and no major differences were detected between the 3 groups. No effects of perceived stress on cognitive function were found. Our results indicate a cognitive impairment in patients receiving maintenance treatment with BUP or MMP compared with healthy controls. Selective attention improved in both patient groups during treatment. We propose that the improvement of attention may facilitate rehabilitation of drug-dependent patients.

Topics: Analgesics, Opioid; Attention; Buprenorphine; Cognition; Humans; Memory; Methadone; Neuropsychological Tests; Opioid-Related Disorders; Patient Dropouts; Perception; Psychomotor Performance; Stress, Psychological; Substance Withdrawal Syndrome; Surveys and Questionnaires; Time Factors; Treatment Outcome

Methadone treatment reduces human immunodeficiency virus (HIV) risk, but the effects of primary-care-based buprenorphine/naloxone on HIV risk are unknown. The purpose of this study was to determine whether primary-care-based buprenorphine/naloxone was associated with decreased HIV risk behavior. We conducted a longitudinal analysis of 166 opioid-dependent persons (129 men and 37 women) receiving buprenorphine/naloxone treatment in a primary care clinic. We compared baseline and 12- and 24-week overall, drug-related, and sex-related HIV risk behaviors using the AIDS/HIV Risk Inventory (ARI). Buprenorphine/naloxone treatment was associated with significant reductions in overall and drug-related ARI scores from baseline to 12 and 24 weeks. Intravenous drug use in the past 3 months was endorsed by 37%, 12%, and 7% of patients at baseline and at 12 and 24 weeks, respectively (p< .001). Sex while you or your partner were "high" was endorsed by 64%, 13%, and 15% of patients at baseline and at 12 and 24 weeks, respectively (p< .001). Inconsistent condom use during sex with a steady partner was high at baseline and did not change over time. We conclude that primary-care-based buprenorphine/naloxone treatment is associated with decreased drug-related HIV risk, but additional efforts may be needed to address sex-related HIV risk when present.

Topics: Adult; Buprenorphine; Female; HIV Infections; Humans; Male; Middle Aged; Naloxone; Opioid-Related Disorders; Primary Health Care; Risk-Taking; Sexual Behavior

To (i) examine the predictors of mortality in a randomized study of methadone versus buprenorphine maintenance treatment; (ii) compare the survival experience of the randomized subject groups; and (iii) describe the causes of death.. Ten-year longitudinal follow-up of mortality among participants in a randomized trial of methadone versus buprenorphine maintenance treatment.. Recruitment through three clinics for a randomized trial of buprenorphine versus methadone maintenance.. A total of 405 heroin-dependent (DSM-IV) participants aged 18 years and above who consented to participate in original study.. Baseline data from original randomized study; dates and causes of death through data linkage with Births, Deaths and Marriages registries; and longitudinal treatment exposure via State health departments. Predictors of mortality examined through survival analysis.. There was an overall mortality rate of 8.84 deaths per 1000 person-years of follow-up and causes of death were comparable with the literature. Increased exposure to episodes of opioid treatment longer than 7 days reduced the risk of mortality; there was no differential mortality among methadone versus buprenorphine participants. More dependent, heavier users of heroin at baseline had a lower risk of death, and also higher exposure to opioid treatment. Older participants randomized to buprenorphine treatment had significantly improved survival. Aboriginal or Torres Strait Islander participants had a higher risk of death.. Increased exposure to opioid maintenance treatment reduces the risk of death in opioid-dependent people. There was no differential reduction between buprenorphine and methadone. Previous studies suggesting differential effects may have been affected by biases in patient selection.

Topics: Adolescent; Adult; Australia; Buprenorphine; Cause of Death; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Methadone; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Treatment Outcome

This was a 6-month, randomized, flexible-dose study comparing the effects of methadone (Meth) and buprenorphine (Bup) on retention rate and substance use in a sample of 140 opioid-dependent, primarily heroin-addicted, patients who had been without opioid substitution therapy in the 4 weeks prior to the study. The major aims were to compare the efficacy of Bup and Meth in a flexible dosing regimen and to identify possible predictors of outcome. There were no major inhomogeneities between treatment groups. All patients also received standardized psychosocial interventions. Mean daily dosages after the induction phase were 44-50 mg for Meth and 9-12 mg for Bup. Results from this study indicate a favourable outcome, with an overall retention rate of 52.1% and no significant differences between treatment groups (55.3% vs. 48.4%). Substance use decreased significantly over time in both groups and was non-significantly lower in the Bup group. Predictors of outcome were length of continuous opioid use and age at onset of opioid use, although these were only significant in the Bup group. Mean dosage and other parameters were not significant predictors of outcome. Overall, the results of this study give further evidence that substitution treatment is a safe and effective treatment for drug dependence. Meth and Bup are equally effective. Duration of continuous opioid use and age at onset were found to have predictive value for negative outcome. The intensity of withdrawal symptoms showed the strongest correlation with drop-out. Future studies are warranted to further address patient profiles and outcome under different substitution regimens.

Topics: Adult; Analysis of Variance; Buprenorphine; Chi-Square Distribution; Double-Blind Method; Female; Humans; Male; Methadone; Narcotics; Opioid-Related Disorders; Predictive Value of Tests; Prospective Studies; Substance Withdrawal Syndrome; Survival Analysis; Time Factors; Treatment Outcome

The registration of combination buprenorphine/naloxone, a formulation designed to reduce risk of diversion, has led some Australian jurisdictional authorities to allow treatment without direct observation of dosing for stable, opioid-dependent patients.. To compare two approaches (1) initiating treatment with observed dosing, then allowing patients who demonstrate stability to change to unobserved dosing; or (2) initiating patients with unobserved dosing, subsequently requiring those who fail to stabilize to change to observed treatment.. This study builds on an RCT comparing efficacy of observed and unobserved treatment at 3 months. At the conclusion of the RCT, clinically "stable" subjects were allocated to continue without observed dosing, while those who did not demonstrate stability were allocated to observed dosing. Subjects were followed for a further 3 months. Primary end-point was retention in treatment.. Of 119 subjects randomised, 70 were retained in treatment to 3 months. Forty-five stable subjects were allocated to unobserved dosing, 25 to observation. Unstable subjects allocated to observed treatment were more likely to drop out thereafter (OR 2.14, 95% CI 1.09-4.19). There was a non-significant trend for people initiated with observed dosing to be better retained during the allocation phase; at 6 months, 13 subjects (22%) from the original unobserved group, and 22 (34%) from the observed group, were retained in treatment (chi2=2.10, 1 df, p=0.15).. Withdrawal of unobserved doses led to marked attrition from treatment. If access to unobserved dosing is to be restricted to stable patients, it appears preferable to initiate dosing with observation and allow unobserved doses for people who successfully stabilize, than to initiate with unobserved doses and transfer unstable patients to observation.

Topics: Adult; Australia; Buprenorphine; Directly Observed Therapy; Drug Administration Schedule; Drug Combinations; Female; Follow-Up Studies; Humans; Male; Methadone; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Patient Dropouts; Proportional Hazards Models; Secondary Prevention; Self Administration; Substance Abuse Treatment Centers; Treatment Outcome

The authors evaluated the efficacy of an interactive, computer-based behavioral therapy intervention, grounded in the community reinforcement approach (CRA) plus voucher-based contingency management model of behavior therapy. Our randomized, controlled trial was conducted at a university-based research clinic. Participants comprised 135 volunteer adult outpatients who met DSM-IV criteria for opioid dependence. All participants received maintenance treatment with buprenorphine and were randomly assigned to one of three treatments: (a) therapist-delivered CRA treatment with vouchers, (b) computer-assisted CRA treatment with vouchers, or (c) standard treatment. The therapist-delivered and computer-assisted CRA plus vouchers interventions produced comparable weeks of continuous opioid and cocaine abstinence (M = 7.98 and 7.78, respectively) and significantly greater weeks of abstinence than the standard intervention (M = 4.69; p < .05), yet participants in the computer-assisted CRA condition had over 80% of their intervention delivered by an interactive computer program. The comparable efficacy obtained with computer-assisted and therapist-delivered therapy may enable more widespread dissemination of the evidence-based CRA plus vouchers intervention in a manner that is cost-effective and ensures treatment fidelity.

Topics: Adult; Alcohols; Behavior Therapy; Buprenorphine; Computer-Aided Design; Double-Blind Method; Female; Humans; Male; Narcotic Antagonists; Opioid-Related Disorders; Reinforcement, Psychology; Severity of Illness Index; Treatment Outcome

Buprenorphine has considerable abuse potential. Patients who are maintained on buprenorphine (for opioid dependence) further use additional doses besides its maintenance dose. Subjective effects of the additional doses of buprenorphine in patients on buprenorphine maintenance patients is focused in this study.. Nineteen subjects who were maintained on buprenorphine 4mg, s/l per day for at least 1month were admitted and given three additional doses of buprenorphine 2mg, s/l at the interval of 2h each and subjective effects were assessed with the help of standard tools after 2h of each dose and the next day also. Drug was given in a cumulative dose design in the inpatient unit of a de-addiction centre.. Dysphoria and sleepiness increased while euphoria and drug liking decreased with additional doses of buprenorphine. These changes were statistically significant and were highest at maximum cumulative dose of 10mg.. Results suggest that abuse liability of buprenorphine in these subjects is low in higher doses. However, these findings need to be replicated in this group of patients to make a comment on clinical implication.

Topics: Adult; Buprenorphine; Chi-Square Distribution; Drug Administration Schedule; Heroin Dependence; Humans; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Surveys and Questionnaires

Buprenorphine (BUP) is effective in the treatment of opioid dependence when given on alternating days, probably as a result of long-lasting occupation of micro opioid receptors (microORs). This study examined the duration of action of BUP at microORs and correlations with pharmacokinetic and pharmacodynamic outcomes in 10 heroin-dependent volunteers.. Availability of microOR (measured with positron emission tomography and [(11)C]-carfentanil), plasma BUP concentration, opioid withdrawal symptoms, and blockade of hydromorphone (HYD; heroin-like agonist) effects were measured at 4, 28, 52, and 76 hours after omitting the 16 mg/d dose of BUP in a study reported elsewhere.. Relative to heroin-dependent volunteers maintained on BUP placebo, whole-brain microOR availability was 30%, 54%, 67%, and 82% at 4, 28, 52, and 76 hours after BUP. Regions of interest showed similar effects. Plasma concentrations of BUP were time dependent, as were withdrawal symptoms, carbon dioxide sensitivity and extent of HYD blockade. Availability of microOR was also correlated with BUP plasma concentration, withdrawal symptoms, and HYD blockade.. Together with our previous findings, it appears that microOR availability predicts changes in pharmacokinetic and pharmacodynamic measures and that about 50%-60% BUP occupancy is required for adequate withdrawal symptom suppression (in the absence of other opioids) and HYD blockade.

Topics: Adult; Analgesics, Opioid; Area Under Curve; Brain; Brain Mapping; Buprenorphine; Double-Blind Method; Drug Administration Schedule; Female; Fentanyl; Humans; Hydromorphone; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Positron-Emission Tomography; Receptors, Opioid, mu; Respiration; Time Factors; Tritium

Many drug users present to primary care requesting detoxification from illicit opiates. There are a number of detoxification agents but no recommended drug of choice. The purpose of this study is to compare buprenorphine with dihydrocodeine for detoxification from illicit opiates in primary care.. Open label randomised controlled trial in NHS Primary Care (General Practices), Leeds, UK. Sixty consenting adults using illicit opiates received either daily sublingual buprenorphine or daily oral dihydrocodeine. Reducing regimens for both interventions were at the discretion of prescribing doctor within a standard regimen of not more than 15 days. Primary outcome was abstinence from illicit opiates at final prescription as indicated by a urine sample. Secondary outcomes during detoxification period and at three and six months post detoxification were recorded.. Only 23% completed the prescribed course of detoxification medication and gave a urine sample on collection of their final prescription. Risk of non-completion of detoxification was reduced if allocated buprenorphine (68% vs 88%, RR 0.58 CI 0.35-0.96, p = 0.065). A higher proportion of people allocated to buprenorphine provided a clean urine sample compared with those who received dihydrocodeine (21% vs 3%, RR 2.06 CI 1.33-3.21, p = 0.028). People allocated to buprenorphine had fewer visits to professional carers during detoxification and more were abstinent at three months (10 vs 4, RR 1.55 CI 0.96-2.52) and six months post detoxification (7 vs 3, RR 1.45 CI 0.84-2.49).. Informative randomised trials evaluating routine care within the primary care setting are possible amongst drug using populations. This small study generates unique data on commonly used treatment regimens.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Codeine; Female; Follow-Up Studies; Humans; Inactivation, Metabolic; Male; Opioid-Related Disorders; Practice Guidelines as Topic; Primary Health Care; United Kingdom

Factors associated with satisfaction among patients receiving primary care-based buprenorphine/naloxone are unknown.. To identify factors related to patient satisfaction in patients receiving primary care-based buprenorphine/naloxone that varied in counseling intensity (20 vs 45 minutes) and office visit frequency (weekly vs thrice weekly).. One hundred and forty-two opioid-dependent subjects.. Demographics, drug treatment history, and substance use status at baseline and during treatment were collected. The primary outcome was patient satisfaction at 12 weeks.. Patients' mean overall satisfaction score was 4.4 (out of 5). Patients were most satisfied with the medication and ancillary services and indicated strong willingness to refer a substance-abusing friend for the same treatment. Patients were least satisfied with their interactions with other opioid-dependent patients, referrals to Narcotics Anonymous, and the inconvenience of the treatment location. Female gender (beta = .17, P = .04) and non-White ethnicity/race (beta = .17, P = .04) independently predicted patient satisfaction. Patients who received briefer counseling and buprenorphine/naloxone dispensed weekly had greater satisfaction than those whose medication was dispensed thrice weekly (mean difference 4.9, 95% confidence interval 0.08 to 9.80, P = .03).. Patients are satisfied with primary care office-based buprenorphine/naloxone. Providers should consider the identified barriers to patient satisfaction.

Topics: Adult; Buprenorphine; Female; Humans; Male; Middle Aged; Naloxone; Office Visits; Opioid-Related Disorders; Patient Satisfaction; Primary Health Care; Treatment Outcome

The study is a preliminary investigation to compare the effectiveness of buprenorphine and methadone as opiate detoxification treatments. The sample comprised 123 drug misusers who were dependent upon opiates only or who were codependent upon opiates and benzodiazepines. Drug misusers dependent upon methadone doses up to 70 mg were eligible for the study. Detoxification took place within a specialist inpatient drug-dependence unit. Withdrawal symptom severity was assessed on a daily basis by means of the Short Opiate Withdrawal Scale. Outcome was assessed for reductions in severity of withdrawal symptoms, treatment retention, and treatment completion. Buprenorphine detoxification was associated with less severe opiate withdrawal symptoms than methadone. Opiate/Benzodiazepine codependent patients reported less severe withdrawal symptoms during treatment with buprenorphine than with methadone and were also more likely to complete detoxification when treated with buprenorphine.

Topics: Adult; Anti-Anxiety Agents; Benzodiazepines; Buprenorphine; Diazepam; Female; Humans; Male; Methadone; Narcotic Antagonists; Opioid Peptides; Opioid-Related Disorders; Severity of Illness Index; Sex Factors; Substance Withdrawal Syndrome

We evaluated the utility of sweat testing for monitoring of drug use in outpatient clinical settings and compared sweat toxicology with urine toxicology and self-reported drug use during a randomized clinical trial of the efficacy of buprenorphine for treatment of opioid dependence in primary care settings. All study participants (N = 63) were opiate-dependent, treatment-seeking volunteers. The results based on toxicology tests obtained from 188 properly worn and unadulterated patches (out of 536 applied) show that the level of agreement between positive sweat test results and positive urine results was 33% for opiates and 92% for cocaine. The findings of this study, that there is a low acceptability of sweat patch testing by patients (only 54.3% were brought back attached to the skin) and that weekly sweat testing is less sensitive than weekly urine testing in detecting opiate use, suggest limited utility of sweat patch testing in outpatient clinical settings.

Topics: Buprenorphine; Humans; Opioid-Related Disorders; Patch Tests; Patient Acceptance of Health Care; Sensitivity and Specificity; Substance Abuse Detection; Sweat

Acute doses of buprenorphine can precipitate withdrawal in opioid dependent persons. The likelihood of this withdrawal increases as a function of the level of physical dependence.. To test the acute effects of sublingual buprenorphine/naloxone tablets in volunteers with a higher level of physical dependence. The goal was to identify a dose that would precipitate withdrawal (Phase 1), then determine if withdrawal could be attenuated by splitting this dose (Phase 2).. Residential laboratory study; subjects (N=16) maintained on 100mg per day of methadone. Phase 1: randomized, double blind, triple dummy, within subject study. Conditions were sublingual buprenorphine/naloxone (4/1, 8/2, 16/4, 32mg/8mg), intramuscular naloxone (0.2mg), oral methadone (100mg), or placebo. Medication conditions were randomized, but buprenorphine/naloxone doses were ascending within the randomization. Phase 2: Conditions were methadone, placebo, naloxone, 100% of the buprenorphine/naloxone dose that precipitated withdrawal in Phase 1 (full dose), and 50% of this dose administered twice in a session (split dose). Analyses covaried by trough methadone serum levels.. Six subjects did not complete the study. Of the 10 who completed, 3 tolerated up to 32mg/8mg of buprenorphine/naloxone without evidence of precipitated withdrawal. For the seven completing both phases, split doses generally produced less precipitated withdrawal compared to full doses.. There is considerable between subject variability in sensitivity to buprenorphine's antagonist effects. Low, repeated doses of buprenorphine/naloxone (e.g., 2mg/0.5mg) may be an effective mechanism for safely dosing this medication in persons with higher levels of physical dependence.

Topics: Administration, Sublingual; Adult; Buprenorphine; Cognition Disorders; Double-Blind Method; Drug Combinations; Female; Humans; Male; Methadone; Middle Aged; Naloxone; Neuropsychological Tests; Opioid-Related Disorders; Psychomotor Disorders; Substance Withdrawal Syndrome

To evaluate driving aptitude and traffic-relevant performance at peak and trough medication levels in opioid-dependent patients receiving maintenance therapy with either buprenorphine (mean: 13.4 mg) or methadone (52.7 mg) and a medication-free control group, the Addiction Clinic at Medical University Vienna conducted a prospective, open-label trial where 40 opioid-dependent patients maintained either on buprenorphine or methadone were assessed regarding their traffic-relevant performance. Using the standardized Act and React Testsystem (ART) 2020 Standard test battery, traffic-relevant performance was analysed 1.5 h (peak level) and 20 h (trough level) after administration of opioid maintenance therapy. Results showed that patients at trough level had a significantly higher percentage of incorrect reactions (p = 0.03) and more simple errors (p = 0.02) than patients at peak level as well as methadone-maintained patients at peak level tended to perform less well than buprenorphine-maintained patients in some of the test items, e.g. methadone-maintained patients at trough level had a higher number of delayed reactions in the RST3 phase 2 test (p = 0.09) and answered fewer questions correctly in the visual structuring ability test (p = 0.04). This investigation indicates that opioid-maintained patients did not differ significantly at peak vs.trough level in the majority of the investigated items and that both substances do not appear to affect traffic-relevant performance dimensions when given as a maintenance therapy in a population where concomitant consumption would be excluded.

Topics: Adult; Attention; Austria; Automobile Driving; Buprenorphine; Decision Making; Female; Humans; Male; Metabolic Clearance Rate; Methadone; Narcotics; Neuropsychological Tests; Opioid-Related Disorders; Prospective Studies; Reaction Time

Benzodiazepine abuse is common among methadone- and buprenorphine-maintained patients; however interactions between these drugs under high dose conditions have not been adequately examined under controlled conditions.. To investigate the effects of co-administering diazepam with methadone or buprenorphine under high dose conditions.. Double-blind, randomly ordered, 2 x 2 cross-over design in which the effects of diazepam dose (0mg versus 40 mg) and opioid dose (100% versus 150% normal dose) were examined over four sessions in methadone- and buprenorphine-maintained patients.. Four methadone- and seven buprenorphine-prescribed patients without concurrent dependence on other substances or significant medical co-morbidity.. Physiological (pulse rate, blood pressure, pupil size, respiratory rate and peripheral SpO2), subjective (ARCI, VAS ratings) and performance (reaction time, cancellation task and Digit Symbol Substitution Test, DSST) measures were taken prior to and for 6h post-dosing.. High dose diazepam was associated with time-dependent increases in the intensity of subjective drug effects (strength of drug effect, sedation) and decreases in psychological performance (reaction time, DSST) for both methadone and buprenorphine patients. These effects were generally independent of the opioid dose administered. High dose opioid administration (150% normal dose) was associated with reductions in overall SpO2 levels and performance (reaction time, DSST) in the methadone patients, but had virtually no impact on pharmacodynamic responses in the buprenorphine group.. High dose diazepam significantly alters subjective drug responses and psychological performance in patients maintained on methadone and buprenorphine.

Topics: Adult; Buprenorphine; Cross-Over Studies; Diazepam; Double-Blind Method; Drug Interactions; Drug Therapy, Combination; Half-Life; Humans; Metabolic Clearance Rate; Methadone; Opioid-Related Disorders; Oxygen

Many physicians are still skeptic to treat opioid dependants, with or without maintenance treatment, for hepatitis C (HCV) because of concerns about psychiatric comorbidity, stability and adherence. In Norway, there are about 3,500 patients participating in the restrictive medication-assisted rehabilitation (LAR) programs in which all patients are given methadone or buprenorphine maintenance therapy. This study was undertaken to determine whether HCV combination therapy with pegylated interferon alpha-2a plus ribavirin is feasible, efficient and safe in this patient group.. Seventeen patients with HCV genotype 3a were treated for 24 weeks. To optimize compliance, the treatment was given from a department of infectious diseases in cooperation with an LAR center. All injections were given in the LAR center and the patients were given psychosocial support.. The compliance was 100%. All responded to the therapy and 16 (94%) were sustained responders.. This study indicates that compliance and treatment outcome of opioid dependants on methadone or buprenorphine maintenance after 24 weeks of HCV treatment corresponds to that for non-dependants if extra support is given. The treatment should be undertaken in collaboration with specialists in addiction medicine, hepatology and infectious diseases.

Topics: Administration, Oral; Adult; Antiviral Agents; Buprenorphine; Comorbidity; Drug Therapy, Combination; Feasibility Studies; Female; Hepatitis C, Chronic; Humans; Injections, Subcutaneous; Interferon alpha-2; Interferon-alpha; Male; Methadone; Middle Aged; Narcotics; Norway; Opioid-Related Disorders; Patient Compliance; Pilot Projects; Polyethylene Glycols; Recombinant Proteins; Ribavirin; Social Support; Substance Abuse, Intravenous

Two tablet formulations of buprenorphine (a buprenorphine mono-product, Subutex, and a buprenorphine/naloxone combination product, Suboxone) are available for use in the treatment of opioid addiction; however, the bulk of the clinical studies supporting its approval by the US Food and Drug Administration (FDA) were conducted with a sublingual liquid preparation. To assist the clinician in interpreting the relevant literature in establishing dosing parameters for prescription of tablet buprenorphine, this study was designed to compare the steady state: (1) pharmacokinetics and bioavailability, and (2) physiological, subjective and objective opiate effects of two 8 mg buprenorphine tablets (16 mg) to those of 1 ml (8 mg/ml) buprenorphine solution based upon early reports suggesting that the bioavailability of the tablet was approximately 50% of that of the liquid.. Randomized, open-label, two-way crossover study.. Inpatient hospitalization for 21 days.. Twenty-four male and females in general good health and meeting DSM-IV criteria for opiate dependence.. Subjects received one of the two buprenorphine formulations in the first 10-day period, and the other for the second 10-day period with no washout.. Pharmacokinetic analyses, opiate effects and adverse events.. Drug steady state was reached by Day 7 of each 10-day period, area under the curve for 16 mg (two 8 mg) tablets was higher than the solution. The only non-kinetic statistically significant difference observed between the formulations was in changes in total opioid agonist score.. The serum concentration achieved by 16 mg of tablet buprenorphine is higher than that of the 8 mg solution, although differences between physiologic, subjective and objective opioid effects were not noted. The relative bioavailability of tablet versus solution is estimated to be 0.71; thus, with respect to dosing parameters for the tablet, clinicians should consider using less than 16 mg to achieve bioequivalence to the 8 mg solution.

Topics: Adult; Biological Availability; Buprenorphine; Cross-Over Studies; Dosage Forms; Drug Administration Routes; Female; Humans; Male; Narcotic Antagonists; Opioid-Related Disorders

With use of a randomized study design, quality of life (QOL) and physical symptoms of opioid addicts at admission were compared with slow-release oral morphine, methadone, and sublingual buprenorphine maintenance program participants after 6 months of treatment. The study was conducted from February to July 2004 in the outpatient drug user treatment center at University Department of Psychiatry at Innsbruck, providing maintenance treatment programs and detoxification in Tyrol, Austria. One hundred twenty opioid users seeking treatment were compared with 120 opioid-dependent patients retained for 6 months on a slow-release oral morphine, methadone, or sublingual buprenorphine maintenance program. The German version ("Berlin Quality of Life Profile") of the Lancashire Quality of Life Profile was used, and illicit opioid use was determined by urinalysis. Physical symptoms were measured by using the Opioid Withdrawal Scale. Urinalyses revealed a significantly lower consumption of cocaine and opioids in all three substitution groups than in patients at admission (p < 0.001 and p < or = 0.004, respectively). Both the buprenorphine and the methadone maintenance group showed significantly more favorable values than opioid clients at admission for stomach cramps (p < or = 0.002), muscular tension (p < or = 0.027), general pain (p < or = 0.001), feelings of coldness (p < or = 0.000), heart pounding (p < or = 0.008), runny eyes (p < or = 0.047), and aggressions (p < or = 0.009). Patients who received slow-release oral morphine treatment generally showed the least favorable QOL scores compared with patients at admission or sublingual buprenorphine and methadone clients. Patients in the sublingual buprenorphine or methadone program showed nearly the same QOL scores. The buprenorphine and the methadone maintenance group showed significantly more favorable values than opioid clients at admission regarding leisure time (p < or = 0.019), finances (p < or = 0.014), mental health (p < or = 0.010), and overall satisfaction (p < or = 0.010). Slow-release oral morphine is a well-established treatment for pain, but more research is required to evaluate it as a treatment for heroin dependence. The present data indicate that slow-release oral morphine could have some disadvantages compared with sublingual buprenorphine and methadone in QOL, physical symptoms, and additional consumption. The results further suggest that buprenorphine treatment is as effective as methadone in effec

Topics: Adult; Austria; Buprenorphine; Delayed-Action Preparations; Female; Humans; Male; Methadone; Morphine; Opioid-Related Disorders; Quality of Life; Substance Abuse Treatment Centers

To evaluate the efficacy and safety of methadone versus buprenorphine treatment in pregnant opioid-dependent women.. Randomized, double-dummy, double-blind, flexible-dosing comparison study.. Addiction Clinic at the Medical University of Vienna, Austria.. Eighteen women were assigned randomly to receive either methadone (n = 9) or buprenorphine (n = 9) during weeks 24-29 of pregnancy. After dropouts, data were available from 14 cases (six in the methadone and eight in the buprenorphine group).. Sublingual buprenorphine tablets (8-24 mg/day) or oral methadone solution (40-100 mg/day), with matched placebos.. Mothers: retention in treatment, urine toxicology and nicotine use. Neonates: Routine birth data, neonatal abstinence syndrome (NAS) in severity and duration.. There was somewhat greater retention in the buprenorphine group but significantly lowered use of additional opioids in the methadone group (P = 0.047).Neonates: There was earlier onset of NAS in neonates born to the methadone (mean 60 hours) than to the buprenorphine groups (mean 72 hours after last medication); 43% did not require NAS-treatment with short treatment duration in both groups (mean 5 days).. This preliminary study had limited power to detect differences but the trends observed suggest this kind of research is practicable and that further studies are warranted.

Topics: Buprenorphine; Double-Blind Method; Female; Humans; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications

Cardiac arrhythmias have been linked to treatment with methadone and levacetylmethadol. HIV-positive patients often have conditions that place them at risk for QT interval prolongation including HIV-associated dilated cardiomyopathy, coronary artery disease as a consequence of highly active antiretroviral (ARV) therapy-associated metabolic syndrome, and uncorrected electrolyte abnormalities. As of February 14, 2006, no cases of adverse events related to QT interval prolongation have been reported in patients receiving buprenorphine, an opioid partial agonist and the newest drug approved for the treatment of opioid dependence.. To evaluate the effects of buprenorphine/naloxone alone and in combination with 1 of 5 ARV agents (efavirenz, nelfinavir, delavirdine, ritonavir, lopinavir/ritonavir) on the QT interval.. This study was prospective, open-label, and within-subject in design, with subjects serving as their own controls. In 50 HIV-negative, opioid-dependent subjects, electrocardiogram recordings were obtained at baseline, after receiving buprenorphine/naloxone for 2 weeks, and then following buprenorphine/naloxone plus ARV administration for 5-15 days at steady-state. QTc interval measurements were compared using mixed-model, repeated-measures ANOVA. Recent cocaine use and gender were considered covariates.. Buprenorphine/naloxone alone and often in the presence of evidence for recent use of cocaine did not significantly alter the QT interval (p = 0.612). Buprenorphine/naloxone in combination with ARVs caused a statistically, but not clinically, significant increase (p = 0.005) in the QT interval. Subjects receiving buprenorphine/naloxone in combination with either delavirdine or ritonavir had the greatest increase in QTc intervals.. Prolonged QT intervals were not observed in opioid-dependent subjects receiving buprenorphine/naloxone alone. QT interval increases were observed with buprenorphine/naloxone in combination with either delavirdine or ritonavir, which inhibit CYP3A4.

Topics: Adult; Analgesics, Opioid; Antiretroviral Therapy, Highly Active; Buprenorphine; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Electrocardiography; Female; Humans; Long QT Syndrome; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Prospective Studies

Behavioral economic analysis has been used to investigate factors underlying drug consumption in laboratory animals and, increasingly, in human drug abusers. However, there are few studies in heroin abusers, especially those who are not in treatment; such studies may be valuable for understanding the mechanisms of persistent drug use. This study investigated effects of unit price (UP) and pre-session supply of hydromorphone (HYD) on choice and consumption of HYD. Heroin-dependent research volunteers (n=13) stabilized on buprenorphine 8 mg/day completed this eight-session inpatient study. In sessions 1-2, participants sampled two total HYD doses (12 and 24 mg IM) that could be earned in later sessions. In each of the final six sessions, volunteers were given access to a 12-trial choice progressive ratio schedule lasting 3h. On each trial, volunteers could earn a HYD unit dose (1 or 2 mg, for a maximum of 12 or 24 mg, respectively) or money (US dollars 2, for a maximum of US dollars 24). Fixed ratio requirements increased exponentially, generating 24 unit prices for behavioral economic analysis. Before some choice sessions, volunteers could choose (FR 1) to receive extra HYD (12 or 24 mg; at 0915), whereas on other days no supplement was available. HYD choice and peak responding (breakpoint, O(max)) measures increased with unit dose, decreased with pre-session supplements, and were greater among volunteers who used cocaine prior to the experiment. Taking pre-session supplements decreased P(max) and made group-percent HYD consumption more demand-elastic. Consumption was functionally equivalent at differing FR/unit dose combinations. Thus, opioid demand in heroin-dependent individuals not in treatment is a function of drug supply, unit price, and cocaine use.

Topics: Adolescent; Adult; Behavior, Addictive; Buprenorphine; Choice Behavior; Commerce; Costs and Cost Analysis; Drug Administration Schedule; Female; Heroin Dependence; Humans; Hydromorphone; Male; Middle Aged; Narcotics; Opioid-Related Disorders; Urinalysis

This study assessed treatment retention, compliance and completion of a 9-month buprenorphine replacement programme. In addition, changes in drug use and other relevant variables, as well as predictors of completion, were examined. Seventy-five opioid-dependent out-patients (mean age 26 years; 33% females) who aimed for opioid abstinence were enrolled into the study. Assessments were undertaken prior to buprenorphine induction and again at 3, 6 and 9 months. Forty patients (53%) completed the buprenorphine programme. At 9 months, 67 patients (87%) were still in counselling. Mean attendance rates for buprenorphine dosing and counselling sessions were 0.91 and 0.74, respectively. There were significant and persistent reductions in drug use during treatment with, however, a reversed tendency in the 9th month. Psychiatric problems escalated at 9 months, and three patients died during the detoxification phase. Completion was predicted by fewer previous treatment episodes. Detoxification from buprenorphine is associated with substantial psychological distress and an increased death risk. Buprenorphine replacement therapy should be continued until the patient chooses to leave, and close monitoring during the detoxification phase is essential.

Topics: Adult; Ambulatory Care Facilities; Buprenorphine; Counseling; Drug Administration Schedule; Female; Humans; Male; Narcotic Antagonists; Norway; Opioid-Related Disorders; Outpatients; Patient Compliance; Risk Factors; Stress, Psychological; Substance Withdrawal Syndrome; Treatment Outcome

This study compared the relative efficacy of low-magnitude, contingent monetary vouchers, contingent buprenorphine medication, and standard counseling in promoting abstinence from illicit opioids and cocaine among opioid-dependent adults. Following an 8-week baseline period during which participants received buprenorphine maintenance treatment with no contingencies in place, 60 participants were randomly assigned to one of 3 treatment groups for 12 weeks: (a) Participants in the voucher group earned vouchers for each opioid- and cocaine-negative urine sample, in accordance with an escalating schedule. Continuous abstinence resulted in voucher earnings equivalent to a total of 269 US dollars, which participants could exchange for material reinforcers of their choice. (b) Participants in the medication contingency group received half their scheduled buprenorphine dose for clinic attendance and the other half for remaining abstinent from opiates and cocaine. Thus, they received only half of their scheduled dose on submission of an opioid- and/or cocaine-positive urine sample. (c) Participants in standard treatment did not receive programmed consequences contingent on urinalysis results. All participants were maintained with buprenorphine according to a 3-times-per-week dosing regimen and participated in behavioral drug counseling. Retention rate did not significantly differ across the groups; however, participants in the medication contingency group achieved significantly more weeks of continuous abstinence from opiates and cocaine compared with participants in the voucher group (Ms = 5.95 and 2.90, respectively). Results suggest that the use of medication-based contingencies in combination with behavioral therapy in promoting drug abstinence may have clinical utility. Limitations of the study are discussed.

Topics: Adult; Behavior Therapy; Buprenorphine; Cocaine-Related Disorders; Female; Health Care Costs; Humans; Male; Middle Aged; Opioid-Related Disorders; Reinforcement Schedule

The optimal level of counseling and frequency of attendance for medication distribution has not been established for the primary care, office-based buprenorphine-naloxone treatment of opioid dependence.. We conducted a 24-week randomized, controlled clinical trial with 166 patients assigned to one of three treatments: standard medical management and either once-weekly or thrice-weekly medication dispensing or enhanced medical management and thrice-weekly medication dispensing. Standard medical management was brief, manual-guided, medically focused counseling; enhanced management was similar, but each session was extended. The primary outcomes were the self-reported frequency of illicit opioid use, the percentage of opioid-negative urine specimens, and the maximum number of consecutive weeks of abstinence from illicit opioids.. The three treatments had similar efficacies with respect to the mean percentage of opioid-negative urine specimens (standard medical management and once-weekly medication dispensing, 44 percent; standard medical management and thrice-weekly medication dispensing, 40 percent; and enhanced medical management and thrice-weekly medication dispensing, 40 percent; P=0.82) and the maximum number of consecutive weeks during which patients were abstinent from illicit opioids. All three treatments were associated with significant reductions from baseline in the frequency of illicit opioid use, but there were no significant differences among the treatments. The proportion of patients remaining in the study at 24 weeks did not differ significantly among the patients receiving standard medical management and once-weekly medication dispensing (48 percent) or thrice-weekly medication dispensing (43 percent) or enhanced medical management and thrice-weekly medication dispensing (39 percent) (P=0.64). Adherence to buprenorphine-naloxone treatment varied; increased adherence was associated with improved treatment outcomes.. Among patients receiving buprenorphine-naloxone in primary care for opioid dependence, the efficacy of brief weekly counseling and once-weekly medication dispensing did not differ significantly from that of extended weekly counseling and thrice-weekly dispensing. Strategies to improve buprenorphine-naloxone adherence are needed. (ClinicalTrials.gov number, NCT00023283 [ClinicalTrials.gov].).

Topics: Adult; Buprenorphine; Cocaine-Related Disorders; Combined Modality Therapy; Counseling; Female; Humans; Male; Naloxone; Narcotic Antagonists; Opioid-Related Disorders

The efficacies of three opioid substitution medications for reducing HIV risk behaviors in opioid-dependent patients were assessed in a randomized double-blind clinical trial comparing levomethadyl acetate [corrected] (LAAM), buprenorphine (BUP), and methadone (METH). Individually optimized flexible dosing was used for each group, with weekly possible doses of 255-391 mg of LAAM, 56-112 mg of BUP, and 420-700 mg of METH. An interview regarding specific HIV risk behaviors, including injecting, equipment sharing, and sexual activity, yielded data for pretreatment and four in-study time points for 137 subjects. Declines in risk behaviors during treatment were evident in all groups for most measures of injecting and equipment sharing. Only the METH group showed consistent declines in measures of sexual behaviors. These results demonstrate that all three medications can be highly effective in decreasing HIV risk behaviors when the dose is optimized. Reductions in sexual behaviors for the METH group are consistent with known METH side effects.

Topics: Adult; Buprenorphine; Double-Blind Method; Drug Administration Schedule; Female; HIV Infections; Humans; Male; Methadone; Methadyl Acetate; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Risk-Taking

Buprenorphine has a long duration of action that allows less than daily dosing for opioid dependence, but pharmacologic characterization of buprenorphine's duration of effects over multiple days is incomplete.. This study assessed opioid blockade and spontaneous withdrawal effects of buprenorphine/naloxone (B/N) over a 98-h period.. Residential opioid-dependent volunteers (n = 8) were maintained, in randomized sequence, on each of three different daily sublingual B/N doses (8/2, 16/4, 32/8 mg). After 2 weeks on each maintenance dose, participants underwent challenge sessions on each weekday for 1 week. Challenges consisted of within-session, ascending dose administration of IM hydromorphone (H: 0, 6, and 12 mg). During that week, active B/N dose was given only on Monday; double-blind placebo was administered on the remaining weekdays. Thus, these sessions assessed the extent of both opioid blockade and spontaneous withdrawal at 2, 26, 50, 74, and 98 h after the last active B/N dose.. All three maintenance doses provided substantial but incomplete blockade against opioid agonist effects for 98 h. The extent of blockade diminished steadily but modestly over this time and did not differ as a function of B/N maintenance dose. In general, participants did not report marked spontaneous opioid withdrawal, although mild withdrawal effects were observed as time since the last active B/N dose increased. However, withdrawal did not differ as a function of B/N maintenance dose.. These findings suggest that B/N doses greater than 8/2 mg provide minimal incremental value in terms of opioid blockade and withdrawal suppression.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Hydromorphone; Naloxone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Substance Withdrawal Syndrome

The growing tendency among opioid addicts to misuse multiple other drugs should lead clinicians and researchers to search for new pharmacological strategies in order to prevent life-threatening complications and minimize withdrawal symptoms during polydrug detoxification.. A non-randomised, open-label in-patient detoxification study was used to compare the short-time efficacy of a standardised regimen comprising 6 days Buprenorphine and 10 days Valproate (BPN/VPA) (n = 12) to a control group (n = 50) who took a 10-day traditional Clonidine/Carbamazepine (CLN/CBZ) regimen. Sixty-two dependent subjects admitted to a detoxification unit were included, all dependent on at least opioids and benzodiazepines. Other dependencies were not excluded.. In the BPN/VPA group, 8 out of 12 patients (67%) completed treatment compared with 25 of 50 patients (50%) in the CLN/CBZ group; this difference between the groups was non-significant (p = 0.15). Withdrawal symptoms were reduced in both groups, but only the BPN/VPA group achieved a reduction in withdrawal symptoms from day one. The difference between the two groups was significantly in favour of the BPN/VPA group for days 2 (p < 0.001), 3 (p < 0.05), 4 (p < 0.001), 5 (p < 0.01), 7 (p < 0.01) and 8 (p < 0.05). The BPN/VPA combination did not affect blood pressure, pulse or liver function, and the total burden of side-effects was experienced as modest. There appeared to be no pharmacological interactions of clinical concern, based on measurement of Buprenorphine and Valproate serum levels. Both the patients and the staff were satisfied with the standardised treatment combination.. Overall, the combination of Buprenorphine and Valproate seems to be a safe and promising method for treating multiple drug withdrawal symptoms. The results of this study suggest that the BPN/VPA combination is potentially a better detoxification treatment for polydrug withdrawal than the traditional treatment with Clonidine and Carbamazepine. However, a randomised, double-blind study with a larger sample size to confirm our results is recommended.

Topics: Adult; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Buprenorphine; Carbamazepine; Clonidine; Comorbidity; Drug Therapy, Combination; Female; Hospitalization; Humans; Male; Opioid-Related Disorders; Substance Withdrawal Syndrome; Substance-Related Disorders; Treatment Outcome; Valproic Acid

Untreated opioid dependence adversely affects the care of human immunodeficiency virus (HIV)-positive patients. Buprenorphine, a partial opioid agonist, is available for maintenance treatment of opioid dependence in HIV specialty settings. We investigated the feasibility and efficacy of integrating buprenorphine, along with 2 levels of counseling, into HIV clinical care.. HIV-positive, opioid-dependent patients were enrolled in a 12-week pilot study and randomized to receive daily buprenorphine/naloxone treatment along with either brief physician management or physician management combined with nurse-administered drug counseling and adherence management. Primary outcomes included treatment retention; illicit drug use, assessed by urine toxicology test and self-report; CD4 lymphocyte counts; and log(10) HIV type 1 (HIV-1) RNA levels.. Of the 16 patients who received at least 1 dose of buprenorphine, 13 (81%) completed 12 weeks of treatment. The proportion of opioid-positive weekly urine test results decreased from 100% at baseline to 32% (month 1), 20% (month 2), and 16% (month 3). Only 4 patients reported any opioid use (in the prior 7 days) during the 12-week study. CD4 lymphocyte counts remained stable over the course of the study. The mean log(10) HIV-1 RNA level (+/- standard deviation) declined significantly, from 3.66+/-1.06 log(10) HIV-1 RNA copies/mL at baseline to 3.0+/-0.57 log(10) HIV-1 RNA copies/mL at month 3 (P<.05). No significant differences based on counseling intervention were detected. All 13 patients who completed the study continued to receive treatment in an extension phase of at least 0-15 months' duration.. We conclude that it is feasible to integrate buprenorphine into HIV clinical care for the treatment of opioid dependence. Patients experienced good treatment retention and reductions in their opioid use. HIV biological markers remained stable or improved during buprenorphine/naloxone treatment.

Topics: Administration, Sublingual; Adult; Antiretroviral Therapy, Highly Active; Buprenorphine; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; HIV Infections; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Pilot Projects; Probability; Reference Values; Risk Factors; Treatment Outcome

This randomized clinical trial evaluated the relative efficacy of three buprenorphine dosing schedules. Opioid-dependent adults were randomly assigned to receive buprenorphine seven, 3 or 2 days per week for 24 weeks. Daily maintenance doses were 4, 8, 10, or 12 mg of the sublingual buprenorphine solution. Participants who attended the clinic daily received a maintenance dose of buprenorphine daily. Participants who attended the clinic thrice weekly received double their maintenance dose on Monday and Wednesday, followed by a triple dose on Friday. Participants who attended the clinic twice weekly received quadruple their maintenance dose of buprenorphine on Monday and triple their maintenance dose on Friday. Results demonstrated that all dosing regimens were of comparable efficacy in promoting treatment retention, opioid and cocaine abstinence, and reductions in HIV risk behavior (especially as related to drug use) and severity of life problems. Predictor analyses identified sub-populations of opioid-dependent individuals that may have a more positive treatment outcome under each buprenorphine dosing condition. Less-than-daily dosing schedules may provide the opportunity for treatment programs to serve a greater number of opioid-dependent patients and reduce the risk of medication diversion, which may, in turn, have a positive impact on community support of science-based treatment for opioid-dependence.

Topics: Adult; Buprenorphine; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Opioid-Related Disorders

There are approximately 12,000 opioid dependants in Norway. Methadone-assisted treatment was approved in Norway in 1998, buprenorphine in 2000. This study compares the efficacy of methadone (n = 25) and buprenorphine (n = 25) assisted maintenance treatment in a group of long-term (> 10 years) opioid dependant.. After randomisation patients received either 16 mg sublingual buprenorphine or individually adjusted methadone (mean 106 mg, range 80 - 160) for 26 weeks, with a rehabilitation programme run in parallel.. After 180 days, patient retention was highest in the methadone group (85 % vs. 36 %, p < 0.0005). Days in treatment were 167 vs. 114 (95 % CI for difference 53 days (26-80), p < 0.001). Positive urine test rates for opiates (20 % vs 24 %, p < 0.01) and cannabis (33 % vs 45 %, p < 0.001) were lower in the methadone group which also had lower self-reported risk behaviour and psychological distress. However, only those on buprenorphine reported significant improvement in physical health. For older, long-term opioid dependants with significant co-morbidity and unsuccessful medication-free treatment, high-dose methadone maintenance appears to be the treatment of choice. However, in cases where methadone is poorly tolerated, buprenorphine therapy may be a good alternative.

Topics: Adult; Buprenorphine; Female; Humans; Male; Methadone; Narcotics; Opioid-Related Disorders; Surveys and Questionnaires; Treatment Outcome

Physicians may prescribe buprenorphine for opioid agonist maintenance treatment outside of narcotic treatment programs, but treatment guidelines for patients with co-occurring cocaine and opioid dependence are not available. This study compares effects of buprenorphine and methadone and evaluates the efficacy of combining contingency management with maintenance treatment for patients with co-occurring cocaine and opioid dependence.. Subjects with cocaine and opioid dependence (N=162) were provided manual-guided counseling and randomly assigned in a double-blind design to receive daily sublingual buprenorphine (12-16 mg) or methadone (65-85 mg p.o.) and to contingency management or performance feedback. Contingency management subjects received monetary vouchers for opioid- and cocaine-negative urine tests, which were conducted three times a week; voucher value escalated during the first 12 weeks for consecutive drug-free tests and was reduced to a nominal value in weeks 13-24. Performance feedback subjects received slips of paper indicating the urine test results. The primary outcome measures were the maximum number of consecutive weeks abstinent from illicit opioids and cocaine and the proportion of drug-free tests. Analytic models included two-by-two analysis of variance and mixed-model repeated-measures analysis of variance.. Methadone-treated subjects remained in treatment significantly longer and achieved significantly longer periods of sustained abstinence and a greater proportion drug-free tests, compared with subjects who received buprenorphine. Subjects receiving contingency management achieved significantly longer periods of abstinence and a greater proportion drug-free tests during the period of escalating voucher value, compared with those who received performance feedback, but there were no significant differences between groups in these variables during the entire 24-week study.. Methadone may be superior to buprenorphine for maintenance treatment of patients with co-occurring cocaine and opioid dependence. Combining methadone or buprenorphine with contingency management may improve treatment outcome.

Topics: Adult; Analgesics, Opioid; Behavior Therapy; Buprenorphine; Cocaine-Related Disorders; Combined Modality Therapy; Comorbidity; Female; Humans; Male; Methadone; Opioid-Related Disorders; Substance Abuse Detection; Token Economy; Treatment Outcome

This study compared the safety and withdrawal discomfort associated with transitioning pregnant opioid-dependent women from short-acting morphine onto buprenorphine or methadone under well-controlled double-blind conditions. Participants (n=18) were patients in a comprehensive treatment setting and were part of a larger randomized controlled trial comparing the neonatal abstinence syndrome in mothers treated with individualized doses of sublingual buprenorphine or oral methadone. Methadone was first given to all patients within 24h of treatment admission. After written informed consent was signed (3-5 days post-admission), methadone was discontinued and Immediate Release Morphine (IRM) was initiated. The initial total daily dose of IRM was six times the last daily methadone dose. The daily dose of IRM was divided in four daily doses. Induction onto double-blind, double dummy (i.e., two medications were administered with only one being active) methadone or buprenorphine was accomplished over 3 days (i.e., induction). Withdrawal scores during the IRM and induction onto randomized medication were judged mild and not statistically different for both methadone (mean dose 53.5 mg) and buprenorphine (mean dose 10.9 mg). No significant differences between medication groups were observed when individual withdrawal items were examined. No observed differences in safety measures including fetal movement, maternal physiological parameters of body temperature, heart rate and blood pressure were observed between groups. Transitioning opioid-dependent pregnant women from IRM to methadone or buprenorphine during the second trimester of pregnancy can be conducted with similar comfort and safety.

Topics: Adult; Buprenorphine; Double-Blind Method; Female; Humans; Methadone; Morphine; Opioid-Related Disorders; Pregnancy; Substance Withdrawal Syndrome

We evaluated the influence of psychotherapy attendance on treatment outcome in 90 dually (cocaine and heroin) dependent outpatients who completed 70 days of a controlled clinical trial of sublingual buprenorphine (16 mg, 8 mg, or 2 mg daily, or 16 mg every other day) plus weekly individual standardized interpersonal cognitive psychotherapy. Treatment outcome was evaluated by quantitative urine benzoylecgonine (BZE) and morphine levels (log-transformed), performed three times per week. Repeated-measures linear regression was used to assess the effects of psychotherapy attendance (percent of visits kept), medication group, and study week on urine drug metabolite levels. Mean psychotherapy attendance was 71% of scheduled visits. Higher psychotherapy attendance was associated with lower urine BZE levels, and this association grew more pronounced as the study progressed (p=0.04). The inverse relationship between psychotherapy attendance and urine morphine levels varied by medication group, being most pronounced for subjects receiving 16 mg every other day (p=0.02). These results suggest that psychotherapy can improve the outcome of buprenorphine maintenance treatment for patients with dual (cocaine and opioid) dependence.

Topics: Administration, Sublingual; Adult; Buprenorphine; Cocaine-Related Disorders; Combined Modality Therapy; Female; Humans; Male; Narcotic Antagonists; Opioid-Related Disorders; Patient Compliance; Psychotherapy; Treatment Outcome

Topics: Administration, Oral; Adult; Automobile Driving; Buprenorphine; Delayed-Action Preparations; Humans; Morphine; Narcotics; Opioid-Related Disorders; Psychomotor Performance

Office-based buprenorphine holds the promise of bringing patients who have never received pharmacotherapy into treatment. In a cross-sectional and longitudinal analysis, we compared patients entering a clinical trial of buprenorphine in a Primary Care Clinic (PCC) and those entering a local Opioid Treatment Program (OTP) and we compared the clinical characteristics and treatment outcomes of PCC patients with no history of methadone treatment (new-to-treatment) to those with prior methadone treatment. PCC subjects (N=96) were enrolled in a 26-week randomized clinical trial of office-based buprenorphine/naloxone provided in a PCC. OTP subjects (N=94) were enrolled in methadone maintenance during the same time period. PCC subjects compared with OTP subjects were more likely to be male (77% versus 55%, p<0.01), full-time employed (46% versus 15%, p<0.001), have no history of methadone treatment (46% versus 61%, p<0.05), have fewer years of opioid dependence (10 versus 15, p<0.001), and lower rates of injection drug use (IDU) (44% versus 60%, p=0.03). The new-to-treatment PCC subjects were younger (36 years versus 41 years, p=0.001), more likely to be white (77% versus 57%, p=0.04), had fewer years of opioid dependence (7 versus 14, p<0.001), were less likely to have a history of IDU (35% versus 54%, p=0.07), and had lower rates of hepatitis C (25% versus 61%, p=0.002) than subjects with prior methadone treatment. Abstinence and treatment retention were comparable in both groups. The results suggest that office-based treatment of opioid dependence is associated with new types of patients entering into treatment. Treatment outcomes with buprenorphine in a PCC do not vary based on history of prior methadone treatment.

Topics: Adolescent; Adult; Aged; Buprenorphine; Cross-Sectional Studies; Female; Humans; Male; Mental Health Services; Middle Aged; Narcotic Antagonists; Office Visits; Opioid-Related Disorders; Practice Patterns, Physicians'

The clinical effectiveness of buprenorphine-naloxone (bup-nx) and clonidine for opioid detoxification in in-patient and out-patient community treatment programs was investigated in the first studies of the National Institute of Drug Abuse Clinical Trials Network.. Diagnostic and Statistical Manual version IV (DSM IV)-diagnosed opioid-dependent individuals seeking short-term treatment were randomly assigned, in a 2 : 1 ratio favoring bup-nx, to a 13-day detoxification using bup-nx or clonidine.. A total of 113 in-patients (77 bup-nx, 36 clonidine) and 231 out-patients (157 bup-nx, 74 clonidine) participated. Supportive interventions included appropriate ancillary medications and standard counseling procedures guided by a self-help handbook. The criterion for treatment success was defined as the proportion of participants in each condition who were both retained in the study for the entire duration and provided an opioid-free urine sample on the last day of clinic attendance. Secondary outcome measures included use of ancillary medications, number of side effects reported and withdrawal and craving ratings.. A total of 59 of the 77 (77%) in-patients assigned to the bup-nx condition achieved the treatment success criterion compared to eight of the 36 (22%) assigned to clonidine, whereas 46 of the 157 (29%) out-patients assigned to the bup-nx condition achieved the treatment success criterion, compared to four of the 74 (5%) assigned to clonidine.. The benefits of bup-nx for opioid detoxification are supported and illustrate important ways in which clinical research can be conducted in community treatment programs.

Topics: Adult; Buprenorphine; Clonidine; Female; Humans; Inactivation, Metabolic; Male; Naloxone; Narcotic Antagonists; Opioid-Related Disorders

Cognitive impairment in drug-dependent patients under methadone maintenance treatment has been reported before. We assessed whether patients under buprenorphine, a partial mu-opioid agonist, perform better in cognitive tests measuring psychomotor performance as described in previous nonrandomized studies.. We performed a randomized clinical trial in 62 drug-dependent patients under either buprenorphine or methadone treatment. Sixteen patients dropped out of maintenance therapy, before the testing was performed, after 8 to 10 weeks of treatment. Several subtests of the Act & React Test System test battery were used measuring visual perception, selective attention, vigilance, reactivity, and stress tolerance.. Although there were no differences in cognitive function at baseline, patients under buprenorphine treatment showed partially better results in some of the domains tested. The used tests are relevant when assessing driving ability. There was a significant correlation between dose of buprenorphine and some test results. We also found a correlation between age and reaction time and between duration of opioid dependence and results in some subtests. INTERPRETATIONS (CONCLUSIONS): When comparing both treatments in drug dependent patients, buprenorphine produces partially less impairment on cognitive functions in some of the subtests of the psychomotor battery than methadone. This difference is specially relevant when it comes to driving ability and social functioning.

Topics: Adult; Aging; Attention; Automobile Driving; Buprenorphine; Cognition; Female; Humans; Male; Memory, Short-Term; Methadone; Middle Aged; Narcotic Antagonists; Neuropsychological Tests; Opioid-Related Disorders; Psychomotor Performance; Reaction Time; Verbal Behavior; Visual Perception

Twenty-six in-patients with Diagnostic and Statistical Manual version IV (DSM-IV) criteria for opioid dependence were selected at random to receive either a combination of an 11-day low-dose buprenorphine and a 14-day carbamazepine regimen (n = 14) or a combination of an 11-day methadone and a 14-day carbamazepine regimen (n = 12) in a double-blind, randomized 14-day in-patient detoxification treatment. Patients with buprenorphine and carbamazepine showed a significantly better psychological state after the first and second weeks of treatment. Above all, the buprenorphine-treated patients demonstrated a less marked tiredness, sensitiveness and depressive state as well as a more prominent elevated mood during the detoxification process. Seven non-completers (after 7 days: four of 12 = 33.3%; after 14 days: seven of 12 = 58.3%) were treated with methadone and carbamazepine and five non-completers (after 7 days: two of 14 = 14.3%; after 14 days: five of 14 = 35.7%) received buprenorphine and carbamazepine. The difference in the overall dropout rate after day 14 was not significant. The present study supports the hypothesis that the combination of buprenorphine and carbamazepine leads to a better clinical outcome than does a combination of methadone and carbamazepine in the detoxification of opioid addicts with additional multiple drug abuse. The buprenorphine and carbamazepine-regimen provides a more effective short-term relief of affective disturbances than does methadone and carbamazepine. No severe side effects occurred during the treatment period in both groups.

Topics: Adult; Anticonvulsants; Buprenorphine; Carbamazepine; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Hospitalization; Humans; Inactivation, Metabolic; Male; Methadone; Mood Disorders; Narcotic Antagonists; Opioid-Related Disorders

The prevalence of heroin and other opioid use has markedly increased among adolescents in the last decade; however, virtually no research has been conducted to identify effective treatments for this population.. To evaluate the relative efficacy of 2 pharmacotherapies, the partial opioid agonist buprenorphine hydrochloride and the centrally active alpha(2)-adrenergic blocker clonidine hydrochloride, in the detoxification of opioid-dependent adolescents.. A double-blind, double-dummy, parallel-groups randomized controlled trial conducted in a university-based research clinic from October 2001 to December 2003. Patients were a volunteer sample of 36 adolescents who met DSM-IV criteria for opioid dependence (ages 13-18 years eligible).. Participants were randomly assigned to a 28-day, outpatient, medication-assisted withdrawal treatment with either buprenorphine or clonidine. Both medications were provided along with thrice weekly behavioral counseling and incentives contingent on opiate abstinence. Postdetoxification, all participants were offered the opportunity for continued treatment with the opiate antagonist, naltrexone hydrochloride.. Treatment retention, opiate abstinence, and human immunodeficiency virus risk behavior, along with measures of withdrawal and medication effects.. A significantly greater percentage of adolescents who received buprenorphine were retained in treatment (72%) relative to those who received clonidine (39%) (P<.05). For those in the buprenorphine group, a significantly higher percentage of scheduled urine test results were opiate negative (64% vs 32%; P = .01). Participants in both groups reported relief of withdrawal symptoms and drug-related human immunodeficiency virus risk behavior. Those in the buprenorphine condition generally reported more positive effects of the medication. No evidence of opioid intoxication or psychomotor impairment was observed. Sixty-one percent of participants in the buprenorphine condition and 5% of those in the clonidine group initiated treatment with naltrexone.. Combining buprenorphine with behavioral interventions is significantly more efficacious in the treatment of opioid-dependent adolescents relative to combining clonidine and behavioral interventions.

Topics: Administration, Cutaneous; Adolescent; Adrenergic alpha-Agonists; Adrenergic alpha-Antagonists; Behavior Therapy; Buprenorphine; Clonidine; Combined Modality Therapy; Double-Blind Method; HIV Infections; Humans; Narcotic Antagonists; Opioid-Related Disorders; Psychomotor Performance; Risk-Taking; Substance Withdrawal Syndrome; Treatment Outcome

We evaluated peak plasma concentrations, trough concentrations, and the 24-hour area under the concentration curve (AUC(0-24 h)) during maintenance with sublingual (SL) liquid or tablet formulations in 57 opiate-dependent volunteers. Study participants were assigned randomly to one of three SL daily buprenorphine dose pairs and maintained for 2 weeks with the liquid formulation followed by 2 weeks with the corresponding tablet dose. Plasma samples were obtained after at least 10 days of maintenance with the liquid formulation and after at least 10 days of that with the tablet formulation. The bioequivalence of the tablet compared with the liquid doses ranged from 57% to 75% based on peak concentrations, from 102% to 108% based on trough concentrations, and from 66% to 86% based on 24-hour AUC, but there was a large intersubject and intrasubject variability in plasma concentrations, with greater variability following tablets than liquid. Measures of withdrawal symptoms or illicit opioid use were not associated with buprenorphine dose, formulation, or plasma buprenorphine levels.

Topics: Administration, Sublingual; Adult; Buprenorphine; Female; Humans; Male; Metabolic Clearance Rate; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Pharmaceutical Solutions; Substance Withdrawal Syndrome; Tablets; Treatment Outcome

This is the first trial to compare the relationship of opioid plasma concentrations in methadone-versus buprenorphine-maintained subjects. Sixty subjects (19 females and 41 males) seeking treatment who met Diagnostic and Statistical Manual version IV (DSM-IV) criteria for opioid dependence were recruited and treated at the Drug Addiction Outpatient Clinic at the University of Vienna. Of these, 44 (11 female and 33 male) were included in the analyses of plasma concentrations. Subjects received either daily sublingual buprenorphine (2 mg or 8 mg tablets; maximum daily dose: 8 mg) or oral methadone (racemic R-/S-methadone) and were maintained on a stable dose after an induction period of 2 weeks. Mean dose and mean plasma concentrations were correlated on an individual and collective basis. Correlation was 0.51 for buprenorphine, whereas the score for methadone was 0.69. Intra-individual variation was much higher for buprenorphine (p<0.0001), while the concentration-to-dose ratio was very small. Based on the differences of the pharmacokinetics of blood plasma of the two agents, we tried to explain the differences in the acceptance of treatment, which was significantly lower in the buprenorphine-maintained group. No such differences could be evaluated between completers and dropouts in buprenorphine-maintained subjects, neither concerning withdrawal scores nor dose, plasma concentration, concentration-to-dose ratios or intra-individual variation.

Topics: Administration, Oral; Administration, Sublingual; Adolescent; Adult; Buprenorphine; Dose-Response Relationship, Drug; Female; Humans; Long-Term Care; Male; Methadone; Middle Aged; Opioid-Related Disorders; Patient Acceptance of Health Care; Patient Dropouts; Statistics as Topic; Substance Withdrawal Syndrome

This study examined (1) predictors of treatment outcome for opioid-dependent participants in a single-site controlled trial comparing methadone, buprenorphine, and LAAM treatments and (2) the extent to which various subpopulations of patients may have more successful outcomes with each medication. The relationships between patient demographics, drug use history, and psychological status and outcome measures of treatment retention, opiate use, and cocaine use were assessed. We believe this study to be the first to demonstrate that predictors of treatment success appear to be largely similar in LAAM, buprenorphine, and methadone treatment for opioid dependence. We did not find any factors that would strongly guide selection of one medication over others.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Double-Blind Method; Female; Humans; Male; Methadone; Methadyl Acetate; Middle Aged; Opioid-Related Disorders; Prospective Studies; Receptors, Opioid, mu; Regression Analysis; Treatment Outcome

To investigate whether a buprenorphine opiate detoxification regimen can be considered to be at least as clinically effective as a lofexidine regimen.. An open-label randomized controlled trial (RCT) using a non-inferiority approach. Non-inferiority is demonstrated if, within a 95% confidence interval, buprenorphine performs within a preset tolerance limit of clinically acceptable difference in outcomes and completion rates between the two treatments.. Individuals ready for heroin detoxification were given information about the trial and invited to participate. Consenting participants (n = 210) were then randomized to one of the two treatments. Detoxification was undertaken in a specialist out-patient clinic according to predefined protocols. The primary outcome was whether or not an individual completed the detoxification. Abstinence at 1-month follow-up was used as a secondary outcome measure. Additional secondary outcome measures were substance use, dependence, psychological health, social satisfaction, and treatment satisfaction. Data were also collected for individuals who declined randomization and instead chose their treatment (n = 271).. A total of 46% of those on lofexidine and 65% of those on buprenorphine completed detoxification. Of these, 35.7% of the lofexidine and 45.9% of the buprenorphine groups reported abstinence at 1 month. Of those not completing detoxification abstinence was reported at 27.5% and 29.0%, respectively; 271 individuals who opted not to be allocated randomly and instead chose one of the two treatments produced similar results. Buprenorphine is at least as effective as lofexidine detoxification treatment. Whether or not individuals were randomized to, or chose, a treatment appeared not to affect the study's outcome.

Topics: Adolescent; Adult; Buprenorphine; Clonidine; Community Mental Health Services; Female; Humans; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Treatment Outcome

The goal of this study was to compare the effects of 1, 3 and 8 mg per day doses of buprenorphine in the maintenance treatment of opium-dependent subjects in Iran over a treatment period of 12 months. Participants were randomized to three equal groups (171 subjects per group) of opium-dependent individuals who met the DSM-IV criteria for opioid dependence and were seeking treatment. They were treated in an urban outpatient clinic, offering a 1-hour weekly individual counseling session. Overall, 282 subjects (55%) completed the 12 months study. Completion rates by dosage group were 46 (26.9%) for the 1 mg dose group, 102 (59.6%) for the 3 mg dose group, and 134 (78.4%) for the 8 mg dose group (p =.000). These findings are consistent with previous reports of effective buprenorphine use in western countries as a suitable maintenance treatment for opium dependence.

Topics: Adult; Aged; Aged, 80 and over; Buprenorphine; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Iran; Male; Middle Aged; Narcotic Antagonists; Odds Ratio; Opioid-Related Disorders; Opium

Buprenorphine is a partial mu-opiate agonist and kappa-opiate antagonist with established efficacy in the treatment of opiate dependence. Its efficacy for cocaine dependence is uncertain. This study evaluated buprenorphine for the treatment of concomitant cocaine and opiate dependence.. Two hundred outpatients currently dependent on both cocaine and opiates were randomly assigned to double-blind groups receiving a sublingual solution of buprenorphine (2, 8, or 16 mg daily, or 16 mg on alternate days, or placebo), plus weekly individual drug abuse counseling, for 13 weeks. The chief outcome measures were urine concentrations of opiate and cocaine metabolites (quantitative) and proportion of urine samples positive for opiates or cocaine (qualitative). Group differences were assessed by use of mixed regression modeling.. The target dose of buprenorphine was achieved in 179 subjects. Subjects receiving 8 or 16 mg buprenorphine daily showed statistically significant decreases in urine morphine levels (P =.0135 for 8 mg and P <.001 for 16 mg) or benzoylecgonine concentrations (P =.0277 for 8 mg and P =.006 for 16 mg) during the maintenance phase of the study. For the 16-mg group, mean benzoylecgonine concentrations fell from 3715 ng/mL during baseline to 186 ng/mL during the withdrawal phase; mean morphine concentrations fell from 3311 ng/mL during baseline to 263 ng/mL during withdrawal. For the 8-mg group, mean benzoylecgonine concentrations fell from 6761 ng/mL during baseline to 676 ng/mL during withdrawal; mean morphine concentrations fell from 3890 ng/mL during baseline to 661 ng/mL during withdrawal. Qualitative urinalysis showed a similar pattern of results. Subjects receiving the highest dose showed concomitant decreases in both urine morphine and benzoylecgonine concentrations. There were no significant group differences in treatment retention or adverse events.. A sublingual buprenorphine solution at 16 mg daily is well tolerated and effective in reducing concomitant opiate and cocaine use. The therapeutic effect on cocaine use appears independent of that on opiate use.

Topics: Administration, Sublingual; Adult; Buprenorphine; Cocaine-Related Disorders; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Narcotic Antagonists; Opioid-Related Disorders; Patient Compliance; Treatment Outcome

Based on its unique pharmacological profile, buprenorphine may produce less impairment in psychomotor and cognitive performance than methadone. However, the few studies that have investigated the performance effects of buprenorphine in opioid-abusing volunteers examined effects of single acute doses rather than effects of repeated dosing and included a very limited range of measures. The present inpatient study evaluated dose-related effects of repeated administration of the buprenorphine/naloxone combination product (8/2, 16/4, 32/8 mg, sublingual tablets) in eight opioid-dependent volunteers on performance of a broad range of tasks, following a period of 7-10 days of dosing at each level, in a double-blind, within-subject, crossover design. The testing battery included measures of psychomotor speed, time perception, conceptual flexibility, focused attention, working memory, long-term/episodic memory, and metamemory. Supporting the hypothesis of limited impairment with buprenorphine, results revealed minimal impairment in performance as buprenorphine/naloxone dose was increased four-fold. The only significant effect of dose was an impairment in episodic/long-term memory (recognition memory) performance at the highest dose (32/8 mg) relative to the two lower doses. Future studies incorporating larger sample sizes and non-drug controls, as well as directly comparing buprenorphine to methadone and LAAM are needed to further test the hypothesis of limited impairment with buprenorphine.

Topics: Adult; Buprenorphine; Cognition Disorders; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Memory Disorders; Naloxone; Narcotic Antagonists; Neuropsychological Tests; Opioid-Related Disorders; Psychomotor Disorders

Heroin is a synthetic opioid with an extensive illicit market leading to large numbers of people becoming addicted. Heroin users often present to community treatment services requesting detoxification and in the UK various agents are used to control symptoms of withdrawal. Dissatisfaction with methadone detoxification 8 has lead to the use of clonidine, lofexidine, buprenorphine and dihydrocodeine; however, there remains limited evaluative research. In Leeds, a city of 700,000 people in the North of England, dihydrocodeine is the detoxification agent of choice. Sublingual buprenorphine, however, is being introduced. The comparative value of these two drugs for helping people successfully and comfortably withdraw from heroin has never been compared in a randomised trial. Additionally, there is a paucity of research evaluating interventions among drug users in the primary care setting. This study seeks to address this by randomising drug users presenting in primary care to receive either dihydrocodeine or buprenorphine.. The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) project is a pragmatic randomised trial which will compare the open use of buprenorphine with dihydrocodeine for illicit opiate detoxification, in the UK primary care setting. The LEEDS project will involve consenting adults and will be run in specialist general practice surgeries throughout Leeds. The primary outcome will be the results of a urine opiate screening at the end of the detoxification regimen. Adverse effects and limited data to three and six months will be acquired.

Topics: Adolescent; Adult; Buprenorphine; Codeine; England; Follow-Up Studies; Health Services Research; Heroin Dependence; Humans; Methadone; Narcotic Antagonists; Opioid-Related Disorders; Primary Health Care; State Medicine; Substance Abuse Detection; Treatment Outcome

In recent years, interest in shortening of opioid detoxification has increased with the rising demands to find more cost-effective approaches for treatment of opioid dependence. This study was designed to evaluate the efficacy of administration of high doses of buprenorphine during 24 h in the management of acute opioid withdrawal. A total of 40 treatment-seeking opioid dependents were admitted and randomly assigned to two groups in a double blind, parallel trial. Buprenorphine was administered intramuscularly. Twenty patients received 12 mg buprenorphine in 24 h and the remaining 20 patients treated with conventional doses of buprenorphine tapered down over 5 days. Variables that were assessed included retention in treatment, rates of successful detoxification, the Subjective Opiate Withdrawal Scale (OOWS) scores, the Objective Opiate Withdrawal Scale (SOWS) scores, intensity of craving, drug side effects, and levels of hepatic enzymes (ALT and AST). There was no significant difference between the two groups on most variables. The main difference was in the time that maximal withdrawal symptoms occurred, which in the experimental protocol group appeared early while in the conventional protocol group appeared later during the detoxification period. Moreover, the experimental protocol was not only tolerated well but also accompanied with significantly less elevation in the ALT levels compared to the conventional treatment. However, patients in this group used more indomethacin and trazodone for symptom palliation. This study suggests that administration of high doses of buprenorphine in 24 h may be a reasonable approach for shortening of opioid detoxification. However, a larger study to confirm our results is warranted.

Topics: Adult; Analysis of Variance; Buprenorphine; Double-Blind Method; Drug Administration Schedule; Female; Humans; Iran; Male; Narcotic Antagonists; Opioid-Related Disorders; Statistics, Nonparametric

The present study compared in a clinical non-experimental setting the efficacy of buprenorphine (BUP) and methadone (METH) in the treatment of opioid dependence: all the subjects included in the study showed severe long-lasting heroin addiction. Participants (154) were applicants to a 12 weeks treatment program, who were assigned to either METH (78) (mean doses 81.5 +/- 36.4 mg) or BUP (76) (mean doses 9.2 +/- 3.4 mg) treatment. Aim of the study was to evaluate patient/treatment variables possibly influencing retention rate, abstinence from illicit drugs and mood changes. METH patients showed a higher retention rate at week 4 (78.2 versus 65.8) (P < 0.05), but BUP and METH were equally effective in sustaining retention in treatment and compliance with medication at week 12 (61.5 versus 59.2). Retention rate was influenced by dose, psychosocial functioning and not by psychiatric comorbidity in METH patients. In contrast, BUP maintained patients who completed the observational period showed a significantly higher rate of depression than those who dropped out (P < 0.01) and the intention to treat sample (P < 0.05). No relationship between retention and dose, or retention and psychosocial functioning was evidenced for BUP patients. The risk of positive urine testing was similar between METH and BUP, as expression of illicit drug use in general. At week 12, the patients treated with METH showed more risk of illicit opioid use than those treated with BUP (32.1% versus 25.6%) (P < 0.05). Negative urines were associated with higher doses in both METH and BUP patients. As evidenced for retention, substance abuse history and psychosocial functioning appear unable to influence urinalyses results in BUP patients. Buprenorphine maintained patients who showed negative urines presented a significantly higher rate of depression than those with positive urines (P < 0.05). Alternatively, psychiatric comorbidity was found unrelated to urinalyses results in METH patients. Our data need to be interpreted with caution because of the observational clinical methodology and non-random procedure. The present findings provide further support for the utility of BUP in the treatment of opioid dependency and demonstrate efficacy equivalent to that of METH during a clinical procedure. BUP seems to be more effective than METH in patients affected by depressive traits and dysphoria, probably due to antagonist action on kappa-opioid receptors. Psychosocial functioning and addiction severi

Topics: Adult; Analysis of Variance; Buprenorphine; Female; Heroin Dependence; Humans; Male; Methadone; Opioid-Related Disorders; Predictive Value of Tests; Treatment Outcome

In Australia, maintenance treatment for opioid dependence involves supervised daily administration of a dose of methadone or buprenorphine. A sublingual tablet combining buprenorphine and naloxone in a 4:1 ratio (Suboxone) has been developed, designed to deter diversion and intravenous misuse, and may be suitable for unsupervised administration. The aim of this study was to investigate the tolerability of Suboxone, and investigate whether unsupervised administration can be effective in stabilized patients. Employed patients on buprenorphine maintenance, who had ceased heroin use, were switched to Suboxone and provided with weekly supplies of medication to take without supervised administration. Subjects were monitored closely with weekly clinical reviews, and research interviews at baseline, 3 and 6 months. Only 11% of people receiving buprenorphine met eligibility criteria. Seventeen subjects were recruited. Fifteen were retained for the full 6 months. No subject appeared destabilized by unsupervised dosing. Suboxone was well tolerated. The current trial demonstrated that unsupervised administration with regular clinical monitoring can be effective in selected patients. However, using access to unsupervised dosing to promote abstinence from heroin probably limits the potential benefits of unsupervised administration to a very small proportion of patients.

Topics: Adult; Buprenorphine; Drug Combinations; Female; Humans; Male; Middle Aged; Naloxone; Opioid-Related Disorders; Pilot Projects; Tablets

Buprenorphine is a mu-opioid partial agonist that is marketed in a sublingual formulation as a treatment for opioid dependence. A microcapsule depot sustained-release formulation has been developed which may offer effective treatment of opioid dependence while also minimizing risks of illicit diversion or patient non-compliance. The present study examined the efficacy of depot buprenorphine in suppressing the opioid withdrawal syndrome and in attenuating the effects of exogenous opioid challenge.. A placebo-controlled, double-blind, randomized trial.. A closed residential research facility.. A total of 15 opioid-dependent participants were enrolled into the 6-week study.. Fifteen participants were randomized to receive a single subcutaneous depot injection containing buprenorphine (58 mg) or placebo. Two participants, both of whom received placebo, terminated participation after depot administration. Thirteen participants (six buprenorphine, seven placebo) completed the 6-week study and were assessed throughout the study for signs and symptoms of opioid withdrawal and for response to weekly subcutaneous challenges with 3 mg hydromorphone.. Subjective, physiological and observer-rated indices of opioid withdrawal and opioid agonist effects.. Depot buprenorphine provided more effective relief from opioid withdrawal than placebo, as evidenced by significantly fewer buprenorphine participants requiring supplemental medications for withdrawal suppression after depot administration compared to participants receiving placebo. In the weekly hydromorphone challenge sessions, depot buprenorphine significantly reduced opioid response on measures of subjective effects and pupillary diameter.. Results from this double-blind, placebo-controlled study indicate that depot buprenorphine is effective in providing both withdrawal suppression and opioid blockade. Future studies examining additional doses and repeated dosing regimens with depot buprenorphine are warranted.

Topics: Adult; Buprenorphine; Capsules; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Injections, Subcutaneous; Male; Narcotic Antagonists; Opioid-Related Disorders; Receptors, Opioid, mu; Statistics, Nonparametric; Treatment Outcome

Comparison of buprenorphine vs. methadone to determine which medication is better for the detoxification of young opioid addicts.. 93 consecutive opioid-dependent patients (ICD-10) from an in-patient detoxification unit for adolescents were investigated, of which 42 chose buprenorphine and 51 chose methadone for detoxification. Both groups did not differ with regard to different sociodemographic and addiction-specific variables such as age, gender, initiation of drug consumption and duration of opioid intake.. 23.5 % of the methadone patients and 38.1 % of the buprenorphine patients finished detoxification successfully, in addition the buprenorphine patients finished detoxification 1.62 days earlier. There was no significant difference concerning these items.. Buprenorphine seems to be at least as effective as methadone for opioid withdrawal in young addicts.

Topics: Adolescent; Adult; Buprenorphine; Female; Germany; Humans; Male; Methadone; Narcotics; Opioid-Related Disorders; Treatment Outcome

Research suggests that buprenorphine may possess antidepressant activity. The Beck Depression Inventory was completed at baseline and 3 months by heroin dependent subjects receiving either buprenorphine or methadone maintenance as part of a larger, pre-existing, double blind trial conducted by NDARC (Australia). Depressive symptoms improved in all subjects, with no difference between methadone and buprenorphine groups, suggesting no differential benefit on depressive symptoms for buprenorphine compared to methadone.

Topics: Adult; Buprenorphine; Depression; Female; Humans; Male; Methadone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Severity of Illness Index; Surveys and Questionnaires

In maintenance patients methadone has been shown to produce considerable changes in opioid effects and withdrawal over the dosing interval. As a partial agonist buprenorphine may be expected to produce smaller changes, but the nature and magnitude of these changes have only been described for single doses. In the present study opioid effects and withdrawal were described in patients maintained on buprenorphine. Twenty four opioid dependent subjects were administered 16 mg buprenorphine tablets sublingually for 10 days. On day 10 plasma samples were collected and physiological, subjective and observer-rated measures collected pre-dose and at 14 time points during the dosing interval. No significant respiratory depression was observed. Consistent with the partial agonist properties of buprenorphine, other physiological and subjective changes were also of small magnitude. However, even at a once daily dose of 16 mg some patients experienced significant opioid withdrawal that was maximal at the end of the dosing interval. Buprenorphine maintenance should be associated with a high level of safety and a low level of disruption caused by changing opioid effects over the dosing interval, but some patients may require high doses or other strategies to completely suppress withdrawal.

Topics: Administration, Sublingual; Adult; Buprenorphine; Cross-Over Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Narcotics; Neurologic Examination; Opioid-Related Disorders; Substance Withdrawal Syndrome

To assess the efficacy of buprenorphine compared with methadone maintenance therapy for opioid dependence in a large sample using a flexible dosing regime and the marketed buprenorphine tablet.. Patients were randomized to receive buprenorphine or methadone over a 13-week treatment period in a double-blind, double-dummy trial.. Three methadone clinics in Australia.. Four hundred and five opioid-dependent patients seeking treatment.. Patients received buprenorphine or methadone as indicated clinically using a flexible dosage regime. During weeks 1-6, patients were dosed daily. From weeks 7-13, buprenorphine patients received double their week 6 dose on alternate days.. Retention in treatment, and illicit opioid use as determined by urinalysis. Self-reported drug use, psychological functioning, HIV-risk behaviour, general health and subjective ratings were secondary outcomes.. Intention-to-treat analyses revealed no significant difference in completion rates at 13 weeks. Methadone was superior to buprenorphine in time to termination over the 13-week period (Wald chi 2 = 4.371, df = 1, P = 0.037), but not separately for the single-day or alternate-day dosing phases. There were no significant between-group differences in morphine-positive urines, or in self-reported heroin or other illicit drug use. The majority (85%) of the buprenorphine patients transferred to alternate-day dosing were maintained in alternate-day dosing.. Buprenorphine did not differ from methadone in its ability to suppress heroin use, but retained approximately 10% fewer patients. This poorer retention was due possibly to too-slow induction onto buprenorphine. For the majority of patients, buprenorphine can be administered on alternate days.

Topics: Adult; Buprenorphine; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Methadone; Narcotic Antagonists; Opioid-Related Disorders; Treatment Outcome

During 3 months where contingency management (CM) had an escalating value for each consecutive drug-free urine (escalating CM), cocaine- and heroin-abusing patients significantly increased drug-free urines. The 'escalating CM' was eliminated during months 4-6 to assess any reduction in drug-free urines.. Patients who completed a 3-month, randomized, double-blind, trial evaluating CM versus non-CM and desipramine (DMI) versus placebo, had an 'escalating CM' eliminated during months 4-6. The CM and non-CM groups were compared using thrice-weekly urine samples.. Out-patient buprenorphine maintenance for 6 months.. All 75 of the 160 original study patients who completed month 3 of the clinical trial.. The 'escalating CM' was eliminated for all 3 months and during months 5 and 6 the response requirement was also increased to two and then three consecutive drug-free urines in order to obtain a voucher.. Urine toxicology for opiates and cocaine.. After eliminating the 'escalating CM', the CM group showed a decline in combined opioid- and cocaine-free urines. This decline within the CM group was greater in those treated with DMI than placebo.. Buprenorphine with DMI maintained drug abstinence after eliminating the 'escalating CM', but not after increasing the response requirement, suggesting the need for more intensive psychosocial interventions during CM.

Topics: Adult; Antidepressive Agents, Tricyclic; Behavior Control; Buprenorphine; Cocaine-Related Disorders; Desipramine; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Narcotics; Opioid-Related Disorders; Token Economy; Treatment Outcome

Co-dependence on opiates and cocaine occurs in about 60% of patients entering methadone treatment and has a poor prognosis. However, we recently found that desipramine (DMI) could be combined with buprenorphine to significantly reduce combined opiate and cocaine use among these dually dependent patients. Furthermore, contingency management (CM) has been quite potent in reducing cocaine abuse during methadone maintenance. To test the efficacy of combining CM with these medications we designed a 12-week, randomized, double blind, four cell trial evaluating DMI (150 mg/day) or placebo plus CM or a non-contingent voucher control in 160 cocaine abusers maintained on buprenorphine (median 16 mg daily). Cocaine-free and combined opiate and cocaine-free urines increased more rapidly over time in those treated with either DMI or CM, and those receiving both interventions had more drug-free urines (50%) than the other three treatment groups (25-29%). Self reported opiate and cocaine use and depressive and opioid withdrawal symptoms showed no differences among the groups and symptom levels did not correlate with urine toxicology results. Lower DMI plasma levels (average 125 ng/ml) were associated with greater cocaine-free urines. DMI and CM had independent and additive effects in facilitating cocaine-free urines in buprenorphine maintained patients. The antidepressant appeared to enhance responsiveness to CM reinforcement.

Topics: Adult; Aged; Ambulatory Care; Analysis of Variance; Antidepressive Agents, Tricyclic; Buprenorphine; Cocaine-Related Disorders; Connecticut; Desipramine; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Narcotics; Opioid-Related Disorders; Treatment Outcome

The aim of this study was to assess the efficacy of methadone compared with buprenorphine maintenance therapy in heroin-dependent patients over a treatment period of 18 weeks. Subjects were randomized to receive either methadone or buprenorphine in a comparative double-blind study and consisted of 164 heroin-dependent male patients who met the DSM-IV criteria for heroin dependence and were seeking treatment. The 164 subjects included 41 patients in 1-mg, 41 patients in 3-mg, and 41 patients in 8-mg dosage group of buprenorphine, and also 41 patients in the 30-mg dosage group of methadone. The mean age was 31.4 years for total buprenorphine group and 33.7 years for methadone group (the mean age differences in 4 groups were not statistically significant). Subjects received buprenorphine at a dose of 1, 3, or 8 mg per day or methadone at a dose of 30 mg per day and were treated in an urban outpatient clinic, offering a 1-hour weekly individual counseling session. Days retained in treatment were measured. Completion rates by buprenorphine dosage group were 29.3% for the 1-mg dose group, 46.3% for the 3-mg dose group, 68.3% for the 8-mg dose group, and 61% for the 30-mg methadone dose group. Retention in the 8-mg dose group was significantly better than in the 1-mg dose group (p=.00041) and in the 3-mg dose group (p=.045); other comparison (1 mg dose with 3 mg dose) was not significant. Methadone group was significantly better than 1mg buprenorphine dose group (p=.004), but was not significantly different from 3 mg buprenorphine dose group (p=.18) or 8 mg buprenorphine dose group (p=.49). The results support the efficacy of buprenorphine for outpatient treatment of heroin dependence and seem to indicate that the highest dose (8 mg) of buprenorphine was the best of the three doses of buprenorphine, and also support the superiority of 30 mg of methadone compared to 1 mg dose of buprenorphine for Iranian heroin-dependent patients to increase their retention in treatment.

Topics: Adult; Buprenorphine; Dose-Response Relationship, Drug; Double-Blind Method; Heroin; Humans; Iran; Male; Methadone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Treatment Outcome

Office-based treatment of opiate addiction with a sublingual-tablet formulation of buprenorphine and naloxone has been proposed, but its efficacy and safety have not been well studied.. We conducted a multicenter, randomized, placebo-controlled trial involving 326 opiate-addicted persons who were assigned to office-based treatment with sublingual tablets consisting of buprenorphine (16 mg) in combination with naloxone (4 mg), buprenorphine alone (16 mg), or placebo given daily for four weeks. The primary outcome measures were the percentage of urine samples negative for opiates and the subjects' self-reported craving for opiates. Safety data were obtained on 461 opiate-addicted persons who participated in an open-label study of buprenorphine and naloxone (at daily doses of up to 24 mg and 6 mg, respectively) and another 11 persons who received this combination only during the trial.. The double-blind trial was terminated early because buprenorphine and naloxone in combination and buprenorphine alone were found to have greater efficacy than placebo. The proportion of urine samples that were negative for opiates was greater in the combined-treatment and buprenorphine groups (17.8 percent and 20.7 percent, respectively) than in the placebo group (5.8 percent, P<0.001 for both comparisons); the active-treatment groups also reported less opiate craving (P<0.001 for both comparisons with placebo). Rates of adverse events were similar in the active-treatment and placebo groups. During the open-label phase, the percentage of urine samples negative for opiates ranged from 35.2 percent to 67.4 percent. Results from the open-label follow-up study indicated that the combined treatment was safe and well tolerated.. Buprenorphine and naloxone in combination and buprenorphine alone are safe and reduce the use of opiates and the craving for opiates among opiate-addicted persons who receive these medications in an office-based setting.

Topics: Administration, Sublingual; Adult; Ambulatory Care; Buprenorphine; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Narcotics; Office Visits; Opioid-Related Disorders; Treatment Outcome

Depression is common among patients who abuse both opiates and cocaine, and its treatment has had mixed success. This study compares buprenorphine-maintained patients with lifetime major depressive disorder (MDD, N = 53) with those never depressed (ND, N = 96) on cocaine and opiate-free urines during a 12-week outpatient double-blind, placebo-controlled, randomized clinical trial. The 149 subjects were assigned to four groups: 1) desipramine (DMI) + contingency management (CM); 2) DMI + noncontingency management (NCM); 3) placebo + CM; and 4) placebo + NCM. Depression assessments included Hamilton Depression Rating Scale, Center for Epidemiological Studies Depression Inventory, and Structured Clinical Interview for DSM-IV interview for diagnosis of lifetime MDD. Urine toxicologies were performed thrice weekly and the CES-D was performed monthly. The MDD group had a larger proportion of females (45% vs 21%, P = 0.02) and were more likely to be married (13.2% vs 7.3%, P = 0.02) than the ND group. Treatment retention did not vary by depression status. Hierarchical Linear Modeling found that depressive symptoms decreased comparably across the four treatment groups. Although participation in CM improved drug-free urines more for patients with MDD than for the ND group (Z = 2.44, P = 0.01), treatment with DMI was significantly more efficacious for the ND group than for the MDD group (Z = -2.89, P = 0.003). These results suggest that patients with MDD may respond better to behavioral treatments such as CM than to desipramine plus buprenorphine. The ND cocaine-abusing, opiate-dependent patients may be more responsive to the anticraving effects of DMI.

Topics: Adult; Aged; Antidepressive Agents, Tricyclic; Buprenorphine; Cocaine-Related Disorders; Comorbidity; Depressive Disorder, Major; Desipramine; Diagnosis, Dual (Psychiatry); Double-Blind Method; Female; Humans; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Prognosis; Psychiatric Status Rating Scales; Treatment Outcome

While methadone is currently the primary pharmacotherapy used in the treatment of heroin dependence in Australia, levo-alpha-acetyl-methodol (LAAM) and buprenorphine are new pharmacotherapies that are being examined as alternatives to methadone maintenance treatment. The aim of this research is to consider the effects of the methadone, buprenorphine and LAAM, as used in maintenance pharmacotherapy for heroin dependence, upon simulated driving. Clients stabilised in methadone, LAAM and buprenorphine treatment programs for 3 months, and a control group of non-drug-using participants, took part in this study which involved operating a driving simulator over a 75 min period. All participants attended one session without alcohol and one session with alcohol at around the 0.05% blood alcohol level. Simulated driving skill was measured through standard deviations of lateral position, speed and steering wheel angle, and reaction time to a subsidiary task was also measured. While alcohol impaired all measures of driving performance, there were no differences in driving skills across the four participant groups. These findings suggest that typical community standards around driving safety should be applied to clients stabilised in methadone, LAAM and buprenorphine treatment. The findings are important in terms of the widespread implementation of these treatment options in Victoria given that a large proportion of pharmacotherapy clients drive.

Topics: Adult; Automobile Driving; Buprenorphine; Drug Combinations; Ethanol; Female; Humans; Male; Methadone; Methadyl Acetate; Narcotics; Opioid-Related Disorders; Victoria

This study examined the usefulness of baseline cocaine urine toxicology results and self-reported days of cocaine use in predicting treatment response in cocaine- and opioid-dependent subjects. Ninety-nine male and 52 female subjects, maintained on buprenorphine, participated in a 24-week, randomized, double-blind, four-cell trial that evaluated desipramine (150 mg/d) or placebo plus contingency management or a noncontingent voucher control. Out of 151, 102 (67%) subjects had cocaine-positive and 49 (32%) cocaine-negative urines at the beginning of treatment. For the previous 30 days before study participation, 91 (60%) subjects reported using cocaine 15 or less days (low baseline cocaine use) and 60 (40%) subjects reported more than 15 days (high baseline cocaine use). By using the treatment effectiveness score (TES) as the outcome measure, a negative urine for cocaine at baseline predicted a better outcome during a 24-week trial for cocaine and opioid use. There also was a significant interaction between baseline cocaine urine results and desipramine response with the urine cocaine-negative group showing greater desipramine response than placebo for opioid and cocaine use. Self-reported cocaine use at baseline did not show significant predictive power for TES scores during the clinical trial. These results suggest that baseline cocaine urine results should be considered as stratifying variables in clinical trials for cocaine dependence.

Topics: Adult; Analysis of Variance; Antidepressive Agents, Tricyclic; Buprenorphine; Cocaine-Related Disorders; Desipramine; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Patient Compliance; Self Disclosure; Time Factors; Token Economy; Treatment Outcome

Over the last few years, there has been a growing tendency for opioid addicts to abuse multiple drugs, although many patients are in substitution therapy with methadone. Abuse of multiple drugs leads to a more complicated withdrawal syndrome; it is therefore necessary to investigate new drug strategies as a treatment for detoxification. Buprenorphine appears to be an effective and safe drug in opioid-addicted patient detoxification. In this study, we have compared the short-term efficacy of an 11-day low-dose buprenorphine/14-day carbamazepine regime [BPN/CBZ] (n = 14) to an 11-day methadone/14-day carbamazepine regime [MET/CBZ] (n = 12) in a double-dummy, randomized 14-day inpatient detoxification treatment study. Twenty-six inpatients met the DSM-IV criteria for opioid dependence and were included in this study. All patients abused various additional drugs. Fourteen of 26 patients (53.8 %) completed the study. Seven non-completers (seven of 12 = 58.3 %) were treated with methadone/carbamazepine and five non-completers (five of 14 = 35.7 %) received buprenorphine/carbamazepine, but the difference in the dropout rate was not significant. However, patients with buprenorphine/carbamazepine showed significantly fewer withdrawal symptoms after the first two weeks of treatment. The present study supports the hypothesis that buprenorphine/carbamazepine is more effective than methadone/carbamazepine in detoxification strategies for opioid addict with additional multiple drug abuse. No severe side effects occurred during treatment in either group.

Topics: Adult; Anticonvulsants; Buprenorphine; Carbamazepine; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Methadone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Substance-Related Disorders; Treatment Outcome

The goal of this study was to evaluate the efficacy of 1-, 3-, and 8-mg per day doses of buprenorphine in the maintenance treatment of opium-dependent patients over a 6-month treatment period. Participants were 513 opium-dependent individuals who were seeking treatment in an urban outpatient clinic, offering a 1-hr weekly individual counseling session. Overall, 305 patients (59.5%) completed the 6-month study. Completion rates by dosage group were 33.9% for the 1-mg dose group, 64.3% for the 3-mg dose group, and 80.1% for the 8-mg dose group-each significantly different from the other two groups. The results support the efficacy and safety of buprenorphine for outpatient treatment of opium dependence and seem to indicate that the highest dose (8 mg) of buprenorphine was the best of the three doses for Iranian opium-dependent patients to increase their retention in treatment.

Topics: Adult; Aged; Aged, 80 and over; Buprenorphine; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Iran; Male; Middle Aged; Narcotics; Opioid-Related Disorders; Outpatients; Patient Acceptance of Health Care

Buprenorphine is an opioid agonist-antagonist used in the treatment of opioid dependence. Naloxone has been combined with buprenorphine to decrease the parenteral abuse potential of buprenorphine. This addition of naloxone may also confer further opioid blockade efficacy.. To test the opioid blockade efficacy of sublingual buprenorphine/naloxone versus buprenorphine alone and determine whether: (1) the blockade efficacy of buprenorphine/naloxone varies between the time of expected maximal and minimal effects of naloxone, (2) the blockade efficacy of buprenorphine/naloxone and buprenorphine varies as a function of maintenance dose level, and (3) there are adaptive changes over time associated with repeated daily dosing of buprenorphine/naloxone and buprenorphine.. Residential subjects ( n=6) were maintained on different double-blind dose levels of buprenorphine/naloxone (4/1, 8/2, 16/4, 32/8 mg) and buprenorphine (32 mg) for 6-day periods and challenged with parenteral doses of hydromorphone (12 mg) in laboratory sessions.. There was no evidence of additional opioid blockade efficacy conferred by combining naloxone with buprenorphine. Higher doses of buprenorphine/naloxone provided greater blockade of hydromorphone effects. Changes over time associated with repeated daily dosing of buprenorphine/naloxone and buprenorphine were minimal.. The addition of naloxone to buprenorphine may deter the parenteral abuse of buprenorphine/naloxone, but it does not enhance the therapeutic efficacy of buprenorphine. The blockade efficacy of buprenorphine/naloxone is dose related; however, doses up to 32/8 mg buprenorphine/naloxone provide only partial blockade when subjects receive a high dose of an opioid agonist.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hydromorphone; Male; Naloxone; Narcotic Antagonists; Opioid-Related Disorders

To evaluate the effect of a 4 mg/day sublingual dose of buprenorphine in the maintenance treatment of opium dependence in comparison with a 1 mg/day dose over an 18-week treatment period. As a secondary objective, the results were determined concurrently for subjects treated with a 2 mg/day dose.. Subjects were assigned randomly to three dosage groups.. 330 consecutive (320 men and 10 women) opium addicts who met the DSM-IV criteria for opioid dependence and were seeking treatment.. Subjects received a 1, 2 or 4 mg/day dose of buprenorphine and were treated in an outpatient clinic where they also received a weekly 1-hour clinical counseling session.. Addiction Severity Index, retention in treatment, and illegal opioid use as determined by random urine testing.. The mean age was 37.5 years (SD=11.4, range 19-72). Overall, 194 (58.8%) of the patients completed the 18 week study. Completion rates by dosage groups were 47.3% for the 1 mg group, 58.2% for the 2 mg group and 70.9% for the 4 mg group (chi(2)=12.7, df=2, P=0.0017).. The results support the efficacy and safety of buprenorphine for opium addiction and suggest that an adequate dose of buprenorphine would help to increase the success rate.

Topics: Adult; Aged; Buprenorphine; Chi-Square Distribution; Female; Humans; Iran; Male; Middle Aged; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Opium

The utility of the crossover design in substance abuse research was examined in a 26-week, double-blind clinical trial that evaluated the efficacy of desipramine (0 or 150 mg/day) in 109 male and female cocaine- and opiate-dependent patients maintained on buprenorphine (12 mg/day) or methadone (65 mg/day). After being stabilized on buprenorphine or methadone (weeks 1-2), half of the patients were randomly assigned to receive desipramine for the first half of the trial and placebo for the second, with the order reversed for the second half. Analyses using hierarchical linear models (HLM) indicated that desipramine reduced the use of opiates only when administered at the start (rather than the middle) of the trial, whereas cocaine use was reduced when desipramine was introduced at either time.

Topics: Adult; Analgesics, Opioid; Antidepressive Agents, Tricyclic; Buprenorphine; Clinical Trials as Topic; Cocaine-Related Disorders; Cross-Over Studies; Desipramine; Double-Blind Method; Female; Humans; Male; Methadone; Middle Aged; Narcotics; Opioid-Related Disorders; Placebos; Time Factors; Treatment Outcome

The effect of sublingual buprenorphine on cigarette smoking was examined in 23 adult men with DSM III-R diagnosis of concurrent opiate and cocaine dependence. After admission to a clinical research ward, subjects were detoxified with methadone (10-50 mg/day), then were drug-free for 6 days before random assignment to either 4 or 8 mg/day of buprenorphine. Gradually increasing daily sublingual doses of buprenorphine were administered for 5 days, then subjects were maintained on 4 or 8 mg/day of buprenorphine for 12 days. Each subject's preferred brand of cigarettes was available ad libitum throughout the study. Five responses (FR 5) on a key were required to earn each cigarette. The time and number of cigarettes were recorded by an automated cigarette dispenser. Subjects acquired significantly more cigarettes during the buprenorphine induction and maintenance phases (25.5+/-2.0) than during the drug-free phase (18.5+/-1.8; p<0.0002). During buprenorphine induction, the number of cigarettes acquired was positively correlated with increasing doses of buprenorphine (p<0.001) and the inter-cigarette interval was significantly shorter during buprenorphine maintenance than during drug-free conditions (p<0.001). These data showed that daily administration of the partial mu opioid agonist buprenorphine was associated with increased smoking in men concurrently dependent on opiates and cocaine. These findings are consistent with previous reports of opioid-cigarette interactions.

Topics: Administration, Sublingual; Adult; Buprenorphine; Cocaine-Related Disorders; Humans; Inpatients; Male; Narcotic Antagonists; Opioid-Related Disorders; Smoking; Treatment Outcome

To evaluate whether buprenorphine. even without additional control and psychosocial treatment and support, alleviates the problems faced by patients waiting for medication assisted rehabilitation (MAR).. A randomized, double-blind, 12-week study of Subutex versus placebo without additional support as an interim therapy.. One hundred and six patients, 70 males and 36 females, waiting for MAR in Oslo. The average age was 38 years with an average history of heroin use of 20 years. Fifty-five patients were assigned to buprenorphine and 51 to a placebo.. Subutex or placebo sublingual tablets were given under supervision in a daily dose of 16 mg with the exception of a double dose on Saturday and no dose on Sunday.. Retention, compliance, self-reported drug-abuse, wellbeing and mental health.. The average number of days of participation was significantly higher in the buprenorphine group, 42 (median: 29) compared to 14 (median: 11) for the placebo group (P < 0.001). The retention of patients after 12 weeks was 16 patients in the buprenorphine group and one patient in the placebo group. The buprenorphine group had a larger decrease in reported opioid use (p < 0.001) and in reported use of other drugs, tablets and alcohol abuse (p < 0.01). The group also showed a stronger increase in wellbeing (p < 0.01) and life satisfaction (p < 0.05). None of the participants died.. The patients waiting for MAR benefited significantly from the buprenorphine as an interim therapy according to retention, self-reported use of drugs and wellbeing. However, the patients had difficulties in remaining in treatment over time without psychosocial support.

Topics: Adult; Buprenorphine; Double-Blind Method; Female; Humans; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Patient Compliance; Treatment Outcome

This study compared the safety and efficacy of sublingual buprenorphine tablets with oral methadone in a population of opioid-dependent individuals in a double-blind, randomized, 6-week trial using a flexible dosing procedure. Fifty-eight patients seeking treatment for opioid dependence were recruited in three outpatient facilities and randomly assigned to substitution with buprenorphine or methadone. The retention rate was significantly better in the methadone maintained group (90 vs. 56%; P<0.001). Subjects completing the study in both the treatment groups had similar proportions of opioid positive urine samples (buprenorphine 62%; methadone 59%) and positive urine specimens, as well as mean heroin craving scores decreased significantly over time (P=0.035 and P<0.001). The proportion of cocaine-positive toxicology results did not differ between groups. At week six mean stabilization doses were 10.5 mg per day for the sublingual buprenorphine tablet, and 69.8 mg per day for methadone, respectively. Patient performance during maintenance was similar in both the groups. The high attrition rate in the buprenorphine group during the induction phase might reflect inadequate induction doses. Thus, buprenorphine is a viable alternative for methadone in short-term maintenance treatment for heroin dependence if treatment induction is done with adequate dosages.

Topics: Adult; Analysis of Variance; Behavior, Addictive; Buprenorphine; Chi-Square Distribution; Double-Blind Method; Female; Heroin Dependence; Humans; Male; Methadone; Narcotic Antagonists; Opioid-Related Disorders; Patient Compliance

Buprenorphine is a partial mu opioid agonist under development as a sublingual (SL) medication for opioid dependence treatment in the United States. Because buprenorphine may be abused, tablets combining buprenorphine with naloxone in a 4:1 ratio have been developed to reduce that risk. Low doses of injected buprenorphine/naloxone have been tested in opioid-dependent subjects, but higher doses (more than 2 mg of either medication) and direct comparisons to SL buprenorphine/naloxone have not been examined.. To assess and compare the effects of intramuscular (i.m.) versus SL buprenorphine/naloxone in opioid-dependent volunteers.. Opioid-dependent volunteers were maintained on 40 mg per day of oral hydromorphone while on a residential research ward. After safety testing in two pilot subjects, participants (n = 8) were tested with both i.m. and SL buprenorphine/naloxone (1/0.25, 2/0.5, 4/1, 8/2, 16/4 mg); i.m. hydromorphone (10 mg) and naloxone (0.25 mg); both i.m. and SL buprenorphine alone (8 mg); and placebo. Test sessions were twice per week; dosing was double-blind.. Intramuscular buprenorphine/naloxone produced dose-related increases on indices of opioid antagonist effects. Effects were consistent with naloxone-precipitated withdrawal, and were short-lived. As withdrawal effects dissipated, euphoric opioid agonist effects from buprenorphine did not appear. Sublingual buprenorphine/naloxone produced neither opioid agonist nor antagonist effects.. Intramuscular injection of buprenorphine/naloxone precipitates withdrawal in opioid dependent persons; therefore, the combination has a low abuse potential by the injection route in this population. Sublingual buprenorphine/naloxone by tablet is well tolerated in opioid dependent subjects, and shows neither adverse effects (i.e., precipitated withdrawal) nor a high abuse potential (i.e., opioid agonist effects).

Topics: Administration, Sublingual; Adolescent; Adult; Affect; Buprenorphine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Hydromorphone; Injections, Intramuscular; Male; Middle Aged; Naloxone; Narcotic Antagonists; Narcotics; Observer Variation; Opioid-Related Disorders; Psychomotor Performance; Substance Withdrawal Syndrome

Patients on methadone maintenance therapy are relatively intolerant of pain, a finding hypothesized to reflect a hyperalgesic state induced by chronic opioid administration. To explore if the intrinsic activity of the opioid maintenance agent might affect expression of hyperalgesia in this population, withdrawal latency for cold-pressor (CP) pain was compared between small groups of methadone-maintained (n = 18), buprenorphine-maintained (n = 18), and matched control (n = 18) subjects. The opioid-maintained groups had equal and significantly shorter withdrawal latencies than controls, however it is possible that high rates of continued illicit opioid use precluded finding differences between methadone and buprenorphine groups. Differential effects of maintenance agent were found for the few subjects without illicit opioid use, such that withdrawal latencies for methadone-maintained (n = 5) were less than for buprenorphine-maintained (n = 7) which were less than controls (n = 18). Diminished pain tolerance in patients receiving opioid maintenance treatment has significant clinical implications. More research is needed to determine if buprenorphine offers advantages over methadone in this regard.

Topics: Adult; Buprenorphine; Cold Temperature; Female; Humans; Male; Methadone; Middle Aged; Opioid-Related Disorders; Pain Threshold; Reaction Time

Opioid-dependent outpatients may be more likely to present for pharmacological treatment if less than daily dosing can be arranged. These studies compared opioid withdrawal symptoms during 24-, 72-, and 120-hour buprenorphine dosing regimens and evaluated participants' preferences for these different dosing regimens.. Thirty-three opioid-dependent participants received daily sublingual maintenance doses of 4 mg/70 kg (n = 14) or 8 mg/70 kg (n = 19) of liquid buprenorphine.. In Study I participants received, in a random order, three dosing regimens for five repetitions of each: daily maintenance doses every 24 hours (4 or 8 mg/70 kg), triple the daily maintenance dose every 72 hours (12 or 24 mg/70 kg) and quintuple the daily maintenance dose every 120 hours (20 or 40 mg/70 kg). Doses were administered under double-blind procedures, and placebos were administered on the interposed days during the latter two regimens. Subjective and observer ratings of opioid withdrawal symptoms were assessed daily prior to receipt of each dose. In Study II, a new group of participants received each of the three dosing regimens under open-dosing procedures and then chose between the different dosing regimens.. Opioid withdrawal symptoms increased significantly during the every-fifth-day dosing regimen in both the blind- and open-dosing studies. In the choice phase of Study II, only one participant (7%) chose quintuple-every-fifth-day dosing over all other dosing options.. These results suggest that the maximum duration of action of buprenorphine is less than 5 days when five times the daily maintenance dose is provided.

Topics: Adult; Analysis of Variance; Appointments and Schedules; Buprenorphine; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Narcotics; Opioid-Related Disorders; Patient Compliance; Patient Satisfaction; Substance Withdrawal Syndrome; Treatment Outcome

Care for opioid users changed greatly in France in 1996 when general practitioners (GP) were allowed to prescribe high-dose sublingual buprenorphine (Subutex((R))) for maintenance treatment of major opioid dependence. In order to evaluate treatment benefits, a prospective epidemiological 2-year follow-up was initiated in May 1996 with the participation of 105 French GPs.. A cohort of outpatient opioid users who started high-dose sublingual buprenorphine maintenance therapy at study onset or who had recently started were included in a prospective epidemiological study by GPs involved in management of drug abusers. Patients were followed for 2 years with collection of standardized information at 1, 3, 6, 12, and 24 months. The main evaluation criteria were follow-up by the same GP throughout the study and retention in the care system 2 years later. For patients who fulfilled these criteria, secondary end points were analyzed: information about buprenophine prescription, social status, and hepatitis B and C and HIV seroconversions.. The 101 GPs included 919 patients and 909 were analyzed 2 years later. At study onset, a majority of the patients (70.6%) were taking an ongoing maintenance treatment, 10.5% had previously received such a treatment and the treatment was initiated for 18.8%. At the end of the study, 508 patients (55.9%) were still being followed by the same GP and 101 (11.1%) were followed by another healthcare provider (another GP, hospital or specialized center). No information about the care giver was available for 82 patients (9%). Among the other patients, 123 (13.5%) were lost to follow-up, 24 (2.6%) had moved, 23 (2.6%) were incarcerated, 11 (1.2%) had successfully discontinued drug usage and 7 (0.8%) had died. Other reasons for unsuccessful follow-up by the same GP were mainly (for 6 patients each): relapse, switch to methadone, no medical information, non-compliance with scheduled controls. Among the patients followed by the same GP, declaration of heroin and drug intake significantly decreased (p<0.001), and social status (GAF scale) and TMSP evaluation significantly improved (p<0.001). The social situation (housing condition and work) also improved significantly (p<0.001). The rate of buprenorphine treatment was 84% with longer and less fractionated prescriptions. The HBV, HBC and HIV seroconversion rates were low in this high-risk population (2.7%, 4.1% and 0.8% respectively).. This two-year follow-up of 909 opioid users showed that nearly 70% of the patient remained within the healthcare system, mainly with the same GP or more rarely with another practitioner. Among the 508 patients still followed by the same GP, maintenance treatment with high-dose buprenorphine was observed in more than 80% of the patients. These patients had a significantly improved social status, a significant decrease in drug intake and a significant improvement in their social adaptation and severity of drug abuse.

Topics: Adult; Ambulatory Care; Buprenorphine; Drug Prescriptions; Employment; Family Practice; Female; Follow-Up Studies; France; Hepatitis B; Hepatitis C; HIV Infections; Housing; Humans; Male; Narcotics; Opioid-Related Disorders; Patient Compliance; Risk Factors; Severity of Illness Index; Socioeconomic Factors; Treatment Outcome

That the problem of drug addiction is still growing up, so there is the necessity for widen of treatment panel for psychoactive substances abuse, especially for opiates. Because of the fact, that substituting treatment became to be popular in patients' opinion, more attention were paid on new medicine-buprenorphine. It is an agonist- antagonist of opiates' receptors. Buprenorphine has been successfully used in long-term treatment in United States and in Western Europe. Treatment with buprenorphine has been started in Poland in Toxicological Department in Kraków. This article shows outcomes of substituting treatment with buprenorphine in period from December 2000 to February 2001.

Topics: Adolescent; Adult; Buprenorphine; Female; Humans; Male; Methadone; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Treatment Outcome

This study evaluated the efficacy of a combination tablet formulation of buprenorphine containing 8 mg of buprenorphine and 2 mg of naloxone for every other day treatment and whether increasing the daily maintenance dose was essential for maintaining an efficacious alternate-day treatment. Twenty-six opioid-dependent outpatients completing a 16-day baseline entered a double-blind, placebo-controlled, triple crossover trial. Twenty-one days of daily combination tablet administration were compared to two different 21-day periods of alternate-day buprenorphine administration where subjects received either 8 or 16 mg of the combination tablet every other day with placebo on the interposed day. Fifty-four percent (14/26) of subjects completed the study, but only two subjects dropped out during the 16-mg alternate-day condition. Rates of medication compliance, illicit opioid use and subject- and observer-rated measures of opioid effects did not distinguish daily from alternate-day treatments in subjects completing the study. However, pupillary diameter was significantly increased during 8-mg alternate-day compared to the 8-mg daily or 16-mg alternate-day treatment. These data replicate earlier findings describing the acceptability of alternate-day buprenorphine treatment using multiples of the daily maintenance dose and extend these findings by establishing the clinical efficacy of daily and alternate-day dosing regimens with the combination buprenorphine naloxone tablet. This study also suggests slightly improved outcomes during alternate-day treatment using multiples of the daily dose.

Topics: Adult; Analysis of Variance; Buprenorphine; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Female; Humans; Male; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Pupil; Statistics, Nonparametric; Surveys and Questionnaires; Treatment Outcome

This study was aimed at determining whether thrice-weekly administration of buprenorphine is as effective as daily administration for treating opioid dependence. A total of 60 treatment-seeking opioid addicts were randomly assigned to take buprenorphine tablets sublingually either every day (8 mg) or thrice-weekly (16 mg on Mondays and Wednesdays and 24 mg on Fridays) over the course of a 12-week, double-blind, parallel trial. The buprenorphine dosing schedule had no significant effect on treatment retention. The rates of opioid-positive urine tests were significantly higher among those subjects who were given buprenorphine thrice weekly (58.5%) than among those who took it daily (46.6%). An analysis of the completers did not detect a significant effect of buprenorphine dosing schedule. The results obtained in our clinical trials indicate the advisability of daily doses of buprenorphine, at least at the beginning of a maintenance programme.

Topics: Adult; Analysis of Variance; Behavior, Addictive; Buprenorphine; Double-Blind Method; Female; Humans; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Treatment Outcome

Clinical trials carried out to compare methadone and buprenorphine in the treatment of opioid dependence have generally employed an alcoholic solution of buprenorphine, which has a bioavailability superior to that of the tablets. Since the product available for large scale use is in tablet form, one intended to verify the efficacy of this formulation. In a multicentre randomised controlled double blind study, 72 opioid dependent patients were assigned to treatment with buprenorphine (8 mg/day) or methadone (60 mg/day) for a period of 6 months. The two compounds did not show any significant difference with regard to urinalyses: the average percentage of analyses proving negative was 60.4% for patients assigned to buprenorphine, and 65.5% for those assigned to methadone. With regard to retention, a non-significant trend in favour of methadone was observed. Patients completing the trial improved significantly in terms of psychosocial adjustment and global functioning, as ascertained by the DSM-IV-GAF and symptom checklist-90 (SCL-90) scales, and this was independent of the treatment group. Finally, in the case of buprenorphine, patients who dropped out differed significantly from those who stayed, in terms of a higher level of psychopathological symptoms, and a lower level of psychosocial functioning. The results of the study further support the utility of buprenorphine for the treatment of opioid dependence.

Topics: Adolescent; Adult; Behavior, Addictive; Buprenorphine; Double-Blind Method; Female; Humans; Male; Methadone; Multivariate Analysis; Narcotics; Opioid-Related Disorders; Tablets

Buprenorphine is a promising alternative to methadone or levo-acetyl alpha methadol for opioid agonist maintenance treatment, and thrice-weekly dosing would facilitate its use for this purpose.. After a 3-day induction, opioid-dependent patients (n = 92) were randomly assigned to daily clinic attendance and 12-weeks maintenance treatment with sublingual buprenorphine administered double blind either daily (n = 45; 16 mg/70 kg) or thrice weekly (n = 47; 34 mg/70 kg on Fridays and Sundays and 44 mg/70 kg on Tuesdays). Outcome measures include retention, results of 3x/week urine toxicology tests, and weekly self-reported illicit drug use.. There were no significant differences at baseline in important social, demographic, and drug-use features. Retention was 71% in the daily and 77% in the 3x/week conditions. The proportion of opioid-positive urine tests decreased significantly from baseline in both groups and averaged 57% (daily) and 58% in 3x/week. There were no significant differences between groups in self-reported number of bags of heroin used for any day of the week, including Thursdays (48-72 hours following the last buprenorphine dose for subjects in the 3x/week condition), or in medication compliance (92%, 91%) and counseling attendance (82%, 82%).. At an equivalent weekly dose of 112 mg/70 kg, thrice-weekly and daily sublingual buprenorphine appear comparable in efficacy with regard to retention and reductions in illicit opioid and other drug use. These findings support the potential for utilizing thrice-weekly buprenorphine dosing in novel settings.

Topics: Adult; Buprenorphine; Cocaine-Related Disorders; Double-Blind Method; Female; Heroin Dependence; Humans; Male; Narcotic Antagonists; Opioid-Related Disorders; Psychiatric Status Rating Scales

Buprenorphine is an opioid agonist-antagonist under development in the United States as a sublingual medication for treatment of opioid dependence. Buprenorphine may be abused; therefore, tablets combining buprenorphine with naloxone have been developed with the intent of reducing the abuse risk in people physically dependent upon opioids. The characteristics and abuse potential of buprenorphine and buprenorphine/naloxone tablets in non-dependent opioid abusers have not been determined. Non-parenteral abuse of opioids such as buprenorphine may be more likely in people who have less severe substance abuse disorders (e.g., are not physically dependent upon opioids).. To assess the abuse potential of sublingual buprenorphine and buprenorphine/naloxone tablets in non-dependent opioid abusers.. Subjects (n=7) were tested with sublingual buprenorphine (4, 8, 16 mg), sublingual buprenorphine/naloxone (1/0.25, 2/0.5, 4/1, 8/2, 16/4 mg), as well as intramuscular hydromorphone as an opioid agonist control (2, 4 mg) and placebo in laboratory sessions conducted twice per week. Dosing was double-blind and double-dummy.. The higher doses of both buprenorphine and buprenorphine/naloxone produced similar opioid agonist-like effects. The onset of these effects was slowed, consistent with the sublingual route of administration, and the magnitude of effects was moderate. There was no evidence to suggest the addition of naloxone attenuated buprenorphine's opioid agonist effects in this population when buprenorphine was delivered by the sublingual route.. These results suggest that sublingual buprenorphine and buprenorphine/naloxone may both be abused by opioid users who are not physically dependent upon opioids.

Topics: Administration, Sublingual; Adult; Analgesics, Opioid; Buprenorphine; Drug Combinations; Humans; Hydromorphone; Injections, Intravenous; Male; Middle Aged; Motor Activity; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Tablets; Time Factors

To compare opioid withdrawal symptoms during 24-, 48-, 72- and 96-hour buprenorphine dosing regimens and to evaluate subjects' preferences for these different dosing schedules.. Fourteen opioid-dependent subjects participated in this study. They received daily sublingual maintenance doses of 4 mg/70 kg (n = 4) or 8 mg/70 kg (n = 10) of buprenorphine.. In the first study subjects received, in a random order, four dosing regimens for five repetitions of each: daily maintenance doses every 24 hours (4 or 8 mg/70 kg), double the daily maintenance dose every 48 hours (8 or 16 mg/70 kg), triple the daily maintenance dose every 72 hours (12 or 24 mg/70 kg), and quadruple the daily maintenance dose every 96 hours (16 or 32 mg/70 kg). Measures of subjective and observer opioid withdrawal symptoms were assessed prior to receipt of each dose. In a second study, subjects chose between the different dosing regimens.. Some withdrawal ratings increased during the less frequent dosing schedules in the first study. In the second study, 46% of subjects preferred the quadruple-every-fourth-day dosing regimen over every other option, and only 14% preferred to be dosed daily.. These results suggest that some opioid-dependent outpatients are willing and able to endure the withdrawal symptoms associated with less than daily dosing, and a twice-weekly dosing regimen may be possible.

Topics: Adult; Analysis of Variance; Buprenorphine; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Narcotics; Opioid-Related Disorders; Substance Withdrawal Syndrome; Treatment Outcome

We used an open-labeled, 21-day inpatient detoxification treatment to compare the short-term effects of a 10-day buprenorphine plus 19-day carbamazepine regimen (n = 15) to a 14-day oxazepam plus 19-day carbamazepine regimen (n = 12) during rapid detoxification from opioids and other abused drugs. Somatic and psychopathological changes were assessed using the following rating scales: ASI, HAMD, SCL-90-R, and SOWS. Eighteen of 27 patients (67%) completed the study. Four dropouts (27%) were treated with buprenorphine/carbamazepine (BPN/CBZ) and the other five dropouts (42%) were treated with oxazepam/carbamazepine (OXA/CBZ). Repeated measures analysis of variance showed that SOWS scores were significantly less pronounced with BPN-CBZ than with OXA/CBZ. On the first day of admission, no significant difference in HAMD scores was detected (BPN/CBZ 11.6, BPN/CBZ 1.0). On day 14, HAMD was significantly less pronounced in BPN/CBZ (3.0) than in OXA/CBZ (6.1). BPN/CBZ showed a significant improvement in the ASI score on days 7 and 14 compared with OXA/CBZ. Three of nine items of the SCL-90-R showed a trend toward less pronounced outcome in BPN-CBZ. No severe side effects occurred during treatment in either group. The buprenorphine/carbamazepine regimen provided significantly more effective relief from affect disturbances and withdrawal syndromes than the oxazepam/carbamazepine regimen. The pharmacological basis of these effects of buprenorphine (kappa-antagonism activity,mu-agonism activity) are discussed.

Topics: Adult; Affect; Analgesics, Non-Narcotic; Analysis of Variance; Anti-Anxiety Agents; Anxiety; Buprenorphine; Carbamazepine; Clinical Protocols; Drug Therapy, Combination; Female; Humans; Male; Narcotic Antagonists; Opioid-Related Disorders; Oxazepam; Prospective Studies; Psychiatric Status Rating Scales; Substance Withdrawal Syndrome; Substance-Related Disorders; Treatment Outcome

Opioid dependence is a chronic, relapsing disorder with important public health implications.. In a 17-week randomized study of 220 patients, we compared levomethadyl acetate (75 to 115 mg), buprenorphine (16 to 32 mg), and high-dose (60 to 100 mg) and low-dose (20 mg) methadone as treatments for opioid dependence. Levomethadyl acetate and buprenorphine were administered three times a week. Methadone was administered daily. Doses were individualized except in the group assigned to low-dose methadone. Patients with poor responses to treatment were switched to methadone.. There were 55 patients in each group; 51 percent completed the trial. The mean (+/-SE) number of days that a patient remained in the study was significantly higher for those receiving levomethadyl acetate (89+/-6), buprenorphine (96+/-4), and high-dose methadone (105+/-4) than for those receiving low-dose methadone (70+/-4, P<0.001). Continued participation was also significantly more frequent among patients receiving high-dose methadone than among those receiving levomethadyl acetate (P=0.02). The percentage of patients with 12 or more consecutive opioid-negative urine specimens was 36 percent in the levomethadyl acetate group, 26 percent in the buprenorphine group, 28 percent in the high-dose methadone group, and 8 percent in the low-dose methadone group (P=0.005). At the time of their last report, patients reported on a scale of 0 to 100 that their drug problem had a mean severity of 35 with levomethadyl acetate, 34 with buprenorphine, 38 with high-dose methadone, and 53 with low-dose methadone (P=0.002).. As compared with low-dose methadone, levomethadyl acetate, buprenorphine, and high-dose methadone substantially reduce the use of illicit opioids.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Cocaine-Related Disorders; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Methadone; Methadyl Acetate; Middle Aged; Narcotics; Opioid-Related Disorders; Treatment Outcome

Buprenorphine and naloxone sublingual (s.l.) dose formulations may decrease parenteral buprenorphine abuse. We evaluated pharmacologic interactions between 8 mg s.l. buprenorphine combined with 0, 4, or 8 mg of naloxone in nine opiate-dependent volunteers stabilized on 8 mg s.l. buprenorphine for 7 days. Combined naloxone and buprenorphine did not diminish buprenorphine's effects on opiate withdrawal nor alter buprenorphine bioavailability. Opiate addicts stabilized on buprenorphine showed no evidence of precipitated opiate withdrawal after s.l. buprenorphine-naloxone combinations. Buprenorphine and naloxone bioavailability was approximately 40 and 10%, respectively. Intravenous buprenorphine and naloxone produced subjective effects similar to those of s.l. buprenorphine and did not precipitate opiate withdrawal.

Topics: Administration, Sublingual; Adult; Blood Pressure; Buprenorphine; Female; Heart Rate; Humans; Injections, Intravenous; Male; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Time Factors

Cocaine abuse occurs in 40% to 60% of patients entering opioid maintenance treatment, and effective pharmacotherapies are needed for this combined dependence.. This 13-week, randomized, double-blind, placebo-controlled trial evaluated the efficacy of desipramine hydrochloride (0 or 150 mg/d) plus buprenorphine hydrochloride (12 mg/d) or methadone hydrochloride (65 mg/d) in 180 opioid-dependent cocaine abusers (124 men, 56 women). Supervised urine samples were obtained thrice weekly, and self-reported cocaine and heroin use was reported once weekly. Desipramine plasma levels were determined at weeks 4 and 10.. In men, opioid abstinence was increased more rapidly over time when treated with methadone than with buprenorphine, whereas cocaine abstinence was increased more with buprenorphine than with methadone. In women, opioid abstinence was increased the least rapidly when treated with buprenorphine plus placebo, while cocaine abstinence was increased more rapidly over time when treated with methadone than with buprenorphine. Regardless of sex or opioid medication, desipramine increased opioid and cocaine abstinence more rapidly over time than placebo. Self-reported opioid use confirmed these findings. Desipramine plasma levels were higher in women than in men, particularly those on buprenorphine maintenance. Higher desipramine plasma levels were associated with greater opioid, but not cocaine, abstinence.. Desipramine may be a useful adjunctive medication in facilitating opioid and cocaine abstinence in opioid-maintained patients. The efficacy of opioid medications to treat opioid or cocaine dependence may differ by sex. These findings highlight the importance of including sex as a factor when examining treatment outcome in these types of trials.

Topics: Adult; Analgesics, Opioid; Antidepressive Agents, Tricyclic; Buprenorphine; Cocaine-Related Disorders; Comorbidity; Desipramine; Drug Administration Schedule; Drug Therapy, Combination; Female; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Sex Factors; Treatment Outcome

Sublingual buprenorphine is a promising new treatment for opiate dependence, but its opioid agonist effects pose a risk for parenteral abuse. A formulation combining buprenorphine with the opiate antagonist naloxone could discourage such abuse. The effects of three intravenous (IV) buprenorphine and naloxone combinations on agonist effects and withdrawal signs and symptoms were examined in 12 opiate-dependent subjects. Following stabilization on a daily dose of 60 mg morphine intramuscularly, subjects were challenged with IV doses of buprenorphine alone (2 mg) or in combination with naloxone in ratios of 2:1, 4:1, and 8:1 (1, 0.5, or 0.25 mg naloxone), morphine alone (15 mg) or placebo. Buprenorphine alone did not precipitate withdrawal and had agonist effects similar to morphine. A naloxone dose-dependent increase in opiate withdrawal signs and symptoms and a decrease in opioid agonist effects occurred after all drug combinations. Buprenorphine with naloxone in ratios of 2:1 and 4:1 produced moderate to high increases in global opiate withdrawal, bad drug effect, and sickness. These dose ratios also decreased the pleasurable effects and estimated street value of buprenorphine, thereby suggesting a low abuse liability. The dose ratio of 8:1 produced only mild withdrawal symptoms. Dose combinations at 2:1 and 4:1 ratios may be useful in treating opiate dependence.

Topics: Adult; Affect; Buprenorphine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Morphine; Naloxone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Substance Withdrawal Syndrome

Buprenorphine (BUP)-maintained patients were first exposed to various BUP doses and then chose between BUP doses and money. In the choice phase, they had 10 units exchangeable for units of BUP (constant at 3 mg/unit) or money (varied from $0.30 to $20/unit). They chose BUP exclusively (30 mg) when the money alternative was low. As available money increased, they selected lower daily BUP doses (down to 3 mg). An economic analysis indicated demand for BUP was inelastic; changes in drug intake were proportionally lower than changes in price. Subjective reports of agonist and withdrawal effects increased > 200% when high and low BUP doses, respectively, were given during the exposure phase. In the choice phase, subjective drug effects were constant regardless of the BUP dose selected. Thus, BUP dose selection varies with the magnitude of alternative reinforcers, and subjective drug effects depend on whether doses are self- or experimenter-selected.

Topics: Adult; Analgesics, Opioid; Behavior; Buprenorphine; Humans; Male; Opioid-Related Disorders; Reinforcement, Psychology; Self Administration; Substance Withdrawal Syndrome

This study evaluated plasma buprenorphine concentrations 24-72 h following sublingual administration of a dose of buprenorphine solution, ranging from 16 mg/70 kg to 44 mg/70 kg, administered on a daily or thrice-weekly schedule. Additionally, this study evaluated the effects of different thrice-weekly buprenorphine dose schedules on opiate use and withdrawal symptoms.. Opiate dependent subjects (n = 10) were maintained in an outpatient clinic for two 3-week periods at each of three thrice-weekly buprenorphine dose schedules (providing a weekly total buprenorphine dose of 64, 84 and 112 mg) and for 1 week of a daily buprenorphine dose of 16 mg/70 kg. Plasma samples were obtained 24, 48 and 72 h following administration of buprenorphine. Urine samples were also collected and opiate withdrawal symptoms, agonist effects and the use of heroin, cocaine, alcohol and other drugs, were assessed.. Plasma levels showed a wide range of intra- and inter-subject variability. Nonetheless, higher doses of buprenorphine resulted in higher plasma concentrations at each time point and plasma concentration decreased with time. There were no significant differences in heroin use across dosing. Rates of withdrawal symptoms were low and did not differ across dosing schedules.. In the two highest dose schedules, plasma levels 72 h following the administration of the highest dose and at 48 h after the lower dose, were comparable to plasma concentrations at 24 h following daily administration of 16 mg/70 kg of buprenorphine.

Topics: Administration, Sublingual; Buprenorphine; Cocaine; Dose-Response Relationship, Drug; Double-Blind Method; Ethanol; Female; Heroin; Humans; Male; Narcotics; Opioid-Related Disorders; Substance Withdrawal Syndrome; Time Factors

Recent theories of substance abuse have used value discounting of delayed rewards to partly explain the decision to take drugs. Normative-economic theory holds that an exponential function describes the effects of delay on discounting, whereas the matching law posits a hyperbolic discounting function. The ability of these functions to describe 18 human heroin-dependent individuals' monetary- and heroin-reward delay-discounting functions was assessed. In the 1st condition, participants chose between immediate and delayed hypothetical monetary rewards. Delayed rewards were $1,000, and the immediate reward amount was adjusted until choices reflected indifference. In the 2nd condition, participants chose between immediate and delayed heroin (the delayed amount was that which each participant reported he or she could purchase with $1,000). The hyperbolic function produced significantly higher R2 values and significantly lower sums of squared error values. Consistent with previous findings, delayed heroin rewards were discounted at a significantly higher rate than were delayed monetary rewards.

Topics: Adult; Buprenorphine; Female; Heroin; Humans; Male; Motivation; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Reward; Time Factors

This study compared 24-, 48-, 72-, and 96-hour buprenorphine dosing regimens in opioid-dependent outpatients.. Fourteen subjects received buprenorphine in a double-blind, placebo-controlled crossover trial. Daily sublingual maintenance doses were 4 mg/70 kg (n = 5) and 8 mg/70 kg (n = 9). After a stabilization period of maintenance administration, subjects received, in a random order, four dosing regimens for five repetitions of each regimen: a maintenance dose every 24 hours, a doubled maintenance dose every 48 hours, a tripled maintenance dose every 72 hours, and a quadrupled maintenance dose every 96 hours. In the latter three dosing regimens, subjects received placebo on the interposed day(s). Study participation was contingent on opioid abstinence and daily clinic attendance. Measures of subjective opioid agonist and withdrawal effects were assessed daily.. Relative to standard maintenance dosing, none of the higher doses induced agonist effects. Changes in indices of subjective withdrawal effects were noted as the time since the last active dose increased during intermittent dosing regimens, but the magnitude of these effects was relatively low and was comparable to those found in other alternate-day dosing studies.. These results support the feasibility and safety of twice weekly buprenorphine dosing regimens.

Topics: Adult; Buprenorphine; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Feasibility Studies; Female; Humans; Male; Middle Aged; Narcotics; Opioid-Related Disorders; Treatment Outcome

The efficacy of buprenorphine in opioid dependent patients (n = 20) was compared to methadone maintained subjects (n = 20) in a randomized comparison trial. Sublingual application of buprenorphine as an alternative synthetical opioid is being compared to methadone during a 24 week study period. A trend (p = 0.06) could be found in the retention rate of investigated patients being maintained on a mean dosage of 63 mg oral applicable methadone (racemat of L- and D-methadone) in comparison to the group on a mean dosage of 7.3 mg buprenorphine (sublingual tablets). The dropout-rate of 11 subjects at the end of the study in the buprenorphine group was higher when compared to the dropout-rate of 5 in the methadone group. There was no significant difference between the two groups over the treatment period in respect to additional consumption of opiates, benzodiazepines and cocaine as evaluated through urine toxicology. The result in regard to compliance over the study period demonstrates that methadone appears to be the more successful oral opioid (p = 0.04). Nevertheless, efficacy of buprenorphine in maintenance could be demonstrated in the remaining subjects, and further studies with higher daily doses and a higher number of subjects have to be performed.

Topics: Administration, Sublingual; Adult; Buprenorphine; Female; Humans; Male; Methadone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Patient Dropouts; Substance Abuse Detection; Treatment Outcome

Administration of double the maintenance dose of buprenorphine has been shown to permit every-other-day dosing. Whether longer periods between dosing can be achieved is unknown.. To examine whether triple the maintenance dose can be administered every 72 h without opioid withdrawal or intoxication.. Sixteen opioid-dependent outpatients each received three conditions (1) the maintenance dose of buprenorphine every 24 h, (2) double the maintenance dose every 48 h, and (3) triple the maintenance dose every 72 h under double-blind placebo-controlled conditions. Each conditions was imposed in a random sequence for 21-22 days. Self report and observer measures were taken at 24-h intervals.. No significant differences were observed on measures of opioid agonist and withdrawal effects between the dosing conditions. However, averaging effects across conditions may obscure important within-condition effects. When conditions were analyzed by individual days within a condition, several significant effects were observed. For example, 24 h after administration of triple the maintenance dose, significant effects were observed in eight opioid agonist measures. Also, 72 h after administration of triple the maintenance dose, significant effects were observed on four measures of withdrawal. Neither adverse medical reactions nor excessive opioid intoxication were observed.. These results suggest that buprenorphine may be administered safely every 72 h by tripling the maintenance dose, with only minimal withdrawal complaints. Importantly, this 72-h dosing may permit patients to attend clinic thrice weekly without the use of take-home doses.

Topics: Adult; Buprenorphine; Cross-Over Studies; Double-Blind Method; Female; Humans; Male; Narcotics; Opioid-Related Disorders; Patient Compliance; Psychiatric Status Rating Scales; Pupil

To evaluate the effectiveness of buprenorphine compared with methadone maintenance therapy in opiate addicts over a treatment period of 24 weeks.. Subjects were randomized to receive either buprenorphine or methadone in an open, comparative study.. Subjects were recruited and treated at the drug addiction outpatient clinic at the University of Vienna.. Sixty subjects (19 females and 41 males) who met DSM-IV criteria for opioid dependence and were seeking treatment.. Subjects received either sublingual buprenorphine (2-mg or 8-mg tablets; maximum daily dose 8 mg) or oral methadone (racemic D -/+ L-methadone; maximum daily dose 80 mg). A stable dose was maintained following the 6-day induction phase.. Assessment of treatment retention and illicit substance use (opiates, cocaine and benzodiazepines) was made by urinalysis.. The retention rate was significantly better in the methadone maintained group (p < 0.05) but subjects completing the study in the buprenorphine group had significantly lower rates of illicit opiate consumption (p = 0.04).. The results support the superiority of methadone with respect to retention rate. However, they also confirm previous reports of buprenorphine use as an alternative in maintenance therapy for opiate addiction, suggesting that a specific subgroup may be benefiting from buprenorphine. This is the first comparative trial to use sublingual buprenorphine tablets: previously published comparison studies refer to 30% solutions of buprenorphine in alcohol.

Topics: Adolescent; Adult; Ambulatory Care; Ambulatory Care Facilities; Buprenorphine; Female; Humans; Male; Methadone; Narcotics; Opioid-Related Disorders

This study a) compared the effects of buprenorphine versus methadone maintenance on benzodiazepine and alcohol use and b) evaluated the prognostic significance of gender and psychopathology and their interaction with maintenance treatment. Eighty male and 36 female patients were randomly assigned to daily sublingual buprenorphine (4 or 12 mg) or oral methadone (20 or 65 mg). Maintenance medication was not associated with significant differences in alcohol or benzodiazepine use. Rates of abstinence from illicit opioids were significantly higher for females, within the buprenorphine 4-mg group, females also had significantly better retention, lower rates of opioid-positive urine samples, and higher rates of abstinence from illicit opioids. Lifetime sedative dependence was associated with significantly better retention, decreased rates of cocaine-positive urine samples, and increased rates of cocaine abstinence; among buprenorphine- but not methadone-maintained patients, it was also associated with increased rates of abstinence from illicit opioids.

Topics: Adult; Alcoholism; Antisocial Personality Disorder; Benzodiazepines; Buprenorphine; Cocaine-Related Disorders; Comorbidity; Depressive Disorder; Double-Blind Method; Female; Humans; Male; Methadone; Opioid-Related Disorders; Patient Dropouts; Prognosis; Sex Factors; Substance Abuse Detection; Substance-Related Disorders; Treatment Outcome

Alternate-day buprenorphine dosing was compared to daily dosing in opioid-dependent outpatients and choice of alternate-day versus daily dosing was assessed. Four dosing schedules were presented in random order under blind and open dosing conditions. Subjects received two exposures to each dosing schedule. During daily dosing, subjects received maintenance doses every 24 h. During blind alternate-day dosing, subjects received double maintenance doses every 48 h; placebo was interposed on intervening days. During open alternate-day dosing, subjects received twice their maintenance dose on Monday, Wednesday and Friday and maintenance doses on Sunday. After completing two exposures to each dosing schedule, subjects chose either daily or alternate-day schedules each week for 1 month. Study participation was contingent on daily attendance and opioid abstinence. Ten subjects were exposed to the four conditions once. Seven subjects repeated these conditions and participated in the choice phase. The effects of daily versus alternate-day dosing were not influenced by blind or open dosing conditions. Subjects' ratings of withdrawal, "sick" and sedation were lower during daily than during alternate-day dosing, but the difference between treatments was small. Nonetheless, subjects still chose alternate-day dosing on 96% of occasions, suggesting that the subject-rated differences between dosing schedules were not influential. These results extend prior findings to open-dosing conditions, and replicate the safety and acceptability of alternate-day buprenorphine treatment. Choice of alternate-day buprenorphine administration underscores the procedure's clinical utility and potential use as a positive reinforcer to enhance opioid treatment.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Double-Blind Method; Female; Humans; Male; Middle Aged; Opioid-Related Disorders; Patient Dropouts; Psychiatric Status Rating Scales; Substance Withdrawal Syndrome; Treatment Outcome

The present study, conducted as part of the development of a buprenorphine/naloxone combination product, was designed to evaluate the individual and combined effects of intravenously administered buprenorphine and naloxone. This in-patient trial used a randomized, double-blind, crossover design. Ten opioid-dependent male subjects were stabilized and maintained on morphine, 15 mg given intramuscularly four times daily. Then, at 48- to 72-h intervals, subjects received one of the following by intravenous injection: (1) placebo, (2) morphine 15 mg, (3) buprenorphine 2 mg, (4) buprenorphine 2 mg/naloxone 0.5 mg, and (5) naloxone 0.5 mg. Both naloxone and buprenorphine/naloxone produced significant (P < 0.005) opioid withdrawal effects compared to placebo as assessed with the CINA scale, an instrument which utilizes subject- and observer-reported, as well as physiological parameters. The combination of buprenorphine with naloxone in a 4:1 ratio produced opioid antagonist-like effects which should limit its potential for intravenous abuse by opioid addicts.

Topics: Adult; Analysis of Variance; Area Under Curve; Behavior, Addictive; Buprenorphine; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Humans; Injections, Intravenous; Male; Middle Aged; Morphine; Naloxone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Substance Withdrawal Syndrome; Time Factors; Veterans

To evaluate the safety and efficacy of an 8 mg/day sublingual dose of buprenorphine in the maintenance treatment of heroin addicts by comparison with a 1 mg/day dose over a 16-week treatment period. As a secondary objective, outcomes were determined concurrently for patients treated with two other dose levels.. Patients were randomized to four dosage groups and treated double-blind.. Twelve outpatient opiate maintenance treatment centers throughout the United States.. Two hundred and thirty-nine women and 497 men who met the DSM-III-R criteria for opioid dependence and were seeking treatment.. Patients received either 1, 4, 8 or 16 mg/day of buprenorphine and were treated in the usual clinical context, including a 1-hour weekly clinical counseling session.. Retention in treatment, illicit opioid use as determined by urine toxicology, opioid craving and global ratings by patient and staff. Safety outcome measures were provided by clinical monitoring and by analysis of the reported adverse events.. Outcomes in the 8 mg group were significantly better than in the 1 mg group in all four efficacy domains. No deaths occurred in either group. The 8 mg group did not show an increase in the frequency of adverse events. Most reported adverse effects were those commonly seen in patients treated with opioids.. The findings support the safety and efficacy of buprenorphine and suggest that an adequate dose of buprenorphine will be a useful addition to pharmacotherapy.

Topics: Buprenorphine; Double-Blind Method; Female; Humans; Male; Narcotic Antagonists; Opioid-Related Disorders; Treatment Outcome

Information concerning the association between marijuana use and opioid dependence and its treatment is needed to determine effective clinical guidelines for addressing marijuana use among opioid abusers.. Marijuana use was assessed in 107 people enrolled in treatment for opioid dependence.. Univariate comparisons of marijuana users and non-users and multivariate regression analyses were performed to examine associations between marijuana use and socio-demographic, psychosocial, medical and substance-use variables. The relationship between marijuana use and treatment outcome was also explored in a subset of this sample who received treatment that included buprenorphine detoxification and behavior therapy (N = 79).. Sixty-six per cent of participants were current marijuana users and almost all (94%) continued to use during treatment. Users were less likely to be married than non-users, and more likely to report financial difficulties, be involved in drug dealing and engage in sharing of needles (p < 0.05). A unique effect of marijuana use on drug dealing and sharing needles was retained after statistically controlling for the influence of heroin and alcohol use and other socio-demographic variables. No significant adverse relations were observed between marijuana use and treatment outcome.. Pending a more comprehensive understanding of the function and consequences of marijuana use on psychosocial functioning, it appears that progress in treatment for opioid dependence can be made without mandating that patients abstain from marijuana use.

Topics: Adult; Analysis of Variance; Buprenorphine; Humans; Marijuana Abuse; Narcotic Antagonists; Opioid-Related Disorders; Treatment Outcome

As a maintenance agent for opioid dependency, buprenorphine offers advantages such as a lower level of dependence and minimal withdrawal symptoms, due to its partial agonist properties at the micro-opioid receptor. Previous studies have shown 8 mg sublingual buprenorphine to be equivalent to 60 mg oral methadone in terms of retention rate and opioid-negative urine levels. In a 24-week, ongoing European study, 34 opioid-dependent subjects were assessed; 16 receiving buprenorphine and 18 methadone. A free dosing schedule was used with no upper limit for methadone dosing but with a maximum buprenorphine dose of 8 mg. Screening prior to the study excluded subjects with polysubstance dependence, somatic disease and/or HIV infection. Primary outcome measures were abstinence from other drugs, for which subjects provided weekly urine samples for analysis of opioids, cocaine and benzodiazepines, and retention in treatment. Patients in the buprenorphine group provided a greater proportion of negative urine samples, in particular cocaine-negative samples, compared with the methadone group, although this was not statistically significant. Retention in the buprenorphine group was significantly lower than in the methadone group, suggesting that the 8 mg buprenorphine limit may have biased the results in favour of methadone, and that this dose may have been too low for those subjects with high levels of dependence. However, buprenorphine is clearly effective in the more motivated subjects and further investigation in this subgroup is recommended.

Topics: Adolescent; Adult; Buprenorphine; Dose-Response Relationship, Drug; Female; Humans; Male; Methadone; Narcotics; Opioid-Related Disorders

In France, during the 1990s, there have been some rapid developments in the treatment of opioid addiction with the introduction of legal substitution agents. Originally, some patients were treated with morphine sulfate, but this was superseded by high dose buprenorphine (Subutex(R)) and methadone. This resulted in those patients originally treated with morphine being transferred to either of these two licensed products. A study investigating the effects of the transition from morphine to either buprenorphine or methadone was undertaken. Supplementary to this, a trial investigating transition between these new compounds was also conducted. The primary outcome measures for these trials were retention rate, which was assessed at 5, 9 and 12 months, and the precipitation of withdrawal symptoms. The studies showed that transferring patients between substitution agents can be accomplished without severe withdrawal symptoms, although specific management may be required for transfer from high doses of methadone to buprenorphine. High long-term retention rates were observed in the studies, with most drop-outs occurring directly after transfer. Results suggest that patients on long-term buprenorphine maintenance therapy may have good compliance in comparison with other agents.

Topics: Adult; Buprenorphine; Dose-Response Relationship, Drug; Female; Humans; Male; Methadone; Morphine; Narcotics; Opioid-Related Disorders

A three-centre, randomised, double-blind study was designed to compare the efficacy and safety of buprenorphine and methadone. This was the first European study to compare these agents and was based on a previous trial performed in the US. Opioid-dependent subjects were randomised to receive either sublingual buprenorphine or oral methadone daily. Both objective and subjective measures of efficacy were monitored weekly, and safety parameters were regularly monitored over the entire six-week study. Urinalysis showed that the two treatments were similar with a slight increase in opioid-negative urines noted in both groups. The retention rate in the buprenorphine group was lower than in the methadone group, although it has been suggested that the buprenorphine dose may have been too low for some patients. None of the side effects noted were considered serious and all were attributable to chronic opioid dependence. Experience of two years substitution treatment in Fribourg suggests that initial induction onto buprenorphine allows for patients to be subgrouped before being given the most appropriate maintenance agent. Further investigation is required into the different dose-related effects of buprenorphine seen in particular subsets of addicts.

Topics: Adult; Buprenorphine; Double-Blind Method; Female; Humans; Male; Narcotics; Opioid-Related Disorders; Switzerland

Buprenorphine (BUP) is an alternative to methadone (METH) maintenance. However, there are few studies on the switching of patients from METH to BUP. Eighteen volunteers who had been maintained on METH for 1-19 years were recruited for a residential cocaine self-administration study. All subjects were maintained on 60 mg METH for up to 1 1/2 weeks before the 7-day changeover (60, 40, 30, 30, 0 mg METH; 4, 8 mg BUP). Fifteen subjects successfully completed the transfer from METH to BUP, experiencing moderate withdrawal symptoms, as measured by the Subjective Opiate Withdrawal Scale (SOWS). Withdrawal symptoms were the highest during the first assessment of the day, at the time of BUP administration. SOWS scores returned to baseline 4 days after the switchover. This study demonstrates that within a supportive inpatient setting, research volunteers can be rapidly switched from high-maintenance doses of METH to BUP with an acceptable degree of tolerability.

Topics: Adult; Anti-Anxiety Agents; Anxiety; Buprenorphine; Clonidine; Cocaine; Drug Administration Schedule; Female; Humans; Inpatients; Male; Methadone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Oxazepam; Substance Abuse Treatment Centers; Substance Withdrawal Syndrome; Sympatholytics; Treatment Outcome

Buprenorphine, a partial mu-agonist and kappa-antagonist, has been proposed as an alternative to methadone for maintenance treatment of opioid dependence, especially for patients with concurrent cocaine dependence or abuse. This study evaluated whether higher maintenance doses of buprenorphine and methadone are superior to lower doses for reducing illicit opioid use and whether buprenorphine is superior to methadone for reducing cocaine use.. A total of 116 subjects were randomly assigned to 1 of 4 maintenance treatment groups involving higher or lower daily doses of sublingual buprenorphine (12 or 4 mg) or methadone (65 or 20 mg) in a double-blind, 24-week clinical trial. Outcome measures included retention in treatment and illicit opioid and cocaine use as determined by urine toxicology testing and self-report.. There were significant effects of maintenance treatment on rates of illicit opioid use, but no significant differences in treatment retention or the rates of cocaine use. The rates of opioid-positive toxicology tests were lowest for treatment with 65 mg of methadone (45%), followed by 12 mg of buprenorphine (58%), 20 mg of methadone (72%), and 4 mg of buprenorphine (77%), with significant contrasts found between 65 mg of methadone and both lower-dose treatments and between 12 mg of buprenorphine and both lower-dose treatments.. The results support the superiority of higher daily buprenorphine and methadone maintenance doses vs lower doses for reducing illicit opioid use, but the results do not support the superiority of buprenorphine compared with methadone for reducing cocaine use.

Topics: Adult; Buprenorphine; Cocaine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Methadone; Opioid-Related Disorders; Substance-Related Disorders; Treatment Outcome

This trial assessed whether behavioral treatment improves outcome during a 26-week outpatient opioid detoxification. Thirty-nine opioid-dependent adults were assigned randomly to a buprenorphine dose-taper combined with either behavioral or standard treatment. Behavioral treatment included (a) a voucher incentive program for providing opioid-free urine samples and engaging in verifiable therapeutic activities and (b) the community reinforcement approach, a multicomponent behavioral treatment. Standard treatment included lifestyle counseling. Fifty-three percent of the patients receiving behavioral treatment completed treatment, versus 20% receiving standard treatment. The percentage of patients achieving 4, 8, 12, and 16 weeks of continuous opioid abstinence were 68, 47, 26, and 11 for the behavioral group and 55, 15, 5, and 0 for the standard group, respectively. Behavioral treatment improved outcomes during outpatient detoxification.

Topics: Adult; Behavior Therapy; Buprenorphine; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Substance Abuse Detection; Treatment Outcome

Buprenorphine is a partial agonist at the mu-opioid receptor that has been proposed as an alternative to traditional full agonist maintenance therapy for the treatment of opioid addiction. We report on a clinical trial in which the relative safety and efficacy of long-term fixed-dose buprenorphine maintenance was examined in comparison to low- and high-dose methadone maintenance.. Two hundred twenty-five treatment-seeking opioid addicts (46 women, 179 men) were randomly assigned to receive, in a double-blind manner, either 8 mg/d of buprenorphine, 30 mg/d of methadone, or 80 mg/d of methadone maintenance over a 1-year period. Objective and subjective measures of efficacy (urine toxicology, retention, craving, and withdrawal symptoms) were examined at the study midpoint and at termination, and safety data were tabulated over the entire 52-week study period.. Patients assigned to high-dose methadone maintenance performed significantly better on measures of retention, opioid use, and opioid craving than either the low-dose methadone or the buprenorphine group at both 26-week and 52-week time points. Performance on these measures was virtually identical between the latter two groups. No serious adverse health effects attributable to buprenorphine were noted.. Buprenorphine maintenance at 8 mg/d appears to be less than optimally efficacious under the conditions of the present study. Continued research is needed to reconcile these findings with the more positive results reported by other investigative groups. There are no apparent health risks associated with long-term buprenorphine maintenance at this dosage.

Topics: Adult; Buprenorphine; Cocaine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Heroin Dependence; Humans; Male; Methadone; Opioid-Related Disorders; Placebos; Substance Abuse Detection; Substance-Related Disorders; Treatment Outcome

Sublingual buprenorphine appears useful in the treatment of opiate dependence. A combination sublingual dose of buprenorphine and naloxone could have less potential for parenteral use by opiate-dependent individuals. To estimate the abuse potential of a combination formulation, we assessed the parenteral effects of a buprenorphine and naloxone combination in untreated heroin addicts.. Eight healthy, opiate-dependent daily users of heroin were given, under double-blind conditions on four separate occasions, either (1) 2 mg buprenorphine, (2) 2 mg naloxone, (3) 2 mg buprenorphine and 2 mg naloxone combined, or (4) placebo as a single intravenous infusion during a 30-second interval. Opiate agonist and antagonist physiologic and subjective effects were measured. Data were analyzed by analysis of variance.. Buprenorphine increased opiate intoxication and relieved withdrawal. The buprenorphine and naloxone combination precipitated opiate withdrawal and was unpleasant and dysphoric in all subjects. Fifty percent of the subjects were unable to distinguish between naloxone alone and the combined medications during the first hour of testing.. The buprenorphine and naloxone combination has a low abuse potential in opiate-dependent daily heroin users.

Topics: Adult; Buprenorphine; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opioid-Related Disorders

The effects of p.o. methadone or sublingual buprenorphine maintenance on i.v. cocaine self-administration and the response to experimenter-administered cocaine were evaluated in 12 methadone-maintained individuals. Participants lived in a clinical research center during the 4- to 5-week protocol. After stabilization on 80 mg/day methadone, half the participants were first tested during buprenorphine maintenance (8 mg/day with p.o. placebo) and half were first tested during methadone maintenance (60 mg/day with sublingual placebo). After testing on the alternate medication, all participants were returned to their entry level of methadone. Testing consisted of three daily sessions of fixed cocaine dosing (four injections; 0, 16 and 48 mg/70 kg) and three daily sessions of cocaine self-administration with a choice procedure (16, 32 and 48 mg/70 kg vs. $5). The transition from methadone to buprenorphine engendered moderate withdrawal symptoms (score of 12 on the subjective opiate withdrawal scale), which returned to base-line levels (score of 4 on the subjective opiate withdrawal scale) before testing during buprenorphine maintenance. Buprenorphine maintenance significantly reduced "I want cocaine" scores by 15% during fixed-dosing sessions. Subjective effects of fixed cocaine doses, including increased ratings of "high," "stimulated" and "good drug effect," were not affected by the maintenance medication. Heart rate was consistently 9 beats/min less, regardless of cocaine dose, during methadone maintenance. In comparison with methadone, buprenorphine maintenance decreased cocaine self-administration when 16- or 32-mg doses were available, but not when 48 mg was available. Thus, buprenorphine may have greater efficacy than methadone for controlling cocaine abuse among individuals dependent on opioids.

Topics: Adult; Buprenorphine; Cocaine; Dose-Response Relationship, Drug; Female; Humans; Infusions, Intravenous; Male; Methadone; Opioid-Related Disorders; Self Administration; Substance Withdrawal Syndrome; Surveys and Questionnaires

This article reports results for patients who completed the 16-week maintenance phase of a double-blind clinical trial comparing buprenorphine (N = 43; average dose = 9.0 mg/day sublingually) with methadone (N = 43; average dose = 54 mg/day orally) in the outpatient treatment of opioid dependence. In addition to pharmacotherapy, treatment during the clinical trial included individual counseling, weekly group therapy, and on-site medical services. Patients in both medication groups showed significant and substantial improvements over time in areas of psychosocial functioning, as assessed by the Addiction Severity Index, rates of urinalysis tests positive for opioids, and self-reports of opioid withdrawal symptoms, illicit opioid use, and cocaine use. Buprenorphine and methadone produced very similar outcomes on the wide array of outcome measures assessed, and improvements for both groups were large and occurred rapidly after treatment entry. A trend toward continued improvement in opioid-positive urines over time was noted for the buprenorphine but not the methadone group. These results provide further evidence of the efficacy of buprenorphine in the treatment of opioid dependence and provide a characterization of the time course of effects for buprenorphine and methadone. In addition, these results demonstrate the benefits of drug abuse treatment, both for drug and alcohol use and in other areas of psychosocial functioning.

Topics: Adolescent; Adult; Alcoholism; Buprenorphine; Cocaine; Double-Blind Method; Female; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Substance Abuse Detection; Substance Withdrawal Syndrome; Treatment Outcome

We assessed cognitive function following heroin and cocaine detoxification and investigated whether buprenorphine treatment improves the disruptive effects of detoxification. Three groups of male volunteers meeting DSM-III-R criteria for concurrent opiate and cocaine dependence were tested using an auditory oddball paradigm before and after detoxification, and again on the 15th day of either buprenorphine or placebo treatment. There were no significant differences in P300 amplitude, latency, or topographic distribution between drug-dependent subjects and controls on admission day. Following detoxification there was a significant decrease in P300 amplitude in the drug-dependent group at a time when self-reported signs of withdrawal were minimal. Buprenorphine treatment significantly reversed the P300 amplitude decrement following detoxification, whereas placebo-treated subjects continued to show depressed P300 amplitudes. These data demonstrate that buprenorphine treatment is effective in eliminating detoxification-induced impairments in one measure of cognitive ability.

Topics: Adult; Arousal; Attention; Brain Mapping; Buprenorphine; Cerebral Cortex; Cocaine; Event-Related Potentials, P300; Heroin Dependence; Humans; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Reaction Time; Substance Withdrawal Syndrome

Buprenorphine, a partial mu opioid agonist, is an experimental medication under development for the treatment of opioid dependence as an alternative to methadone maintenance. The present study examined the relationship between level of opioid physical dependence and response to buprenorphine administration as part of a program to develop procedures for transferring patients from methadone to buprenorphine treatment. This laboratory study characterized the agonist and antagonist effects of acute doses of buprenorphine and methadone in subjects maintained on either 30 (n = 7) or 60 (n = 6) mg/day oral methadone. Test doses of placebo [sl. and PO), methadone (15, 30, and 60 mg PO) and buprenorphine (2, 4, and 8 mg sl.) were administered to volunteers residing on a closed residential unit. Subjective, physiological, observer-rated, and cognitive/psychomotor measures were collected for 6.5 h after test doses. Test doses of methadone, but not buprenorphine, constricted pupils and produced dose-related increases on subjective report measures reflecting opioid agonist drug effects. Agonist effects of methadone were more prominent in the 30 mg than in the 60 mg methadone maintenance condition. Buprenorphine, but not methadone, precipitated opioid withdrawal signs and symptoms that were more prominent in the 60 mg than in the 30 mg methadone maintenance condition. These findings suggest that abrupt transition from methadone to buprenorphine may produce patient discomfort that is positively related to both methadone maintenance dose and buprenorphine transition dose.

Topics: Administration, Oral; Adult; Buprenorphine; Dose-Response Relationship, Drug; Humans; Male; Methadone; Middle Aged; Opioid-Related Disorders; Substance Withdrawal Syndrome; Time Factors

Six opioid-dependent in-patients were maintained on daily sublingual doses of buprenorphine at 2, 6, and 12 mg/day for five days at each dose in a randomized, balanced sequence. Placebo buprenorphine was substituted for the next three days, and challenge doses of the mu agonist hydromorphone were administered on the three days. Planned comparisons in a 3-factor ANOVA showed dose-dependent hydromorphone effects, significant blockade of 'high' by the 12 mg buprenorphine dose, and no differences on hydromorphone-induced 'high' across 72 h of active buprenorphine. The data suggest that the blockade by buprenorphine of 'high' persists for at least 72 h after the last dose of buprenorphine.

Topics: Administration, Sublingual; Adult; Buprenorphine; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Hydromorphone; Male; Neurologic Examination; Opioid-Related Disorders; Single-Blind Method; Substance Withdrawal Syndrome; Time Factors

This study compared the efficacy of buprenorphine to methadone for decreasing cocaine use in patients with combined opioid and cocaine use. Participants (n = 51) were enrolled in a 26-week treatment program and randomly assigned to either buprenorphine or methadone. Dosing was double-blind and double-dummy. Patients were stabilized on either 8 mg sublingual buprenorphine or 50 mg oral methadone, with dose increases given in response to continued illicit cocaine use or opioid use through week 16 of treatment. Maximum doses possible were 16 mg buprenorphine and 90 mg methadone. Average doses achieved were 11.2 mg buprenorphine and 66.6 mg methadone; 49% of the patients received the maximum doses possible. Urine samples were collected three times per week, and there was no significant difference in the rate of cocaine positive urines for the intent-to-treat sample (69% for buprenorphine versus 63% for methadone). For patients who remained in treatment through the flexible dosing period (n = 28), there were significant decreases in cocaine positive urines over time (P < 0.01), but no significant differences between groups or group x time effects. Buprenorphine and methadone were equally effective on measures of treatment retention, urine results for opioids, and compliance with attendance and counseling. These results demonstrate no selective efficacy of either buprenorphine or methadone in attenuating cocaine use in this population, but do provide further support for the equivalent efficacy of buprenorphine and methadone in the treatment of opioid dependence.

Topics: Adolescent; Adult; Buprenorphine; Cocaine; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Methadone; Opioid-Related Disorders; Patient Compliance; Psychiatric Status Rating Scales; Substance-Related Disorders; Treatment Outcome

Eight opioid-dependent individuals were maintained on daily sublingual buprenorphine (8 mg) for 28 days and assigned randomly to one of two outpatient detoxification schedules under double-blind, double-dummy conditions. The two detoxification schedules were buprenorphine gradual (36 days; N = 3) or buprenorphine rapid (12 days; N = 5). Outcome variables were subject- and observer-ratings of opioid withdrawal, treatment retention and illicit-opioid use. Outcome measures were similar for the two groups during buprenorphine maintenance. Increases in subject-rated opioid withdrawal and illicit-opioid use, and a drop in treatment retention occurred during rapid detoxification. Stable subject-rated opioid withdrawal and treatment retention, and less illicit-opioid use occurred during gradual detoxification. These data suggest that gradual reduction in buprenorphine dose is likely to produce superior treatment outcomes than more rapid buprenorphine detoxification.

Topics: Administration, Sublingual; Adult; Buprenorphine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Neurologic Examination; Opioid-Related Disorders; Patient Compliance; Substance Withdrawal Syndrome; Treatment Outcome

In a 6-month randomized trial comparing 125 opiate-dependent patients who were assigned to four treatment groups (2 or 6 mg of buprenorphine and 35 or 65 mg of methadone), we examined the effects of cocaine use on opiate withdrawal symptoms measured on a 25-item scale on which the scores range from 0 to 75. For the methadone-maintained patients receiving the relatively low dose (35 mg), weekly withdrawal symptoms were highest when the urine toxicology for that week indicated no cocaine use. Similar associations were found for buprenorphine. Thus, when using cocaine at a low maintenance opiate dose, persistent opiate withdrawal symptoms were reduced, which is consistent with previous naloxone-precipitated withdrawal studies. Interestingly, with a higher dose of buprenorphine (6 mg), cocaine may have increased opiate withdrawal symptoms, suggesting a possible mechanism for the reduction of illicit cocaine abuse also recently observed in another study in patients treated with high dose (120 mg) methadone maintenance. This has led to a two-component model for the relationship between cocaine and opiate withdrawal-like symptoms at high versus low opiate maintenance dose. This two-component model also reconciles the contradictory findings of prior studies.

Topics: Adult; Buprenorphine; Cocaine; Comorbidity; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Methadone; Neurologic Examination; Opioid-Related Disorders; Substance Abuse Detection; Substance Withdrawal Syndrome; Substance-Related Disorders

We compared the short-term efficacy of a high-dose, 3 day regimen of buprenorphine to a standard 5-day course of clonidine in attenuating the signs and symptoms of the acute opioid abstinence syndrome during rapid detoxification from heroin in 25 men and women admitted to a closed inpatient research ward for this randomized, double-blind, parallel-group trial. Among the 18 completers, there were no significant differences between the buprenorphine and clonidine groups on five subjective and six physiological measures. However, clonidine lowered blood pressure and buprenorphine provided more effective early relief of withdrawal symptoms.

Topics: Adult; Baltimore; Buprenorphine; Clonidine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Heroin Dependence; Humans; Male; Middle Aged; Opioid-Related Disorders; Substance Abuse Treatment Centers; Substance Withdrawal Syndrome; Urban Population

Thirty-nine methadone maintenance patients were included in a 9-day, double blind, randomized, inpatient detoxification trial. Methadone was tapered to 10 mg/day and then patients were assigned to one of these 3 protocols: clonidine (0.3-0.9 mg/day), lefetamine (60-240 mg/day), buprenorphine (0.15-0.9 mg/day). Buprenorphine treatment was significantly superior to clonidine and to lefetamine (F = 3.96 df = 2, 29 P < 0.05) in controlling objective, subjective and psychological withdrawal symptomatology. Clonidine was more effective than lefetamine in suppressing withdrawal in the first 3 days of treatment (day 3: F = 4.10 df = 2, 30 P < 0.05), and this trend was apparent on the objective and psychological items. In addition to evaluations of the efficacy of the single drugs used, the study showed that tapering methadone to low doses before entering the pharmacologically assisted discontinuation phase was clinically acceptable in detoxification from long-term methadone treatment.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Clonidine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Heroin Dependence; Humans; Male; Methadone; Neurologic Examination; Opioid-Related Disorders; Patient Admission; Phenethylamines; Substance Withdrawal Syndrome

This study compared the efficacy of buprenorphine and methadone in the treatment of opioid dependence.. Participants (N = 164) were relatively treatment-naive, opioid-dependent applicants to a 26-week treatment program who were randomly assigned to either methadone or buprenorphine treatment. Dosing was double-blind and double-dummy. Patients were stabilized on a regimen of either methadone, 50 mg, or buprenorphine, 8 mg, with dose changes possible through week 16 of treatment. Urine samples were collected three times a week, and weekly counseling was provided.. Buprenorphine (mean dose = 8.9 mg/day) and methadone (mean dose = 54 mg/day) were equally effective in sustaining retention in treatment, compliance with medication, and counseling regimens. In both groups, 56% of patients remained in treatment through the 16-week flexible dosing period. Overall opioid-positive urine sample rates were 55% and 47% for buprenorphine and methadone groups, respectively; cocaine-positive urine sample rates were 70% and 58%. Evidence was obtained for the effectiveness of dose increases in suppressing opioid, but not cocaine, use among those who received dose increases.. The results of this study provide further support for the utility of buprenorphine as a new medication in the treatment of opioid dependence and demonstrate efficacy equivalent to that of methadone when used during a clinically guided flexible dosing procedure.

Topics: Administration, Oral; Administration, Sublingual; Adult; Buprenorphine; Cocaine; Comorbidity; Double-Blind Method; Female; Humans; Male; Methadone; Middle Aged; Opioid-Related Disorders; Patient Compliance; Substance Abuse Detection; Substance-Related Disorders; Treatment Outcome

Thirteen opioid-dependent outpatients participated in a double-blind, placebo-controlled, crossover trial. Twenty-one days of daily sublingual buprenorphine administration were compared to 21-days of alternate-day buprenorphine administration where patients received twice their daily maintenance dose every other day with placebo on the interposed day. Observer- and subject-rated measures of opioid agonist and withdrawal effects, pupillary diameter, and dose identifications were collected daily. Ten subjects (77%) completed the study (n = 6, 4 mg/70 kg; n = 4, 8 mg/70 kg); 8 subjects (62%) participated in a second crossover. Sixteen of seventeen measures of opioid agonist and withdrawal effects obtained during alternate-day administration did not differ significantly from those obtained during daily dosing in the ten subjects completing the study. The only significant difference observed was in subject-rated agonist effects, which were significantly lower during alternate-day than daily administration. No differences were observed between treatments on any measure for the eight subjects completing a second crossover. These data suggest that buprenorphine can be administered safely every 48 hours by doubling the maintenance dose. This alternate-day schedule permits patients to attend the clinic less frequently without the risk of diversion associated with take-home doses, may be cost-effective for programs, and may be useful in settings in which travel to the clinic is a barrier to treatment.

Topics: Administration, Sublingual; Adult; Buprenorphine; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Opioid-Related Disorders; Patient Compliance; Substance Withdrawal Syndrome

Topics: Buprenorphine; Drug Administration Schedule; Humans; Methadone; Opioid-Related Disorders; Research Design; United States

Buprenorphine at 2 mg and 6 mg daily was compared with methadone at 35 mg and 65 mg during 24 weeks of maintenance among 125 opioid-dependent patients. As hypothesized, 6 mg of buprenorphine were superior to 2 mg of buprenorphine in reducing illicit opioid use, but higher dosage did not improve treatment retention. Self-reported illicit opioid use declined substantially in all groups, but by the third month, significantly more heroin abuse was reported at 2 mg than at 6 mg of buprenorphine or of methadone. From an initial average of $1860/month, month 3 usage dropped to $41 (methadone 65 mg), $73 (methadone 35 mg), $118 (buprenorphine 6 mg), and $351/month (buprenorphine 2 mg). Days of use also dropped from 29 days to 1.7 (methadone 65 mg), 2.8 (methadone 35 mg), 4.0 (buprenorphine 6 mg), and 6.6 days/month (buprenorphine 2 mg). This relatively low efficacy for 2 mg of buprenorphine persisted through month 6 of the trial, with 7.2 days/month and $235/month of use for buprenorphine at 2 mg versus 1.9 days/month and $65/month for the other three groups. Increased opioid abuse also was associated with significantly greater and persistent opioid withdrawal symptoms. Our secondary hypothesis, that buprenorphine would be equivalent to methadone in efficacy, was not supported. Treatment retention was significantly better on methadone (20 vs. 16 weeks), and methadone patients had significantly more opioid-free urines (51% vs. 26%). Abstinence for at least 3 weeks was also more common on methadone than buprenorphine (65% vs. 27%).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Buprenorphine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Heroin Dependence; Humans; Male; Methadone; Opioid-Related Disorders; Substance Abuse Detection; Treatment Outcome

The spontaneous physical dependence of buprenorphine was assessed in opioid addicts who switched from heroin to sublingual or intravenous buprenorphine. Twenty-two patients were randomly assigned to double-blind administration of methadone (n = 11) or placebo (n = 11) for 13 days after abrupt withdrawal of buprenorphine. Methadone was administered according to four pre-established dosing schedules depending on the previous amount of daily consumed buprenorphine. No methadone-treated patient required modification of the therapeutic regimen, whereas eight of eleven placebo-treated patients needed treatment with methadone. Buprenorphine withdrawal syndrome was of opioid type, began somewhat more slowly, and showed a peak until day 5. The occurrence, time-course and characteristics of buprenorphine withdrawal syndrome make it necessary to reconsider the abuse potential of this analgesic.

Topics: Adult; Buprenorphine; Double-Blind Method; Female; Heroin Dependence; Humans; Male; Methadone; Neurologic Examination; Opioid-Related Disorders; Substance Abuse Treatment Centers; Substance Withdrawal Syndrome

Forty drug misusers receiving treatment in Baltimore completed questionnaires, originally administered to drug misusers in London, about their reasons for seeking help and their worries about the treatment. Seeking help was related to the experiences of addiction, loss of control over life and financial and family difficulties. The main fears were of failing treatment. These responses are similar to those obtained in the London group. There was little correlation between objective assessment and subjects' views of their problems. This study illustrates the complexities of coming for treatment and it emphasises the need for social and medical help.

Topics: Adult; Bromocriptine; Buprenorphine; Cocaine; Desipramine; Fear; Female; Fluoxetine; Humans; Male; Methadone; Middle Aged; Motivation; Opioid-Related Disorders; Patient Acceptance of Health Care; Phencyclidine Abuse; Substance Abuse Treatment Centers; Substance-Related Disorders; Urban Population

Topics: Adult; Blood Pressure; Buprenorphine; Double-Blind Method; Female; Humans; Male; Methadone; Methoxyhydroxyphenylglycol; Naloxone; Naltrexone; Opioid-Related Disorders; Substance Withdrawal Syndrome

This study represents the largest clinical trial reported to date that demonstrated the efficacy of buprenorphine for opioid dependence treatment (Johnson et al. 1992). Although the study design was adequate to demonstrate differences between treatment groups, there has not been a consensus regarding the most appropriate method for analyzing various outcome measures of this and similar studies. To present a comprehensive review of these methods, other chapters in this monograph focus on various analytical techniques for assessing one of these measures--urine toxicology screens--for illicit opioids.

Topics: Adult; Buprenorphine; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Methadone; Middle Aged; Opioid-Related Disorders; Patient Compliance; Placebos; Research Design

To assess the efficacy of buprenorphine for short-term maintenance/detoxification.. A randomized, double-blind, parallel group study comparing buprenorphine, 8 mg/d, methadone, 60 mg/d, and methadone, 20 mg/d, in a 17-week maintenance phase followed by an 8-week detoxification phase.. Outpatient facilities at the Addiction Research Center, Baltimore, Md.. One hundred sixty-two volunteers seeking treatment for opioid dependence.. In addition to the medication, counseling using a relapse prevention model was offered but not required.. Retention time in treatment, urine samples negative for opioids, and failure to maintain abstinence.. Throughout the maintenance phase, retention rates were significantly greater for buprenorphine (42%) than for methadone, 20 mg/d (20%, P less than .04); the percentage of urine samples negative for opioids was significantly greater for buprenorphine (53%, P less than .001) and methadone, 60 mg/d (44%, P less than .04), than for methadone, 20 mg/d (29%). Failure to maintain abstinence during the maintenance phase was significantly greater for methadone, 20 mg/d, than for buprenorphine (P less than .03). During the detoxification phase, no differences were observed between groups with respect to urine samples negative for opioids. For the entire 25 weeks, retention rates for buprenorphine (30%, P less than .01) and methadone, 60 mg/d (20%, P less than .05), were significantly greater than for methadone, 20 mg/d (6%). All treatments were well tolerated, with similar profiles of self-reported adverse effects. The percentages of patients who received counseling did not differ between groups.. Buprenorphine was as effective as methadone, 60 mg/d, and both were superior to methadone, 20 mg/d, in reducing illicit opioid use and maintaining patients in treatment for 25 weeks.

Topics: Adult; Buprenorphine; Double-Blind Method; Female; Heroin; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Narcotics; Opioid-Related Disorders; Proportional Hazards Models

Topics: Buprenorphine; Clinical Trials as Topic; Double-Blind Method; Humans; Naloxone; Naltrexone; Opioid-Related Disorders; Placebos; Substance Withdrawal Syndrome

Subjective, physiological and behavioral effects of subcutaneously administered hydromorphone (6 mg), naloxone (0.2 mg), buprenorphine (0.2 and 0.3 mg), and two buprenorphine-naloxone combinations (buprenorphine 0.2 mg plus naloxone 0.2 mg and buprenorphine 0.3 mg plus naloxone 0.2 mg) were assessed under double-blind conditions in six opioid-dependent volunteers. Physiologic measures and subject- and observer-rated behavioral responses were measured before dosing and for 120 min after drug administration. Hydromorphone decreased pupil diameter and respiration, increased blood pressure and increased scores on subjective measures indicating opioid-like effects. Buprenorphine given alone had no significant effect on any variable measured. Naloxone given alone produced opioid abstinence-like effects which were measurable on subject- and observer-rated behavioral measures and physiological measures. Buprenorphine in combination with naloxone somewhat attenuated the naloxone-precipitated withdrawal response. Overall, the naloxone-buprenorphine combinations produced effects which were qualitatively similar to the effects of naloxone alone, suggesting a low potential for abuse of the combination product by opioid-dependent individuals.

Topics: Adult; Blood Pressure; Body Temperature; Buprenorphine; Cognition; Heart Rate; Humans; Hydromorphone; Male; Naloxone; Opioid-Related Disorders; Psychomotor Performance; Respiration; Substance Withdrawal Syndrome

On June 1, 2021, Vermont repealed all criminal penalties for possessing 224 milligrams or less of buprenorphine. We examined the potential impact of decriminalization with a survey of Vermont clinicians who prescribed buprenorphine within the past year.. All 638 Vermont clinicians with a waiver to prescribe buprenorphine were emailed the survey by Vermont Department of Health; 117 responded. We estimated the prevalence of the following four outcomes, for all responding clinicians and stratified by clinician demographics and practice characteristics: awareness of decriminalization, beliefs about the effects of decriminalization, support for decriminalization, and changes in practice resulting from decriminalization.. 72 (62%) prescribers correctly stated that Vermont does not have criminal penalties for buprenorphine possession. 107 (91%) support decriminalization. 56 (48%) believe that, because buprenorphine is decriminalized, their patients are more likely to give, sell, or trade the buprenorphine that is prescribed to them to someone else. However, only 5 providers (4%) said they now prescribe to fewer patients.. The great majority of Vermont clinicians who prescribe buprenorphine support its decriminalization and have not changed their prescribing practices because of decriminalization.. In 2021, Vermont repealed criminal penalties for buprenorphine possession.We surveyed Vermont (n = 117) buprenorphine prescribers about decriminalization.91% of providers support decriminalization.48% of providers believe decriminalization will increase diversion of medications.Only 4% of providers prescribe to fewer patients because of decriminalization.

Topics: Buprenorphine; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Practice Patterns, Physicians'; Surveys and Questionnaires; Vermont

Medication for opioid use disorder (MOUD) is an effective, evidence-based treatment, but significant gaps in implementation remain. We evaluate one novel approach to address this gap: a Hub and Spoke model to increase buprenorphine access and management.. This outcome evaluation was guided by the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework using secondary data analysis of clinical and administrative data to characterize program outcomes for program Reach, Effectiveness, Adoption, and Maintenance. Implementation was assessed through a chart review of provider progress notes and through key informant interviews with program staff to understand why this site was able to introduce a novel approach to MOUD.. Nearly half of patients with opioid use disorder (45.48%, n=156) were reached by the program over 2 years. Of those, 91.67% had 1 or more program visits after an initial intake appointment, and 78.85% had a buprenorphine prescription. Patients in the program were 2.44 times more likely to have a buprenorphine prescription than those in comparator site that did not have a Hub and Spoke program (95% CI: 1.77-3.37; P <0.001). There was significantly greater program reach in year 1 than year 2, suggesting rapid initial uptake followed by modest program growth. Key informant interviews illustrated several themes regrading program implementation, including the importance of process champions, the beneficial impact of MOUD for patients, and addressing facility performance metrics. A supportive organizational culture and a receptive climate were also key factors for implementation.. This program led to rapid improvement in MOUD uptake across the facility. Future efforts should focus on improving program maintenance, including supporting the exchange of patients from the hub to appropriate spokes.

Topics: Benchmarking; Buprenorphine; Humans; Opioid-Related Disorders; Organizational Culture; Pilot Projects

Severe skin and soft tissue infections related to injection drug use have increased in concordance with a shift to heroin and illicitly manufactured fentanyl. Opioid agonist therapy medications (methadone and buprenorphine) may improve long-term outcomes by reducing injection drug use. We aimed to examine the association of medication use with mortality among people with opioid use-related skin or soft tissue infections.. An observational cohort study of Medicaid enrollees aged 18 years or older following their first documented medical encounters for opioid use-related skin or soft tissue infections during 2007-2018 in North Carolina. The exposure was documented medication use (methadone or buprenorphine claim) in the first 30 days following initial infection compared with no medication claim. Using Kaplan-Meier estimators, we examined the difference in 3-year incidence of mortality by medication use, weighted for year, age, comorbidities, and length of hospital stay.. In this sample, there were 13,286 people with opioid use-related skin or soft tissue infections. The median age was 37 years, 68% were women, and 78% were white. In Kaplan-Meier curves for the total study population, 12 of every 100 patients died during the first 3 years. In weighted models, for every 100 people who used medications, there were four fewer deaths over 3 years (95% confidence interval = 2, 6).. In this study, people with opioid use-related skin and soft tissue infections had a high risk of mortality following their initial healthcare visit for infections. Methadone or buprenorphine use was associated with reductions in mortality.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Female; Hospitalization; Humans; Male; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Soft Tissue Infections

France has one of the highest opioid agonist treatment (OAT) coverage rates in the world. French general practitioners (GPs) are providing the majority of prescriptions. However, a fall in the number of GPs initiating buprenorphine has been observed over the last decade.. The objective of this study was to explore the obstacles and facilitators to the involvement of GPs in the prescription of buprenorphine. A qualitative study comprising 14 individual interviews and a focus group bringing together 5 GPs was conducted among GPs based in France between June 2021 and March 2022. We performed data analysis using a grounded theory methodology.. The interviews showed a great diversity in the level of involvement of GPs, depending on their experience, their representations of patients with OUD, their mode of exercise, and their personal preferences. The negative representations of the patients associated with the feeling of physical and ethical endangerment, the feeling of powerlessness, the fear of a disruption of the practice and the feeling of incompetence appeared at the forefront of the difficulties stated. Conversely, the strengthening of initial training and the facilitation of access to self-training tools and multidisciplinarity, the consideration of opioid use disorder (OUD) as a chronic illness with the application of a patient-centered motivational approach, as well as the defining and respecting one's own limits when prescribing buprenorphine seem to be the keys to a balanced and fulfilling practice.. Raising awareness of the frequency of OUD appeared to be an additional lever to enhance the interest of the GPs concerned. Additional studies focusing on the evolution of professional practices would be necessary to extend these findings.

Topics: Buprenorphine; General Practitioners; Humans; Opioid-Related Disorders; Prescriptions; Professional Practice

Monthly injectable extended-release buprenorphine (XR-BUP) can address several systemic and individual barriers to consistent sublingual buprenorphine treatment for patients with opioid use disorder (OUD). Real-world evaluations of XR-BUP in the outpatient addiction treatment setting are limited. The purpose of this study was to compare 6-month treatment retention and urine drug tests between patients who initiated XR-BUP compared to those who were prescribed but did not initiate XR-BUP in a low-barrier addiction medicine specialty clinic.. We conducted a retrospective cohort study of adults with OUD prescribed XR-BUP between 12/1/2018 and 12/31/2020 in a low-barrier addiction medicine specialty clinic to compare 6-month treatment retention between patients who initiated XR-BUP and those who were prescribed but did not initiate XR-BUP (comparison group). Secondary outcomes included percent of urine toxicology tests negative for non-prescribed opioids. Multivariable logistic regression models evaluated factors associated with 6-month treatment retention and XR-BUP initiation.. Of the 233 patients prescribed XR-BUP, 148 (63.8 %) identified as non-Hispanic white, 218 (93.6 %) were insured by public insurance (Medicare/Medicaid), and nearly two-thirds were prescribed XR-BUP due to unstable OUD. Approximately 50 % of patients initiated XR-BUP treatment (mean number of injections = 3.7). About 60 % of XR-BUP-treated patients received supplemental sublingual buprenorphine and nearly two-thirds received a 300 mg maintenance dose. Six-month treatment retention was greater in the XR-BUP treatment versus comparison group (70.3 % vs. 36.5 %, p < 0.001). The XR-BUP treatment group had a higher percentage of opioid-negative urine toxicology tests versus the comparison group (67.2 % vs. 36.3 %, p < 0.001). Receipt of XR-BUP was an independent predictor of 6-month treatment retention (OR 5.40, 95 % CI 2.18-13.38). Those prescribed XR-BUP due to unstable OUD had lower odds of treatment retention (OR 0.41, 95 % CI 0.24-0.98) after controlling for receipt of XR-BUP and other variables known to impact retention.. XR-BUP improved 6-month treatment retention and resulted in a greater proportion of opioid-negative urine toxicology tests compared to a comparison group of patients who were prescribed but did not initiate XR-BUP. Patients with unstable OUD had lower odds of XR-BUP initiation, suggesting the need for targeted interventions to increase XR-BUP uptake in this high-risk population.

Topics: Addiction Medicine; Adult; Aged; Analgesics, Opioid; Buprenorphine; Humans; Medicare; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Retrospective Studies; United States

The burden of drug overdose mortality varies by race and ethnicity, with American Indian/Alaska Native (AI/AN), Black, and White people experiencing the largest burden. We analyzed census block group data to evaluate differences in travel distance to opioid treatment programs (OTP) and buprenorphine providers by race and ethnicity.. The Substance Abuse and Mental Health Services Administration provided the addresses of OTPs and buprenorphine providers. The study classified block groups as majority (≥50 %) AI/AN, Black, Asian, White, no single racial majority, or Hispanic. We classified deprivation and rurality using the Area Deprivation Index and Rural-Urban Commuting Area codes. The study applied generalized linear mixed models.. Among all block groups, the median road distance to the nearest OTPs and buprenorphine providers was 8 and 2 miles, respectively. AI/AN-majority block groups had the longest median distances to OTPs (88 miles versus 4-10 miles) and buprenorphine providers (17 miles versus 1-3 miles) compared to other racial or ethnic majority block groups. For OTPs and buprenorphine providers, travel distances were slightly greater in more deprived block groups compared to less deprived block groups. The median distance to the nearest OTPs and buprenorphine providers were larger in micropolitan and small town/rural block groups compared to metropolitan areas.. Disparities exist in travel distance to OTPs and buprenorphine providers. People in block groups with AI/AN-majority, nonmetropolitan, or more deprived designation experience travel disparities accessing treatment. Future research should develop targeted interventions to reduce access to care disparities for individuals with opioid use disorder.

Topics: Analgesics, Opioid; Buprenorphine; Ethnicity; Humans; Opiate Substitution Treatment; Opioid-Related Disorders

Medications for opioid use disorder (MOUD) are the most effective treatment for opioid use disorder (OUD) but remain underutilized. To reduce barriers to MOUD prescribing and increase treatment access, New Jersey's Medicaid program implemented the Office-Based Addiction Treatment (OBAT) Program in 2019, which increased reimbursement for office-based buprenorphine prescribing and established newly reimbursable patient navigation services in OBAT clinics. Using a mixed-methods design, this study aimed to describe stakeholder experiences with the OBAT program and to assess implementation and uptake of the program.. This study used a concurrent, triangulated mixed-methods design, which integrated complementary qualitative (semi-structured interviews) and quantitative (Medicaid claims) data to gain an in-depth understanding of the implementation of the OBAT program. We elicited stakeholder perspectives through interviews with 22 NJ Medicaid MOUD providers and 8 policy key informants, and examined trends in OBAT program utilization using 2019-2020 NJ Medicaid claims for 5380 Medicaid enrollees who used OBAT services. We used cross-case analysis (provider interviews) and a case study approach (key informant interviews) in analyzing qualitative data, and calculated descriptive statistics and trends for quantitative data.. Provider enrollment and utilization of OBAT services increased steadily during the first two years of program implementation. Interviewees reported that enhanced reimbursements for office-based MOUD incentivized greater MOUD prescribing, while coverage of patient navigation services improved patient care. Despite increasing enrollment in the OBAT program, the proportion of primary care physicians in the state who enrolled in the program remained limited. Key barriers to enrollment included: requirements for a patient navigator; concerns about administrative burdens and reimbursement delays from Medicaid; lack of awareness of the program; and beliefs that patients with OUD were better served in comprehensive care settings. Patient navigation was highlighted as a critical and valuable element of the program, but navigator enrollment and reimbursement challenges may have prevented greater uptake of this service.. Implementation of an OBAT model that enhanced reimbursement and provided coverage for patient navigation likely expanded access to MOUD in NJ. Results support initiatives like the OBAT program in improving access to MOUD, but program adaptations, where feasible, could improve uptake and utilization.

Topics: Behavior, Addictive; Biological Transport; Buprenorphine; Humans; Medicaid; Opioid-Related Disorders; United States

In clinical practice, sublingual (SL) buprenorphine-naloxone is prescribed as once daily or split daily dosing for the management of opioid use disorder (OUD). Evidence is lacking that assesses how split daily buprenorphine-naloxone affects OUD outcomes. This study aims to evaluate how the dosing frequency of SL buprenorphine-naloxone impacts therapy effectiveness when treating patients with OUD.. This retrospective analysis included adult outpatients prescribed treatment with SL buprenorphine-naloxone for OUD between July 1, 2016, and March 1, 2020. The study excluded patients with sickle cell disease, recent methadone treatment, or pregnancy. We characterized study groups by dosing frequency, either once daily or split dosing. The study compared retention in treatment, medication adherence, adherence to treatment program, and hospital encounters between groups.. The study screened eight-hundred and seven patients, and included 250 patients newly prescribed SL buprenorphine-naloxone. Fifty-seven patients (22.8 %) were prescribed once daily dosing and 193 patients (77.2 %) were prescribed split daily dosing. The study found no significant differences noted in 12-month rates of treatment retention (52.6 % vs. 45.6 %, p = .35). These outcomes remained similar when assessed at three and six months. Within a year of buprenorphine-naloxone initiation, the study found no differences in the percentage of patients with hospitalizations (26.3 % vs. 38.3 %, p = .10), median number of hospitalizations (2 vs. 2), or proportion of days covered by a prescription ≥80 % (93.3 % vs. 92.0 %, p = .82).. In this study, patients receiving once daily buprenorphine-naloxone had similar treatment outcomes to patients receiving split dosing. Further controlled studies are necessary to evaluate which patients are more likely to benefit from split dosing.

Topics: Adult; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Humans; Narcotic Antagonists; Opioid-Related Disorders; Retrospective Studies; Treatment Outcome

This study aimed to identify the strongest barriers and motivators associated with each step toward buprenorphine prescribing (1. obtaining a waiver, 2. beginning to prescribe, and 3. prescribing to more people) among a sample of Missouri-based medical professionals (N = 130). Item weights (number of endorsements times mean rank of the item's importance) were calculated based on their responses. Across groups, lack of access to psychosocial support services, need for higher levels of care, and clinical complexity were strong barriers. Among non-prescribers (n = 57, 46.3%), administrative burden, potential of becoming an addiction clinic, and concern about misuse and diversion were most heavily weighted. Among prescribers (n = 66, 53.7%), patients' inability to afford medications was a barrier across phases. Prominent motivators among all groups were the effectiveness of buprenorphine, improvement in other health outcomes, and a personal interest in treating addiction. Only prescribers reported the presence of institutional support and mentors as significant motivators.

Topics: Ambulatory Care Facilities; Behavior, Addictive; Buprenorphine; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Practice Patterns, Physicians'

Stigma is described as highly relevant to the treatment context for opioid use disorder (OUD) partly because it is known to influence providers' treatment decisions and care provision. However, further study is needed to directly test the salience of stigmatizing views for healthcare decision-making among providers, and particularly those including medication for opioid use disorder (MOUD). This study assessed whether stigma toward illicit opioid use was associated with a willingness to provide or refer patients for MOUD treatment among a sample of healthcare providers. It also evaluated variation in stigmatizing views as a function of familiarity with OUD and MOUD and provider type.. Structural equation modeling was utilized to evaluate the antecedents and healthcare decision-making consequences associated with stigma based on survey data from a sample of 144 clinicians participating in a buprenorphine waiver training program (30% female).. Providers who have less familiarity with OUD and MOUD and those who are medical students or residents are significantly more likely to endorse stigmatizing views of illicit opioid use. In turn, greater stigma is significantly associated with a lesser willingness to provide treatment or refer patients to MOUD treatment.. Further consideration of stigma is recommended in future research to improve clinical practice and increase the implementation of MOUD treatment. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Topics: Analgesics, Opioid; Buprenorphine; Delivery of Health Care; Female; Health Personnel; Humans; Male; Opiate Substitution Treatment; Opioid-Related Disorders

Prehospital initiation of buprenorphine treatment for Opioid Use Disorder (OUD) by paramedics is an emerging potential intervention to reach patients at greatest risk for opioid-related death. Emergency medical services (EMS) patients who are at high risk for overdose deaths may never engage in treatment as they frequently refuse transport to the hospital after naloxone reversal. The potentially important role of EMS as the initiator for medication for opioid use disorder (MOUD) in the most high-risk patients has not been well described.. This project relies on four interventions: a public access naloxone distribution program, an electronic trigger and data sharing program, an "Overdose Receiving Center," and a paramedic-initiated buprenorphine treatment. For the final intervention, paramedics followed a protocol-based pilot that had an EMS physician consultation prior to administration.. There were 36 patients enrolled in the trial study in the first year who received buprenorphine. Of those patients receiving buprenorphine, only one patient signed out against medical advice on scene. All other patients were transported to an emergency department and their clinical outcome and 7 and 30 day follow ups were determined by the substance use navigator (SUN). Thirty-six of 36 patients had follow up data obtained in the short term and none experienced any precipitated withdrawal or other adverse outcomes. Patients had a 50% (18/36) rate of treatment retention at 7 days and 36% (14/36) were in treatment at 30 days.. In this small pilot project, paramedic-initiated buprenorphine in the setting of data sharing and linkage with treatment appears to be a safe intervention with a high rate of ongoing outpatient treatment for risk of fatal opioid overdoses.

Topics: Analgesics, Opioid; Buprenorphine; Drug Overdose; Emergency Medical Services; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Paramedics; Pilot Projects

With surging opioid-involved overdoses, maintaining access to opioid use disorder (OUD) treatment is critical during the COVID-19 pandemic. We examined changes in transmucosal buprenorphine prescribing for OUD treatment in Kentucky after the national COVID-19 emergency declaration, with a focus on rural-urban differences.. Using 2019-2020 prescription monitoring data, we performed segmented regression analysis for an interrupted time series design to evaluate changes in weekly rates (per 100,000 residents) of dispensed prescriptions, unique individuals with dispensed prescriptions, and average days' supply for dispensed prescriptions of transmucosal buprenorphine.. The weekly rates of dispensed prescriptions and unique individuals with dispensed prescriptions were higher for rural residents than urban residents. After the national COVID-19 emergency declaration, rural and urban residents experienced similar immediate drops in the rate of dispensed prescriptions (rural -33.4; urban -24.3) and unique patients with dispensed prescriptions (rural -25.0; urban -17.1), followed by similar sustained increases. Both measures surpassed the prepandemic levels in mid-June 2020. Patients residing in urban areas received averagely longer prescriptions at baseline (urban: 11.0 days; rural: 10.5 days). The average weekly days' supply increased in the week after the national emergency declaration, but the estimated increase was higher (P = .004) for urban (0.8 days) versus rural (0.5 days) residents.. Transmucosal buprenorphine utilization increased during the COVID-19 pandemic after experiencing interruption during the initial weeks of the pandemic. Future studies should evaluate the contribution of the relaxed telemedicine buprenorphine prescribing regulations during the COVID-19 national emergency on initiation and maintenance of buprenorphine treatment.

Topics: Analgesics, Opioid; Buprenorphine; COVID-19; Humans; Kentucky; Opioid-Related Disorders; Pandemics

Buprenorphine is an effective medication for opioid use disorder that reduces mortality; however, many patients are not retained in buprenorphine treatment, and an optimal length of treatment after which patients can safely discontinue treatment has not been identified. This study measured the association between buprenorphine treatment duration and all-cause mortality among patients who discontinued treatment. Secondary objectives were to measure the association between treatment duration and drug overdose and opioid-related overdoses.. Multi-site cohort study.. Eight US health systems.. Patients who initiated and discontinued buprenorphine treatment between 1 January 2012 and 31 December 2018 (n = 6550). Outcomes occurring after patients discontinued buprenorphine treatment were compared between patients who initiated and discontinued treatment after 8-30, 31-90, 91-180, 181-365 and > 365 days.. Covariate data were obtained from electronic health records (EHRs). Mortality outcomes were derived from EHRs and state vital statistics. Non-fatal opioid and drug overdoses were obtained from diagnostic codes. Four sites provided cause-of-death data to identify fatal drug and opioid-related overdoses. Adjusted frailty regression was conducted on a propensity-weighted cohort to assess associations between duration of the final treatment episode and outcomes.. The mortality rate after buprenorphine treatment was 1.82 per 100 person-years (n = 191 deaths). In regression analyses with > 365 days as the reference group, treatment duration was not associated with all-cause mortality and drug overdose (P > 0.05 for both). However, compared with > 365 days of treatment, 91-180 days of treatment was associated with increased opioid overdose risk (hazard ratio = 2.94, 95% confidence interval = 1.11-7.79).. Among patients who discontinue buprenorphine treatment, there appears to be no treatment duration period associated with a reduced risk for all-cause mortality. Patients who discontinue buprenorphine treatment after 91-180 days appear to be at heightened risk for opioid overdose compared with patients who discontinue after > 365 days of treatment.

Topics: Analgesics, Opioid; Buprenorphine; Cohort Studies; Drug Overdose; Humans; Opiate Overdose; Opiate Substitution Treatment; Opioid-Related Disorders; Retrospective Studies

Mortality from opioid use disorder (OUD) can be reduced for patients who receive opioid agonist treatment (OAT). In the United States (US), OATs have different requirements including nearly daily visits to a dispensing facility for methadone but weekly to monthly prescriptions for buprenorphine. Our objective was to compare mortality rates for buprenorphine and methadone treatments among a large sample of US patients with OUD.. We measured all-cause mortality, overdose mortality, and suicide mortality among US Department of Veterans Affairs patients with a diagnosis of OUD who received OAT from 2010 through 2019. We leveraged substantial and sustained regional variation in prescribing buprenorphine versus methadone as an instrumental variable (IV) and used inverse propensity of treatment weighting to balance relevant covariates across treatment groups. We compared mortality with true two-stage IV using both probit and linear probability models, as well as a reduced form IV model, adjusting for demographics and health status.. Our cohort consisted of 61,997 patients with OUD who received OAT, of whom 92.7% were male with a mean age of 47.9 (SD = 14.1) years. Patients were followed for a median of 2 (IQR = 1,4) calendar years. Across regional terciles, mean methadone prescribing was 4.8%, 19.5%, and 75.1% of OAT patients. All models identified significant reductions in all-cause and suicide mortality for buprenorphine relative to methadone. For example, predicted all-cause mortality from the probit model was 169.7 per 10,000 person years (95% CI, 157.8, 179.6) in the lowest tercile of methadone prescribing compared with 206.1 (95% CI, 196.0, 216.3) in the highest tercile. No difference was identified for overdose mortality.. We found significantly lower all-cause mortality and suicide mortality rates for buprenorphine compared with methadone. Our results support the less restrictive prescribing practices for buprenorphine as OAT in the US.

Topics: Buprenorphine; Drug Overdose; Female; Humans; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; United States

Buprenorphine utilization remains low in the United States. Telemedicine guidelines and flexibilities introduced during the COVID-19 pandemic provide an opportunity to increase patient access to buprenorphine. However, it is not known whether Americans without access to buprenorphine waivered provider, especially those residing in rural counties, have sufficient broadband internet access to support telemedicine.. Administrative data from the Substance Abuse and Mental Health Services Administration's Buprenorphine Treatment Practitioner Locator Tool and the Fixed Broadband Deployment Data from the Federal Communications Commission are utilized to identify counties with low broadband penetration rate and the number of buprenorphine waivered providers with capacity to accept patients within a 30 miles radius.. 23.9% of the US population does not have access to any buprenorphine waivered provider with a capacity to accept new patients within a 30 miles radius. In counties with low broadband penetration rate, 78.9% of residents does not have access to any buprenorphine waivered provider with patient capacity. In rural counties with low broadband penetration rate, 82.3% of the residents does not have access to any buprenorphine waivered provider with patient capacity within a 30 miles radius.. Federal policy initiatives are expected to continue the COVID-19-related telehealth flexibilities and to increase the number of providers available to prescribe buprenorphine, but for that to translate into more patients utilizing treatment via telemedicine, high-speed internet access will be essential. This is particularly salient for residents in rural counties where access to both buprenorphine providers and high-speed internet access is limited.

Topics: Buprenorphine; COVID-19; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Pandemics; Physicians; Telemedicine; United States

Most people with co-occurring opioid use disorder (OUD) and mental illness do not receive effective medications for treating OUD. To investigate perspectives of adults in a publicly-funded mental health system regarding medications for OUD (MOUD), we conducted semi-structured telephone interviews with 13 adults with OUD (current or previous diagnosis) receiving mental health treatment. Themes that emerged included: perceiving or using MOUDs as a substitute for opioids or a temporary solution to prevent withdrawal symptoms; negative perceptions about methadone/methadone clinics; and viewing MOUD use as "cheating". Readiness to quit was important for patients to consider MOUDs. All participants were receptive to discussing MOUDs with their mental health providers and welcomed the convenience of receiving care for their mental health and OUD at the same location. In conclusion, clients at publicly-funded mental health clinics support MOUD treatment, signaling a need to expand access and build awareness of MOUDs in these settings.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders

In this study, adequate forms of treatment and choice of medication in the opioid substitution treatment of opioid-dependent prisoners are discussed from a health-economic perspective with a special focus on depot applications.. Aus einer gesundheitsökonomischen Perspektive werden Überlegungen zu adäquaten Formen der Organisation und Medikamentenwahl in der Opioidsubstitutionsbehandlung opioidabhängiger Gefangenen – v. a. im Hinblick auf Depot-Anwendungen bei der Behandlung – angestellt.

Topics: Analgesics, Opioid; Buprenorphine; Germany; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Prisons

Topics: Buprenorphine; Duration of Therapy; Humans; Opiate Overdose; Opiate Substitution Treatment; Opioid-Related Disorders

Pain management in palliative care (PC) is becoming more complex as patients survive longer with life-limiting illnesses and population-wide trends involving opioid misuse become more common in serious illness. Buprenorphine, a generally safe partial mu-opioid receptor agonist, has been shown to be effective for both pain management and opioid use disorder. It is critical that PC clinicians become comfortable with indications for its use, strategies for initiation while understanding risks and benefits. This article, written by a team of PC and addiction-trained specialists, including physicians, nurse practitioners, social workers, and a pharmacist, offers 10 tips to demystify buprenorphine use in serious illness.

Topics: Analgesics, Opioid; Buprenorphine; Hospice and Palliative Care Nursing; Humans; Opioid-Related Disorders; Palliative Care

Buprenorphine is a frequently used medication for opioid use disorder and misunderstanding buprenorphine's unique pharmacology has historically complicated perioperative analgesia. The purpose of this study was to evaluate the association of perioperative buprenorphine continuation in patients with substance use disorder on perioperative opioid use.. This was a single-center retrospective study at a level 1 trauma academic medical center. Adult patients using outpatient buprenorphine for medication for opioid use disorder admitted with an operating room booking were included. Patients were grouped (continuation, withheld) retrospectively based upon the decision to continue or omit buprenorphine therapy while admitted. The primary outcome of the study was any use of full mu-opioid agonists during days 1-7 of admission. Secondary outcomes included length of stay and average pain scores during days 1-7 of admission.. 43.4% of patients in the continuation cohort used no full mu-opioid agonists during days 1-7 compared to 3.1% of patients in the withheld cohort (P < 0.001). No significant difference in median length of stay was noted (4.7 d [2.8-6.6] versus 6.1 d [4.0-8.2], P = 0.36). There was no statistical difference in average pain scores on postoperative days 1 (5.2 versus 6.9, P = 0.82) and 7 (0 versus 0, P = 0.41).. Perioperative continuation of buprenorphine is associated with reduced use of alternative full mu-opioid agents while admitted without impacting pain scores.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Humans; Opioid-Related Disorders; Pain; Retrospective Studies

Extended-release (ER) monthly injectable buprenorphine offers an alternative to daily sublingual (SL) dosing for treatment of opioid use disorder (OUD) that may be attractive to several patient populations, including those with barriers to adherence and the frequent follow-up that are necessary for traditional SL buprenorphine. Despite the potential benefits of ER-buprenorphine, there are significant barriers to healthcare provider adoption that may prevent utilization in the populations that would benefit.. Our health system began providing clinic-administered ER-buprenorphine as treatment for OUD in May 2018 at a single clinic. Expansion was limited due to difficulties with delayed and inaccurate medication delivery and heavy administrative burden. To facilitate uptake of ER-buprenorphine for patients who could benefit, our integrated health-system specialty pharmacy (HSSP) assumed responsibility for medication distribution and administrative management beginning in October 2019. The HSSP provided accurate medication delivery, alleviated administrative burdens of benefits investigation and Risk Evaluation and Mitigation Strategy compliance, and decreased medication wastage by implementing a medication return process. Subsequently, ER-buprenorphine services were expanded to 4 additional sites, allowing 244 more patients to receive treatment.. HSSP support can provide significant benefit to patients and the health system through coordinating ER-buprenorphine dispensing and delivery.

Topics: Analgesics, Opioid; Buprenorphine; Delivery of Health Care, Integrated; Humans; Opioid-Related Disorders; Patients; Pharmacy

To evaluate the efficacy and safety of utilizing emergency medical services units to administer high dose buprenorphine after an overdose to treat withdrawal symptoms, reduce repeat overdose, and provide a next-day substances use disorder clinic appointment to initiate long-term treatment.. This was a retrospective matched cohort study of patients who experienced an overdose and either received emergency medical services care from a buprenorphine-equipped ambulance or a nonbuprenorphine-equipped ambulance in Camden, New Jersey, an urban community with high overdose rates. There were 117 cases and 123 control patients in the final sample.. Compared with a nonbuprenorphine-equipped ambulance, exposure to a buprenorphine-equipped ambulance was associated with greater odds of engaging in opioid use disorder treatment within 30 days of an emergency medical services encounter (unadjusted odds ratio: 5.62, 95% confidence interval, 2.36 to 13.39). Buprenorphine-equipped ambulance engagement did not decrease repeat overdose compared to the comparison group. Patients who received buprenorphine experienced a decrease in withdrawal symptoms. Their clinical opiate withdrawal scale score decreased from an average of 9.27 to 3.16. buprenorphine-equipped ambulances increased on-scene time by 6.12 minutes.. Patients who encountered paramedics trained to administer buprenorphine and able to arrange prompt substance use disorder treatment after an acute opioid overdose demonstrated a decrease in opioid withdrawal symptoms, an increase in outpatient addiction follow-up care, and showed no difference in repeat overdose. Patients receiving buprenorphine in the out-of-hospital setting did not experience precipitated withdrawal. Expanded out-of-hospital treatment of opiate use disorder is a promising model for rapid access to buprenorphine after an overdose in a patient population that often has limited contact with the health care system.

Topics: Analgesics, Opioid; Buprenorphine; Cohort Studies; Drug Overdose; Emergency Medical Services; Humans; Narcotic Antagonists; Opioid-Related Disorders; Retrospective Studies; Substance Withdrawal Syndrome

Topics: Analgesics, Opioid; Buprenorphine; Humans; Ill-Housed Persons; Opiate Substitution Treatment; Opioid-Related Disorders; Social Problems

Despite their well-established effectiveness, medications for opioid use disorder (MOUD) are widely underutilized across the United States. In the context of a large publicly funded behavioral health system, we examined the relationship between a range of implementation barriers and a substance use disorder treatment agency's level of adoption of MOUD.. We surveyed leadership of publicly funded substance use disorder treatment centers in Philadelphia about the significance of barriers to implementing MOUD related to their workforce, organization, funding, regulations, and beliefs about MOUD's efficacy and safety. We queried leaders on the percentage of their patients with opioid use disorder who receive MOUD and examined associations between implementation barriers and MOUD adoption.. Ratings of regulatory, organizational, or funding barriers of respondents who led high MOUD adopting agencies (N = 20) were indistinguishable from those who led agencies that were low adopting of MOUD (N = 23). In contrast, agency leaders who denied MOUD-belief or workforce barriers were significantly more likely to lead high-MOUD-adopting organizations.. These findings suggest that leadership beliefs about MOUD may be a key factor of the organizational decision to adopt and should be a target of implementation efforts to increase direct provision of these medications.

Topics: Analgesics, Opioid; Buprenorphine; Government Programs; Humans; Leadership; Opiate Substitution Treatment; Opioid-Related Disorders; Perception; United States

Topics: Analgesics, Opioid; Buprenorphine; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Retention in Care

Opioid overdose is a leading cause of death during the immediate time after release from jail or prison. Most jails in the United States do not provide methadone and buprenorphine treatment for opioid use disorder (MOUD), and research in estimating its impact in jail settings is limited. We aimed to test the hypothesis that in-jail MOUD is associated with lower overdose mortality risk post-release.. Retrospective, observational cohort study of 15 797 adults with opioid use disorder who were released from New York City jails to the community in 2011-2017. They experienced 31 382 incarcerations and were followed up to 1 year.. The primary outcomes were death caused by accidental drug poisoning and all-cause death. The exposure was receipt of MOUD (17 119 events) versus out-of-treatment (14 263 events) during the last 3 days before community re-entry. Covariates included demographic, clinical, behavioral, housing, health-care utilization and legal characteristics variables. We performed a multivariable, mixed-effect Cox regression analysis to test association between in-jail MOUD and deaths.. The majority were male (82%) and their average age was 42 years. Receiving MOUD was associated with misdemeanor charges, being female, injection drug use and homelessness. During 1 year post-release, 111 overdose deaths occurred and crude death rates were 0.49 and 0.83 per 100 person-years for in-jail MOUD and out-of-treatment groups, respectively. Accounting for confounding and random effects, in-jail MOUD was associated with lower overdose mortality risk [adjusted hazard ratio (aHR) = 0.20, 95% confidence interval (CI) = 0.08-0.46] and all-cause mortality risk (aHR = 0.22, 95% CI = 0.11-0.42) for the first month post-release.. Methadone and buprenorphine treatment for opioid use disorder during incarceration was associated with an 80% reduction in overdose mortality risk for the first month post-release.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Drug Overdose; Female; Humans; Jails; Male; Methadone; New York City; Opiate Substitution Treatment; Opioid-Related Disorders; Retrospective Studies; United States

The opioid crisis is transitioning to a polydrug crisis, and individuals with co-occurring substance use disorder (SUDs) often have unique clinical characteristics and contextual barriers that influence treatment needs, engagement in treatment, complexity of treatment planning, and treatment retention.. Using Medicaid data for 2017-2018 from four states participating in a distributed research network, this retrospective cohort study documents the prevalence of specific types of co-occurring SUD among Medicaid enrollees with an opioid use disorder (OUD) diagnosis, and assesses the extent to which different SUD presentations are associated with differential patterns of MOUD and psychosocial treatments.. We find that more than half of enrollees with OUD had a co-occurring SUD, and the most prevalent co-occurring SUD was for "other psychoactive substances", indicated among about one-quarter of enrollees with OUD in each state. We also find some substantial gaps in MOUD treatment receipt and engagement for individuals with OUD and a co-occurring SUD, a group representing more than half of individuals with OUD. In most states, enrollees with OUD and alcohol, cannabis, or amphetamine use disorder are significantly less likely to receive MOUD compared to enrollees with OUD only. In contrast, enrollees with OUD and other psychoactive SUD were significantly more likely to receive MOUD treatment. Conditional on MOUD receipt, enrollees with co-occurring SUDs had 10 % to 50 % lower odds of having a 180-day period of continuous MOUD treatment, an important predictor of better patient outcomes. Associations with concurrent receipt of MOUD and behavioral counseling were mixed across states and varied depending on co-occurring SUD type.. Overall, ongoing progress toward increasing access to and quality of evidence-based treatment for OUD requires further efforts to ensure that individuals with co-occurring SUDs are engaged and retained in effective treatment. As the opioid crisis evolves, continued changes in drug use patterns and populations experiencing harms may necessitate new policy approaches that more fully address the complex needs of a growing population of individuals with OUD and other types of SUD.

Topics: Analgesics, Opioid; Buprenorphine; Humans; Medicaid; Opiate Substitution Treatment; Opioid-Related Disorders; Prevalence; Retrospective Studies; United States

Recent studies have shown that early in the COVID-19 pandemic, rates of buprenorphine prescription dispensing for opioid use disorder (OUD) were relatively stable. However, whether that pattern continued later in the pandemic is unclear. This study examines the monthly rate of dispensed buprenorphine prescriptions during the early period and the later period of the pandemic.. The study uses interrupted time series analysis to examine buprenorphine prescription dispensed, average day's supply, payment source, and the number of patients with a dispensed buprenorphine prescription. The study utilized January 2019-April 2021 data from IQVIA National Prescription Audit, PayerTrack and Total Patient Tracker databases.. After an initial increase in the number of patients prescribed buprenorphine in the early period of the pandemic, the monthly rate of patients prescribed buprenorphine increased at a lower rate compared to the pre-pandemic period (6100 vs 4600/month). The study observed a decline in the number of buprenorphine prescriptions dispensed both in levels and growth rate during the pandemic, but an increase occurred in the average day's supply of buprenorphine prescriptions (17 days pre-pandemic vs 18.6 day during the pandemic). Medicaid became the primary payer of buprenorphine prescriptions as the pandemic continued, while buprenorphine prescriptions paid for by private insurance declined.. Expanding and maintaining access to treatment for OUD were key priorities in federal and state responses to the COVID-19 pandemic. The results of our study underscore the importance of policy efforts to help increase buprenorphine prescribing for OUD.

Topics: Analgesics, Opioid; Buprenorphine; COVID-19; Humans; Medicaid; Opioid-Related Disorders; Pandemics; United States

This cohort study examines racial and ethnic differences in the duration of buprenorphine treatment for opioid use disorder in the US from 2006 to 2020.

Topics: Buprenorphine; Duration of Therapy; Ethnicity; Health Status Disparities; Humans; Opioid-Related Disorders; Racial Groups; United States

The opioid epidemic in the United States disproportionately affects Medicaid beneficiaries than other groups. This results in a significant financial burden on state Medicaid programs. In this analysis, we investigate the association of medication for opioid use disorder (MOUD) treatment initiation and linkage to ongoing care on overall healthcare costs of Medicaid Fee-for-Service patients. We conducted a retrospective study among adult patients diagnosed with opioid use disorder (OUD) and who had a clinical encounter at a safety-net institution in Denver Colorado in 2020. Three categories of MOUD status of patients were defined: 1) identified with OUD but did not receive MOUD; 2) initiated MOUD but not linked to ongoing treatment and 3) received MOUD and linked to ongoing treatment. Our outcome variable was per-member per-month total healthcare cost. We estimated a multivariable model to test the association between healthcare cost and MOUD status, while controlling for demographic and risk classification variables. We found that in individuals with OUD who initiated MOUD treatment but were not linked to ongoing care had the highest healthcare cost, while those who were linked to ongoing MOUD treatment had the lowest healthcare cost. MOUD treatment is not only effective at addressing the significant morbidity and mortality burden of OUD but also associated with decreased financial cost, which is disproportionately incurred by Medicaid. Additional policy and care delivery changes are needed to focus efforts to improve linkage to ongoing treatment.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Colorado; Epidemics; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Retrospective Studies; United States

Topics: Adolescent; Analgesics, Opioid; Buprenorphine; Humans; Mental Health; Opiate Substitution Treatment; Opioid-Related Disorders; Social Work

Topics: Analgesics, Opioid; Buprenorphine; Humans; Jails; Opiate Substitution Treatment; Opioid-Related Disorders; Prisons

Opioid use disorders are commonly treated by long-acting agonist opioids including methadone and buprenorphine which could affect various aspects of male reproduction especially spermatogenesis.. We aimed to determine whether detoxification with methadone or buprenorphine was associated with reproductive disorders in male mice.. We orally induced morphine dependence in NMRI male mice, and then performed detoxification programs using either methadone or buprenorphine. Testis architecture and sperm parameters including sperm nuclear DNA integrity, mitochondrial activity, oxidative stress in seminal plasma, and routine sperm parameters were assessed to find the involved mechanisms.. The number of Leydig cells and the thickness of germinal epithelium reduced following morphine use and increased differently after detoxification with methadone or buprenorphine. Morphine dependence and detoxification with methadone and buprenorphine had different effects on sperm parameters. Morphine altered chromatin integrity, mitochondrial activity, and oxidative stress in sperm. Detoxification with methadone improved mitochondrial activity but worsened chromatin integrity, whereas detoxification with buprenorphine improved neither chromatin integrity nor mitochondrial activity. Seminal plasma oxidative stress was higher in the treated groups compared to control groups but was comparable among treatment groups. Our study revealed that long-term morphine use followed by detoxification with methadone or buprenorphine impairs testis structure and sperm parameters. Detoxification from morphine use with methadone and buprenorphine led to different preclinical outcomes in semen quality parameters, including chromatin integrity. Therefore, clinical detoxification protocols should be performed more cautiously, considering the desire of the individuals to reproduce.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Chromatin; Male; Methadone; Mice; Morphine; Morphine Dependence; Opiate Substitution Treatment; Opioid-Related Disorders; Reproduction; Semen; Semen Analysis

Most people who need and want treatment for opioid addiction cannot access it. Among those who do get treatment, only a fraction receive evidence-based, life-saving medications for opioid use disorder (MOUD). MOUD access is not simply a matter of needing more clinicians or expanding existing treatment capacity. Instead, many facets of our health systems and policies create unwarranted, inflexible, and punitive practices that create life-threatening barriers to care. In the USA, opioid use disorder care is maximally disruptive. Minimally disruptive medicine (MDM) is a framework that focuses on achieving patient goals while imposing the smallest possible burden on patients' lives. Using MDM framing, we highlight how current medical practices and policies worsen the burden of treatment and illness, compound life demands, and strain resources. We then offer suggestions for programmatic and policy changes that would reduce disruption to the lives of those seeking care, improve health care quality and delivery, begin to address disparities and inequities, and save lives.

Topics: Buprenorphine; Humans; Medicine; Opioid-Related Disorders; Quality of Health Care

Although opioid-related harms have reached new heights across North America, the size of the gap in opioid agonist therapy (OAT) delivery for opioid-related health problems is unknown in most jurisdictions. This study sought to characterize the gap in OAT treatment using a cascade of care framework, and determine factors associated with engagement and retention in treatment.. A population-based retrospective cohort study.. Ontario, Canada.. Individuals who sought medical care for opioid-related health problems or died from an opioid-related cause between 2005 and 2019.. Monthly treatment status for buprenorphine/naloxone or methadone OAT between 2013 and 2019 (i.e. 'off OAT', 'retained on OAT < 6 months', 'retained on OAT ≥ 6 months').. Of 122 811 individuals in the cohort, 97 516 (79.4%) received OAT at least once during the study period. There was decreasing 6-month treatment retention over time. Model results indicated that males had higher odds of being on OAT each month [odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.23-1.28] but lower odds of OAT retention (OR = 0.90, 95% CI = 0.88-0.92), while the reverse was observed for older individuals (monthly: OR = 0.76 per 10-year increase, 95% CI = 0.76-0.77; retention: OR = 1.36 per 10-year increase, 95% CI = 1.34-1.38) and individuals with higher neighbourhood income (e.g. highest income quintile, monthly: OR = 0.79, 95% CI = 0.77-0.82; highest income quintile, retention: OR = 1.15, 95% CI = 1.11-1.20). Individuals residing in rural areas and with a history of mental health diagnoses had poorer outcomes overall, including lower odds of being on OAT each month (rural: OR = 0.75, 95% CI = 0.73-0.78; mental health: OR = 0.89, 95% CI = 0.87-0.92) and OAT retention (rural: OR = 0.79, 95% CI = 0.77-0.82; mental health: OR = 0.81, 95% CI = 0.78-0.83), as well as higher risk of starting/stopping OAT [rural, starting OAT: hazard ratio (HR) = 1.07, 95% CI = 1.05-1.10; mental health, starting OAT: HR = 1.20, 95% CI: 1.18-1.23; rural, stopping OAT: HR = 1.24, 95% CI: = 1.22-1.26; mental health, stopping OAT: HR = 1.11, 95% CI = 1.09-1.13]. Individuals with a history of mental health diagnoses also had a higher risk of death, regardless of OAT status (off OAT death: HR = 1.49, 95% CI = 1.33-1.66; on OAT death: HR = 1.20, 95% CI = 1.09-1.31).. Factors influencing engagement and declining retention in treatment with opioid agonist therapy in Ontario's health system include age, sex and neighbourhood income, as well as mental health diagnoses or residing in rural regions.

Topics: Analgesics, Opioid; Buprenorphine; Humans; Male; Methadone; Ontario; Opiate Substitution Treatment; Opioid-Related Disorders; Retrospective Studies

Persons with opioid use disorder (OUD) may present with infectious complications from injection drug use; thus, infectious diseases (ID) physicians are uniquely positioned to treat OUD. Buprenorphine is safe and effective for OUD but remains underutilized. The prevalence and geographic distribution of ID physicians who are waivered to prescribe buprenorphine are unknown.. This cross-sectional study merged data from several publicly available datasets from 1 November 2021 to 15 January 2022. Our primary outcome was the proportion of ID physicians possessing buprenorphine waivers in the United States. We identified individual- and county-level characteristics associated with buprenorphine waiver possession. We then used geospatial analysis to determine the geographic distribution of waivered ID physicians.. We identified 6372 ID physicians in the United States, among whom 170 (2.7%) possessed waivers. Most ID physicians (97.3%) practiced in metropolitan counties. In our multivariable analysis, ID physicians had lower odds of having a waiver for every 10-year increase since graduating medical school (OR: .79; 95% CI: .68-.91). ID physicians practicing in counties with a higher proportion of uninsured residents had lower odds of having a waiver (OR: .75; 95% CI: .62-.90). Among counties with ≥1 ID physician (n = 729), only 11.2% had ≥1 waivered ID physician.. We found an extremely low prevalence and skewed geographic distribution of ID physicians with buprenorphine waivers. Our findings suggest an urgent need to increase the workforce of ID physicians waivered to prescribe buprenorphine and a call for increased integration of OUD education into ID training and continuing medical education.

Topics: Buprenorphine; Communicable Diseases; Cross-Sectional Studies; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Physicians; Practice Patterns, Physicians'; Prevalence; United States

Topics: Alcohol Drinking; Buprenorphine; Emergency Service, Hospital; Humans; Narcotic Antagonists; Opioid-Related Disorders

We present a 37-year-old male who misuses 12 g of gabapentin per day associated with dependence and withdrawal. He had a previous history of opioid use disorder (OUD) which has been in remission. An outpatient gradual dose reduction regimen was tried and failed and the patient decided to discontinue gabapentin abruptly. Symptomatic medication to relieve gabapentin withdrawal was also unsuccessful and resulted in the reinstatement of OUD. Finally, the patient was stabilized using buprenorphine maintenance treatment and discontinued opioids and gabapentin misuse. The clinical implications and significance of taking regulatory actions to control gabapentin misuse have been discussed.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Gabapentin; Humans; Male; Opioid-Related Disorders

Prior research suggests a potential relationship between the nonmedical use of gabapentin and use of opioid agonist medications (OAMs), buprenorphine and methadone. However, this research has been limited in scope and understanding despite increases in gabapentin prescribing in opioid use disorder (OUD) treatment settings and increased detection in opioid overdose fatalities.. Data were analyzed for 346 participants of a follow-up program to an ongoing national opioid surveillance program of new entrants to treatment for opioid use disorder. Data were sourced from a cross-sectional online survey distributed in July/August 2021.. Lifetime exposure to gabapentin was reported by 60.0 % of the sample, while lifetime history of nonmedical use was reported by 43.2 %. Of those nonmedically using gabapentin, 50.0 % did so while also on a dosage of either buprenorphine or methadone, with 28.4 % engaged in concurrent nonmedical use of both gabapentin and OATs. Motivations for concurrent nonmedical use included high-seeking (38.6 %), self-management of pain/physical symptoms (33.3 %), and self-management of OUD (22.2 %).. Gabapentin exposure in treatment-seeking persons with OUD appears to be quite common, and use, both medically and nonmedically, frequently occurs alongside OAMs. Motivations for concurrent nonmedical use of gabapentin and OATs mirrors motivations for off-label prescribing by healthcare providers, but may also serve as a form of self-management of OUD when OAM regimens are interrupted, insufficiently prescribed or prescribed at insufficient dosages. Further research should seek to understand the risks versus benefits of gabapentin in OAM treatment settings.

Topics: Analgesics, Opioid; Buprenorphine; Cross-Sectional Studies; Gabapentin; Humans; Methadone; Motivation; Opiate Substitution Treatment; Opioid-Related Disorders; Pain

Primary care providers (PCPs) are essential to increasing access to office-based buprenorphine medication treatment for opioid use disorder (B-MOUD). Barriers to B-MOUD prescribing are well-documented, but there is little information regarding incentives to overcome these barriers.. To identify optimal incentives for PCPs to promote B-MOUD prescribing and compare incentive preferences across provider and practice characteristics.. We surveyed PCPs using best-worst scaling (BWS) to prioritize seven potential incentives for B-MOUD prescribing (monetary compensation, paid vacation, protected time, professional development, reduced workload, service recognition, clinical resources). We then used a direct elicitation approach to determine preferred incentive levels (e.g., monetary thresholds) and types (e.g., specific clinical resources).. Primary care physicians and advanced practice providers (APPs) at a large Department of Veterans Affairs healthcare system.. B-MOUD prescribing incentive preferences and relative preference levels using descriptive statistics and conditional logistic regression with relative importance scale transformation (coefficients sum to 100, higher coefficient=greater importance).. Fifty-three PCPs responded (73% response), including 47% APPs and 36% from community-based clinics. Reduced workload (relative importance score=26.8), protected time (18.7), and clinical resources (16.8) were significantly more preferred (Ps < 0.001) than professional development (10.5), paid vacation (10.3), or service recognition (1.5). Relative importance of monetary compensation varied between physicians (12.6) and APPs (17.5) and between PCPs located at a medical center (11.4) versus community clinic (22.3). APPs were more responsive than physicians to compensation increases of $5000 and $12,000 but less responsive to $25,000; trends were similar for medical center versus community clinic PCPs. The most frequently requested clinical resource was on-demand consult access to an addiction specialist.. Interventions promoting workload reductions, protected time, and clinical resources could increase access to B-MOUD in primary care. Monetary incentives may be additionally needed to improve B-MOUD prescribing among APPs and within community clinics.

Topics: Analgesics, Opioid; Buprenorphine; Humans; Motivation; Opiate Substitution Treatment; Opioid-Related Disorders; Primary Health Care

During the COVID pandemic, overall buprenorphine treatment appeared to remain relatively stable, despite some studies suggesting a decrease in patients starting buprenorphine. There is a paucity of empirical information regarding patterns of buprenorphine treatment during the pandemic.. To better understand the patterns of buprenorphine episodes during the pandemic and how those patterns compared to pre-pandemic patterns.. Pharmacy claims representing approximately 92% of all prescriptions filled at retail pharmacies in all 50 US states and the District of Columbia.. Individuals filling buprenorphine prescriptions indicated for treatment of opioid use disorder.. The number of active, starting, and ending buprenorphine treatment episodes March 13 to December 1, 2020, and the expected number of such episodes in 2020 based on the growth in treatment episodes from March 13 to December 1, 2019.. The observed number of active buprenorphine episodes in December 2020 was comparable to the expected number, but new treatment episodes starting between March 13 and December 1, 2020, were 17.2% fewer than expected based on the 2019 experience. Similarly, the number of episodes that ended between March 13 and December 1, 2020, was 16.0% fewer than expected. Decreases from expected episode starts and ends occurred throughout the period but were greatest in the 2 months after the declaration of the public health emergency.. Beneath the apparent stability of buprenorphine patient numbers during the pandemic, the flow of individuals receiving buprenorphine treatment changed substantially. Our findings shed light on how policy changes meant to support buprenorphine prescribing influenced prescribing dynamics during that period, suggesting that while policy efforts may have been successful in maintaining existing patients in treatment, that success did not extend to individuals not yet in treatment.

Topics: Analgesics, Opioid; Buprenorphine; COVID-19; Humans; Opioid-Related Disorders; Retrospective Studies

Topics: Analgesics, Opioid; Buprenorphine; COVID-19; Humans; Jails; Opiate Substitution Treatment; Opioid-Related Disorders; Pandemics; Qualitative Research

Increasing access to opioid use disorder (OUD) treatment is critical to curbing the opioid epidemic, particularly for rural residents who experience numerous health and health care disparities, including higher overdose death rates and limited OUD treatment access compared with urban dwellers. Buprenorphine-naloxone is an evidence-based treatment for OUD that is well suited for rural areas. However, providers must have a specialized federal waiver to prescribe the medication. Despite the acceleration of the opioid epidemic in rural areas and the recent liberalization of federal buprenorphine-naloxone prescribing laws, few providers hold buprenorphine-naloxone prescribing waivers and even fewer prescribe the medication.. This study explores barriers and facilitators to buprenorphine-naloxone prescribing among nurse practitioners (NPs) working in primary care settings in eastern North Carolina.. Individual interviews were conducted with 13 NPs working in primary care settings in eastern North Carolina. Qualitative thematic analysis was used to identify perceived barriers and facilitators to buprenorphine-naloxone prescribing.. Analysis found prescribing barriers related to OUD stigma, perceived knowledge, federal and state regulation, and prescribing resources and found facilitators related to adopting a person-centered approach, developing prescriber skills, and access to prescribing resources.. The barriers and facilitators that NPs experience related to buprenorphine prescribing for OUD are similar to those faced by physicians, although the barriers arguably more profound. Future research should consider how to mitigate these prescribing barriers to facilitate NP buprenorphine prescribing for OUD.. To our knowledge, this is the first qualitative study of NP buprenorphine-naloxone prescribing in rural areas. Given the prominence of OUD in rural regions and the key role NPs play in primary care provision, this study lays import groundwork for developing interventions to support buprenorphine-naloxone prescribing by NPs practicing in rural regions.

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Humans; Nurse Practitioners; Opiate Substitution Treatment; Opioid-Related Disorders; Primary Health Care

Limited information exists regarding individual subgroups of recovery from opioid use disorder (OUD) following treatment and how these subgroups may relate to recovery trajectories. We used multi-dimensional criteria to identify OUD recovery subgroups and longitudinal transitions across subgroups.. In a national longitudinal observational study in the United States, individuals who previously participated in a clinical trial for subcutaneous buprenorphine injections for treatment of OUD were enrolled and followed for an average of 4.2 years after participation in the clinical trial.. We identified recovery subgroups based on psychosocial outcomes including depression, opioid withdrawal and pain. We compared opioid use, treatment utilization and quality of life among these subgroups.. Three dimensions of the recovery process were identified: depression, opioid withdrawal and pain. Using these three dimensions, participants were classified into four recovery subgroups: high-functioning (minimal depression, mild withdrawal and no/mild pain), pain/physical health (minimal depression, mild withdrawal and moderate pain), depression (moderate depression, mild withdrawal and mild/moderate pain) and low-functioning (moderate/severe withdrawal, moderate depression and moderate/severe pain). Significant differences among subgroups were observed for DSM-5 criteria (P < 0.001) and remission status (P < 0.001), as well as with opioid use (P < 0.001), treatment utilization (P < 0.001) and quality of life domains (physical health, psychological, environment and social relationships; Ps < 0.001, Cohen's fs ≥ 0.62). Recovery subgroup assignments were dynamic, with individuals transitioning across subgroups during the observational period. Moreover, the initial recovery subgroup assignment was minimally predictive of long-term outcomes.. There appear to be four distinct subgroups among individuals in recovery from OUD. Recovery subgroup assignments are dynamic and predictive of contemporaneous, but not long-term, substance use, substance use treatment utilization or quality of life outcomes.

Topics: Analgesics, Opioid; Buprenorphine; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Pain; Quality of Life; Substance Withdrawal Syndrome; United States

Topics: Buprenorphine; Humans; Opioid-Related Disorders; Suicide

Patients with opioid use disorder (OUD) tend to get assigned to one of 3 medications based on the treatment program to which the patient presents (e.g., opioid treatment programs tend to treat patients with methadone, while office-based practices tend to prescribe buprenorphine). It is possible that optimally matching patients with treatment type would reduce the risk of return to regular opioid use (RROU). We analyzed data from 3 comparative effectiveness trials from the US National Institute on Drug Abuse Clinical Trials Network (CTN0027, 2006-2010; CTN0030, 2006-2009; and CTN0051 2014-2017), in which patients with OUD (n = 1,459) were assigned to treatment with either injection extended-release naltrexone (XR-NTX), sublingual buprenorphine-naloxone (BUP-NX), or oral methadone. We learned an individualized rule by which to assign medication type such that risk of RROU during 12 weeks of treatment would be minimized, and then estimated the amount by which RROU risk could be reduced if the rule were applied. Applying our estimated treatment rule would reduce risk of RROU compared with treating everyone with methadone (relative risk (RR) = 0.79, 95% confidence interval (CI): 0.60, 0.97) or treating everyone with XR-NTX (RR = 0.71, 95% CI: 0.47, 0.96). Applying the estimated treatment rule would have resulted in a similar risk of RROU to that of with treating everyone with BUP-NX (RR = 0.92, 95% CI: 0.73, 1.11).

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Humans; Methadone; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders

Current WHO guidelines recommend using methadone or buprenorphine as maintenance treatments for maternal opioid use disorder. However, buprenorphine-naloxone, with a lower abuse risk than buprenorphine monotherapy or methadone, offers a potentially beneficial alternative, but scientific evidence on its effects on pregnancies, fetuses, and newborns is scarce. This paper compares the outcomes of the pregnancies, deliveries, and newborns of women on buprenorphine-naloxone, buprenorphine, or methadone maintenance treatments. According to the hypothesis, as a maintenance treatment, buprenorphine-naloxone does not have more adverse effects than buprenorphine, whereas methadone is more complicated.. In this population-based study, 172 pregnant women on medical-assisted treatments were followed-up at Helsinki University Women's Hospital (Finland). Women receiving the same opioid maintenance treatment from conception to delivery and their newborns were included. Consequently, 67 mother-child dyads met the final inclusion criteria. They were divided into three groups based on their opioid pharmacotherapy. The outcomes were compared among the groups and, where applicable, with the Finnish population.. The buprenorphine-naloxone and buprenorphine groups showed similar outcomes and did not significantly differ from each other in terms of maternal health during pregnancies, deliveries, or newborns. Illicit drug use during the pregnancy was common in all groups, but in the methadone group it was most common (p = 0.001). Most neonates (96%) were born full-term with good Apgar scores. They were of relatively small birth size, with those in the methadone group tending to be the smallest. Of the neonates 63% needed pharmacological treatment for neonatal opioid withdrawal syndrome. The need was lower in the buprenorphine-based groups than in the methadone group (p = 0.029).. Buprenorphine-naloxone seems to be as safe for pharmacotherapy for maternal opioid use disorder as buprenorphine monotherapy for both mother and newborn. Hence it could be a choice for oral opioid maintenance treatment during pregnancy, but larger studies are needed before changing the official recommendations. Women on methadone treatment carry multifactorial risks and require particularly cautious follow up. Furthermore, illicit drug use is common in all treatment groups and needs to be considered for all patients with opioid use disorder.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Female; Humans; Illicit Drugs; Infant, Newborn; Methadone; Mothers; Opioid-Related Disorders; Parturition; Pregnancy; Pregnancy Complications

Depressive symptoms are common in patients seeking medication treatment for opioid use disorder (MOUD treatment) and decrease quality of life but have been inconsistently related to opioid treatment outcomes. Here, we explore whether depressive symptoms may only be related to adverse treatment outcomes among individuals reporting high opioid use-related coping motives (i.e., use of opioids to change affective states) and high trait impulsivity, two common treatment targets.. Patients seeking MOUD treatment (N = 118) completed several questionnaires within two weeks of their treatment intake. Treatment outcomes (opioid-positive urine screens and days retained in treatment) were extracted from treatment records. Moderation analyses controlling for demographic characteristics and main effects were conducted to explore interaction effects between depressive symptoms and two distinct moderators.. Depressive symptoms were only related to opioid use during early treatment among patients reporting high opioid use-related coping motives (B = 2.67, p =.004) and patients reporting high trait impulsivity (B = 2.01, p =.039). Further, depressive symptoms were only inversely related to days retained among individuals with high opioid use-related coping motives (B = -10.12, p =.003).. Individuals presenting to treatment with opioid-related coping motives and/or impulsivity in the context of depressive symptoms may confer unique risk for adverse treatment outcomes. Clinicians may wish to consider these additive risk factors when developing their treatment plan.

Topics: Analgesics, Opioid; Buprenorphine; Depression; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Quality of Life; Treatment Outcome

To assess the effectiveness and cost-effectiveness of office-based buprenorphine treatment (OBBT) in the U.S.. We performed a model-based analysis of buprenorphine treatment provided in a primary care setting for the U.S. population with OUD.. Buprenorphine treatment provided in a primary care setting.. Fatal and nonfatal overdoses and deaths over five years, discounted lifetime quality-adjusted life years (QALYs), costs.. For a cohort of 100,000 untreated individuals who enter OBBT, approximately 9350 overdoses would be averted over five years; of these, approximately 900 would have been fatal. OBBT compared to no treatment would yield 1.07 incremental lifetime QALYs per person at an incremental cost of $17,000 per QALY gained when using a healthcare perspective. If OBBT is half as effective and twice as expensive as assumed in the base case, the incremental cost when using a healthcare perspective is $25,500 per QALY gained. Using a limited societal perspective that additionally includes patient costs and criminal justice costs, OBBT is cost-saving compared to no treatment even under pessimistic assumptions about efficacy and cost.. Expansion of OBBT would be highly cost-effective compared to no treatment when considered from a healthcare perspective, and cost-saving when reduced criminal justice costs are included. Given the continuing opioid crisis in the U.S., expansion of this care option should be a high priority.

Topics: Buprenorphine; Cost-Benefit Analysis; Humans; Opioid-Related Disorders; Quality-Adjusted Life Years

Topics: Analgesics, Opioid; Buprenorphine; Delayed-Action Preparations; Humans; Narcotic Antagonists; Opioid-Related Disorders

Drug overdoses have reached a historic milestone of over 100,000 deaths in a single year, 75,673 related to opioids. The acceleration in opioid-related deaths coupled with stark health inequities demands a close examination of opioid use disorder (OUD) treatment barriers and swift consideration of policy changes.. The aim of this buprenorphine policy analysis is to summarize existing buprenorphine barriers and present policy solutions to improve access and actualize the contributions of Advanced Practice Registered Nurses (APRNs).. The policy analysis follows five sequential steps: (1) defining the problem, (2) identifying key stakeholders, (3) assessing the landscape of relevant policies, (4) describing viable policy options, and (5) making final recommendations.. Although there are laudable efforts to improve buprenorphine access, such as the new buprenorphine guidelines issued in April 2021, without larger-scale changes to federal, state, and scope of practice laws, overdose rates will continue to rise. We recommend a multipronged policy approach to improve buprenorphine treatment access, including eliminating the DEA X waiver, improving OUD education, and adopting full practice authority for APRNs in all states.. Incremental change is no longer sufficient to address opioid overdose deaths. Bolder and coordinated policy action is possible and necessary to empower the full clinical workforce to apply evidence-based life-saving treatments for OUD. The critical contributions of nurses in advancing equitable access to OUD care are emphasized in the National Academy of Medicine's Report, Future of Nursing: Charting a Path to Achieve Health Equity. Nurses are named as instrumental in improving buprenorphine access. Policy changes that acknowledge and build on evidence-based treatment expansion strategies are sorely needed.. One of the most robust tools to combat opioid overdose deaths is buprenorphine, a partial opioid agonist, and gold standard medication treatment for OUD, but only 5% of the prescribing workforce possess the required Drug Enforcement Agency (DEA) X waiver. A growing body of evidence demonstrates that Advanced Practice Registered Nurses are accelerating the growth in waiver update and buprenorphine use, despite the considerable barriers and limitations described in this policy analysis.

Topics: Analgesics, Opioid; Buprenorphine; Humans; Opiate Overdose; Opiate Substitution Treatment; Opioid-Related Disorders; Policy Making