buprenorphine--naloxone-drug-combination and Opioid-Related-Disorders

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

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

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

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

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

With the widespread growth of ambulatory surgery centers (ASCs), the number and diversity of operations performed in the outpatient setting continue to increase. In parallel, there is an increase in the proportion of patients with a history of chronic opioid use and misuse undergoing elective surgery. Patients with such opioid tolerance present a unique challenge in the ambulatory setting, given their increased requirement for postoperative opioids. Guidelines for managing perioperative pain, anticipating postoperative opioid requirements and a discharge plan to wean off of opioids, are therefore needed.. Expert guidelines suggest using multimodal analgesia including non-opioid analgesics and regional/neuraxial anesthesia whenever possible. However, there exists variability in care, resulting in challenges in perioperative pain management. In a recent study of same-day admission patients, anesthesiologists correctly identified most opioid-tolerant patients, but used non-opioid analgesics only half the time. The concept of a focused ambulatory pain specialist on site at each ASC has been suggested, who in addition to providing safe anesthesia, could intervene early once problematic pain issues are recognized. This review focuses on perioperative pain management in three subsets of patients who exhibit opioid tolerance: those on large doses of opioids (including abuse-deterrent formulations) for chronic non-malignant or malignant pain; those who have ongoing opioid misuse; and those who were prior addicts and are now on methadone/suboxone maintenance. We also discuss perioperative pain management for patients who have implanted devices such as spinal cord stimulators and intrathecal pain pumps.

Topics: Acute Pain; Analgesics, Opioid; Anesthesia, Conduction; Buprenorphine, Naloxone Drug Combination; Chronic Pain; Drug Tolerance; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pain, Postoperative; Perioperative Care; Surgicenters

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 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

Excessive prescribing, increased potency of opioids, and increased availability of illicit heroin and synthetic analogs such as fentanyl has resulted in an increase of overdose fatalities. Medications for opioid use disorder (MOUD) significantly reduces the risk of overdose when compared with no treatment. Although the use of buprenorphine as an agonist treatment for opioid use disorder (OUD) is growing significantly, barriers remain which can prevent or delay treatment. In this study we examine non-traditional routes which could facilitate entry into buprenorphine treatment programs.. Relevant, original research publications addressing entry into buprenorphine treatment published during the years 1989-2019 were identified through PubMed, PsychInfo, PsychArticles, and Medline databases. We operationalized key terms based on three non-traditional paths: persons that entered treatment via the criminal justice system, following emergencies, and through community outreach.. Of 462 screened articles, twenty studies met the inclusion criteria for full review. Most studies were from the last several years, and most (65%) were from the Northeastern region of the United States. Twelve (60%) were studies suggesting that the criminal justice system could be a potentially viable entry route, both pre-release or post-incarceration. The emergency department was also found to be a cost-effective and viable route for screening and identifying individuals with OUD and linking them to buprenorphine treatment. Fewer studies have documented community outreach initiatives involving buprenorphine. Most studies were small sample size (mean = < 200) and 40% were randomized trials.. Despite research suggesting that increasing the number of Drug Addiction Treatment Act (DATA) waived physicians who prescribe buprenorphine would help with the opioid treatment gap, little research has been conducted on routes to increase utilization of treatment. In this study, we found evidence that engaging individuals through criminal justice, emergency departments, and community outreach can serve as non-traditional treatment entry points for certain populations. Alternative routes could engage a greater number of people to initiate MOUD treatment.

Topics: Buprenorphine, Naloxone Drug Combination; Criminal Law; Emergency Service, Hospital; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; United States

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- 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

The process by which state Medicaid programs develop their preferred drug lists, and determine which medications require prior authorization, is opaque to many clinicians. This process is a synthesis of cost and clinical information. For cost, the federal Medicaid Drug Rebate Program establishes mandatory rebates that pharmaceutical manufacturers must pay state Medicaid programs. In addition, state Medicaid programs may also negotiate supplemental rebates whereby, in exchange for a preferred position on the preferred drug list, manufacturers pay an additional rebate. These supplemental rebates are most important in therapeutic classes with multiple brand competitors (e.g., medication treatments for opioid use disorder). For clinical information, state Medicaid programs convene pharmaceutical and therapeutics committees, drug utilization review boards, or both, composed of a variety of stakeholders such as practicing clinicians. Cost factors such as federal rebate calculations and supplemental rebate negotiations may lead to counterintuitive preferred drug lists, for example, a state Medicaid program requiring prior authorization for a generic medication but not for its brand equivalent (e.g., buprenorphine/naloxone products). Because of states' reliance on rebates, mandates to remove prior authorization may have the unintended consequence of increasing costs significantly through the loss of rebate negotiating power. In the face of high and rising medication costs, state Medicaid programs are also implementing innovative policy approaches to maintain access and control costs, such as targeted rebate negotiation and value-based pricing. Through participation in state Medicaid program clinical advisory committees, individual clinicians can have a powerful voice. Interested clinicians should consider joining to inform policy and help ensure their patients' needs are met.

Topics: Adult; Aged; Buprenorphine, Naloxone Drug Combination; Cost Control; Drug Costs; Drug Industry; Drug Utilization; Humans; Medicaid; Opioid-Related Disorders; Prior Authorization; United States

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

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 (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

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

Opioid dependence (OD) is an increasing clinical and public health problem worldwide. International guidelines recommend opioid substitution treatment (OST), such as methadone and buprenorphine, as first-line medication treatment for OD. A negative aspect of OST is that the medication used can be diverted both through sale on the black market, and the unsanctioned use of medications. Daily supervised administration of medications used in OST has the advantage of reducing the risk of diversion, and may promote therapeutic engagement, potentially enhancing the psychosocial aspect of OST, but costs more and is more restrictive on the client than dispensing for off-site consumption.. The objective of this systematic review is to compare the effectiveness of OST with supervised dosing relative to dispensing of medication for off-site consumption.. We searched in Cochrane Drugs and Alcohol Group Specialised Register and Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, Web of Science from inception up to April 2016. Ongoing and unpublished studies were searched via ClinicalTrials.gov (www.clinicaltrials.gov) and World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (http://www.who.int/ictrp/en/).All searches included non-English language literature. We handsearched references on topic-related systematic reviews.. Randomised controlled trials (RCTs), controlled clinical trials (CCTs), and prospective controlled cohort studies, involving people who are receiving OST (methadone, buprenorphine) and comparing supervised dosing with dispensing of medication to be consumed away from the dispensing point, usually without supervision.. We used the standard methodological procedures expected by Cochrane.. Six studies (four RCTs and two prospective observational cohort studies), involving 7999 participants comparing supervised OST treatment with unsupervised treatment, met the inclusion criteria. The risk of bias was generally moderate across trials, but the results reported on outcomes that we planned to consider were limited. Overall, we judged the quality of the evidence from very low to low for all the outcomes.We found no difference in retention at any duration with supervised compared to unsupervised dosing (RR 0.99, 95% CI 0.88 to 1.12, 716 participants, four trials, low-quality evidence) or in retention in the shortest follow-up period, three months (RR 0.94; 95% CI 0.84 to 1.05; 472 participants, three trials, low-quality evidence). Additional data at 12 months from one observational study found no difference in retention between groups (RR 0.94, 95% CI 0.77 to 1.14; n = 300).There was no difference in abstinence at the end of treatment (self-reported drug use) (67% versus 60%, P = 0.33, 293 participants, one trial, very low-quality evidence); and in diversion of medication (5% versus 2%, 293 participants, one trial, very low-quality evidence).Regarding our secondary outcomes, we did not found a difference in the incidence of adverse effects in the supervised compared to unsupervised control group (RR 0.63; 96% CI 0.10 to 3.86; 363 participants, two trials, very low-quality evidence). Data on severity of dependence were very limited (244 participants, one trial) and showed no difference between the two approaches. Data on deaths were reported in two studies. One trial reported two deaths in the supervised group (low-quality evidence), while in the cohort study all-cause mortality was found lower in regular supervision group (crude mortality rate 0.60 versus 0.81 per 100 person-years), although after adjustment insufficient evidence existed to suggest that regular supervision was protective (mortality rate ratio = 1.23, 95% CI = 0.67 to 2.27).No studies reported pain symptoms, drug craving, aberrant opioid-related behaviours, days of unsanctioned opioid use and overdose.. Take-home medication strategies are attractive to treatment services due to lower costs, and place less restrictions on clients, but it is unknown whether they may be associated with increased risk of diversion and unsanctioned use of medication. There is uncertainty about the effects of supervised dosing compared with unsupervised medication due to the low and very low quality of the evidence for the primary outcomes of interest for this review. Data on defined secondary outcomes were similarly limited. More research comparing supervised and take-home medication strategies is needed to support decisions on the relative effectiveness of these strategies. The trials should be designed and conducted with high quality and over a longer follow-up period to support comparison of strategies at different stages of treatment. In particular, there is a need for studies assessing in more detail the risk of diversion and safety outcomes of using supervised OST to manage opioid dependence.

Topics: Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Directly Observed Therapy; Humans; Methadone; Observational Studies as Topic; Opiate Substitution Treatment; Opioid-Related Disorders; Prescription Drug Diversion; Randomized Controlled Trials as Topic

To advise physicians on which treatment options to recommend for specific patient populations: abstinence-based treatment, buprenorphine-naloxone maintenance, or methadone maintenance.. PubMed was searched and literature was reviewed on the effectiveness, safety, and side effect profiles of abstinence-based treatment, buprenorphine-naloxone treatment, and methadone treatment. Both observational and interventional studies were included.. Both methadone and buprenorphine-naloxone are substantially more effective than abstinence-based treatment. Methadone has higher treatment retention rates than buprenorphine-naloxone does, while buprenorphine-naloxone has a lower risk of overdose. For all patient groups, physicians should recommend methadone or buprenorphine-naloxone treatment over abstinence-based treatment (level I evidence). Methadone is preferred over buprenorphine-naloxone for patients at higher risk of treatment dropout, such as injection opioid users (level I evidence). Youth and pregnant women who inject opioids should also receive methadone first (level III evidence). If buprenorphine-naloxone is prescribed first, the patient should be promptly switched to methadone if withdrawal symptoms, cravings, or opioid use persist despite an optimal buprenorphine-naloxone dose (level II evidence). Buprenorphine-naloxone is recommended for socially stable prescription oral opioid users, particularly if their work or family commitments make it difficult for them to attend the pharmacy daily, if they have a medical or psychiatric condition requiring regular primary care (level IV evidence), or if their jobs require higher levels of cognitive functioning or psychomotor performance (level III evidence). Buprenorphine-naloxone is also recommended for patients at high risk of methadone toxicity, such as the elderly, those taking high doses of benzodiazepines or other sedating drugs, heavy drinkers, those with a lower level of opioid tolerance, and those at high risk of prolonged QT interval (level III evidence).. Individual patient characteristics and preferences should be taken into consideration when choosing a first-line opioid agonist treatment. For patients at high risk of dropout (such as adolescents and socially unstable patients), treatment retention should take precedence over other clinical considerations. For patients with high risk of toxicity (such as patients with heavy alcohol or benzodiazepine use), safety would likely be the first consideration. However, the most important factor to consider is that opioid agonist treatment is far more effective than abstinence-based treatment.

Topics: Age Factors; Buprenorphine, Naloxone Drug Combination; Evidence-Based Medicine; Female; Health Status; Humans; Methadone; Narcotic Antagonists; Opioid-Related Disorders; Patient Preference; Primary Health Care; Risk Factors; Risk Reduction Behavior; Social Environment; Young Adult

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 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

Topics: Administration, Buccal; Animals; Buprenorphine, Naloxone Drug Combination; Chemistry, Pharmaceutical; Clinical Trials as Topic; Humans; Opioid-Related Disorders

Opioid dependence is associated with high levels of morbidity, yet sparse data exists regarding the health-related quality of life (HRQoL) of individuals with opioid dependence, particularly following treatment initiation. To inform cost-effectiveness analyses of treatment modalities, this study investigates short-term changes in HRQoL following enrollment into opioid agonist treatment (OAT), across treatment modalities and patient subgroups.. Data was analyzed from the Starting Treatment with Agonist Replacement Therapies (START) and Prescription Opioid Addiction Treatment Studies (POATS) randomized controlled trials. Participants included individuals dependent on prescription opioids (POs) or heroin, receiving limited-term or time-unlimited treatment. PO- or heroin-users in START received buprenorphine/naloxone (BUP/NX) or methadone (MET) over 24 weeks. PO-users in POATS received psychosocial care and short-term (4-week) taper with BUP/NX, with non-responders offered subsequent extended (12-week) stabilization and taper. HRQoL was assessed using the short-form SF-6D while in and out of OAT, with distinction between MMT and BUP/NX in START. Linear mixed effects regression models were fitted to determine the independent effects of OAT on HRQoL and characterize HRQoL trajectories.. Treatment had a similar immediate and modest positive association with HRQoL in each patient subgroup. The association of OAT on HRQoL was statistically significant in each model, with effect sizes between 0.039 (heroin-users receiving BUP/NX) and 0.071 (PO-users receiving MET). After initial improvement, HRQoL decreased slightly, or increased at a diminished rate.. OAT, whether delivered in time-limited or unlimited form, using BUP/NX or MET, is associated with modest immediate HRQoL improvements, with diminishing benefits thereafter.

Topics: Adult; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Cost-Benefit Analysis; Female; Health Status; Heroin; Humans; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Quality of Life; 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

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

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

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

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

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

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

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

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

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

Opioids accounted for 75% of drug overdoses in the USA in 2020, with rural states particularly impacted by the opioid crisis. While medication-assisted treatment (MAT) with Suboxone remains one of the more efficacious treatments for opioid use disorder (OUD), approximately 40% of people receiving Suboxone for outpatient MAT for OUD (MOUD) relapse within the first 6 months of treatment. We developed the smartphone app-based intervention OptiMAT as an adjunctive intervention to improve MOUD outcomes. The aims of this study are to (1) evaluate the efficacy of adjunctive OptiMAT use in reducing opioid misuse among people receiving MOUD and (2) evaluate the role of specific OptiMAT features in reducing opioid misuse, including the use of GPS-driven just-in-time intervention.. We will conduct a two-arm, single-blind, randomized controlled trial of adults receiving outpatient MOUD in the greater Little Rock AR area. Participants are English-speaking adults ages 18 or older recently enrolled in outpatient MOUD at one of our participating study clinics. Participants will be allocated via 1:1 randomized block design to (1) MOUD with adjunctive use of OptiMAT (MOUD+OptiMAT) or (2) MOUD without OptiMAT (MOUD-only). Our blinded research statistician will evaluate differences between the two groups in opioid misuse (as determined by quantitative urinalysis conducted by clinical lab staff blinded to group membership) during the 6-months following study enrolment. Secondary analyses will evaluate if OptiMAT-usage patterns within the MOUD+OptiMAT group predict opioid misuse or continued abstinence.. This study will test if adjunctive use of OptiMAT improve MOUD outcomes. Study findings could lead to expansion of OptiMAT into rural clinical settings, and the identification of OptiMAT features which best predict positive clinical outcome could lead to refinement of this and similar smartphone app-based interventions.. ClinicalTrials.gov identifier: NCT05336188 , registered March 21, 2022.

Topics: Adult; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Randomized Controlled Trials as Topic; Single-Blind Method; Smartphone; Treatment Outcome

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

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

Limited research has explored sex differences in opioid use disorder medication (MOUD) treatment outcomes. The purpose of this study was to examine MOUD initiation onto buprenorphine-naloxone (BUP-NX) versus extended-release naltrexone (XR-NTX) by sex, and sex differences in clinical and psychosocial outcomes.. Using data from a 24-week open-label comparative effectiveness trial of BUP-NX or XR-NTX, this study examined MOUD initiation (i.e., receiving a minimum one XR-NTX injection or first BUP-NX dose) and 24-week self-report outcomes. We used regression models to estimate the probability of MOUD initiation failure among the intent-to-treat sample (N = 570), and the main and interaction effects of sex on outcomes of interest among the subsample of participants who successfully initiated MOUD (n = 474).. In the intent-to-treat sample, the odds of treatment initiation failure were not significantly different by sex. In the subsample of successful MOUD initiates, the effect of treatment on employment at week 24 was significantly moderated by sex (p = .003); odds of employment were not significantly different among males by MOUD type; females randomized to XR-NTX versus BUP-NX had 4.63 times greater odds of employment (p < .001). Males had significantly lower odds of past 30-day exchanging sex for drugs versus females (adjusted odds ratios [aOR] = 0.10, p = .004), controlling for treatment and baseline outcomes.. Further research should explore how to integrate employment support into OUD treatment to improve patient outcomes, particularly among women.. The current study addressed gaps in the literature by examining sex differences in MOUD initiation and diverse treatment outcomes in a large, national sample.

Topics: Buprenorphine, Naloxone Drug Combination; Delayed-Action Preparations; Female; Humans; Male; Naltrexone; Opioid-Related Disorders; Treatment Outcome

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

Chronic pain is highly prevalent among patients with opioid use disorder (OUD). However, little is known about how pharmacological treatments for OUD, for example, extended-release naltrexone (XR-NTX) and buprenorphine-naloxone (BUP-NX), affect pain. To begin addressing this question, we performed a secondary analysis of pain data on a large prospective 24-week, open-label, randomized-controlled comparative effectiveness trial of XR-NTX versus BUP-NX (X:BOT trial). Participants' pain status was measured by the EuroQol (EQ-5D). Based on their responses to the pain question at baseline, participants were dichotomized into "Pain" versus "No Pain" categories. Participant's pain status was evaluated every 4 weeks. A mixed effects longitudinal logistic regression model was fitted to examine the differential effect of XR-NTX versus BUP-NX on pain, modelling pain at all available follow-up assessments, adjusted for age, sex, and baseline pain. A total of 474 individuals who were successfully inducted onto their assigned medications were included in this analysis. Among participants endorsing pain at baseline, substantial reductions in pain were observed over the course of the study in both treatment groups. Howecver reduction in pain was slightly greater in the group treated with XR-NTX than the one treated with BUP-NX (OR = 1.60 [95% CI: 1.07-2.40], P = 0.023). Future research using instruments and design specifically focused on pain could extend the present observations and evaluate their clinical significance.

Topics: Buprenorphine, Naloxone Drug Combination; Chronic Pain; Delayed-Action Preparations; Humans; Injections, Intramuscular; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Prospective Studies

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

Our study aimed to (1) examine the effect of adjunctive high-definition transcranial direct current stimulation (HD-tDCS) in craving and withdrawal among patients with opioid use disorder on buprenorphine-naloxone, and (2) examine effect of HD-tDCS changes in glutamate-glutamine and γ-aminobutyric acid (GABA) at the left dorsolateral prefrontal cortex (DLPFC) among patients with opioid use disorder on buprenorphine-naloxone.. This was a pilot randomized double-blind, sham-controlled parallel-group study. A total of 28 patients on buprenorphine-naloxone (6/1.5 mg/d) were randomly allocated into 2 groups for active and sham HD-tDCS stimulation. High-definition transcranial direct current stimulation was administered twice daily for consecutive 5 days, from days 2 to 6. The Clinical Opiate Withdrawal Scale (COWS), the Desire for Drug Questionnaire (DDQ), the Obsessive-Compulsive Drug Use Scale (OCDUS), and glutamate-glutamine and GABA at DLPFC via proton magnetic resonance spectroscopy were measured at baseline and on day 7.. Both active and sham groups had comparable changes in DDQ, OCDUS (except 2 subcomponents), COWS, and glutamate-glutamine and GABA at DLPFC. In the active HD-tDCS group, statistically significant reductions were observed in DDQ, OCDUS, and COWS but not in glutamate-glutamine and GABA.. The adjunctive active HD-tDCS group showed comparable changes in craving and withdrawal, and glutamate-glutamine and GABA at DLPFC compared with sham HD-tDCS. Craving and withdrawal but not glutamate-glutamine and GABA at DLPFC decreased significantly with adjunctive HD-tDCS. Future studies with larger sample size and online assessment of glutamate-glutamine and GABA would enhance our knowledge.

Topics: Brain; Buprenorphine, Naloxone Drug Combination; Craving; Double-Blind Method; Electroconvulsive Therapy; gamma-Aminobutyric Acid; Glutamates; Glutamine; Humans; Opioid-Related Disorders; Pilot Projects; Prefrontal Cortex; Proton Magnetic Resonance Spectroscopy; Transcranial Direct Current Stimulation

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

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

Topics: Buprenorphine, Naloxone Drug Combination; Cognition; Cognitive Remediation; Computers; Humans; Male; Opioid-Related Disorders

People who inject drugs (PWID) are at risk for HIV and opioid overdose. We piloted PARTNER UP, a telemedicine-based program to provide PWID with access to both oral pre-exposure prophylaxis (PrEP) for HIV prevention and medication for opioid use disorder (MOUD) through two syringe services programs (SSPs) in North Carolina. We conducted a qualitative evaluation to assess the acceptability and feasibility of PARTNER UP from the participant perspective.. PARTNER UP participants met with a provider for an initial in-person visit at the SSP, followed by weekly telemedicine visits in month 1 and then monthly telemedicine visits until program end at month 6. Using a qualitative descriptive study design, we conducted in-depth interviews with a subsample of PARTNER UP participants at 1 month and 4 months. Informed by the technology acceptance model, we assessed participant perceptions of the usefulness and ease of use of PARTNER UP, as well as their intent to continue to use the program's components. We audio-recorded all interviews with participants' permission and used applied thematic analysis to analyze the verbatim transcripts.. We interviewed 11 of 17 people who participated in PARTNER UP-10 in the month 1 interview and 8 in the month 4 interview. Nearly all participants were motivated to join for consistent and easy access to buprenorphine/naloxone (i.e., MOUD); only a few joined to access PrEP. Most were comfortable accessing healthcare at the SSP because of their relationship with and trust toward SSP staff, and accessing services at the SSP was preferred compared with other healthcare centers. Some participants described that telemedicine allowed them to be honest and share more information because the visits were not in-person and they chose the location, although the initial in-person meeting was helpful to build provider trust and rapport. Most participants found the visit schedule to be feasible, although half described needing to reschedule at least once. Nearly all participants who were interviewed intended to continue with MOUD after the program ended, whereas none were interested in continuing with PrEP.. Participant narratives suggest that the PARTNER UP telemedicine program was acceptable and feasible. Future studies should continue to explore the benefits of embedding both PrEP and MOUD into SSPs with larger numbers of participants. Trial registration Clinicaltrials.gov Identifier: NCT04521920.

Topics: Buprenorphine, Naloxone Drug Combination; Feasibility Studies; HIV Infections; Humans; Opioid-Related Disorders; Substance Abuse, Intravenous; Syringes; Telemedicine

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

Compare the risk of relapse to heroin and other illicit opioids among opioid-dependent patients receiving treatment with extended-release naltrexone (XR-NTX) or buprenorphine-naloxone (BP-NLX).. Re-analyzed data from a 12-week multicenter, open-label, randomized treatment study with a subsequent 36-week open-label follow-up study. All patients, N = 143, had completed detoxification and received at least one dose of study medication.. Of 143 patients (72% men), mean age 36 years, 71 received XR-NTX and 72 BP-NLX. The risk of first relapse and the risk of any relapse to heroin and other illicit opioids were both significantly lower in the XR-NTX group compared with the BP-NLX group (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.28-0.76; P = .002, and HR, 0.11; 95% CI, 0.04-0.29; P < .001, respectively) and (HR, 0.15; 95% CI, 0.09-0.27; P < .001 and HR, 0.05; 95% CI, 0.03-0.09; P < .001, respectively). There was a stable low risk of relapse among participants receiving XR-NTX in the follow-up.. Compared to BP-NLX, patients on XR-NTX had a substantially reduced risk of relapse to illicit opioids and showed a stable low risk of relapse over time in longer-term treatment.. Our data support XR-NTX as a first-line treatment option for patients with opioid addiction both in short and longer-term treatment. This is the first European study showing that XR-NTX significantly reduces the risk of first and any relapse to heroin use in opioid-dependent patients compared to BP-NLX. Our data contradict previous data from the X:BOT study, showing no significant difference in relapse risk between the groups in a 6-month randomised controlled trial. (© 2021 Authors. The American Journal on Addictions published by Wiley Periodicals LLC on behalf of The American Academy of Addiction Psychiatry). (Am J Addict 2021;30:451-458).

Topics: Adult; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Delayed-Action Preparations; Female; Follow-Up Studies; Humans; Injections, Intramuscular; Male; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Recurrence

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

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

The distinct pharmacological properties and clinical uses of extended-release naltrexone (XR-NTX) and sublingual buprenorphine-naloxone (BUP-NX) present challenges in analyzing patient outcomes.. We conducted a secondary analysis of a multi-site randomized trial comparing XR-NTX with sublingual BUP-NX treatment for opioid use disorder initiated during inpatient detoxification and continued in outpatient treatment. Urine testing data for non-study opioids from the last 22 weeks of the 24-week trial were analyzed in both a per-protocol sample (n = 474 participants who received at least one dose of medication) and a completers sample (n = 211 participants who received all XR-NTX doses or all BUP-NX prescriptions). The present analyses sought to identify differences in the weekly percentages of opioid-positive urine tests between participants treated with the two medications.. The proportion of opioid-positive tests in both conditions was less than 20 % for 21 of the 22 weeks in the per-protocol sample and all 22 weeks in the completers sample. Generalized linear mixed model analyses revealed a significant treatment (XR-NTX vs. BUP-NX) X week (weeks 3-24) interaction in the per-protocol sample but not the completers sample. In the per-protocol analysis, the BUP-NX, compared to XR-NTX, had significantly greater proportions of opioid-positive tests in 14 out of the 22 weeks.. Longitudinal modeling approaches that utilize flexible procedures for handling missing data can offer a different perspective on study findings. Results from the present analyses suggest that XR-NTX appeared to be somewhat more effective than BUP-NX in reducing illicit opioid use in the per-protocol sample.

Topics: Administration, Sublingual; Adult; Ambulatory Care; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Delayed-Action Preparations; Female; Humans; Injections, Intramuscular; Male; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders

Buprenorphine/naloxone (Suboxone) is a current first-line treatment for opioid use disorder (OUD). The standard induction method of buprenorphine/naloxone requires patients to be abstinent from opioids and therefore experience withdrawal symptoms prior to induction, which can be a barrier in starting treatment. Rapid micro-induction (micro-dosing) involves the administration of small, frequent does of buprenorphine/naloxone and removes the need for a period of withdrawal prior to the start of treatment. This study aims to compare the effectiveness and safety of rapid micro-induction versus standard induction of buprenorphine/naloxone in patients with OUD.. This is a randomized, open-label, two-arm, superiority, controlled trial comparing the safety and effectiveness of rapid micro-induction versus standard induction of buprenorphine/naloxone for the treatment of OUD. A total of 50 participants with OUD will be randomized at one Canadian hospital. The primary outcome is the completion of buprenorphine/naloxone induction with low levels of withdrawal. Secondary outcomes are treatment retention, illicit drug use, self-reported drug use behaviour, craving, pain, physical health, safety, and client satisfaction.. This is the first randomized controlled trial to compare the effectiveness and safety of rapid micro-induction versus standard induction of buprenorphine/naloxone. This study will thereby generate evidence for a novel induction method which eliminates substantial barriers to the use of buprenorphine/naloxone in the midst of the ongoing opioid crisis. Trial registration ClinicalTrials.gov, NCT04234191; date of registration: January 21, 2020; https://clinicaltrials.gov/ct2/show/NCT04234191.

Topics: Adult; British Columbia; Buprenorphine, Naloxone Drug Combination; Female; Humans; Hydromorphone; Male; Opiate Substitution Treatment; Opioid-Related Disorders; Randomized Controlled Trials as Topic; Research Design; Substance Withdrawal Syndrome

Opioid use disorder (OUD) treatment outcomes are poorer for young adults than older adults. Developmental differences are broadly implicated, but particular vulnerability factor interactions are poorly understood. This study sought to identify moderators of OUD relapse between age groups.. This secondary analysis compared young adults (18-25) to older adults (26+) from a comparative effectiveness trial ("XBOT") that randomized (N = 570) participants to extended-release naltrexone or sublingual buprenorphine-naloxone. We explored the relationship between 25 prespecified patient baseline characteristics and relapse to regular opioid use by age group and treatment condition, using logistic regression.. Young adults (n = 111) had higher rates of 24-week relapse than older adults (n = 459) (70.3% vs 58.8%) and differed on a number of specific characteristics, including more smokers, more intravenous opioid use, and more cannabis use. No significant moderators predicted relapse, in either three-way or two-way interactions.. No baseline factors were identified as moderating the relationship between age group and opioid relapse, nor any interactions between baseline characteristics, age group, and treatment condition to predict opioid relapse. Poorer treatment outcomes for young adults are likely associated with multiple developmental vulnerabilities rather than any single predominant factor. Although not reaching significance, several characteristics (using heroin, smoking tobacco, high levels of depression/anxiety, or treatment because of family/friends) showed higher odds ratio point estimates for relapse in young adults than older adults. This is the first study to explore moderators of worse OUD treatment outcomes in young adults, highlighting the need to identify predictor variables that could inform treatment enhancements. (Am J Addict 2021;00:1-12).

Topics: Aged; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Delayed-Action Preparations; Humans; Naltrexone; Opiate Substitution Treatment; Opioid-Related Disorders; Young Adult

Sublingual buprenorphine-naloxone and extended-release injection naltrexone are effective treatments, with distinct mechanisms, for opioid use disorder. The authors examined whether patients' demographic and clinical characteristics were associated with better response to one medication or the other.. In a multisite 24-week randomized comparative-effectiveness trial of assignment to buprenorphine-naloxone (N=287) compared with extended-release naltrexone (N=283) comprising inpatients planning to initiate medication treatment for opioid use disorder, 50 demographic and clinical characteristics were examined as moderators of the effect of medication assignment on relapse to regular opioid use and failure to initiate medication. Moderator-by-medication interactions were estimated using logistic regression with correction for multiple testing.. In the intent-to-treat sample, patients who reported being homeless had a lower relapse rate if they were assigned to receive extended-release naltrexone (51.6%) compared with buprenorphine-naloxone (70.4%) (odds ratio=0.45, 95% CI=0.22, 0.90); patients who were not homeless had a higher relapse rate if they were assigned to extended-release naltrexone (70.9%) compared with buprenorphine-naloxone (53.1%) (odds ratio=2.15, 95% CI=1.44, 3.21). In the subsample of patients who initiated medication, the interaction was not significant, with a similar pattern of lower relapse with extended-release naltrexone (41.4%) compared with buprenorphine (68.6%) among homeless patients (odds ratio=0.32, 95% CI=0.15, 0.68) but less difference among those not homeless (extended-release naltrexone, 57.2%; buprenorphine, 52.0%; odds ratio=1.24, 95% CI=0.80, 1.90). For failure to initiate medication, moderators were stated preference for medication (failure was less likely if the patient was assigned to the medication preferred), parole and probation status (fewer failures with extended-release naltrexone for those on parole or probation), and presence of pain and timing of randomization (more failure with extended-release naltrexone for patients endorsing moderate to severe pain and randomized early while still undergoing medically managed withdrawal).. Among patients with opioid use disorder admitted to inpatient treatment, homelessness, parole and probation status, medication preference, and factors likely to influence tolerability of medication initiation may be important in matching patients to buprenorphine or extended-release naltrexone.

Topics: Administration, Sublingual; Adult; Buprenorphine, Naloxone Drug Combination; Delayed-Action Preparations; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Treatment Outcome; Young Adult

Relapse is common in treatment for opioid use disorders (OUDs). Pain and depression often co-occur during OUD treatment, yet little is known about how they influence relapse among patients with a primary diagnosis of prescription opioid use disorder (POUD). Advanced statistical analyses that can simultaneously model these two conditions may lead to targeted clinical interventions.. The objective of this study was to utilize a discrete survival analysis with a growth mixture model to test time to prescription opioid relapse, predicted by parallel growth trajectories of depression and pain, in a clinical sample of patients in buprenorphine/naloxone treatment. The latent class analysis characterized heterogeneity with data collected from the National Institute of Drug Abuse Clinical Trials Network project (CTN-0030).. Results suggested that a 4-class solution was the most parsimonious based on global fit indices and clinical relevance. The 4 classes identified were: 1) low relapse, 2) high depression and moderate pain, 3) high pain, and 4) high relapse. Odds ratios for time-to-first use indicated no statistically significant difference in time to relapse between the high pain and the high depression classes, but all other classes differed significantly.. This is the first longitudinal study to characterize the influence of pain, depression, and relapse in patients receiving buprenorphine and naloxone treatment. These results emphasize the need to monitor the influence of pain and depression during stabilization on buprenorphine and naloxone. Future work may identify appropriate interventions that can be introduced to extend time-to-first prescription opioid use among patients.

Topics: Adult; Buprenorphine, Naloxone Drug Combination; Depression; Female; Follow-Up Studies; Humans; Latent Class Analysis; Longitudinal Studies; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Pain; Predictive Value of Tests; Recurrence

Few studies examine the effectiveness of treatments for opioid use disorder (OUD) among Black individuals despite recent evidence suggesting opioid overdose death rates are, in some cases, highest and increasing at a faster rate among Black people compared to other racial/ethnic groups. This secondary analysis study investigated treatment preference, retention, and relapse rates amongst a subgroup of 73 Black participants with OUD (81% male, mean age 39.05, SD = 11.80) participating in a 24-week multisite randomized clinical trial ("X:BOT") comparing the effectiveness of extended-release naltrexone (XR-NTX) and sublingual buprenorphine-naloxone (BUP-NX) between 2014 and 2017. Chi-square analyses were used to investigate treatment preference assessed at baseline, and logistic regression analyses were used to investigate differences in the odds of retention and relapse assessed over the 24-week course of treatment between treatment groups. Our findings suggest no differences in preference for XR-NTX versus BUP-NX. However, similar to the parent trial, there was an induction hurdle such that only 59.5% of those randomized to XR-NTX successfully initiated medication compared to 91.6% of those randomized to BUP-NX (OR = 0.13, 95% CI = 0.04, 0.52). No significant differences were found in treatment retention (intention-to-treat: OR = 1.19, 95% CI = 0.43, 3.28; per-protocol [i.e., those who initiated medication]: OR = 0.60, 95% CI = 0.20, 1.82) or relapse rates between treatment groups (intention-to-treat: OR = 1.53, 95% CI = 0.57, 4.13; per-protocol: OR = 0.69, 95% CI = 0.23, 2.06). Although there is a significant initiation hurdle with XR-NTX, once inducted, both medications appear similar in effectiveness, but as in the main study, dropout rates were high. Future research is needed on how to improve adherence.

Topics: Adult; Black or African American; Buprenorphine, Naloxone Drug Combination; Delayed-Action Preparations; Female; Humans; Injections, Intramuscular; Male; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders

To examine the health-related quality-of-life (HRQoL) of persons with opioid use disorder (OUD) seeking treatment in an inpatient detoxification or short-term residential setting; continuing treatment as outpatients.. We conducted a secondary analysis of data from a clinical trial (N = 508) where participants were randomized to extended-release naltrexone or buprenorphine-naloxone for the prevention of opioid relapse. We used a generalized structural equation regression mixture model to identify associations of HRQoL (EQ-5D) trajectories, including latent characteristics, over the 24-week trial and 36-week follow-up period, among participants who reported HRQoL beyond baseline. This novel framework accounted for baseline and time-varying characteristics, while simultaneously identifying latent classes.. We identified two subpopulations: HRQoL "pharmacotherapy responsive" (82.3 %) and HRQoL "characteristic sensitive" (17.7 %). The pharmacotherapy responsive subpopulation was characterized by a shortterm HRQoL improvement and then stable HRQoL over time, and by a positive association between HRQoL and receiving pharmacotherapy in the past 30 days. The characteristic sensitive subpopulation was characterized by an initial improvement in HRQoL with a gradual decline over time, and no significant HRQoL response to pharmacotherapy. HRQoL changes over time in this subpopulation were more influenced by baseline demographic, socioeconomic, and psychosocial characteristics.. Our findings suggest that while HRQoL may be improved and sustained through targeted efforts to promote use of pharmacotherapy for many persons with OUD, an identifiable subpopulation may require additional services that address socioeconomic and psychosocial issues to achieve HRQoL benefits. Our analysis provides insight for improving individualized care for persons with opioid use disorder seeking treatment.

Topics: Adult; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Female; Humans; Male; Middle Aged; Naltrexone; Opiate Substitution Treatment; Opioid-Related Disorders; Quality of Life

Nationwide efforts seek to address the opioid epidemic by increasing access to medications for opioid use disorder (OUD), particularly with buprenorphine. A poorly understood challenge is that among individuals with OUD who do receive buprenorphine, many do not adhere to the pharmacotherapy long enough to achieve sustained benefits. We aimed to identify factors associated with buprenorphine treatment utilization over time.. We used random-intercept modeling to identify factors associated with buprenorphine treatment utilization over 2 years after first follow-up by 789 individuals with OUD who had participated in a multi-site randomized clinical trial of buprenorphine compared to methadone. Key predictors were participants' reports of buprenorphine treatment accessibility and acceptability (assessed at first follow-up) and their interaction effects, controlling for baseline randomization status, sociodemographics, and other covariates.. Approximately 9.3-11.2% of participants utilized buprenorphine treatment over the 2 years of follow-up. Interaction effects indicated that individuals who perceived buprenorphine to be both accessible and acceptable were most likely to use buprenorphine during follow-up, controlling for other factors. In contrast, individuals who perceived buprenorphine to be unacceptable were least likely to use buprenorphine, regardless the level of perceived access to the medication. Buprenorphine treatment utilization was also negatively associated with Hispanic ethnicity, West coast context, and cumulative months receiving methadone treatment and incarceration during follow-up.. To engage more individuals with OUD in long-term treatment with buprenorphine, interventions should target buprenorphine treatment acceptability, in addition to increasing buprenorphine access, and tailor efforts to meet the needs of vulnerable populations.. The START Follow-up Study on ClinicalTrials.gov (NCT01592461).

Topics: Adolescent; Adult; Aged; Buprenorphine, Naloxone Drug Combination; Female; Follow-Up Studies; Health Services Accessibility; Humans; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Acceptance of Health Care; Prospective Studies; Young Adult

To advance our understanding of medication treatments for opioid use disorders (OUDs), identification of distinct subgroups and factors associated with differential treatment response is critical. We examined trajectories of opioid use for patients with OUD who were randomized to (but not in all cases inducted onto) buprenorphine-naloxone (BUP-NX) or extended-release naltrexone (XR-NTX), and identified characteristics associated with each trajectory.. Growth mixture models (GMMs) were run to identify distinct trajectories of days of opioid use among a subsample of 535 individuals with OUD who participated in a 24-week randomized controlled trial (RCT; 2014-2016) of BUP-NX (n = 281) or XR-NTX (n = 254).. Four distinct opioid use trajectory classes were identified for BUP-NX (near abstinent/no use (59%); low use (13.2%); low use, increasing over time (15%); and moderate use, increasing over time (12.8%)). Three distinct opioid use trajectory classes were found for XR-NTX (near abstinent/no use (59.1%); low use (14.6%); and moderate use, increasing over time (26.4%)). Across both BUP-NX and XR-NTX, the near abstinent/no use class had the highest number of medical management visits. Within BUP-NX, the low use class had a greater proportion of individuals with a previous successful treatment history compared with other classes. Within XR-NTX, the moderate use, increasing over time class had the highest proportion of Hispanic participants compared with other classes.. Findings highlight the significant heterogeneity of opioid use during a RCT of BUP-NX and XR-NTX and factors associated with opioid use patterns including medical management visits and history of treatment success.

Topics: Adult; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Delayed-Action Preparations; Female; Humans; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Treatment Outcome

It has been estimated that approximately 15% of people who are incarcerated in the US have histories of opioid use disorder. Relapse to opioid use after release from prison poses a serious risk of HIV infection. Prison-initiated buprenorphine may help to reduce HIV infection given the association between opioid use and HIV-risk behaviors.. The present study is a secondary analysis of longitudinal data gathered from a randomized controlled trial of buprenorphine-naloxone for people who were incarcerated (N = 211) between 2008 and 2012. It compares the impact of assignment to initiate buprenorphine in prison (N = 106 randomized, N = 104 analyzed) versus in the community (N = 107 randomized, N = 107 analyzed) and whether or not participants entered community treatment on the frequency of HIV-risk behaviors in the 12 months following release from prison. Data were analyzed hierarchically and for each outcome variable, a multilevel, over-dispersed Poisson model was fit to the data. Outcome variables were the number of times the following behaviors occurred in the last 30 days: (1) having sex without a condom (2) injecting drugs (3) using unsterilized needles, and (4) sharing injection paraphernalia.. Participants assigned to begin buprenorphine in the community experienced a greater decrease in injection drug use over time compared to participants assigned to begin buprenorphine in prison. There were no significant associations between treatment assignment or community treatment entry and instances of having sex without a condom, sharing injection paraphernalia, or using unsterilized needles.. Overall, the present study did not find support for the initiation of buprenorphine in prison (as opposed to the community) as a means to reduce incidences of HIV-risk behaviors. Avenues for future research in the nexus of HIV-risk reduction, criminal justice, and pharmacotherapy are discussed. Trial registration This study was supported by the National Institute on Drug Abuse (NIDA), Buprenorphine for Prisoners (PI: Kinlock; R01DA021579). ClinicalTrials.gov identifier: NCT00574067.

Topics: Adolescent; Adult; Buprenorphine, Naloxone Drug Combination; Female; HIV Infections; Humans; Male; Needle Sharing; Opioid-Related Disorders; Prisons; Risk-Taking; Socioeconomic Factors; Substance Abuse, Intravenous; United States; Unsafe Sex; Young Adult

Compared to the general population, smoking rates are 2-4 times higher among individuals with opioid use disorders (OUDs). These smokers also have poor long-term cessation rates, even with pharmacotherapy or other interventions. Low success rates with traditional approaches may prompt smokers with OUDs to try more novel products like electronic cigarettes (ECIGs). This pilot study was designed to examine the feasibility, acceptability, and effect of ECIGs on smoking behavior among smokers with OUD.. Participants (N = 25) were daily smokers receiving buprenorphine/naloxone for OUD at an outpatient clinic. They were randomized to use a second-generation ECIG (0 or 18 ng/ml nicotine) ad libitum for two weeks while completing assessments via text messaging daily, and also via in-person visits at baseline, end of the two-week intervention, and a 4-week follow-up.. Feasibility was evidenced by high enrollment (93.9%) and retention (70.9%) rates. ECIG adherence was relatively high as measured by self-report (80.6% active, 91.7% placebo), while the average volume of liquid used per week was low (~3 ml). Both ECIG doses produced reductions in self-reported cigarettes per day that were not supported by average carbon monoxide levels. Biologically-confirmed smoking abstinence was observed in 8% of participants.. Preliminary results suggest that smokers with OUD are interested in using ECIGs, but their adherence may be less than ideal. Poor medication adherence rates are often observed in this disparate population, and future work should consider the use of other ECIG device types and a combination of methods to verify and quantify ECIG use.

Topics: Adult; Buprenorphine, Naloxone Drug Combination; Carbon Monoxide; Cigarette Smoking; Electronic Nicotine Delivery Systems; Female; Humans; Male; Narcotic Antagonists; Nicotine; Nicotinic Agonists; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Compliance; Pilot Projects; Self Report; Vaping; Young Adult

The purpose of the study is to evaluate the efficacy and safety of buprenorphine/naloxone sublingual tablets for the treatment of opioid dependence in Chinese adults.. This multicenter, double-blind, placebo-controlled study included four periods: induction (3-5 days), stabilization (7-21 days), randomization/treatment (6 weeks), and postmedication follow-up (1 week). A total of 442 participants with opioid dependence were enrolled; 260 were randomized to buprenorphine/naloxone or placebo. The primary outcome was retention in treatment, defined as the time from randomization to treatment completion or treatment failure. Secondary outcomes included maximum consecutive days of abstinence from opioids, self-reported craving and opioid withdrawal symptoms, and urine drug screen results. Safety assessments included adverse event reporting, electrocardiograms, clinical laboratory tests, vital signs, and prior/concomitant medications.. The median treatment retention time (95% confidence internal) with buprenorphine/naloxone was 32 days (26-38) versus 6 days (5-8) for placebo, with a Cox hazard ratio of 0.28 (95% confidence interval, 0.21-0.38; P < 0.0001). The median maximum consecutive days of abstinence (95% confidence interval) was: buprenorphine/naloxone, 21 days (26-38); placebo, 5 days (5-8) with a Cox hazard ratio of 0.38 (95% confidence interval, 0.25-0.60; P < 0.0001). Withdrawal and craving symptoms were significantly milder with buprenorphine/naloxone versus placebo (P < 0.001). Urine drug screen results indicated significantly lower opioid usage in the buprenorphine/naloxone group compared with placebo (P < 0.001). The most commonly reported adverse events in the buprenorphine/naloxone group during treatment were aspartate aminotransferase increased and nasopharyngitis.. Efficacy and safety results from this clinical trial support a positive benefit-risk ratio for buprenorphine/naloxone sublingual tablet use in the treatment of an opioid-dependent Chinese population.

Topics: Administration, Sublingual; Adolescent; Adult; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; China; Double-Blind Method; Female; Humans; Male; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Outcome Assessment, Health Care; Young Adult

Extended-release naltrexone (XR-NTX) is a promising alternative treatment of opioid addiction but has never been compared with opioid agonist treatment for effects on symptoms of anxiety, depression, and insomnia.. To investigate whether XR-NTX unmasks or reinforces current comorbid symptoms of anxiety, depression, or insomnia compared with opioid agonist treatment.. In this prospective randomized clinical trial, 159 men and women aged 18 to 60 years with opioid dependence were randomized to 12 weeks of treatment with either XR-NTX or combined buprenorphine-naloxone (BP-NLX) followed by a 9-month, open-label treatment study with participant choice of 1 of these 2 drugs. The study was conducted at outpatient addiction clinics in 5 urban hospitals in Norway, with the clinical trial performed from November 1, 2012, to October 23, 2015, and the follow-up study completed on July 23, 2016. All analyses were conducted using an intention-to-treat sample.. Extended-release naltrexone hydrochloride, 380 mg, administered as an injection every 4 weeks or flexible doses (4-24 mg; target dosage 16 mg/d) of daily oral combined BP-NLX.. Every 4 weeks, symptoms of anxiety and depression were assessed using the 25-item Hopkins Symptom Checklist, and symptoms of insomnia were assessed using the Insomnia Severity Index.. In total, 159 participants were randomized to treatment with either XR-NTX (n = 80) or BP-NLX (n = 79), and 105 participants (66.0%) completed the trial. The treatment groups showed similar distributions of age (mean [SD], 36.4 [8.8] vs 35.7 [8.5] years), sex (61 [76.3%] women and 54 [68.4%] men), and duration of heroin use (mean [SD], 6.9 [5.8] vs 6.7 [5.2] years). For the clinical trial period, no overall differences were detected between treatment groups for anxiety (effect size [95% CI], -0.14 [-0.47 to 0.19]) or depression (effect size [95% CI], -0.12 [-0.45 to 0.21]) scores, but the insomnia score was significantly lower in the XR-NTX group (effect size [95% CI], -0.32 [-0.61 to -0.02]; P = .008). In the follow-up period, no overall differences could be detected in the effect size [95% CI] of scores for anxiety (0.04 [-0.34 to 0.42]), depression (-0.04 [-0.42 to 0.33]), or insomnia (0.04 [-0.33 to 0.42]) between participants continuing with and participants switching to XR-NTX. No significant sex differences between the 2 treatment groups were detected.. Comorbid symptoms of anxiety, depression, or insomnia in abstinence-motivated persons with opioid dependence should not prevent switching from treatment with an opioid agonist to treatment with XR-NTX.. ClinicalTrials.gov Identifier: NCT01717963.

Topics: Administration, Oral; Adolescent; Adult; Anxiety; Buprenorphine, Naloxone Drug Combination; Comorbidity; Delayed-Action Preparations; Depression; Female; Follow-Up Studies; Humans; Injections, Intramuscular; Male; Middle Aged; Naltrexone; Opioid-Related Disorders; Sleep Initiation and Maintenance Disorders; Young Adult

It is presently unclear whether extended-release naltrexone hydrochloride treatment induces pain or aggravates existing pain among individuals with opioid use disorders. We assessed changes in pain among individuals receiving treatment with either extended-release naltrexone hydrochloride or buprenorphine-naloxone hydrochloride.. This randomized prospective open-label clinical study included 143 participants (aged 18-60 years) with opioid dependencies, recruited from outpatient addiction clinics at five urban hospitals in Norway. After in-patient detoxification from opioids, patients were randomized to 12-week treatment with either long-acting naltrexone (380 mg intramuscularly injected every four weeks) or buprenorphine-naloxone (flexible 4-16 mg sublingual doses daily). This phase was followed by a 9-month open-treatment study with the participant's choice of either naltrexone or buprenorphine-naloxone. Changes in pain were assessed every 4 weeks using the Norwegian Short-Form of McGill Pain Questionnaire.. Throughout the study period, we found no increase in mean sensory pain, affective pain, or present pain intensity on the McGill Pain Questionnaire, in either treatment group, including the subgroups of participants with chronic pain. Participants who switched from buprenorphine-naloxone to extended-release naltrexone treatment after week 12 reported no increase in pain intensity during longer-term treatment. Women experienced significantly more affective pain symptoms than men (p = .01).. Among individuals with opioid use disorder, switching from daily opioid use to long-acting naltrexone did not induce pain, or aggravate mild-to-moderate chronic pain.. In opioid-dependent individuals, mild-to-moderate chronic pain was not influenced by opioid agonist or antagonist treatment.. Clinicaltrials.gov #NCT01717963, first registered: Oct 28, 2012. Protocol version # 3C, June 12th 2012. (Am J Addict 2018;XX:1-9).

Topics: Adult; Buprenorphine, Naloxone Drug Combination; Chronic Pain; Female; Humans; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Norway; Opiate Substitution Treatment; Opioid-Related Disorders; Pain Measurement

To compare long-term criminal justice outcomes among opioid-dependent individuals randomized to receive buprenorphine or methadone.. A 5-year follow-up was conducted in 2011-14 of 303 opioid-dependent participants entering three opioid treatment programs in California, USA in 2006-09 and randomized to receive either buprenorphine/naloxone or methadone.. Participants received buprenorphine/naloxone (BUP; n = 179) or methadone (MET; n = 124) for 24 weeks and then were tapered off their treatment over ≤ 8 weeks or referred for ongoing clinical treatment. Midway through the study, the randomization scheme was switched from 1 : 1 BUP : MET to 2 : 1 because of higher dropout in the BUP arm.. Study outcomes included arrests and self-reported incarceration. Predictors included randomization condition (buprenorphine versus methadone), age, gender, race/ethnicity, use of cocaine, drug injection in the 30 days prior to baseline and study site. Treatment status (buprenorphine, methadone, none) during follow-up was included as a time-varying covariate.. There was no significant difference by randomization condition in the proportion arrested (buprenorphine: 55.3%, methadone: 54.0%) or incarcerated (40.9%, 47.3%) during follow-up. Among methadone-randomized individuals, arrest was less likely with methadone treatment (0.50, 0.35-0.72) during follow-up (relative to no treatment) and switching to buprenorphine had a lower likelihood of arrest than those receiving no treatment (0.39, 0.18-0.87). Among buprenorphine-randomized individuals, arrest was less likely with receipt of buprenorphine (0.49, 0.33-0.75) during follow-up and switching to methadone had a similar likelihood of arrest as methadone-randomized individuals receiving no treatment. Likelihood of arrest was also negatively associated with older age (0.98, 0.96-1.00); it was positively associated with Hispanic ethnicity (1.63, 1.04-2.56), cocaine use (2.00, 1.33-3.03), injection drug use (2.19, 1.26-3.83), and study site.. In a US sample of people treated for opioid use disorder, continued treatment with either buprenorphine or methadone was associated with a reduction in arrests relative to no treatment. Cocaine use, injection drug use, Hispanic ethnicity and younger age were associated with higher likelihood of arrest.

Topics: Adult; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; California; Criminal Law; Female; Follow-Up Studies; Humans; Male; Methadone; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Patient Outcome Assessment

Regional human immunodeficiency virus (HIV) prevalence rates are high in people with history of injection drug use, including those managed with maintenance opioids. Fostemsavir (FTR) is an oral prodrug of temsavir, a first-in-class attachment inhibitor that binds HIV-1 gp120, preventing initial HIV attachment and entry into host immune cells. Here we determine the impact of FTR on the pharmacokinetics of opioids methadone (MET: R-, S- and total) or buprenorphine and norbuprenorphine (BUP and norBUP) when coadministered.. Study 206216 (NCT02666001) was a Phase I, open-label study, assessing the effect of FTR 600 mg (extended-release formulation) twice daily on pharmacokinetics of MET or BUP and norBUP, in non-HIV-infected participants on stable maintenance therapy with MET (40-120 mg; n = 16) or BUP plus naloxone (8-24 mg plus 2-6 mg; n = 16); pharmacodynamic response was assessed using standard opioid rating scales.. Following coadministration with FTR, dose-normalized MET (R-, S- and total) exposures (maximum concentration in plasma, area under the plasma concentration-time curve over the dosing interval and concentration in plasma at 24 hours) increased 9-15% and BUP and norBUP exposures increased 24-39%. The 90% confidence interval ranges for MET (1.01-1.21) and BUP and norBUP (1.03-1.69) were within respective no-effect ranges (0.7-1.43 and 0.5-2.0). Opioid pharmacodynamic scores were similar with and without MET/BUP with no symptoms of withdrawal/overdose; no new safety signal for FTR when combined with a stable opioid regimen.. FTR did not impact MET and had no clinically significant impact on BUP pharmacokinetics. Standardized assessments of opioid pharmacodynamics were unchanged throughout FTR administration with MET or BUP. FTR can be administered with MET or BUP without dose adjustment.

Topics: Adult; Anti-HIV Agents; Buprenorphine, Naloxone Drug Combination; Cross-Over Studies; Drug Interactions; Female; HIV Infections; HIV-1; Humans; Male; Methadone; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Organophosphates; Piperazines; Young Adult

Extended-release naltrexone (XR-NTX), an opioid antagonist, and sublingual buprenorphine-naloxone (BUP-NX), a partial opioid agonist, are pharmacologically and conceptually distinct interventions to prevent opioid relapse. We aimed to estimate the difference in opioid relapse-free survival between XR-NTX and BUP-NX.. We initiated this 24 week, open-label, randomised controlled, comparative effectiveness trial at eight US community-based inpatient services and followed up participants as outpatients. Participants were 18 years or older, had Diagnostic and Statistical Manual of Mental Disorders-5 opioid use disorder, and had used non-prescribed opioids in the past 30 days. We stratified participants by treatment site and opioid use severity and used a web-based permuted block design with random equally weighted block sizes of four and six for randomisation (1:1) to receive XR-NTX or BUP-NX. XR-NTX was monthly intramuscular injections (Vivitrol; Alkermes) and BUP-NX was daily self-administered buprenorphine-naloxone sublingual film (Suboxone; Indivior). The primary outcome was opioid relapse-free survival during 24 weeks of outpatient treatment. Relapse was 4 consecutive weeks of any non-study opioid use by urine toxicology or self-report, or 7 consecutive days of self-reported use. This trial is registered with ClinicalTrials.gov, NCT02032433.. Between Jan 30, 2014, and May 25, 2016, we randomly assigned 570 participants to receive XR-NTX (n=283) or BUP-NX (n=287). The last follow-up visit was Jan 31, 2017. As expected, XR-NTX had a substantial induction hurdle: fewer participants successfully initiated XR-NTX (204 [72%] of 283) than BUP-NX (270 [94%] of 287; p<0·0001). Among all participants who were randomly assigned (intention-to-treat population, n=570) 24 week relapse events were greater for XR-NTX (185 [65%] of 283) than for BUP-NX (163 [57%] of 287; hazard ratio [HR] 1·36, 95% CI 1·10-1·68), most or all of this difference accounted for by early relapse in nearly all (70 [89%] of 79) XR-NTX induction failures. Among participants successfully inducted (per-protocol population, n=474), 24 week relapse events were similar across study groups (p=0·44). Opioid-negative urine samples (p<0·0001) and opioid-abstinent days (p<0·0001) favoured BUP-NX compared with XR-NTX among the intention-to-treat population, but were similar across study groups among the per-protocol population. Self-reported opioid craving was initially less with XR-NTX than with BUP-NX (p=0·0012), then converged by week 24 (p=0·20). With the exception of mild-to-moderate XR-NTX injection site reactions, treatment-emergent adverse events including overdose did not differ between treatment groups. Five fatal overdoses occurred (two in the XR-NTX group and three in the BUP-NX group).. In this population it is more difficult to initiate patients to XR-NTX than BUP-NX, and this negatively affected overall relapse. However, once initiated, both medications were equally safe and effective. Future work should focus on facilitating induction to XR-NTX and on improving treatment retention for both medications.. NIDA Clinical Trials Network.

Topics: Administration, Oral; Adult; Buprenorphine, Naloxone Drug Combination; Delayed-Action Preparations; Female; Humans; Injections, Intramuscular; Male; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Research Design

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

Rates of non-medical use of opioids, and opioid use disorders (OUD) have been rising throughout North America. Methadone and buprenorphine/naloxone are the recommended first-line treatment options for OUD in Canada. Most studies to date have been conducted among heroin users, in controlled settings, and using similar strict dosing schedules (i.e., daily witnessed ingestion) despite buprenorphine/naloxone's superior safety profile, which allows a more flexible take-home dosing schedule. This study was designed to assess the relative effectiveness of buprenorphine/naloxone- and methadone-based models of opioid agonist therapy (OAT) for the treatment of prescription opioid use disorder (POUD) in routine clinical care.. OPTIMA is a multicenter, open-label, pragmatic, randomized, two-arm, non-inferiority, 24-week study comparing the relative effectiveness of buprenorphine/naloxone (provided via flexible take-home doses) to methadone (provided via daily witnessed ingestion) models of OAT for the treatment of POUD. Approximately 276 non-pregnant adults meeting DSM-5 criteria for OUD, currently not in OAT, will be randomized across 7 Canadian sites. The primary outcome is reduction of non-medical opioid use, measured by bi-weekly urine drug screens during the 24-week study period. Secondary outcomes include treatment retention and satisfaction, safety, medication adherence, and patient engagement.. The OPTIMA study is the first randomized clinical trial to compare the relative effectiveness of buprenorphine/naloxone (flexible take-home doses) versus methadone (daily witnessed ingestion) models of OAT for POUD in real-world clinical settings. This study will generate urgently needed evidence towards treatment options to guide the health system response to the ongoing opioid crisis.. NCT03033732.

Topics: Adult; Analgesics, Opioid; Behavior Observation Techniques; Buprenorphine, Naloxone Drug Combination; Canada; Drug Administration Schedule; Female; Humans; Male; Methadone; Narcotic Antagonists; Needs Assessment; Opiate Substitution Treatment; Opioid-Related Disorders; Prescription Drug Overuse; Substance Abuse Detection

Although buprenorphine/naloxone (bup/nal) is well-established as a safe and effective treatment for opioid use disorders (OUDs), there are few studies reporting 12-month outcomes of patients receiving bup/nal in formerly drug-free outpatient programs.. To examine 12-month outcomes by bup/nal treatment enrollment status among a cohort of African American patients enrolled in a clinical trial.. This analysis builds upon a randomized trial of 300 opioid-dependent African American bup/nal patients in two outpatient programs in Baltimore, MD. A subset of participants (N = 133, n = 47 female) were tracked for a 12-month follow-up interview.. The participants receiving bup/nal at 12 months had significantly fewer opioid-positive urine screens (44% v. 73%) and days of self-reported heroin use (M [SE] = 1.13 [.34] v. 7.12 [1.44]) than the out-of-bup/nal-treatment group (both ps ≤ .001). Similarly, those receiving bup/nal reported significantly fewer days of cocaine use (M [SE] = 0.85 [0.23] v. 2.88[0.75]) and alcohol use (M [SE] = 1.44 [0.38] v. 3.69 [1.04]; both ps<.05). There were no significant differences related to criminal activity, quality of life, and most ASI composite scores. Models adjusting for the baseline value, prior treatment experience, and assigned study condition largely confirmed these findings, except that participants in treatment had fewer days of crime and higher psychological quality of life scores compared to those out-of-treatment.. Those receiving bup/nal at 12 months had significantly lower rates of illicit opioid use than those who were not. Approaches to improve bup/nal treatment retention and reengagement of patients with OUD are needed.

Topics: Alcohol Drinking; Analgesics, Opioid; Black or African American; Buprenorphine, Naloxone Drug Combination; Cocaine; Crime; Female; Follow-Up Studies; Humans; Male; Middle Aged; Opioid-Related Disorders; Quality of Life; Treatment Outcome

Primary care clinics are opportune settings in which to deliver substance use disorder (SUD) treatment, but little is known about which patients initiate treatment in these settings.. Using secondary data from a RCT that aimed to integrate SUD treatment into a federally qualified health center (FQHC) using an organizational readiness and collaborative care (CC) intervention, we examined patient-level predictors of initiation of evidence-based practices for opioid and/or alcohol use disorders (OAUDs): a brief behavioral treatment (BT) based on motivational interviewing and cognitive behavioral therapy and medication-assisted treatment (MAT) (extended-release injectable naltrexone (XR-NTX) for patients with an alcohol use disorder or opioid use disorder and buprenorphine/naloxone (BUP/NX) for patients with an opioid use disorder). Using the Andersen model of health care access, we tested bivariate and multivariate logistic regression models to assess associations between patient factors and initiation of BT and MAT.. Twenty-three percent of all participants (N = 392) received BT and 13% received MAT. In the multivariate model examining factors associated with initiation of BT, being of "other" or "multiple" races compared with being White (OR = 0.45, CI = 0.22, 0.92), being homeless (OR = 0.45, CI = 0.21, 0.97) and having been arrested within 90 days of baseline (OR = 0.21 CI = 0.63, 0.69) were associated with significantly lower odds of initiating BT. Greater self-stigma (OR = 1.60, CI = 1.06, 2.42), receiving MAT (OR = 5.52, CI = 2.34, 12.98), and having received the CC study intervention (OR = 12.95, CI = 5.91, 28.37) were associated with higher odds of initiating BT. In the multivariate model examining patient factors associated with initiating MAT, older age (OR = 1.07, CI = 1.03, 1.11), female gender (OR = 3.05, CI = 1.25, 7.46), having a diagnosis of heroin abuse or dependence (with or without alcohol abuse or dependence compared with have a diagnosis of alcohol dependence only (OR = 3.03, CI = 1.17, 7.86), and having received at least one session of BT (OR = 6.42, CI = 2.59, 15.94), were associated with higher odds of initiating MAT.. Individuals who initiate BT for OAUDs in a FQHC are less likely to be homeless and more likely to have greater self-stigma. Those who receive MAT are more likely to be of older age, female, and to have a diagnosis of heroin abuse or dependence, with or without concomitant alcohol abuse or dependence, rather than alcohol abuse or dependence alone. Receiving collaborative care (e.g., a warm handoff, and follow-up by a care coordinator) may be critical to initiating BT. Receiving at least one session of BT is associated with higher odds of receiving MAT, and receiving MAT is associated with higher odds of receiving BT. The Andersen model of health care access provides some insight into who initiates BT and MAT for OAUD treatment in FQHC-based primary care; further research is needed to explore system-level factors that may also influence treatment initiation.

Topics: Adult; Age Factors; Alcoholism; Buprenorphine, Naloxone Drug Combination; Cognitive Behavioral Therapy; Cooperative Behavior; Female; Health Services Accessibility; Humans; Logistic Models; Male; Middle Aged; Motivational Interviewing; Multivariate Analysis; Naltrexone; Opioid-Related Disorders; Primary Health Care; Psychotherapy, Brief; Sex Factors

Opioid use disorder (OUD) is a chronic, relapsing condition with severe negative health consequences. Previous studies have reported that 5-year opioid abstinence is a good predictor of reduced likelihoods of relapse, but factors that shape long-term opioid abstinence are poorly understood. The present study is based on data from a prospective study of 699 adults with OUD who had been randomized to either methadone or buprenorphine/naloxone and who were followed for at least 5 years. During the 5 years prior to the participants' last follow-up interview, 232 (33.2%) had achieved 5-year abstinence from heroin. Of those 232, 145 (20.7% of the total) had remained abstinent from both heroin and other opioids (e.g., hydrocodone, oxycodone, other opioid analgesics, excluding methadone or buprenorphine). Compared to non-abstinent individuals, those in both categories of opioid abstinence had lower problem severity in health and social functioning at the final follow-up. Logistic regression results indicated that cocaine users and injection drug users were less likely to achieve 5-year heroin abstinence, whereas Hispanics (vs. whites) and those treated in clinics on the West Coast (vs. East) were less likely to achieve 5-year abstinence from heroin and other opioids. For both abstinence category groups, abstinence was positively associated with older age at first opioid use, lower impulsivity, longer duration of treatment for OUD, and greater social support. Reducing cocaine use and injection drug use and increasing social support and retention in treatment may help maintain long-term abstinence from opioids among individuals treated with agonist pharmacotherapy.

Topics: Adolescent; Adult; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Female; Follow-Up Studies; Humans; Male; Methadone; Middle Aged; Opioid-Related Disorders; Time Factors; Young Adult

While buprenorphine/naloxone (B/N) is approved for opioid use disorder treatment, effective delivery of B/N comes with significant challenges. Most notably, many patients do not take medication daily as prescribed; this non-adherence worsens treatment outcomes, increases healthcare costs, and leads to persistent worries of diversion among providers and policymakers. The present study examines the feasibility, usability, and acceptability of MySafeRx-a mobile technology platform integrating motivational coaching, adherence monitoring, and electronic pill dispensing designed to address the challenges of office-based opioid treatment (OBOT) with B/N.. The MySafeRx platform integrates electronic pill dispensers, text-messaging, and videoconferencing to provide supervised self-administration of medication and daily motivational coaching through an Android app interface. High-risk early adults (18-39 years old) who were enrolled in OBOT with B/N and had documented illicit opioid use in the past month during opioid agonist therapy (n = 12) participated in a 28-day single-arm observational study of the MySafeRx platform in addition to standard care.. Two-thirds of participants who completed the study achieved an average of > 5 days per week of supervised B/N self-administration. Visual confirmation of medication adherence was demonstrated for an average of 72% of study days among all participants. All participants achieved platform technical proficiency within 60 min, reporting good levels of usability and acceptability. Illicit opioid abstinence rates confirmed by urine toxicology increased by 53% during MySafeRx but fell 43% within 3 weeks post-intervention.. The MySafeRx medication adherence and remote coaching mobile platform is acceptable and can be feasibly implemented in real-world opioid use disorder treatment settings during high-risk periods (i.e., initial stabilization, after illicit opioid lapse), resulting in reduced illicit opioid use; however, the effect did not last after intervention completion, suggesting longer duration or extended taper of program may be needed. ClinicalTrials.Gov NCT02942199 10/24/16 https://clinicaltrials.gov/ct2/show/NCT02942199.

Topics: Adolescent; Adult; Buprenorphine, Naloxone Drug Combination; Female; Humans; Male; Medication Adherence; Mentoring; Mobile Applications; Motivation; Opioid-Related Disorders; Patient Satisfaction; Pilot Projects; Reminder Systems; Smartphone; Text Messaging; Videoconferencing; Young Adult

To estimate the costs of providing extended-release injectable naltrexone (XR-NTX) and buprenorphine-naloxone (BUP-NX) following inpatient detoxification using data derived from a multisite randomized controlled trial at 8 US community-based treatment programs.. Cost data were collected for 3 intervention phases: program start-up, inpatient detoxification, and up to 24 weeks of medication induction and management visits (post detoxification). Cost analyses were from the healthcare sector perspective (2015 US$); patient costs are also reported.. We conducted site visits, administered a cost survey to treatment programs, and analyzed study data on medication and services utilization. Nationally representative sources were used to estimate unit costs. Uncertainty was evaluated in sensitivity analyses.. Mean start-up costs were $1071 per program for XR-NTX and $828 per program for BUP-NX. Mean costs per participant were $5416 for XR-NTX (57% detoxification, 37% medication, 3% provider, 3% patient) and $4148 for BUP-NX (64% detoxification, 12% medication, 10% provider, 14% patient). Total cost per participant ranged by site from $2979 to $8963 for XR-NTX and from $2521 to $6486 for BUP-NX.. For treatment providers, offering XR-NTX and/or BUP-NX as part of existing detoxification treatment modalities generates modest costs in addition to the costs of detoxification, which vary substantially among the 8 sites. From the patient's perspective, the costs associated with medication management visits may be a barrier for some individuals considering these treatments.

Topics: Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Costs and Cost Analysis; Delayed-Action Preparations; Humans; Injections, Intramuscular; Narcotic Antagonists; Opioid-Related Disorders; Recurrence; United States

The multi-site Prescription Opioid Addiction Treatment Study (POATS), conducted by the National Drug Abuse Treatment Clinical Trials Network, was the largest clinical trial yet conducted with patients dependent upon prescription opioids (N=653). In addition to main trial results, the study yielded numerous secondary analyses, and included a 3.5-year follow-up study, the first of its kind with this population. This paper reviews key findings from POATS and its follow-up study.. The paper summarizes the POATS design, main outcomes, predictors of outcome, subgroup analyses, the predictive power of early treatment response, and the long-term follow-up study.. POATS examined combinations of buprenorphine-naloxone of varying duration and counseling of varying intensity. The primary outcome analysis showed no overall benefit to adding drug counseling to buprenorphine-naloxone and weekly medical management. Only 7% of patients achieved a successful outcome (abstinence or near-abstinence from opioids) during a 4-week taper and 8-week follow-up; by comparison, 49% of patients achieved success while subsequently stabilized on buprenorphine-naloxone. Long-term follow-up results were more encouraging, with higher abstinence rates than in the main trial. Patients receiving opioid agonist treatment at the time of follow-up were more likely to have better outcomes, though a sizeable number of patients succeeded without agonist treatment. Some patients initiated risky use patterns, including heroin use and drug injection. A limitation of the long-term follow-up study was the low follow-up rate.. POATS was the first large-scale study of the treatment of prescription opioid dependence; its findings can influence both treatment guidelines and future studies.

Topics: Adult; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Combined Modality Therapy; Counseling; Follow-Up Studies; Heroin Dependence; Humans; Male; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Prescription Drug Misuse

Buprenorphine/naloxone, methadone and lofexidine are medications with utility in the treatment of opiate withdrawal. We report the first randomised controlled trial to compare the effects of these two medications on withdrawal symptoms and outcome during opiate induction/stabilisation and detoxification. A double-blind randomised controlled trial was conducted in an outpatient satellite clinic of a specialist drug service. Eighty opiate dependent individuals meeting DSM-IV criteria for opiate dependence, using ⩽ ½ g heroin smoked/chased or ¼ g heroin injected or ⩽ 30mg methadone, with ⩽ 3 years of opioid dependency, underwent a short-term opiate treatment programme involving induction/stabilisation on methadone 30mg or buprenorphine/naloxone 4mg/1mg, followed by detoxification (where the methadone group was assisted by lofexidine). The main outcome measures were urine drug screens for opiates and withdrawal and craving questionnaires. There were no overall differences in positive urine drug screens and drop-outs during any phase of the study. During induction/stabilisation, withdrawal symptoms subsided more slowly for buprenorphine/naloxone than for methadone, and craving was significantly higher in the buprenorphine/naloxone group ( p<0.05, 95% confidence interval -3.5, -0.38). During detoxification, withdrawal symptoms were significantly greater and the peak of withdrawal was earlier for the methadone/lofexidine group than the buprenorphine/naloxone group ( p<0.01, 95% confidence interval 3.0, 8.3). Methadone/lofexidine and buprenorphine/naloxone had comparable outcomes during rapid outpatient stabilisation and detoxification in low dose opiate users.

Topics: Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Clonidine; Craving; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Methadone; Narcotic Antagonists; Opioid-Related Disorders; Substance Withdrawal Syndrome; 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

To date, extended-release naltrexone hydrochloride has not previously been compared directly with opioid medication treatment (OMT), currently the most commonly prescribed treatment for opioid dependence.. To determine whether treatment with extended-release naltrexone will be as effective as daily buprenorphine hydrochloride with naloxone hydrochloride in maintaining abstinence from heroin and other illicit substances in newly detoxified individuals.. A 12-week, multicenter, outpatient, open-label randomized clinical trial was conducted at 5 urban addiction clinics in Norway between November 1, 2012, and December 23, 2015; the last follow-up was performed on October 23, 2015. A total of 232 adult opioid-dependent (per DSM-IV criteria) individuals were recruited from outpatient addiction clinics and detoxification units and assessed for eligibility. Intention-to-treat analyses of efficacy end points were performed with all randomized participants.. Randomization to either daily oral flexible dose buprenorphine-naloxone, 4 to 24 mg/d, or extended-release naltrexone hydrochloride, 380 mg, administered intramuscularly every fourth week for 12 weeks.. Primary end points (protocol) were the randomized clinical trial completion rate, the proportion of opioid-negative urine drug tests, and number of days of use of heroin and other illicit opioids. Secondary end points included number of days of use of other illicit substances. Safety was assessed by adverse event reporting.. Of 159 participants, mean (SD) age was 36 (8.6) years and 44 (27.7%) were women. Eighty individuals were randomized to extended-release naltrexone and 79 to buprenorphine-naloxone; 105 (66.0%) completed the trial. Retention in the extended-release naltrexone group was noninferior to the buprenorphine-naloxone group (difference, -0.1; with 95% CI, -0.2 to 0.1; P = .04), with mean (SD) time of 69.3 (25.9) and 63.7 (29.9) days, correspondingly (P = .33, log-rank test). Treatment with extended-release naltrexone showed noninferiority to buprenorphine-naloxone on group proportion of total number of opioid-negative urine drug tests (mean [SD], 0.9 [0.3] and 0.8 [0.4], respectively, difference, 0.1 with 95% CI, -0.04 to 0.2; P < .001) and use of heroin (mean difference, -3.2 with 95% CI, -4.9 to -1.5; P < .001) and other illicit opioids (mean difference, -2.7 with 95% CI, -4.6 to -0.9; P < .001). Superiority analysis showed significantly lower use of heroin and other illicit opioids in the extended-release naltrexone group. No significant differences were found between the treatment groups regarding most other illicit substance use.. Extended-release naltrexone was as effective as buprenorphine-naloxone in maintaining short-term abstinence from heroin and other illicit substances and should be considered as a treatment option for opioid-dependent individuals.. clinicaltrials.gov Identifier: NCT01717963.

Topics: Administration, Oral; Adult; Buprenorphine, Naloxone Drug Combination; Delayed-Action Preparations; Diagnostic and Statistical Manual of Mental Disorders; Drug Monitoring; Female; Humans; Injections, Intramuscular; Male; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Psychiatric Status Rating Scales; Substance Abuse Detection; Treatment Outcome

Among persons with opioid use disorder (OUD), neuropsychological dysfunction is associated with depression, and better neuropsychological function is associated with opioid abstinence. However, it is unknown whether depressive symptomatology or adherence to opiate agonist treatment are associated with neuropsychological change over time.. We recruited 20 buprenorphine/naloxone-treated adults with OUD (M Age = 45.2 years [SD = 8.1]; 25% female) to complete baseline and 6 month visits containing a neuropsychological test battery and self-reported measures of depressive symptomatology and medication adherence.. Depressive symptomatology was not significantly related to neuropsychological change (p's > .05). Greater adherence to buprenorphine/naloxone was associated with improvements in learning, memory, and global functioning (r's = .52-60; p's < .05).. Among OUD patients, greater adherence to buprenorphine/naloxone is associated with improved neuropsychological functioning over time. In contrast, depressive symptomatology is not associated with neuropsychological functioning over time. Supporting adherence to buprenorphine/naloxone may improve and/or preserve learning and memory functioning in individuals treated for OUD.. NCT01108679 . Registered 21 April 2010.

Topics: Adult; Buprenorphine, Naloxone Drug Combination; Cognitive Dysfunction; Depression; Female; Humans; Male; Medication Adherence; Middle Aged; Narcotic Antagonists; Neuropsychological Tests; Opiate Substitution Treatment; Opioid-Related Disorders; Pilot Projects

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

Interim methadone treatment (i.e., temporary medication-only treatment) has been tested in a few U.S. studies as a method for facilitated referral to and initiation of opioid maintenance treatment in heroin dependence. However, despite the favorable safety profile of buprenorphine compared with methadone, interim treatment with buprenorphine rarely has been tested and reported in the scientific literature. The present pilot effectiveness study aims to assess the feasibility of an interim buprenorphine treatment for initiation of individuals with opiate dependence into full-scale opioid maintenance treatment, and to study baseline predictors of successful transfer to full-scale treatment.. Interim treatment was introduced in a high-threshold setting with waiting lists to opioid maintenance treatment. Consecutive patients on the waiting list were offered the option to enter interim treatment. The interim program was a medication-only condition with supervised daily doses of buprenorphine-naloxone. The main outcome was successful transfer to full-scale opioid maintenance treatment, which required a drug-free urine sample.. Forty-four patients entered interim buprenorphine treatment. Among them, 57% (n = 25) were successfully transferred to full-scale treatment after an average of 44 days. Remaining patients could not be transferred, generally because they did not manage to become drug-free. Successful transfer to full-scale treatment was associated with a lower baseline Alcohol Use Disorders Identification Test (AUDIT) score (4.4 vs. 12.6; P < .001) and tended to be associated with lower cannabis use (5.2 vs. 10.4 days during the past 30 days; P = .06) and lower heroin use (7.2 vs. 9.9 days; P = .09) prior to baseline. In a logistic regression analysis, only lower AUDIT score predicted successful treatment entry.. According to these pilot data, supervised buprenorphine-naloxone in a medication-only interim treatment condition appears to be a feasible way to improve treatment initiation in a high-threshold setting. Polydrug use, including higher levels of alcohol consumption, may predict a more complicated course in interim treatment.

Topics: Adult; Buprenorphine, Naloxone Drug Combination; Continuity of Patient Care; Female; Humans; Male; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Pilot Projects; Young Adult

To compare long-term outcomes among participants randomized to buprenorphine or methadone.. Follow-up was conducted in 2011-14 of 1080 opioid-dependent participants entering seven opioid treatment programs in the United States between 2006 and 2009 and randomized (within each program) to receive open-label buprenorphine/naloxone or methadone for up to 24 weeks; 795 participants completed in-person interviews (~74% follow-up interview rate) covering on average 4.5 years.. Outcomes were indicated by mortality and opioid use. Covariates included demographics, site, cocaine use and treatment experiences.. Mortality was not different between the two randomized conditions, with 23 (3.6%) of 630 participants randomized to buprenorphine having died versus 26 (5.8%) of 450 participants randomized to methadone. Opioid use at follow-up was higher among participants randomized to buprenorphine relative to methadone [42.8 versus 31.7% positive opioid urine specimens, P < 0.01, effect size (h) = 0.23 (0.09, 0.38); 5.8 days versus 4.4 days of past 30-day heroin use, P < 0.05, effect size (d) = 0.14 (0.00, 0.28)]. Opioid use during the follow-up period by randomization condition was also significant (F(7,39,600) = 3.16; P < 0.001) due mainly to less treatment participation among participants randomized to buprenorphine than methadone. Less opioid use was associated with both buprenorphine and methadone treatment (relative to no treatment); no difference was found between the two treatments. Individuals who are white or used cocaine at baseline responded better to methadone than to buprenorphine.. There are few differences in long-term outcomes between buprenorphine and methadone treatment for opioid dependence, and treatment with each medication is associated with a strong reduction in opioid use.

Topics: Adolescent; Adult; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Female; Follow-Up Studies; Humans; Male; Methadone; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Random Allocation; Treatment Outcome; Young Adult

With the broad goals of developing a clinical research and training program and disseminating effective opioid use disorder treatments in Iran, this pilot clinical trial compared the effectiveness of oral naltrexone (NTX) and sublingual buprenorphine/naloxone (BNX).. Twelve-week single-site, two-group parallel randomized double-blind clinical trial.. An out-patient clinical research program in Tehran, Iran.. Following medically assisted withdrawal, participants with opioid use disorder were assigned randomly to NTX (n = 51) or BNX (n = 51).. Medications were administered three times per week, double-blind, double-dummy for 12 weeks. All participants received weekly group drug counseling.. The primary outcome was initial duration of opioid abstinence verified by urine toxicology tests. Secondary outcomes included the number of opioid-negative urine tests, treatment retention and proportions with sustained, verified opioid-abstinence for 12 weeks.. Mean [95% confidence interval (CI)] number of days of initial duration of verified abstinence was 28.8 (20.0-37.5) with BNX and 21.6 (14.4-28.7) with NTX (P = 0.205). The mean (95% CI) number of opioid-negative urine tests was 19.7 (17.7-21.6) with BNX and 15.4 (13.1-17.8) with NTX (P = 0.049). The mean (95% CI) number of days in treatment was 70.6 (63.6-77.7) with BNX versus 56.5 (47.8-65.3) with NTX (P = 0.013). The rate of sustained, 12-week opioid abstinence was 16% (8/51) in the BNX group and 8% (4/51) in the NTX group (P = 0.219).. Among patients with opioid use disorder in Iran, sublingual buprenorphine/naloxone was associated with a greater number of opioid-negative urine tests and treatment retention than oral naltrexone, but not significantly greater initial abstinence duration or proportions with sustained abstinence.

Topics: Adult; Ambulatory Care; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Counseling; Double-Blind Method; Humans; Iran; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Substance Abuse Detection

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

Current guidelines for opioid dependence recommend daily maintenance of physical dependence with methadone or buprenorphine, and discourage abstinence due to the high risk of relapse and overdose. Extended-release formulations of the opioid antagonist naltrexone (XR-NTX) block heroin and other opioid agonists competitively for around 4 weeks per administration. XR-NTX thus enables opioid users to experience abstinence from opioid agonists with greatly reduced risk of overdose compared to medication-free abstinence. While XR-NTX has shown promise compared to placebo and daily naltrexone tablets, there is limited information on long-term safety and its performance compared to daily maintenance treatment.. In this five-hospital RCT with long-term follow-up, we aim to recruit n = 180 patients in treatment for opioid dependence and allocate them in an open, randomized manner (1:1) to receive either 4-week XR-NTX or daily buprenorphine-naloxone (BP-NLX) for the duration of 12 weeks. Allocation is open-label due to the risk of overdose during attempts to self-unmask allocation using heroin. Urine drug tests are scheduled every week with follow-up visits & assessment every 4 weeks. Primary outcomes are abstinence from illicit opioids in urine drug tests and self-report, as well as retention in treatment. Secondary outcomes include other substance use, injecting behavior, drug craving, mental health, quality of life, treatment satisfaction, abstinence motivation, opioid agonist effect rating, insomnia, and pain. Observation is continued for another 36 weeks in order to assess longer-term safety, adherence and effectiveness. The study is an investigator-initiated trial, funded by public grants and approved by an Independent Ethical Committee (the Regional Ethical Committee for Research South-East B # 2011/1320) and the Norwegian Medicines Agency.. Despite minor implementation problems, the protocol appears sufficiently robust to generate results of high interest to patients, clinicians and policy makers.. Clinicaltrials.gov # NCT01717963 , first registered: Oct 28, 2012. Protocol version # 3C, June 12th 2012.

Topics: Adult; Buprenorphine, Naloxone Drug Combination; Delayed-Action Preparations; Female; Follow-Up Studies; Humans; Injections, Intramuscular; Male; Naltrexone; Narcotic Antagonists; Norway; Opioid-Related Disorders

Patients with prescription opioid use disorder commonly report relief of chronic pain as the chief reason for first opioid use; indeed, the prevalence of chronic pain is high in this population. Understanding the association between pain severity and subsequent opioid use is crucial for understanding how to manage these conditions simultaneously and has not been examined in this population. The aim of this analysis was to examine the proximal effect of pain severity on opioid use during 12 weeks of buprenorphine-naloxone therapy for patients with chronic pain and prescription opioid use disorder.. This study is a secondary analysis of a national, randomized, controlled trial of buprenorphine-naloxone plus counseling for prescription opioid dependent patients. The association between past-week pain severity and opioid use in the subsequent week was examined in 148 patients presenting with chronic pain at baseline.. Results from a multivariable logistic regression model showed that greater pain severity in a given week was significantly associated with increased odds of opioid use in the following week over the 12-week treatment, even after adjusting for covariates associated with opioid use (aOR=1.15, p<0.001).. Despite previous reports of no association between baseline pain and subsequent opioid use, our findings suggest that patients who experience flare-ups of pain during treatment are prone to relapse to opioid use. Future studies may identify those who are at risk to use opioids by carefully monitoring patterns of their pain intensity over time.

Topics: Adolescent; Adult; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Chronic Pain; Counseling; Female; Humans; Longitudinal Studies; Male; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Pain Management; Prescription Drug Misuse; Recurrence; Severity of Illness Index; Young Adult

For opioid-dependent patients in the US and elsewhere, detoxification and counseling-only aftercare are treatment mainstays. Long-term abstinence is rarely achieved; many patients relapse and overdose after detoxification. Methadone, buprenorphine-naloxone (BUP-NX) and extended-release naltrexone (XR-NTX) can prevent opioid relapse but are underutilized. This study is intended to develop an evidence-base to help patients and providers make informed choices and to foster wider adoption of relapse-prevention pharmacotherapies.. The National Institute on Drug Abuse's Clinical Trials Network (CTN) study CTN-0051, X:BOT, is a comparative effectiveness study of treatment for 24weeks with XR-NTX, an opioid antagonist, versus BUP-NX, a high affinity partial opioid agonist, for opioid dependent patients initiating treatment at 8 short-term residential (detoxification) units and continuing care as outpatients. Up to 600 participants are randomized (1:1) to XR-NTX or BUP-NX.. The primary outcome is time to opioid relapse (i.e., loss of persistent abstinence) across the 24-week treatment phase. Differences between arms in the distribution of time-to-relapse will be compared (construction of the asymptotic 95% CI for the hazard ratio of the difference between arms). Secondary outcomes include proportions retained in treatment, rates of opioid abstinence, adverse events, cigarette, alcohol, and other drug use, and HIV risk behaviors; opioid cravings, quality of life, cognitive function, genetic moderators, and cost effectiveness.. XR-NTX and BUP-NX differ considerably in their characteristics and clinical management; no studies to date have compared XR-NTX with buprenorphine maintenance. Study design choices and compromises inherent to a comparative effectiveness trial of distinct treatment regimens are reviewed.. NCT02032433.

Topics: Buprenorphine, Naloxone Drug Combination; Comparative Effectiveness Research; Cost-Benefit Analysis; Delayed-Action Preparations; Female; Humans; Injections, Intramuscular; Male; Naltrexone; Narcotic Antagonists; National Institute on Drug Abuse (U.S.); Opioid-Related Disorders; Socioeconomic Factors; United States

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

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

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

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

Suboxone(®) is a sublingual tablet of buprenorphine/naloxone, approved for the treatment of opioid dependence. The objective of this study was to quantify the impact of hepatic impairment or hepatitis C virus infection on the pharmacokinetics of buprenorphine or naloxone and their major metabolites.. Forty-three subjects received a single dose of a Suboxone 2.0/0.5-mg tablet. Blood samples were collected up to 168 h and pharmacokinetic parameters were calculated using non-compartmental analysis. Statistical analysis was performed using analysis of covariance.. Pharmacokinetic parameters were derived from 33 subjects. Compared with healthy subjects, for patients with severe hepatic impairment, total and peak exposures increased to 281.4 % [90 % confidence interval 187.1-423.3] and 171.8 % [117.9-250.2] for buprenorphine, 1401.9 % [707.6-2777.5] and 1129.8 % [577.2-2211.4] for naloxone. For moderate hepatic impaired subjects, naloxone total and peak exposure increased to 317.6 % [164.9-611.5] and 270.0  % [141.9-513.9]. For buprenorphine, only total exposure increased to 163.9 % [110.8-242.3]. Changes in maximum observed plasma concentration, area under the plasma concentration-time curve from time zero to time of the last quantifiable concentration, and area under the plasma concentration-time curve from time zero to infinity of buprenorphine or naloxone in subjects with mild hepatic impairment or with hepatitis C virus infection were within twofold of those of healthy subjects. Serious adverse events were not observed.. Severe and moderate hepatic impairment significantly increased exposure of naloxone and to a lesser extent of buprenorphine. Therefore, buprenorphine/naloxone combination products should generally be avoided in patients with severe hepatic impairment and may not be appropriate for patients with moderate hepatic impairment. However, buprenorphine/naloxone products may be used with caution for maintenance treatment in patients with moderate hepatic impairment who have initiated treatment on a buprenorphine product without naloxone [Registered at ClinicalTrials.gov as NCT01846455].

Topics: Adult; Buprenorphine, Naloxone Drug Combination; Case-Control Studies; Female; Hepatitis C; Humans; Liver Diseases; Male; Middle Aged; Opioid-Related Disorders; 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 purpose of this study was to provide a preliminary assessment of the safety, tolerability, symptom control, and acceptability of buprenorphine-naloxone buccal film (BBN) for the maintenance treatment of opioid dependence in patients converted from buprenorphine-naloxone sublingual tablet or film (SLBN), as well as to determine the conversion ratio for switching patients from SLBN to BBN.. This open-label study included adult opioid-dependent subjects stabilized on 8/2 to 32/8 mg/d of SLBN for a minimum of 30 days. Study subjects were converted to a bioequivalent dose of BBN and maintained for 12 weeks.. A total of 249 subjects (mean age 38.7 years, 65.9% male) were converted from SLBN to a single daily dose of BBN, and 79.1% completed the 12-week study. Adverse events and withdrawal symptoms led to discontinuation in 2.4% and 2.0% of BBN-treated subjects, respectively. Rates of constipation reported at baseline declined from 41% just before the initial BBN dose and within 24 hours of the last SLBN dose to 13% after 12 weeks of BBN treatment; treatment-emergent constipation was reported by 2.8% of BBN-treated subjects. Oral mucosal abnormalities were identified in 5% and 0.6% of systematic oral examinations in SLBN- and BBN-treated subjects, respectively. A total of 34 subjects had Clinical Opiate Withdrawal Scale total scores ranging from 10 to 25 (overall mean, 13.8) within 24 hours of taking their last SLBN dose, and scores for these subjects were reduced to a range of 0 to 3 (overall mean, 0.7) at 3 hours after the initial dose of BBN. Treatment compliance was high (108%); <1% of urine samples were buprenorphine-free, and 92.4% of BBN-treated subjects did not have a urine sample that tested positive for a non-prescribed opioid. A total of 91.3% subjects rated the taste of BBN as pleasant or neutral, and 82.5% rated BBN ease of use as easy or neutral. The overall mean final dose of BBN was 8.0/1.4 mg/d, yielding a 2:1 buprenorphine conversion ratio.. Although these results should be considered preliminary due to the open-label design, BBN was overall safe and well tolerated, and seemed to provide adequate symptom control, in the treatment of opioid-dependent subjects previously controlled on SLBN for a minimum of 30 days. There was good adherence to study medication and favorable patient acceptance of the buccal formulation. The SLBN/BBN buprenorphine conversion ratio was 2:1. ClinicalTrials.gov identifier: NCT01666119.

Topics: Administration, Buccal; Administration, Sublingual; Adult; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Chemistry, Pharmaceutical; Drug Substitution; Female; Humans; Male; Medication Adherence; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Substance Withdrawal Syndrome; Treatment Outcome; Young Adult

As the baby boomers age, the number of older adults with comorbid substance use and mental disorders is projected to grow. Little research has examined the potential impact of substance use on older adults' mental health treatment use and unmet treatment need. This study examined these associations among the rapidly growing population of baby boomers and their older counterparts.. Data are from the 2008 to 2012 National Survey on Drug Use and Health (NSDUH) (N = 18,443 respondents aged 50-64 and 11,191 aged 65 +). Age-combined and age-stratified logistic regression analyses were used to examine relationships between alcohol, illicit drug, and tobacco use and mental health problems, treatment use, and perceived unmet treatment need, with sociodemographic characteristics and health status as covariates.. Heavy alcohol, illicit drug, and tobacco use increased the odds of having a mental health problem in both age groups. Compared to those who used alcohol on 1-99 days during the preceding year, lifetime abstainers had significantly lower odds of having received mental health treatment in both age groups. Poorer self-rated health and past-year mental health treatment use increased the odds of perceived unmet treatment need in both age groups, while lifetime abstention in the boomers decreased the odds.. This study's key finding is the lower likelihood of mental health treatment use among lifetime abstainers in both age groups. Further research may identify barriers to treatment use and ways to promote use among both age groups.

Topics: Adolescent; Adult; Age Factors; Alcoholism; Buprenorphine, Naloxone Drug Combination; Comorbidity; Female; Health Services Needs and Demand; Humans; Male; Mental Health Services; Middle Aged; Narcotics; Opioid-Related Disorders; Patient Satisfaction; Population Growth; Prescription Drug Misuse; Quality of Life; Substance-Related Disorders; United States; Utilization Review; Young Adult

The combination of prescription opioid dependence and chronic pain is increasingly prevalent and hazardous to public health. Variability in pain may explain poor prescription opioid addiction treatment outcomes in persons with chronic pain. This study examined pain trajectories and pain volatility in patients with chronic pain receiving treatment for prescription opioid addiction. We conducted secondary analyses of adults with chronic pain (n = 149) who received buprenorphine/naloxone (BUP/NLX) and counseling for 12 weeks in an outpatient, multisite clinical trial. Good treatment outcome was defined as urine-verified abstinence from opioids at treatment endpoint (Week 12) and during at least 2 of the previous 3 weeks. Pain severity significantly declined over time during treatment (b = -0.36, p < .001). Patients with greater pain volatility were less likely to have a good treatment outcome (odds ratio = 0.55, p < .05), controlling for baseline pain severity and rate of change in pain over time. A 1 standard deviation increase in pain volatility was associated with a 44% reduction in the probability of endpoint abstinence. The significant reduction in subjective pain during treatment provides observational support for the analgesic effects of BUP/NLX in patients with chronic pain and opioid dependence. Patients with greater volatility in subjective pain during treatment have increased risk of returning to opioid use by the conclusion of an intensive treatment with BUP/NLX and counseling. Future research should examine underlying mechanisms of pain volatility and identify related therapeutic targets to optimize interventions for prescription opioid addiction and co-occurring chronic pain.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Behavior, Addictive; Buprenorphine, Naloxone Drug Combination; Chronic Pain; Combined Modality Therapy; Counseling; Female; Humans; Male; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Treatment Outcome; Young Adult

Induction is a crucial period of opioid addiction treatment. This study aimed to identify buprenorphine/naloxone (BUP) induction patterns and examine their association with outcomes (opioid use, retention, and related adverse events [AEs]).. The secondary analysis of a study of opioid-dependent adults seeking treatment in eight treatment settings included 740 participants inducted on BUP with flexible dosing.. Latent class analysis models detected six distinctive induction trajectories: bup1-started and remained on low; bup2-started low, shifted slowly to moderate; bup3-started low, shifted quickly to moderate; bup4-started high, shifted to low; bup5-started and remained on moderate; bup6-started moderate, shifted to high dose (Fig. 1). Baseline characteristics, including Clinical Opioid Withdrawal Scale (COWS), were important predictors of retention. When controlled for the baseline characteristics, bup6 participants were three times less likely to drop out the first 7 days than bup1 participants (adjusted hazard ratio (aHR) = .28, p = .03). Opioid use and AEs were similar across trajectories. Participants on ≥16 mg BUP compared to those on <16 mg at Day 28 were less likely to drop out (aHR = .013, p = .001) and less likely to have AEs during the first 28 days (aOR = .57, p = .03).. BUP induction dosing was guided by an objective measure of opioid withdrawal. Participants with higher baseline COWS whose BUP doses were raised more quickly were less likely to drop out in the first 7 days than those whose doses were raised slower.. This study supports the use of an objective measure of opioid withdrawal (COWS) during BUP induction to improve retention early in treatment.

Topics: Adult; Buprenorphine, Naloxone Drug Combination; Drug Administration Schedule; Female; Humans; Male; Narcotic Antagonists; Opioid-Related Disorders; Patient Dropouts; Treatment Outcome; Young Adult

In a previously reported randomized controlled trial, formerly opioid-dependent prisoners were more likely to enter community drug abuse treatment when they were inducted in prison onto buprenorphine/naloxone (hereafter called buprenorphine) than when they received counseling without buprenorphine in prison (47.5% vs. 33.7%, p=0.012) (Gordon et al., 2014). In this communication we report on the results of the induction schedule and the adverse event profile seen in pre-release prisoners inducted onto buprenorphine.. This paper examines the dose induction procedure, a comparison of the proposed versus actual doses given per week, and side effects reported for 104 adult participants who were randomized to buprenorphine treatment in prison. Self-reported side effects were analyzed using generalized estimated equations to determine changes over time in side effects.. Study participants were inducted onto buprenorphine at a rate faster than the induction schedule. Of the 104 (72 males, 32 females) buprenorphine recipients, 64 (37 males, 27 females) remained on medication at release from prison. Nine participants (8.6%) discontinued buprenorphine because of unpleasant opioid side effects. There were no serious adverse events reported during the in-prison phase of the study. Constipation was the most frequent symptom reported (69 percent).. Our findings suggest that buprenorphine administered to non-opioid-tolerant adults should be started at a lower, individualized dose than customarily used for adults actively using opioids, and that non-opioid-tolerant pre-release prisoners can be successfully inducted onto therapeutic doses prior to release.

Topics: Adult; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Counseling; Female; Humans; Male; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Prisoners; Prisons

Sublingual buprenorphine and combination buprenorphine/naloxone (BNX) are effective options for the treatment of opioid dependence. A BNX sublingual tablet approved by the US Food and Drug Administration for the induction and maintenance treatment of opioid-dependence in adults was developed as a higher-bioavailability formulation, allowing for a 30% lesser dose of buprenorphine with bioequivalent systemic exposure compared with another BNX sublingual tablet formulation. No data were previously available comparing the higher-bioavailability BNX sublingual tablet to generic buprenorphine or BNX sublingual film; we therefore evaluated treatment retention during induction and stabilization with the higher-bioavailability BNX sublingual tablet versus generic buprenorphine or BNX sublingual film.. This multicenter, prospective, randomized, parallel-group noninferiority trial was conducted at 43 centers in the United States. Eligible patients were adults aged 18 to 65 years who met the criteria for opioid dependence and had at least mild withdrawal symptoms. On days 1 and 2, patients received blinded, fixed-dose induction with the higher-bioavailability BNX sublingual tablet or generic buprenorphine. On days 3 to 14, patients induced with BNX received open-label, titrated doses of the BNX tablet for stabilization; patients induced with buprenorphine received sublingual BNX film. Co-primary end points were treatment retention on days 3 and 15; noninferiority was concluded if the lower limit of the 95% CI of the between-group difference in treatment retention was ≥-10%. Tolerability was assessed throughout the study period.. A total of 758 opioid-dependent patients were included in the study (BNX sublingual tablet, 383 patients; generic buprenorphine, 375). Day-3 retention rates were 93.9% (309/329) and 92.6% (302/326) with the BNX tablet and buprenorphine, respectively (between-group difference 95% CI, -2.6 to 5.1). Day-15 retention rates were 83.0% (273/329) and 82.5% (269/326) with the BNX tablet and BNX film, respectively (between-group difference 95% CI, -5.3 to 6.3). No unexpected tolerability issues were identified; the safety profile of the BNX sublingual tablet was similar to those of generic buprenorphine and BNX film.. Based on the findings from this study in patients with opioid dependence, the higher-bioavailability BNX sublingual tablet formulation was noninferior to both generic buprenorphine (induction) and BNX film (stabilization). These findings suggest that BNX sublingual tablets are an efficacious and well-tolerated option for induction and early stabilization treatment of opioid dependence. ClinicalTrials.gov identifier: NCT01908842.

Topics: Administration, Sublingual; Adult; Analgesics, Opioid; Biological Availability; Buprenorphine, Naloxone Drug Combination; Female; Humans; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Prospective Studies; Tablets; United States

Opioid use disorders are considered a serious public health problem among young adults. Current treatment is limited to long-term opioid substitution therapy, with high relapse rates after discontinuation. This study evaluated the co-administration of memantine to brief buprenorphine pharmacotherapy as a treatment alternative.. 13-week double-blind placebo-controlled trial evaluating 80 young adult opioid dependent participants treated with buprenorphine/naloxone 16-4mg/day and randomized to memantine (15mg or 30mg) or placebo. Primary outcomes were a change in the weekly mean proportion of opioid use, and cumulative abstinence rates after rapid buprenorphine discontinuation on week 9.. Treatment retention was not significantly different between groups. The memantine 30mg group was significantly less likely to relapse and to use opioids after buprenorphine discontinuation. Among participants abstinent on week 8, those in the memantine 30mg group (81.9%) were significantly less likely to relapse after buprenorphine was discontinued compared to the placebo group (30%) (p<0.025). Also, the memantine 30mg group had significantly reduced opioid use (mean=0, SEM±0.00) compared to the placebo group (mean=0.33, SEM±0.35; p<0.004) during the last 2 weeks of study participation.. Memantine 30mg significantly improved short-term treatment with buprenorphine/naloxone for opioid dependent young adults by reducing relapse and opioid use after buprenorphine discontinuation. Combined short-term treatment with buprenorphine/naloxone may be an effective alternative treatment to long-term methadone or buprenorphine maintenance in young adults.

Topics: Adolescent; Adult; Buprenorphine, Naloxone Drug Combination; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Memantine; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Recurrence; 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

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

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

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

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

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

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

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

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

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

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

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

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 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

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

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

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

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

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

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

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

Management of cancer-associated pain warrants consideration of many factors, including characterization and etiology of the pain, socioeconomic factors, medication tolerance, and substance use history. Kratom (

Topics: Adenocarcinoma of Lung; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Cancer Pain; Humans; Lung Neoplasms; Male; Mitragyna; Opioid-Related Disorders; United States

Buprenorphine-naloxone is an essential part of the response to opioid poisoning rates in North America. Manipulating market exclusivity is a strategy manufacturers use to increase profitability, as evidenced by Suboxone in the USA.. To investigate excess costs of buprenorphine-naloxone due to unmerited market exclusivity (no legal patent or data protection) in Canada.. Using controlled interrupted time-series, this study examined changes in the cost of buprenorphine-naloxone before and after the first generics were listed on public formularies. Methadone cost was the control. Public data from the Canadian Institute of Health Information in British Columbia, Manitoba, and Saskatchewan were used. All buprenorphine-naloxone and methadone claims (2010-2019) accepted for payment by the provincial drug plan/programme were collected. Primary outcome was mean cost per mg of buprenorphine-naloxone after the first listing of generics.. Mean cost per mg of buprenorphine-naloxone before the first listing of generics was $1.21 CAD in British Columbia, $1.27 CAD in Manitoba, and $0.85 CAD in Saskatchewan. Following the introduction of generics, the cost per mg decreased by $0.22 CAD (95% CI - 0.33 to - 0.10; p = 0.0014) in British Columbia, $0.36 CAD (95% CI - 0.58 to - 0.13; p = 0.004) in Manitoba, and $0.27 CAD (95% CI - 0.50 to - 0.05; p = 0.03) in Saskatchewan. Mean cost per mg decreased by $0.26 CAD (95% CI - 0.38 to - 0.13; p = 0.0004) after a third generic was introduced in British Columbia. Excess costs to public formularies during the 4- to 5-year period prior to the listing of generics were $1,992,558 CAD in British Columbia, $80,876 CAD in Manitoba, and $4130 CAD in Saskatchewan. If buprenorphine-naloxone cost $0.61 CAD (mean cost after the third generic entered) instead of $1.21 CAD per mg during the pre-generics period, public payers in British Columbia could have saved $5,016,220 CAD between 2011 and 2015.. Unmerited 6 years of market exclusivity for brand-name buprenorphine-naloxone in Canada resulted in substantial excess costs. There is an urgent need to implement policies that can help reduce costs for high-priority drugs in Canada.

Topics: Buprenorphine, Naloxone Drug Combination; Canada; Costs and Cost Analysis; Drugs, Generic; Humans; Insurance Claim Review; Marketing; Methadone; Opioid-Related Disorders

The introduction of depot buprenorphine for the treatment of opioid dependence allows for reduced dosing frequency compared with conventional treatments, such as oral methadone and sublingual buprenorphine-naloxone. Reduced dosing frequency is perceived to reduce issues such as high out-of-pocket costs, frequent attendance to pharmacies, stigmatisation and the risk of diversion for unsanctioned opioid use. This study aims to explore the experiences of patients receiving depot buprenorphine from an Australian publicly operated drug and alcohol service.. Participants were recruited from the service over a 5-week period in 2021. Twenty-eight participants consented to be involved in a mixed methods quantitative verbal survey and qualitative interview process.. The majority of participants reported satisfaction with depot buprenorphine across the domains of efficacy, convenience and global satisfaction. Participants perceived benefits as increased convenience, reduced stigmatisation and the inability to 'skip' daily Medication Assisted Treatment for Opioid Dependence (MATOD) doses. There were mixed experiences with the ability for depot buprenorphine to 'hold' participants throughout the dosing interval. Reduced contact and disconnection from healthcare services were reported as an issue for some participants when initiating depot buprenorphine.. Patient perceptions of depot buprenorphine appear to be deeply rooted in prior experience with 'conventional' MATOD treatments. Depot buprenorphine is seen to be beneficial socially, personally, and financially by the majority of patients interviewed. The potential for disconnection from services and mixed experiences of efficacy throughout the dosing period may negatively influence patient experience.

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

Medications for opioid use disorder (MOUD) are a life-saving intervention; thus, it is important to address barriers to successful initiation. Spasticity affects many patients with spinal cord injury and can be painful and physically debilitating. Chronic painful conditions can lead to the illicit use of non-prescribed opioids, but fear of pain is a barrier to the initiation of MOUD. In this case report, we describe the novel use of botulinum toxin A injections to treat abdominal spasticity and facilitate Acute Pain Service-led buprenorphine/naloxone initiation in a patient with opioid use disorder and severe abdominal spasticity due to spinal cord injury.. A patient with C4 incomplete tetraplegia and opioid use disorder complicated by abdominal spasticity refractory to oral antispasmodics and self-treating with intravenous heroin was referred to the Acute Pain Service for inpatient buprenorphine/naloxone initiation. The patient began to fail initiation of buprenorphine/naloxone secondary to increased pain from abdominal spasms. The patient was offered ultrasound-guided abdominal muscle chemodenervation with botulinum toxin A, which resulted in the resolution of abdominal spasticity and facilitated successful buprenorphine/naloxone initiation. At 6 months post-initiation, the patient remained abstinent from non-prescribed opioids and compliant with buprenorphine/naloxone 8 mg/2 mg three times a day.. This case report demonstrates that inpatient buprenorphine/naloxone initiation by an Acute Pain Service can improve the success of treatment by addressing barriers to initiation. Acute Pain Service clinicians possess unique skills and knowledge, including ultrasound-guided interventions, that enable them to provide innovative and personalized approaches to care in the complex opioid use disorder population.

Topics: Analgesics, Opioid; Anesthesia, Conduction; Botulinum Toxins, Type A; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Pain; Pain Clinics

Patients with opioid use disorder (OUD) frequently leave the hospital as patient directed discharges (PDDs) because of untreated withdrawal and pain. Short-acting opioids can complement methadone, buprenorphine, and non-opioid adjuvants for withdrawal and pain, however little evidence exists for this approach. We described the safety and preliminary outcomes of short-acting opioid agonist treatment (sOAT) for hospitalized patients with OUD at an academic hospital in Philadelphia, PA.. From August 2021 to March 2022, a pharmacist guided implementation of a pilot sOAT protocol consisting of escalating doses of oxycodone or oral hydromorphone scheduled every four hours, intravenous hydromorphone as needed, and non-opioid adjuvants for withdrawal and pain. All patients were encouraged to start methadone or buprenorphine treatment for OUD. We abstracted data from the electronic health record into a secure platform. The primary outcome was safety: administration of naloxone, over-sedation, or a fall. Secondary outcomes were PDDs and respective length of stay (LOS), discharges on methadone or buprenorphine, and discharges with naloxone. We compared secondary outcomes to hospitalizations in the 12 months prior to the index hospitalization among the same cohort.. Of the 23 cases, 13 (56.5%) were female, 19 (82.6%) were 40 years or younger, and 22 (95.7%) identified as White. Twenty-one (91.3%) regularly injected opioids and four (17.3%) were enrolled in methadone or buprenorphine prior to hospitalization. sOAT was administered at median doses of 200-320 morphine milligram equivalents per 24-h period. Naloxone administration was documented once in the operating room, over-sedation was documented once after unsanctioned opioid use, and there were no falls. The PDD rate was 44% with median LOS 5 days (compared to PDD rate 69% with median LOS 3 days for prior admissions), 65% of sOAT cases were discharged on buprenorphine or methadone (compared to 33% for prior admissions), and 65% of sOAT cases were discharged with naloxone (compared to 19% for prior admissions).. Pilot implementation of sOAT was safe. Compared to prior admissions in the same cohort, the PDD rate was lower, LOS for PDDs was longer, and more patients were discharged on buprenorphine or methadone and with naloxone, however efficacy for these secondary outcomes remains to be established.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Female; Humans; Hydromorphone; Male; Methadone; Naloxone; Opiate Substitution Treatment; Opioid-Related Disorders; Pain

Patients with opioid use disorder may be asked by their clinicians to discontinue maintenance buprenorphine treatment before surgical operations due to concerns that buprenorphine will interfere with acute pain management. However, discontinuation of buprenorphine may not be well tolerated or safe for all patients. We, therefore, administered a survey to better understand the experiences of patients on buprenorphine treatment who had previously undergone painful procedures and had their buprenorphine maintenance treatment either continued or discontinued before the procedure.. After this study received institutional review board approval, patients were invited to participate if they were being prescribed sublingual buprenorphine for treatment of opioid use disorder and had also previously undergone a painful procedure requiring treatment with full agonist opioids. Patients who were eligible and agreed to participate (n = 32) then completed a survey of basic demographics; medical, psychiatric, and substance use histories; and their experience and satisfaction with the treatment of pain and substance use in the perioperative period, including whether buprenorphine was continued or discontinued before their procedure.. Compared with patients whose home dose of buprenorphine was continued (n = 15), patients whose buprenorphine was discontinued preoperatively (n = 17) reported less satisfaction with pain management and were more likely to be prescribed full agonist opioids upon discharge.. Consistent with prior studies, these survey findings suggest that discontinuation of buprenorphine before painful surgeries may be associated with poorer clinical outcomes.. This survey study adds patients' perspective to a growing body of scientific literature suggesting that discontinuation of maintenance buprenorphine treatment before painful procedures may decrease patient satisfaction and increase clinical risk.

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

Limited research examines buprenorphine-naloxone interest among adolescents and young adults (AYA). This longitudinal study examined factors associated with initial buprenorphine-naloxone interest and the time to a positive change in buprenorphine-naloxone interest or enrollment, in addition to identifying reasons for buprenorphine-naloxone disinterest.. The study derived data from a cohort of street-involved AYA in Vancouver, Canada between December 2014 and June 2018. The analysis was restricted to AYA who reported weekly or daily illicit opioid use in the last six months but had not initiated buprenorphine-naloxone. The study examined factors associated with initial buprenorphine-naloxone interest using multivariable logistic regression, while multivariable Cox regression identified factors associated with the time to a positive change in buprenorphine-naloxone interest or actual enrollment over follow-up among AYA initially disinterested in buprenorphine-naloxone.. Of 281 participants who reported weekly illicit opioid use but were not on buprenorphine-naloxone, 52 (18.5 %) AYA reported initial buprenorphine-naloxone interest, while 68 (24.2 %) AYA who were initially disinterested in buprenorphine-naloxone reported interest or enrollment over follow-up. In multivariable logistic regression, initial interest was positively associated with older age (Adjusted Odds Ratio [AOR] = 1.09, 95 % Confidence Interval [CI]: 1.03-1.15), but negatively associated with self-reported Indigenous identity (AOR = 0.22, 95 % CI: 0.07-0.68). In multivariable Cox regression, recent detoxification program access (Adjusted Hazard Ratio [AHR] = 0.85, 95 % CI: 0.73-0.98) was positively associated with the time to a positive change in buprenorphine-naloxone interest or enrollment. Common reasons for buprenorphine-naloxone disinterest included not wanting opioid agonist treatments (OAT) (initial n = 67, follow-up n = 105); not wanting to experience precipitated withdrawal (initial n = 42, follow-up n = 54), being satisfied with or preferring other OAT (initial n = 33, follow-up n = 52), not knowing what buprenorphine-naloxone is (initial n = 27, follow-up n = 9), previous negative treatment experiences (initial n = 19, follow-up n = 20), and wanting to continue opioid use (initial n = 13, follow-up n = 9), among others.. We documented persistent disinterest in buprenorphine-naloxone among AYA, though participants' reasons for disinterest provide insight into the potential benefits of expanding micro-dosing induction; ensuring treatment is culturally safe; and communicating changes in buprenorphine-naloxone programming to AYA. Nevertheless, a need remains to improve the continuum of harm reduction and treatment supports for AYA.

Topics: Adolescent; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Canada; Humans; Longitudinal Studies; Opioid-Related Disorders; Prospective Studies; Young Adult

Opioid use disorder is a major public health concern that accounts for a high number of potential years of life lost. Buprenorphine/naloxone is a recommended treatment for opioid use disorder that can be started in the emergency department (ED). We developed an ED-based program to initiate buprenorphine/naloxone for eligible patients who live with opioid use disorder, and to provide unscheduled, next-day follow-up referrals to an opioid use disorder treatment clinic (in person or virtual) for continuing patient care throughout Alberta.. In this quality improvement initiative, we supported local ED teams to offer buprenorphine/naloxone to eligible patients presenting to the ED with suspected opioid use disorder and refer these patients for follow-up care. Process, outcome, and balancing measures were evaluated over the first 2 years of the initiative (May 15, 2018-May 15, 2020).. The program was implemented at 107 sites across Alberta during our evaluation period. Buprenorphine/naloxone initiations in the ED increased post-intervention at most sites with baseline data available (11 of 13), and most patients (67%) continued to fill an opioid agonist prescription at 180 days post-ED visit. Of the 572 referrals recorded at clinics, 271 (47%) attended their first follow-up visit. Safety events were reported in ten initiations and were all categorized as no harm to minimal harm.. A standardized provincial approach to initiating buprenorphine/naloxone in the ED for patients living with opioid use disorder was spread to 107 sites with dedicated program support staff and adjustment to local contexts. Similar quality improvement approaches may benefit other jurisdictions.. OBJECTIFS: Le trouble lié à la consommation d’opioïdes est une préoccupation majeure en santé publique qui explique le nombre élevé d’années potentielles de vie perdues. La buprénorphine/naloxone est un traitement recommandé pour le trouble lié à l’utilisation d’opioïdes qui peut être commencé au service des urgences (SU). Nous avons mis au point un programme axé sur les urgences pour commencer la buprénorphine/naloxone pour les patients éligibles qui vivent avec un trouble lié à l’utilisation d’opioïdes, et pour fournir suivis des cas référés le jour suivant vers une clinique de soins des troubles liés à l’utilisation d’opioïdes (sur place ou virtuelle) pour les soins continus aux patients partout en Alberta. MéTHODES: Dans le cadre de cette initiative d’amélioration de la qualité, nous avons aidé les équipes locales de SU à offrir la buprénorphine/naloxone aux patients admissibles qui se présentent à la SU avec un trouble présumé de consommation d’opioïdes et à les diriger vers des soins de suivi. Le processus, les résultats et les mesures d’équilibre ont été évalués au cours des deux premières années de l’initiative (du 15 mai 2018 au 15 mai 2020). RéSULTATS: Le programme a été mis en œuvre dans 107 sites en Alberta pendant notre période d’évaluation. Les initiations à la buprénorphine/naloxone à l’urgence ont augmenté après l’intervention dans la plus grande partie de sites pour lesquels des données de référence étaient disponibles (11 sur 13), et la plupart des patients (67 %) ont continué de remplir une ordonnance d’agonistes opioïdes 180 jours après la visite à l’urgence. Sur les 572 renvois enregistrés aux cliniques, 271 (47 %) ont assisté à leur première visite de suivi. Des événements liés à la sécurité ont été signalés dans 10 initiatives et ont tous été classés comme n’ayant causé aucun conséquences à des conséquences minimes.. Une approche provinciale standardisé de lancement de la buprénorphine/naloxone à l’urgence pour les patients atteints d’un trouble lié à la consommation d’opioïdes a été diffusée à 107 sites à l’aide de soutien aux programmes spécialisé et des ajustements aux contextes locaux. Des approches semblables d’amélioration de la qualité pourraient profiter à d’autres juridictions.

Topics: Alberta; Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Emergency Service, Hospital; Humans; Narcotic Antagonists; Opioid-Related Disorders; Quality Improvement; Referral and Consultation

Hospitalizations are a vital opportunity for the initiation of life-saving opioid agonist therapy (OAT) for patients with opioid use disorder. A novel approach to OAT initiation is the use of IV buprenorphine for low dose induction, which allows patients to immediately start buprenorphine at any point in a hospitalization without stopping full agonist opioids or experiencing significant withdrawal.. This is a retrospective case series of 33 patients with opioid use disorder concurrently treated with full agonist opioids for pain who voluntarily underwent low dose induction at a tertiary academic medical center. Low dose induction is the process of initiating very low doses of buprenorphine at fixed intervals with gradual dose increases in patients who recently received or are simultaneously treated with full opioid agonists. Our study reports one primary outcome: successful completion of the low dose induction (i.e. transitioned from low dose IV buprenorphine to sublingual buprenorphine-naloxone) and three secondary outcomes: discharge from the hospital with buprenorphine-naloxone prescription, self-reported pain scores, and nursing-assessed clinical opiate withdrawal scale (COWS) scores over a 6-day period, using descriptive statistics. COWS and pain scores were obtained from day 0 (prior to starting the low dose induction) to day 5 to assess the effect on withdrawal symptoms and pain control.. Thirty patients completed the low dose induction (30/33, 90.9%). Thirty patients (30/33, 90.9%) were discharged with a buprenorphine prescription. Pain and COWS scores remained stable over the course of the study period. Mean COWS scores for all patients were 2.6 (SD 2.8) on day 0 and 1.6 (SD 2.6) on day 5. Mean pain scores for all patients were 4.4 (SD 2.1) on day 0 and 3.5 on day 5 (SD 2.1).. This study found that an IV buprenorphine low dose induction protocol was well-tolerated by a group of 33 hospitalized patients with opioid use disorder with co-occurring pain requiring full agonist opioid therapy. COWS and pain scores improved for the majority of patients. This is the first case series to report mean daily COWS and pain scores over an extended period throughout a low dose induction process.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Pain; Retrospective Studies

In anticipation of COVID-19 related disruptions to opioid use disorder (OUD) care, new provincial and federal guidance for the management of OUD and risk mitigation guidance (RMG) for prescription of pharmaceutical opioids were introduced in British Columbia, Canada, in March 2020. This study evaluated the combined impacts of the COVID-19 pandemic and counteracting OUD policies on enrollment in medications for OUD (MOUD).. Using data from three cohorts of people with presumed OUD in Vancouver, we conducted an interrupted time series analysis to estimate the combined effects impact of the COVID-19 pandemic and counteracting OUD policies on the prevalence of enrollment in MOUD overall, as well as in individual MOUDs (methadone, buprenorphine/naloxone, slow-release oral morphine) between November 2018 and November 2021, controlling for pre-existing trends. In sub-analysis we considered RMG opioids together with MOUD.. We included 760 participants with presumed OUD. In the post-COVID-19 period, MOUD and slow-release oral morphine prevalence rates showed an estimated immediate increase in level (+7.6%, 95% CI: 0.6%, 14.6% and 1.8%, 95% CI: 0.3%, 3.3%, respectively), followed by a decline in the monthly trend (-0.8% per month, 95% CI: -1.4%, -0.2% and -0.2% per month, 95% CI: -0.4, -0.1, respectively). There were no significant changes in the prevalence trends of enrollment in methadone, buprenorphine/naloxone, or when RMG opioids were considered together with MOUD.. Despite immediate improvements in MOUD enrollment in the post-COVID-19 period, this beneficial trend reversed over time. RMG opioids appeared to have provided additional benefits to sustain retention in OUD care.

Topics: Analgesics, Opioid; British Columbia; Buprenorphine; Buprenorphine, Naloxone Drug Combination; COVID-19; Humans; Interrupted Time Series Analysis; Methadone; Morphine Derivatives; Opiate Substitution Treatment; Opioid-Related Disorders; Pandemics

Kratom has been used for different reasons such as pain, opioid withdrawal, and relaxation. Kratom can cause dependence and overdose, and it's classified under 'drugs of concern' by the US Drug Enforcement Administration. Despite these concerns, kratom is legal in most of the United States and many countries around the world with easy accessibility. Literature searches reveal recommendations to use buprenorphine (or buprenorphine-naloxone), which are medications to treat opioid use disorder, in order to treat patients with kratom use disorder; however, there are no formal guidelines available. Buprenorphine (or buprenorphine-naloxone) induction is recommended to be conducted under observation (i.e. in the clinic) in the United States, but COVID-19 has resulted in shifts toward telehealth.. Describe case series of successful management of kratom use disorder using telehealth followed by unobserved buprenorphine-naloxone home induction and highlight implications for future management, including maintenance dosage and induction method.. We present 2 very similar kratom use disorder patients who reported taking 35 g of kratom per day who underwent unobserved buprenorphine-naloxone home induction.. Both were seen via telehealth initially. They reported no adverse effects before, during, or after the unobserved home induction on buprenorphine-naloxone but stabilized on significantly different dosages.. Telehealth followed by unobserved buprenorphine-naloxone induction at home may be an alternative to traditional buprenorphine-naloxone induction where treatment accessibility is limited. In addition to daily doses of kratom use, other factors, such as duration of kratom use and individual psychological factors may determine the most comfortable dose of buprenorphine-naloxone.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Humans; Mitragyna; Opioid-Related Disorders; Pain; United States

Prescribing of buprenorphine and naloxone in the emergency department (ED) has been shown to be an effective intervention. The purpose of this study was to determine the frequency of prescribing of naloxone and buprenorphine and the sub-groups that may be more or less likely to receive treatment.. We used a national electronic health record database to identify patients with opioid poisoning or overdose presenting between January 2019-December 2021. Patients who were prescribed naloxone or buprenorphine were identified in this dataset and then further segmented based on self-identified gender, age, racial and ethnic identity, income categories, and social vulnerability index in order to identify sub-groups that may be less likely to be prescribed treatment.. We found 74,004 patients in the database whom we identified as presenting to the ED with an opioid poisoning or overdose. Overall, 22.8% were discharged with a prescription for naloxone, while 0.9% of patients were discharged with buprenorphine products. Patients were less likely to receive naloxone prescriptions if they were female, White or Pacific Islander, non-Hispanic, not between the ages of 18-65, and non-English speaking. We found the same pattern for buprenorphine prescriptions except that the results were not significant for ethnicity and English-speaking.. Despite evidence supporting its use, buprenorphine is not prescribed from the ED in a substantial proportion of patients. Naloxone is prescribed to a higher percentage, although still a minority of patients receive it. Some sub-groups are disadvantaged in the prescribing of these products. Further study may assist in improving the prescribing of these therapies.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Drug Overdose; Emergency Service, Hospital; Female; Humans; Male; Naloxone; Narcotic Antagonists; Opioid-Related Disorders

Mainstays of opioid overdose prevention include medications for opioid use disorder (e.g., methadone or buprenorphine) and naloxone distribution. Inadequate access to buprenorphine limits its uptake, especially in communities of color, and people with opioid use disorders encounter multiple barriers to obtaining necessary medications including insurance, transportation, and consistent availability of telephones. UMass Memorial Medical Center and our community partners sought to alleviate these barriers to treatment through the deployment of a mobile addiction service, called the Road to Care. Using this approach, multidisciplinary and interprofessional providers deliver holistic addiction care by centering our patients' needs with respect to scheduling, location, and convenience. This program also extends access to buprenorphine and naloxone among people experiencing homelessness. Additional systemic and individualized barriers encountered are identified, as well as potential solutions for future mobile addiction service utilization. Over a two-year period, we have cared for 1,121 individuals who have accessed our mobile addiction service in over 4,567 encounters. We prescribed buprenorphine/naloxone (Suboxone®) to 330 individuals (29.4% of all patients). We have distributed nearly 250 naloxone kits directly on-site or and more than 300 kits via prescriptions to local pharmacies. To date, 74 naloxone rescue attempts have been reported back to us. We have demonstrated that a community-based mobile addiction service, anchored within a major medical center, can provide high-volume and high-quality overdose prevention services that facilitate engagement with additional treatment. Our experience is described as a case study below.

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Community Health Services; Drug Overdose; Humans; Naloxone; Opioid-Related Disorders

Although randomized controlled trials (RCTs) examine "objective" indicators of safety and efficacy of investigational drugs, participants may not perceive study medications as neutral entities. Some medications are imbued with social and cultural meaning, such as stigmatized medications for opioid use disorders. Such perceptions surrounding substance use treatments can extend to the research context and shape RCT participants' experiences with and adherence to study medications.. Considering these complexities in substance use research, we conducted a nested qualitative study within a multi-site, pragmatic RCT in Canada testing two treatments (methadone versus buprenorphine/naloxone) for opioid use disorder. Between 2017 and 2020, we conducted 115 interviews with 75 RCT participants across five trial sites in British Columbia, Alberta, Ontario, and Quebec.. Using an abductive coding approach, we characterized participants by their previous experience with medication for opioid use disorder and by their exposure to drug culture and drug scenes. Across these experience types, we identified systematic differences around participants' perceptions of the study medications, sources of information and expertise, and medication stigma.. Our findings illustrate the critical importance of social context in shaping medication beliefs and study experiences among people who use drugs, with implications for the conduct of future RCTs in substance use.

Topics: British Columbia; Buprenorphine, Naloxone Drug Combination; Humans; Male; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders

We aimed to compare the effectiveness of extended-release naltrexone (XR-NTX) implant and sublingual buprenorphine-naloxone (BUP-NX) in relapse prevention in opiate use disorder (OUD).. Medical records of 400 patients who were treated for OUD between 2016 and 2020 were retrospectively evaluated concerning sociodemographic and clinical characteristics and abstinence duration with either BUP-NX (192 patients) or XR-NTX (208 patients) as maintenance treatments.. The median age of patients using BUP-NX was 25.00, and the median age of patients using XR-NTX was 25.50 (p = .785). The ratio of female patients in the BUP-NX group and the XR-NTX group was 7.3% (n = 14) and 6.7% (n = 14), respectively. A significantly higher abstinence time was observed in the BUP-NX group (median = 4 months) than in the XR-NTX group (median = 3 months) (p = .015). Liver function tests were within the normal ranges at the three time points, which were just before the beginning and in the first and third months of treatment.. These findings suggest that BUP-NX might be more effective than XR-NTX in preventing relapse in OUD and both drugs are safe for the liver. Prospective randomized studies are needed to replicate our results.

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Delayed-Action Preparations; Female; Humans; Injections, Intramuscular; Naltrexone; Narcotic Antagonists; Opiate Alkaloids; Opioid-Related Disorders; Prospective Studies; Retrospective Studies

The primary objective of this study is to identify emergency physician reported barriers to initiating patients on buprenorphine/naloxone in the emergency department (ED) for treatment of opioid use disorder. Secondary objectives include (1) physician reported attitudes about initiating buprenorphine/naloxone in the ED, and (2) comparison of barriers reported based on urban versus rural practice setting.. An online survey was distributed to a convenience sample of attending emergency physicians and resident physicians using the Canadian Association of Emergency Physicians (CAEP) research survey email distribution network.. The survey was sent to 1299 email accounts registered with the CAEP research survey network. We received 121 responses, which is a response rate of 9.3%. The completion rate was 118/121 (97.5%). Most respondents 113/118 (95.7%) reported at least one barrier that prevents them from initiating buprenorphine/naloxone in the ED. The top three reported barriers were (1) lack of allied health care staff who were trained to assist in starting patients on buprenorphine/naloxone in the ED and to help arrange follow-up, (2) time constraints related to patient education on the appropriate and safe use of buprenorphine/naloxone, and (3) access to follow-up resources. The majority of respondents agreed buprenorphine/naloxone was an evidence-based treatment for opioid use disorder and that it is important to make changes in their ED to better facilitate this practice. There was no statistically significant difference in the number of physicians reporting each barrier based on urban versus rural practice setting.. In this convenience sample of physicians working in urban and rural Canadian emergency departments, most physicians perceive barriers that inhibit their ability to initiate buprenorphine/naloxone for patients with opioid use disorder, but overall there is support for making changes to better facilitate this practice.. RéSUMé: OBJECTIFS: L'objectif principal de cette étude est d'identifier les obstacles signalés par les médecins urgentistes à la mise sous buprénorphine/naloxone des patients dans le service des urgences pour le traitement du trouble de l'usage des opiacés. Les objectifs secondaires comprennent (1) les attitudes déclarées par les médecins concernant l'administration de buprénorphine/naloxone aux urgences, et (2) la comparaison des obstacles déclarés en fonction du milieu de pratique urbain par rapport au milieu rural. MéTHODES: Un sondage en ligne a été distribué à un échantillon de commodité d'urgentistes titulaires et de médecins résidents en utilisant le réseau de distribution de courriels de recherche de l'Association canadienne des médecins d'urgence (ACMU). RéSULTATS: L'enquête a été envoyée à 1299 comptes de messagerie enregistrés auprès du réseau d'enquête de recherche ACMU. Nous avons reçu 121 réponses, soit un taux de réponse de 9,3 %. Le taux d'achèvement était de 118/121 (97,5 %). La plupart des répondants 113/118 (95,7 %) ont signalé au moins un obstacle qui les empêche d'initier la buprénorphine/naloxone aux urgences. Les trois principaux obstacles signalés sont les suivants : (1) le manque de personnel paramédical formé pour aider à mettre les patients sous buprénorphine/naloxone aux urgences et à organiser le suivi (2) les contraintes de temps liées à l'éducation des patients sur l'utilisation appropriée et sûre de la buprénorphine/naloxone, et (3) l'accès aux ressources de suivi. La majorité des répondants ont convenu que la buprénorphine/naloxone était un traitement fondé sur des données probantes pour les troubles liés à l'utilisation d'opioïdes et qu'il est important d'apporter des changements à leur service d'urgence pour mieux faciliter cette pratique. Il n'y avait pas de différence statistiquement significative dans le nombre de médecins signalant chaque obstacle selon que le milieu de pratique était urbain ou rural. CONCLUSIONS: Dans cet échantillon de commodité de médecins travaillant dans des services d'urgence canadiens urbains et ruraux, la plupart des médecins perçoivent des obstacles qui les empêchent d'initier la buprénorphine/naloxone pour les patients souffrant de troubles liés à l'utilisation d'opioïdes, mais dans l'ensemble, ils sont favorables à des changements pour mieux faciliter cette pratique.

Topics: Attitude of Health Personnel; Buprenorphine, Naloxone Drug Combination; Canada; Emergency Service, Hospital; Humans; Narcotic Antagonists; Opioid-Related Disorders; Physicians

North America is currently experiencing an epidemic of opioid overdose deaths, driven by the proliferation of fentanyl in the street drug market. Although buprenorphine/naloxone (BUP/NX) is an evidence-based, first-line opioid agonist for the management of opioid use disorder, a key challenge in its prescribing lies in the fact that it can precipitate opioid withdrawal during its initial induction process. At this time, there is minimal literature on the BUP/NX induction process in individuals who use illicit fentanyl regularly.. A case series from a Vancouver, Canada addiction medicine clinic of three fentanyl-exposed patients who experienced unexpected, precipitated withdrawal when initiating BUP/NX.. These cases describe incidents of precipitated opioid withdrawal occurring after unusually long periods of fentanyl abstention. Although fentanyl is experienced as a short-acting opioid, the drug persists much longer in the body's peripheral tissues. Here, we highlight the new challenges fentanyl may pose to current BUP/NX induction strategies, and explore the possibility of a long-acting pharmacokinetic effect of fentanyl in the setting of repeated illicit use.

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

Limited evidence exists in Canada on outcomes related to Opioid Agonist Treatment (OAT) and/or differences between OAT modalities among persons in correctional institutions. This study addresses this knowledge gap by examining key characteristics and outcomes of men in Canadian federal correctional institutions across treatment modalities.. A retrospective cohort of men incarcerated in federal correctional institutions (N = 2833) were classified into four groups - three OAT participant groups: prescribed methadone (M-OAT), prescribed buprenorphine/naloxone (Suboxone®; S-OAT) and those who switched between the two OAT modalities at least once (X-OAT). The fourth group was a non-treatment comparison group (Non-OAT). Two-thirds of study participants were released and examined for post-release outcomes. Descriptive statistics and multi-variate Cox proportional hazards regression were used.. The X-OAT group was more likely than the other study groups to have positive urinalysis tests, disciplinary charges, or institutional security or behavioral incidents. Survival analysis indicated that the X-OAT had an adjusted hazard of a return to custody that was 57% greater than the other groups.. This study indicates that individuals switching OAT modalities are a more complex group needing additional supports, especially for community reintegration. Although few of the returns to custody were due to new offences, a third of participants in the OAT groups had their release revoked, indicating a high need population mostly due to their substance use.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Canada; Humans; Male; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Retrospective Studies

The aim of the study was to assess the acceptance of patients with opioid use disorder (OUD) to switching their opioid dependence treatment (ODT) for a prolonged-release buprenorphine (PRB) injection according to their prior ODT (buprenorphine/naloxone [B/N] or methadone).. This was an observational, retrospective/cross-sectional, multicentre study of adult patients diagnosed with OUD on ODT. Data collected from diaries were analysed to know their interest and opinion on PRB. Questions with fixed response options were included, and several Likert scales were used.. A total of 98 patients were enrolled (B/N: 50.0%, methadone: 50.0%). The mean age was 46.9 ± 8.43 years and 79.6% were males. PRB was similarly perceived by both groups in most variables analysed, receiving a mean score of 7.2/10 (B/N: 7.4, methadone: 7.0; p = 0.520), and approximately 65% of patients said they were willing to switch to PRB (B/N: 63.3%, methadone: 65.3%; p = 0.833). Of these, a higher percentage in the B/N group considered that switching would be easy/very easy (B/N: 90.3%, methadone: 46.9%; p < 0.001) and that they would start PRB when available (B/N: 64.5%, methadone: 34.3%; p = 0.005). More than 90% would prefer the monthly injection (B/N: 93.6%, methadone: 100%; p = 0.514). One-third of patients in both groups were unsure/would not switch their ODT to PRB (B/N: 36.7%, methadone: 34.7%; p = 0.833). The main reason was administration by injection.. Two-thirds of patients would switch their treatment for PRB, and most patients on B/N considered that switching would be easy. PRB could be a suitable alternative for OUD management.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cross-Sectional Studies; Humans; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Perception; Retrospective Studies

Opioid agonist treatment (OAT) is an effective intervention for opioid dependence. Extended-release buprenorphine injections (BUP-XR) may have additional potential benefits over sublingual buprenorphine. This single-arm trial evaluated outcomes among people receiving 48 weeks of BUP-XR in diverse community healthcare settings in Australia, permitting examination of outcomes when BUP-XR is delivered in standard practice.. Participants were recruited from a network of specialist public drug treatment services, primary care and some private practices in three states. Following a minimum 7 days on 8-32 mg of sublingual buprenorphine (±naloxone), participants received monthly subcutaneous BUP-XR injections administered by a healthcare practitioner and completed monthly research interviews. The primary endpoint was retention in treatment at 48 weeks.. Participants (n = 100) were 28% women, mean age 44 years with a long history of OAT (median 5.8 years); heroin was the most common opioid of concern (58%). Treatment retention at 24 and 48 weeks was 86% and 75%, respectively. Participants with past-month injecting drug use (OR 0.23; 95%CI: 0.09-0.61) or heroin use (OR 0.23; 95%CI: 0.08-0.65) at baseline had lower odds of being retained in treatment to 48 weeks. Reductions in multiple forms of extra-medical drug use were observed. Improvements in quality of life, participation in employment, and treatment satisfaction measures were also observed.. This real-world implementation study of BUP-XR demonstrated high retention and treatment satisfaction. This study provides important additional data on the uptake and experience of clients, with relevance for policy makers, health service planners, administrators, and practitioners.. Indivior.. ClinicalTrials.gov Identifier: NCT03809143.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Delayed-Action Preparations; Female; Heroin; Humans; Male; Narcotic Antagonists; Opioid-Related Disorders; Quality of Life

Topics: Adult; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cross-Sectional Studies; Emergency Service, Hospital; Female; Health Care Costs; Humans; Male; Narcotic Antagonists; Opiate Overdose; Opioid-Related Disorders

Buprenorphine-naloxone (BUP-NX) is a first-line treatment for opioid use disorder and has a superior safety profile compared to other forms of opioid agonist therapy. In Canada, restrictions on BUP-NX prescribing were relaxed in 2016, which may have had an effect on rates of diversion and non-prescribed use. We sought to longitudinally examine the reported availability and use of non-prescribed BUP-NX among people who use drugs (PWUD) in an urban Canadian setting.. We collected data from two linked prospective cohorts of PWUD in Vancouver, Canada, and examined self-reported availability and use of non-prescribed BUP-NX over time. We used a multivariable generalized estimating equations model to identify trends and factors associated with the immediate availability (i.e., within 10 min) of non-prescribed BUP-NX.. Among 1617 participants between 2014 and 2020, the immediate availability of non-prescribed BUP-NX increased from 16% to 63% (p<0.001). In the multivariable analysis, factors independently associated with immediate BUP-NX availability included calendar year (adjusted odds ratio = 1.19, 95% confidence interval: 1.15-1.23), along with a number of other variables suggestive of more severe substance use disorders. Only 17 participants ever reported use of non-prescribed BUP-NX.. We observed that BUP-NX has become increasingly available in the unregulated drug supply in recent years but its use has remained infrequent in this setting. These results suggest that relaxed restrictions on BUP-NX prescribing have not been a major driver of increased non-prescribed use in this population.

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Canada; Humans; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Prospective Studies

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; COVID-19; Emergency Service, Hospital; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Retrospective Studies

Buprenorphine is increasingly used to treat pain in patients with sickle cell disease but optimal timing and approach for transitioning patients from full agonist opioids to buprenorphine is unknown. We present the case of a 22-year-old woman with sickle cell disease and acute on chronic pain who transitioned from high-dose oxycodone to buprenorphine/naloxone during a hospital stay for vaso-occlusive episode. Utilizing a microdosing approach to minimize pain and withdrawal, buprenorphine/naloxone was gradually uptitrated while she received full agonist opioids. During the transition, she experienced some withdrawal in the setting of swallowed buprenorphine/naloxone tablets, which were intended to be dosed sublingually. Nevertheless, the transition was tolerable to the patient and her pain and function significantly improved with buprenorphine treatment. This case also highlights the challenges and unique considerations that arise when providing care for the hospitalized patient who is also incarcerated.

Topics: Analgesics, Opioid; Anemia, Sickle Cell; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Female; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Oxycodone; Young Adult

Data from Phase 2 of the Prescription Opioid Addiction Treatment Study (POATS) were used. Two latent transition models were conducted to characterize profiles and transitions between profiles of pain intensity or pain interference (estimated separately).. Each model identified a high and low profile. In the pain interference model, the majority were classified in the low profile at baseline. In the pain intensity model, the majority were classified in the high profile at baseline. In both models, patients were more likely to remain in or transition to the low profiles by Week 12. Worse depression was associated with membership in the high pain interference profile at both timepoints. Women were more likely to be in the high pain intensity profile at baseline. Those in the high pain intensity and high pain interference profiles at Week 12 reported worse mental health quality of life (MH-QOL) at Week 12, as well as high pain intensity and high pain interference at Week 24.. For a subgroup of patients, high pain intensity and high pain interference remains unchanged during BUP/NX maintenance treatment. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Chronic Pain; Female; Humans; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Quality of Life

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

Clinical studies examining once-daily versus multiple-daily dosing of buprenorphine/naloxone in patients with opioid use disorder (OUD) in the absence of comorbid pain are lacking.. This retrospective chart review aimed to compare 100 patients prescribed single-daily buprenorphine/naloxone (n = 50) to those prescribed multiple-daily buprenorphine/naloxone (n = 50) to elucidate the impact that dosing frequency has on negative urine drug screens (UDS) and the number of relapses in OUD.. The once-daily cohort produced 84% negative UDSs compared with 74% in the multiple-daily cohort which was statistically significant (p = .034). There were a total of 43 relapses reported in the once-daily cohort, compared with 141 relapses in the multiple-daily cohort (p < .001). The average number of relapses per patient in the single-daily cohort was 0.68 compared with the multiple-daily cohort average of 2.16 (p < .001). In the once-daily cohort, 14% of patients experienced at least one relapse throughout the study, compared with 31% in the multiple-daily cohort (p < .002). There were no significant differences between time to relapse, adherence to treatment, or treatment retention. Statistically significantly more patients in the multiple-daily cohort were using methamphetamines (p = .005); there were no significant differences between groups with the use of any other illicit or non-prescribed substances.. Once-daily dosing was associated with more negative UDSs and fewer opioid relapses compared with multiple-daily dosing.. This was the first study to evaluate buprenorphine/naloxone dosing frequency for opioid use disorder, in the absence of chronic pain. Additional studies evaluating optimal dosing schedules for relapse prevention are warranted.

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

To characterize comparative risks and benefits of methadone versus buprenorphine/naloxone in a contemporary cohort where the unregulated drug supply is dominated by fentanyl.. Population-based propensity-score matched cohort study conducted in Ontario, Canada among people aged 18+ initiating opioid agonist therapy (OAT) for an opioid use disorder between October 2016 and December 2018 (n = 18 880).. Initiation of methadone versus buprenorphine/naloxone.. The primary outcome was opioid overdose (fatal and non-fatal) while on treatment, with secondary outcomes including opioid overdose (first 30 days of treatment), treatment discontinuation, health-care interactions related to treatment of opioid use disorder, receiving a weekly supply of take-home doses and opioid overdose within 30 days of treatment discontinuation. Outcomes were assessed over 1 year.. Overall, 7517 people initiating buprenorphine were matched to an equal number of methadone-treated individuals. Risk of opioid overdose while on treatment [hazard ratio (HR) = 0.50; 95% confidence interval (CI) = 0.37-0.68] or within the first 30 days of treatment (HR = 0.51, 95% CI = 0.31-0.85) was lower among buprenorphine recipients compared to methadone recipients. In secondary analyses, people initiating buprenorphine had a higher risk of treatment discontinuation within the first year (median time to discontinuation 104 versus 265 days, HR = 1.43, 95% CI = 1.37-1.49), had lower rates of health-care interactions for OUD (186.4 versus 254.3 per person-year; rate ratio = 0.73; 95% CI = 0.72-0.75), and a higher rate of receiving weekly take-home doses (HR = 2.33; 95% CI = 2.20-2.46). Overdose rates in the period following OAT discontinuation were higher than those observed while on treatment, but did not differ significantly by OAT type.. Although treatment retention is higher among methadone recipients, overdose risk is also elevated compared to buprenorphine recipients. These findings demonstrate the benefits of any OAT on avoidance of overdose, particularly following treatment discontinuation and with the increasingly unpredictable drug supply in North America.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cohort Studies; Drug Overdose; Humans; Methadone; Ontario; Opiate Overdose; Opiate Substitution Treatment; Opioid-Related Disorders

In this case-control study (423 Turkish subjects), the functional pro-dynorphin (PDYN) 68-bp VNTR polymorphism was genotyped in opioid users receiving sublingual buprenorphine/naloxone treatment (SBNT; n = 129, 119 males and 10 females), in opioid users (OUD; n = 99, 90 males and 9 females), in alcohol users (AUD; n = 75, 75 males) and in controls (n = 120, 109 males and 11 females) to determine the effect of this polymorphism on different treatment responses, heroin or alcohol dependence as well as age onset of first use. The PDYN 68-bp alleles were determined based on the number of repeats and genotypes were classified as "short/short (SS)", "short-long (SL)" and "long-long (LL)". The intensity of craving, withdrawal, depression and anxiety were measured by the Substance Craving Scale (SCS), the Clinical Opiate Withdrawal Scale (COWS), the Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI), respectively. Healthy controls (5.5 ± 5.8) had significantly lower levels of depressive symptoms compared to OUD (25.4 ± 13.5), AUD (22.5 ± 11.3) and SBNT (19.29 ± 12.2) groups. In OUD group, the LL genotype was associated with decreased intensity of anxiety and depressive symptoms than the SS+SL genotype. The BDI-II scores for PDYN VNTR genotypes within the 4 groups were analysed by two-way ANOVA and statistical differences were found for the groups. SBNT group had significantly lower COWS score than OUD group (1.00 versus 3.00). There were statistically significant differences in the median BAI (11 versus 24) and BDI-II scores (17.5 versus 25) between OUD and SBNT groups, supporting the antidepressant and anxiolytic effects of SBNT in persons with OUD.

Topics: Alcoholism; Analgesics, Opioid; Anxiety; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Case-Control Studies; Craving; Depression; Dynorphins; Female; Humans; Male; Minisatellite Repeats; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Polymorphism, Genetic

In March 2020, the Ontario government declared a state of emergency due to the growing risk of COVID-19. In response, new guidance for the management of opioid agonist therapy (OAT) was released, which included the expansion of eligibility for take-home doses. We investigated the impact of these changes on trends in the distribution of take-home doses of OAT.. We conducted a population-based time series analysis among residents of Ontario, Canada who were dispensed OAT between June 25, 2019 and November 30, 2020. For each week of the study period, we calculated the percentage of people dispensed (a) methadone and (b) buprenorphine/naloxone by the number of take-home doses received. We used interventional autoregressive integrated moving average models to estimate changes in the percentage of people dispensed each category of take-home doses in the weeks following the declaration of the state of emergency and release of the OAT dispensing guidance.. Following the state of emergency and release of the OAT dispensing guidance, there was a significant increase in the percentage of Ontarians dispensed 7 to 13 (3.6% increase; p = 0.033) and 14 or more (0.8% increase; p<0.001) take-home doses of methadone, and in the percentage of people dispensed 7 to 13 (4.3% increase; p = 0.001), 14 to 27 (2.8% increase; p<0.001), and 28 or more (0.3% increase; p = 0.008) take-home doses of buprenorphine/naloxone. There were significant decreases in the percentage of Ontarians receiving daily dispensed buprenorphine/naloxone (-3.1%; p = 0.001), as well as the percentage dispensed 1 to 6 take-home doses of methadone (-4.5%; p = 0.001) and buprenorphine/naloxone (-4.9%; p = 0.001).. The new guidance for dispensing OAT in Ontario resulted in increases in the duration of take-home doses of methadone and buprenorphine/naloxone supplied. However, given that changes were small, strategies to improve retention in OAT and ensure equitable access to take-home dosing should continue.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; COVID-19; Humans; Methadone; Ontario; Opiate Substitution Treatment; Opioid-Related Disorders; Pandemics

Medication for Opioid Use Disorder (MOUD) has been shown to decrease mortality, reduce overdoses, and increase treatment retention for patients with opioid use disorder (OUD) and has become the state-of-the-art treatment strategy in the emergency department (ED). There is little evidence on long-term (6 and 12 month) treatment retention outcomes for patients enrolled in MOUD from the ED.. A prospective observational study used a convenience sample of patients seen at one community hospital ED over 12 months. Patients >18 years with OUD were eligible for MOUD enrollment. After medical screening, patients were evaluated by the addiction care coordinator (ACC) who evaluated and counselled the patient and if eligible, directly connected them with an addiction medicine appointment. Once enrolled, the patient received treatment with buprenorphine in the ED. A chart review was completed for all enrollments during the first year of the program. Treatment retention was determined by review of the prescription drug monitoring program and defined as patients receiving regular suboxone prescriptions at 6 and 12 months after index ED visit date.. From June 2018 - May 2019 the ACCs evaluated patients during 691 visits, screening 571 unique patients. Of the 571 unique patients screened, 279 (48.9%) were enrolled into the MOUD program. 210 (75.3%) attended their first addiction medicine appointment, 151 (54.1%) were engaged in treatment at 1 month, 120 (43.0%) at 3 months, 105 (37.6%) at 6 months, and 97 (34.8%) at 12 months post index ED visit. Self-pay insurance status was associated with a significantly decrease in the odds of long-term treatment retention.. Our ED-initiated MOUD program, in partnership with local addiction medicine services, produced high rates of long-term treatment retention.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Emergency Service, Hospital; Humans; Long-Term Care; Opioid-Related Disorders

To estimate the number of treatment initiations, averted fatal opioid overdoses and the cost-effectiveness associated with offering buprenorphine-naloxone (buprenorphine) treatment on-site within existing syringe service programs (SSPs) in Massachusetts, USA.. This was a cohort-based mathematical model and cost-effectiveness analysis. We derived model inputs from state and national surveillance data, clinical trials and observational cohort studies. We compared an intervention scenario where 30% of SSP clients initiated buprenorphine treatment on-site at least once annually to a status quo scenario where no buprenorphine was available on-site among community treatment providers in Massachusetts, 2020-30. In individuals with opioid use disorder (OUD) we assumed that 80% of SSP clients had recently injected drugs and that treatment within SSPs would have similar or improved retention compared with standard-of-care buprenorphine programs, but higher rates of active opioid use while in treatment.. Number of treatment initiations (i.e. individuals began treatment on a medication for opioid use disorder or entered medically managed withdrawal), averted fatal opioid overdoses, quality-adjusted life-years (QALYs) and life-time discounted costs from a health sector and a limited societal perspective.. The status quo scenario resulted in 23 051 fatal overdoses and 1 511 613 treatment initiations over a 10-year simulation period. An intervention scenario with on-site SSP buprenorphine treatment averted 4797 (-20.8%) fatal opioid overdoses and resulted in 129 359 (+8.6%) additional treatment initiations compared with the status quo. The intervention scenario was the dominating scenario: providing OUD treatment through Massachusetts SSPs cost less (-$3612 per person) with patients accumulating more QALYs (0.2 per person) compared with the status quo scenario.. Offering buprenorphine treatment on-site within syringe service programs has the potential to decrease fatal overdoses substantially, improve treatment engagement and save on costs.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cost-Benefit Analysis; Drug Overdose; Humans; Narcotic Antagonists; Opiate Overdose; Opiate Substitution Treatment; Opioid-Related Disorders; Syringes

We assessed the impact of COVID-19, which includes the declaration of a state of emergency and subsequent release of pandemic-specific OAT guidance (March 17, 2020 to March 23, 2020) on the prevalence of OAT discontinuation.. We conducted a population-based time series analysis using interventional autoregressive integrated moving average models among Ontario residents who were stable (>60 days of continuous use) and not yet stable on OAT. Specifically, we examined whether COVID-19 impacted the weekly percentage of individuals who discontinued OAT, overall and stratified by treatment type (methadone vs. buprenorphine/naloxone). Additionally, we compared demographic characteristics and patient outcomes among people stable on OAT who discontinued treatment during (March 17, 2020 to November 30, 2020) and prior (July 3, 2019 to March 16, 2020) to the pandemic.. The weekly prevalence of OAT discontinuation across the study period ranged between 0.6% and 1.1%, among those stable on treatment compared to 7.3% and 16.6%, among those not stable on treatment. Following COVID-19, there was no significant change in the percentage of Ontarians who discontinued OAT, regardless of whether they were stabilized on treatment. Among those stable on OAT, a similar proportion of patients restarted therapy and experienced opioid-related harm following an OAT discontinuation. However, mortality following OAT discontinuation must be noted, as approximately 1.4% and 0.8% of people who discontinued methadone and buprenorphine/naloxone respectively, died within 30 days of discontinuation.. Trends in the prevalence of OAT discontinuation did not significantly change during the first eight months of the COVID-19 pandemic.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; COVID-19; Humans; Methadone; Ontario; Opiate Substitution Treatment; Opioid-Related Disorders; Pandemics; Prevalence; Time Factors

The COVID-19 pandemic's impact on buprenorphine treatment for opioid use disorder among adolescents and young adults (AYAs) is unknown.. We used IQVIA Longitudinal Prescription Claims, including US AYAs aged 12-29 with at least 1 buprenorphine fill between January 2018 and August 2020, stratifying by age group and insurance. We compared buprenorphine prescriptions in March-August 2019 to March-August 2020.. The monthly buprenorphine prescription rate increased 8.3% among AYAs aged 12-17 but decreased 7.5% among 18- to 24-year-olds and decreased 5.1% among 25- to 29-year-olds. In these age groups, Medicaid prescriptions did not significantly change, whereas commercial insurance prescriptions decreased 12.9% among 18- to 24-year-olds and 11.8% in 25- to 29-year-olds, and cash/other prescriptions decreased 18.7% among 18- to 24-year-olds and 19.9% in 25- to 29-year-olds (p < .001 for all).. Buprenorphine prescriptions paid with commercial insurance or cash among young adults significantly decreased early in the pandemic, suggesting a possible unmet treatment need among this group.

Topics: Adolescent; Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; COVID-19; Humans; Opioid-Related Disorders; Pandemics; United States; Young Adult

Background: Online communities such as Reddit can provide social support for those recovering from opioid use disorder. However, it is unclear whether and how advice-seekers differ from other users. Our research addresses this gap by identifying key characteristics of r/suboxone users that predict advice-seeking behavior. Objective: The objective of this analysis is to identify and describe advice-seekers on Reddit for buprenorphine-naloxone use using text annotation, social network analysis, and statistical modeling techniques. Methods: We collected 5258 posts and their comments from Reddit between 2014 and 2019. Among 202 posts which met our inclusion criteria, we annotated each post to determine which were advice-seeking (n = 137) or not advice-seeking (n = 65). We also annotated each posting user’s buprenorphine-naloxone use status (current versus formerly taking and, if currently taking, whether inducting or tapering versus other stages) and quantified their connectedness using social network analysis. To analyze the relationship between Reddit users’ advice-seeking and their social connectivity and medication use status, we constructed four models which varied in their inclusion of explanatory variables for social connectedness and buprenorphine use status. Results: The stepwise model containing “total degree” (p = 0.002), “using: inducting/tapering” (p < 0.001), and “using: other” (p = 0.01) outperformed all other models. Reddit users with fewer connections and who are currently using buprenorphine-naloxone are more likely to seek advice than those who are well-connected and no longer using the medication, respectively. Importantly, advice-seeking behavior is most accurately predicted using a combination of network characteristics and medication use status, rather than either factor alone. Conclusions: Our findings provide insights for the clinical care of people recovering from opioid use disorder and the nature of online medical advice-seeking overall. Clinicians should be especially attentive (e.g., through frequent follow-up) to patients who are inducting or tapering buprenorphine-naloxone or signal limited social support.

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Humans; Opioid-Related Disorders; Social Media; Social Networking

This Letter to the Editor is a response to Broyan and colleagues who recently published a Case Report presenting data on 28 patients in the United States who identified kratom as their primary substance of use and who were subsequently induced on buprenorphine/naloxone for a reported diagnosis of kratom use disorder. We applaud the authors for helping to advance the science on kratom and recognize the difficulties in conducting kratom-related clinical assessment and research. However, a number of inconsistences and generalizations were identified in this Case Report, which also lacked some critical context. Importantly, such inconsistencies and generalizations can be observed throughout kratom-specific case reports. We feel this is now an important opportunity to highlight these issues that are present in the Broyan and colleagues Case report but emphasize that they are not unique to it. We do this with the hope that by acknowledging these issues it can help inform editors, clinicians, and researchers who may not be familiar with kratom and, as a result of this unfamiliarity, may inadvertently present findings in a manner that could confuse readers and even misinform clinical researchers and practitioners.

Topics: Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Humans; Mitragyna; Opioid-Related Disorders; United States

Prompt access to prescribed buprenorphine/naloxone films (BUP/NX) and naloxone nasal spray (NNS) is vital for patients with opioid use disorder (OUD), but multiple studies have documented pharmacy-level barriers.. A cross-sectional secret shopper telephone audit was conducted in a sample of 5734 actively licensed pharmacies in 11 U.S. states from May 2020-April 2021. Primary outcomes included availability of 14 generic BUP/NX 8/2 mg and one unit of NNS 4 mg. Outcomes were compared by pharmacy type, county metropolitan status, state Medicaid expansion status, and state drug overdose death rate.. Data from 4984 pharmacies (3402 chain and 1582 independent) were analyzed. Both medications were available in 41.2 % of pharmacies, BUP/NX was available in 48.3%, and NNS was available in 69.5%. Chain pharmacies were significantly more likely than independent pharmacies to have both medications available, to have each medication available individually, and to be willing to order BUP/NX. Pharmacies in metropolitan counties were more likely to have BUP/NX available than pharmacies in non-metropolitan counties, pharmacies in Medicaid expansion states were more likely to have both medications available and to have NNS available than pharmacies in non-expansion states, and pharmacies in states with high drug overdose death rates were more likely to have NNS available than pharmacies in states with low drug overdose death rates.. BUP/NX and NNS are not readily accessible in many U.S. pharmacies. Deficits in access are most pronounced in independent pharmacies, though county- and state-level factors may also influence availability of these essential medications.

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cross-Sectional Studies; Drug Overdose; Humans; Naloxone; Narcotic Antagonists; Nasal Sprays; Opioid-Related Disorders; Pharmacies; United States

Opioid agonist therapy (OAT) has been shown to reduce opioid use and related harms. However, many young people are not accessing OAT. This study sought to explore how young people navigated OAT over time, including periods of engagement, disengagement, and avoidance.. Semi-structured, in-depth qualitative interviews were conducted between January 2018 and August 2020 with 56 young people in Vancouver, Canada who reported illicit, intensive heroin and/or fentanyl use. Following the verbatim transcription of longitudinal interviews, an iterative thematic analysis was used to extrapolate key themes.. Young people contemplating OAT expressed fears about its addictiveness. Many experienced pressure from providers and family members to initiate buprenorphine-naloxone, despite a desire to explore other treatment options such as methadone. Once young people initiated OAT, staying on it was difficult and complicated by daily witnessed dosing requirements and strict rules around repeated missed doses, especially for those receiving methadone. Most young people envisioned tapering off OAT in the not-too-distant future.. Findings underscore the importance of working collaboratively with young people to develop treatment plans and timelines, and suggest that OAT engagement and retention among young people could be improved by expanding access to the full range of OAT; updating clinical guidelines to improve access to safer prescription alternatives to the increasingly poisonous, unregulated drug supply; addressing treatment gaps arising from missed doses and take-home dosing; and providing a clear pathway to OAT tapering.

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

Pharmaceutical industry involvement in medical education, research and clinical practice can lead to conflicts of interest. Within this context, this study examined how the 'Suboxone Education Programme', developed and delivered by a pharmaceutical company as part of a federally regulated risk management program, was presented as a solution to various kinds of risks relating to opioid use in public documents from medical institutions across Canada.. These documents were issued during the Canadian opioid crisis, a time when the involvement of industry in health policy was being widely questioned given industry's role in driving the overprescribing of opioid analgesics and contributing to population-level harms.. A critical discourse analysis of 69 documents collected between July 2020 and May 2021 referencing the Suboxone Education Program spanning 13 years (2007-2021) from medical, nursing and pharmacy institutions sourced from every Canadian province and territory. Discursive themes were identified through iterative and duplicate analyses using a semistructured data extraction instrument.. Documents characterised the Programme as addressing iatrogenic risks from overprescribing opioid analgesics, environmental risks from a toxic street drug supply and pharmacological risks relating to the dominant therapeutic alternative of methadone. The programme was identified as being able to address these risks by providing mechanisms to surveil healthcare professionals and to facilitate the prescribing of Suboxone. Medical institutions legitimised the Suboxone Education Programme by lending their regulatory, epidemiological and professional authority.. Addressing risk is considered as a central, moral responsibility of contemporary healthcare services. In this case, moral imperatives to address opioid crisis-related risks overrode other ethical concerns regarding conflicts of interest between industry and public welfare. Failing to address these conflicts potentially imperils efforts of mitigating population health harms by propagating an important driving force of the opioid crisis.

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

In the United States, access to buprenorphine remains low and disparities regarding who receives treatment have emerged. Federal laws have regulated buprenorphine delivery, ultimately limiting its implementation more broadly. At the onset of the COVID-19 pandemic, federal agencies acted quickly to remove a legal barrier, effectively allowing people with opioid used disorder (OUD) to initiate buprenorphine treatment via telemedicine. Leveraging this policy shift, a low barrier buprenorphine treatment initiative via telemedicine was started at syringe service programs in California. We assessed early findings from participants reached by this model of treatment.. In May 2020, buprenorphine treatment was offered through a virtual platform to SSP participants in California. SSP staff connected interested participants to virtual appointments with medical providers in a private location. During these visits, clinicians conducted clinical assessments for diagnosing participants with OUD and developed an unsupervised home induction plan for individuals who were eligible. Participants were prescribed a 7-day supply of up to 16 mg daily buprenorphine or 16 mg buprenorphine-2 mg naloxone and asked to return the following week if interested in continuing treatment.. From May 2020 to March 2021, the SSP-buprenorphine virtual care initiative inducted 115 participants onto treatment with 87% of participants inducted on the same day as their referral. Of those inducted, 58% were between the ages of 30 and 49 and 28% were cisgender female. Regarding participants' method of payment to reimburse buprenorphine costs, 92% of participants were covered by Medicare/Medicaid. Overall, 64% of participants returned for a second buprenorphine prescription refill.. These early findings suggest that this could be a promising approach to improve equity and access to buprenorphine treatment. We encourage policymakers to continue allowing buprenorphine delivery via telemedicine and researchers to study whether this approach improves equity and access to treatment throughout the United States.

Topics: Adult; Aged; Buprenorphine; Buprenorphine, Naloxone Drug Combination; COVID-19 Drug Treatment; Female; Humans; Medicare; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Pandemics; Syringes; Telemedicine; United States

The last decade has shown a remarkable increase in the rates of illicit opioid use in Canada and internationally, which is associated with large increases in opioid related morbidity and mortality. While the differences between methadone and buprenorphine/naloxone in terms of retention have been studied outside Canada, the unique location and design of this study, gives it a specific significance.. This study aims to describe the relative treatment retention rates for first episode opioid replacement treatment between methadone and buprenorphine/naloxone for patients receiving daily witnessed dispensed medications in Nova Scotia.. A longitudinal retrospective descriptive study analyzing secondary data from the Nova Scotia Prescription Monitoring Program on patients 18 years of age and older who started first episode opioid agonist therapy with methadone or buprenorphine/naloxone for opioid use disorder in Nova Scotia between 2014 and 2018. Treatment episode was defined as date of initial opioid agonist prescription until there is a gap of greater than 6 days without receiving opioid agonist medication at a pharmacy.. One thousand eight hundred sixty-seven of whom were analyzed as they had at least 1 day in treatment. There was significant treatment dropout within the first 2 weeks of treatment, which did not show a significant difference between OAT medication (23.4% of buprenorphine/naloxone; 22.2% methadone). Median duration of retention in treatment was 58 days for those treated with buprenorphine/naloxone and 101 days for patients treated with methadone. Multivariate cox proportional hazards model showed that buprenorphine/naloxone use as compared to methadone lead to increased hazard of treatment dropout by 62% (HR = 1.62). Hazard rate of treatment dropout for patients below 25 years of age was calculated. (HR 1.53). Median duration of retention in treatment for this subgroup of patients younger than age 25 was 37.5 days for patients treated with buprenorphine/naloxone and 69 days for patients treated with methadone.. Our data suggests that methadone is a numerically superior medication for opioid use disorder when the metric of treatment retention is viewed in isolation, for our population in Nova Scotia. However, the results should be interpreted carefully considering the number of limitations of this study. There are social/accessibility, pharmacologic/safety, and patient preference factors which are also key in decision making when prescribing opioid agonist therapy. These must all be considered when deciding on which medication to initiate for a patient beginning a new treatment episode with OAT for opioid use disorder. This study should stimulate further research into this important area in addiction medicine.

Topics: Adolescent; Adult; Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Canada; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Retrospective Studies

Due to the poor oral bioavailability of buprenorphine, an oral formulation has not been thought possible. Lyndra Therapeutics is developing a once-weekly long-acting oral product containing buprenorphine. We evaluated the efficacy of this formulation in reducing intravenous (i.v.) fentanyl self-administration by three male and three female rhesus monkeys.. Buprenorphine HCl and naloxone HCl were co-formulated using an 11:1 ratio of buprenorphine:naloxone in a controlled-release gastric residence formulation administered in an oral capsule (LYN-013). Naloxone was included to determine the feasibility of combining naloxone with buprenorphine in the formulation as an abuse deterrent. Complete fentanyl dose-response functions were determined during each session. The efficacy of single doses of 56/5, 112/10 and 168/15 mg buprenorphine/naloxone in reducing fentanyl self-administration was examined over 13 days.. LYN-013 significantly decreased the rate of responding for fentanyl for 3 days and significantly reduced total intake of fentanyl for 8 days. Time to maximal buprenorphine levels (Tmax) ranged between 56 and 68 h for all 3 doses. The maximal buprenorphine level (Cmax) following 168 mg was 2.3 ng/ml which was significantly greater that those observed for 56 mg (1.22 ng/ml) and 112 mg (1.35 ng/ml). Finally, the area-under-curves (AUCtau) were buprenorphine dose-dependently increased from 88 to 127-265 h*ng/ml. There were no signs of non-specific changes in behavior.. A once-weekly oral buprenorphine/naloxone formulation produced sustained suppression of fentanyl self-administration in monkeys suggesting that oral delivery of buprenorphine with this formulation could provide a new opportunity to treat opioid use disorders (OUD).

Topics: Analgesics, Opioid; Animals; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Delayed-Action Preparations; Female; Fentanyl; Macaca mulatta; Male; Naloxone; Narcotic Antagonists; Opioid-Related Disorders

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

Although there is consensus that having a "high-enough" dose of buprenorphine (BUP-NX) or methadone is important for reducing relapse to opioid use, there is debate about what this dose is and how it should be attained. We estimated the extent to which different dosing strategies would affect risk of relapse over 12 weeks of treatment, separately for BUP-NX and methadone.. This was a secondary analysis of three comparative effectiveness trials. We examined four dosing strategies: 1) increasing dose in response to participant-specific opioid use, 2) increasing dose weekly until some minimum dose (16 mg BUP, 100 mg methadone) was reached, 3) increasing dose weekly until some minimum and increasing dose in response to opioid use thereafter (referred to as the "hybrid strategy"), and 4) keeping dose constant after the first 2 weeks of treatment. We used a longitudinal sequentially doubly robust estimator to estimate contrasts between dosing strategies on risk of relapse.. For BUP-NX, increasing dose following the hybrid strategy resulted in the lowest risk of relapse. For methadone, holding dose constant resulted in greatest risk of relapse; the other three strategies performed similarly. For example, the hybrid strategy reduced week 12 relapse risk by 13 % (RR: 0.87, 95 %CI: 0.83-0.95) and by 20 % (RR: 0.80, 95 %CI: 0.71-0.90) for BUP-NX and methadone respectively, as compared to holding dose constant.. Doses should be targeted toward minimum thresholds and, in the case of BUP-NX, raised when patients continue to use opioids.

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

The study aimed to examine the genetic contribution to buprenorphine (BUP) treatment in individuals with opioid use disorder (OUD), with a specific focus on BDNF and OPRM1 genes. A total of 113 controls and 111 OUD patients receiving sublingual BUP/naloxone were enrolled. OPRM1 A118G and BDNF Val66Met polymorphisms were investigated by PCR-FRLP. Plasma BDNF and beta-endorphin levels were assessed by ELISA kits in both groups. Blood BUP levels were measured by LC-MS/MS and normalized with daily BUP dose (BUP/D). OPRM1 A118G and BDNF Val66Met polymorphisms didn't have an effect on plasma beta-endorphin and BDNF levels in OUD patients, respectively. Interestingly, OUD patients had significantly higher plasma BDNF and lower beta-endorphin levels compared to the controls (p < 0.001). A negative and significant correlation between plasma BUP/D and BDNF levels was found. Age onset of first use was associated with OPRM1 A118G polymorphism. The findings indicated that sublingual BUP/naloxone may increase plasma BDNF levels, but may decrease beta-endorphin levels in individuals with OUD. Plasma BDNF level seemed to be decreased in a BUP/D concentration-dependent manner.

Topics: beta-Endorphin; Brain-Derived Neurotrophic Factor; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Chromatography, Liquid; Humans; Opioid-Related Disorders; Receptors, Opioid, mu; Tandem Mass Spectrometry

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

This nationwide study builds on prior research, which suggests that Federally Qualified Health Centers (FQHCs) and other primary care providers are associated with increased access to opioid use disorder (OUD) treatment. We compare health care utilization, spending, and quality for Medicaid patients diagnosed with OUD who receive primary care at FQHCs and Medicaid patients who receive most primary care in other settings, such as physician offices (non-FQHCs). We hypothesized that the integrated care model of FQHCs would be associated with greater access to medication for opioid use disorder (MOUD) and/or behavioral health therapy and lower rates of potentially inappropriate co-prescribing.. This cross-sectional study examined 2012 Medicaid Analytic eXtract files for patients diagnosed with OUD receiving most (>50%) primary care at FQHCs (N = 37,142) versus non-FQHCs (N = 196,712) in all 50 states and Washington DC. We used propensity score overlap weighting to adjust for measurable confounding between patients who received care at FQHCs versus non-FQHCs and increase generalizability of findings given variation in Medicaid programs and substance use policies across states.. FQHC patients displayed higher primary care utilization and fee-for-service spending, and similar or lower utilization and fee-for-service spending for other health service categories. Contrary to our hypotheses, non-FQHC patients were more likely to receive timely (≤90 days) MOUD (buprenorphine, methadone, naltrexone, or suboxone) (Relative Risk [RR] = 1.10, 95% CI: 1.07, 1.12) and more likely be retained in medication treatment (>180 days) (RR = 1.12, 95% CI: 1.09, 1.14). However, non-FQHC patients were less likely to receive behavioral health therapy (mental health or substance use therapy) (RR = 0.90, 95% CI: 0.88, 0.92) and less likely to remain in behavioral health treatment (RR = 0.92, 95% CI: 0.89, 0.94). Non-FQHC patients were more likely to fill potentially inappropriate prescriptions of benzodiazepines and opioids after OUD diagnosis (RR = 1.35, 95% CI: 1.30, 1.40).. Observed patterns suggest that Medicaid patients diagnosed with OUD who obtained primary care at FQHCs received more integrated care compared to non-FQHC patients. Greater care integration may be associated with increased access to behavioral health therapy and quality of care (lower potentially inappropriate co-prescribing) but not necessarily greater access to MOUD.

Topics: Analgesics, Opioid; Benzodiazepines; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cross-Sectional Studies; Delivery of Health Care; Humans; Medicaid; Methadone; Naltrexone; Opioid-Related Disorders; Primary Health Care; United States

Incarcerated clients experience high rates of opioid use disorder and overdose. It is critical that opioid agonist treatment (OAT) is provided in correctional facilities. However, few receive OAT due to concerns about diversion, misuse, and safety. Buprenorphine extended-release (BUP-XR), a monthly buprenorphine depot injection, could be especially advantageous in the correctional setting as it can prevent diversion and misuse, saving staff resources and time. An injection of BUP-XR is costly compared with a monthly supply of buprenorphine/naloxone (BUP/NX) tablets. We demonstrate that when factoring in the added costs of medication preparation, administration, monitoring, and personnel, it is more economical to provide BUP-XR than BUP/NX. Other facilities, by utilizing our cost breakdown, can determine whether BUP-XR is economically advantageous at their own facility.

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Costs and Cost Analysis; Humans; Narcotic Antagonists; Opioid-Related Disorders; Prisons; Tablets

This study examines the association of sublingual buprenorphine/naloxone and dental adverse events using the IQVIA health claims database.

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

To assess differences in the quality of opioid use disorder (OUD) treatment received by Medicare beneficiaries enrolled in health plans that used prior authorization (PA) for buprenorphine-naloxone compared with those enrolled in plans that did not use PA.. Cross-sectional observational study, United States. Continuously enrolled beneficiaries (71 294) with an OUD who filled at least one prescription for buprenorphine-naloxone between March 2012 and July 2017.. Percentage of patients tested for hepatis B, hepatis C, HIV and liver functioning; percentage of patients with urine drug screens and number of urine drug screens; continuous use of buprenorphine-naloxone for at least 180 days; co-use of benzodiazepines; number of outpatient visits with and without an OUD diagnosis.. PA was significantly associated with a lower likelihood of testing for hepatitis B [-3.5, 95% confidence interval (CI) = -4.4, -2.7] and C (-5.9, 95% CI = -6.9, -4.9), but the findings were inconclusive as to whether or not there was a difference in HIV (-1.1, 95% CI = -2.5, 0.4) or liver function testing (1.3, 95% CI = -0.1, 2.7). PA was associated with a lower likelihood of urine drug screening (-25.5, 95% CI = -26.8, -24.1) and with fewer drug screens (-2.5, 95% CI = -3.0, -2.1). Findings were inconclusive as to whether or not there was a difference in continuous use of buprenorphine-naloxone (0.3, 95% CI = -1.2, 1.8). PA was associated with fewer outpatient visits (-2.1, 95% CI = -3.0, -1.2) and fewer outpatient visits with an OUD diagnosis (-1.7, 95% CI = -2.1, -1.3). PA was associated with a lower likelihood of filling benzodiazepine prescriptions before and after buprenorphine-naloxone induction (-28.9, 95% CI = -29.6, -28.3) but a greater likelihood of only using benzodiazepines after buprenorphine-naloxone induction (10.6, 95% CI = 9.3, 11.8).. US Medicare patients subject to prior authorization for buprenorphine-naloxone are not more likely to receive high-quality treatment for opioid use disorder than patients not subject to prior authorization.

Topics: Aged; Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cross-Sectional Studies; Humans; Medicare Part D; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Prior Authorization; United States

In 2018, the Baltimore City Health Department launched a mobile clinic called Healthcare on The Spot, which offers low-threshold buprenorphine services integrated with health care services to meet the needs of people who use drugs. In addition to buprenorphine management, The Spot offers testing and treatment for hepatitis C, sexually transmitted infections, and HIV, as well as pre-exposure prophylaxis for HIV, wound care, vaccinations, naloxone distribution, and case management.. This cohort analysis includes clinical service data from the first 15 months of The Spot mobile clinic, from September 4, 2018, to November 23, 2019. The Spot co-located with the Baltimore syringe services program in five locations across the city. Descriptive data are provided for patient demographics and services provided, as well as percent of patients retained in buprenorphine treatment at one and three months. Logistic regression identified factors associated with retention at three months.. The Spot mobile clinic provided services to 569 individuals from September 4, 2018, to November 23, 2019, including prescribing buprenorphine to 73.8% and testing to more than 70% for at least one infectious disease. Patients receiving a prescription for buprenorphine were more likely to be tested for HIV, hepatitis C, and sexually transmitted infections, as well as receive treatment for hepatitis C and preventive services including vaccination and naloxone distribution. The Spot initiated HIV treatment for four patients and HIV pre-exposure prophylaxis for twelve patients. More than 32% of patients had hepatitis C; nineteen of these patients initiated treatment for hepatitis C with eight having a documented cure. Buprenorphine treatment retention was 56.0% at one month and 26.2% at three months. Patients who were Black or receiving treatment for hepatitis C were more likely to be retained in buprenorphine treatment at three months.. Increasing access to integrated medical services and drug treatment through low-threshold, community-based models of care can be an effective tool for addressing the effects of drug use.

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Hepatitis C; Humans; Mobile Health Units; Naloxone; Opiate Substitution Treatment; Opioid-Related Disorders

Patients with opioid use disorder (OUD) are frequently seen in the ED for opioid-related reasons, which creates an opportunity for ED providers to discuss medications for OUD with their patients. Buprenorphine is a partial mu-opioid agonist that is FDA approved to treat OUD and may be initiated in the ED. Traditionally, buprenorphine therapy was initiated under healthcare provider observation; however, other strategies such as at-home induction have also emerged.. This was a retrospective descriptive analysis of patients aged 18 years or older who received a take-home supply of buprenorphine-naloxone from an urban, academic ED between March 2018 and March 2020. The primary outcome was the proportion of patients who filled a prescription for buprenorphine at three months after index ED visit. The proportion of patients that filled a prescription for buprenorphine at six months was also evaluated. The primary safety endpoint was the proportion of patients with return ED visit within six months related to opioid overdose.. There were 242 patient records reviewed with 155 patients included in final analysis. Seventy (45.2%) patients filled buprenorphine prescriptions at three months, with 64 (41.3%) who filled buprenorphine prescriptions at six months. Seventeen (11%) patients had a return ED visit related to opioid overdose within six months.. Dispensing buprenorphine take-home kits from the ED resulted in continuation of outpatient buprenorphine in almost 50% of patients. Further studies are warranted to define the role of ED-dispensed buprenorphine.

Topics: Adolescent; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Emergency Service, Hospital; Humans; Narcotic Antagonists; Opioid-Related Disorders; Outpatients; Retrospective Studies

Little is known about the relationship between opioid agonist therapy (OAT) and fentanyl use, specifically. This study aimed to estimate the association between current use of different forms of OAT, including methadone, buprenorphine/naloxone (BUP/NX), slow release oral morphine (SROM), or injectable opioid agonist treatment (iOAT), and the likelihood of a fentanyl-positive urine drug test (UDT) as compared to no OAT.. Data were obtained from three community-recruited prospective cohort studies of people who use drugs in Vancouver, Canada from December 2016 through November 2018. Using multivariable Generalized Estimating Equations (GEE), we examined the association between current use of each form of OAT, as compared to no OAT, and fentanyl-positive UDT among participants who use opioids.. The 915 participants contributed 2112 UDTs over a median of two follow-up visits. The majority of UDTs (74.9 %) were positive for fentanyl. After adjustment for a priori defined confounding factors, compared to no OAT, current use of BUP/NX was associated with lower odds of fentanyl-positive UDT (odds ratio [OR] = 0.36, 95 % confidence interval [CI]: 0.22-0.58) while current use of methadone (OR = 0.84, 95 % CI: 0.65-1.07), iOAT (OR = 1.30, 95 % CI: 0.75-2.28), and SROM (OR = 1.34, 95 % CI: 0.74-2.43) were not.. In this cohort of people who use opioids in Vancouver, only use of BUP/NX was associated with lower odds of fentanyl-positive UDT. Our findings highlight high rates of ongoing fentanyl use despite the use of OAT and support the expansion of BUP/NX for the treatment of people who use fentanyl.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Canada; Cohort Studies; Fentanyl; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Prospective Studies

Urine drug screens (UDS) assist in clinical planning and assessment of adherence in opioid agonist treatment (OAT). Urine drug screens may also be used in criminal justice and child protection settings. Buprenorphine (BPN) UDS testing is complex. Immunoassay often does not detect BPN and gas chromatography-mass spectrometry (GC-MS) is needed. A limited understanding of testing can negatively influence UDS interpretation and clinical decision making.. The primary aim was to determine detection rates of BPN in UDS in participants on BPN or buprenorphine/naloxone (BNX) treatment. The secondary aim was to identify if comorbidities, sex, co-prescribed medications, or dosing site and observation were associated with BPN detection.. Public outpatient clinic in a specialist addiction treatment service.. In this retrospective observational study, records of clients on supervised BPN/BNX treatment between September 2017 and 2018 were reviewed.. Data extracted included UDS results, age, sex, indication for BPN, frequency of observed doses, dose of BPN, dosing site, comorbid medical conditions, and medications.. One hundred and sixty-one medical records were reviewed. Ninety-seven (60 percent) underwent screening urine immunoassay. Of these 97, 51 (53 percent) had further GC-MS testing for BPN of which 22 (43 percent) did not detect BPN despite directly observed OAT. Co-prescription of medications known to interact with cytochrome P450 3A4 was associated with nondetection of BPN (p < 0.05). No significant association between median dose, dosing site, and observed dosing and BPN detection was identified.. Urine drug testing for BPN is complex. Failure to detect BPN does not betoken nonadherence to treatment and is associated with co-prescription of drugs interacting with cytochrome P450 3A4.

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

Buprenorphine/naloxone (BPN/NX) is a first-line treatment for opioid use disorder. Conventional treatment guidelines recommend a period of opioid abstinence and the presence of moderate withdrawal before initiation to avoid precipitated withdrawal. A newer approach of "microdosing" removes this requirement and has potential benefits. We present two cases of successful induction of BPN/NX using a microdosing regimen in an inpatient withdrawal unit. Both cases did not result in precipitated withdrawal and did not necessitate prior cessation of other opioids. This case report highlights how the use of microdosing to induct BPN/NX treatment can reduce potential barriers and complications with treatment initiation.

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

Urine drug screening (UDS) is commonly used as part of treatment for opioid use disorder (OUD), including treatment with buprenorphine-naloxone for OUD in a primary care setting. Very little is known about the value of UDS, the optimum screening frequency in general, or its specific use for buprenorphine treatment in primary care. To address this question, we thought that in a stable population receiving buprenorphine-naloxone in the primary care setting it would be useful to know how often UDS yielded expected and unexpected results.. We present a descriptive analysis of UDS results in patients treated with buprenorphine-naloxone for OUD in a primary care setting over a two-year period. An unexpected test result is: 1. A negative test for buprenorphine and/or 2. A positive test for opioids, methadone, cocaine and/or heroin.. A total of 161 patients received care during the study period and a total of 2588 test results were analyzed from this population. We found that 64.4% of the patient population (n = 104 patients) demonstrated both treatment adherence (as measured by buprenorphine positive test results) and no apparent unexpected test findings, as defined by negative tests for opioids, methadone, cocaine and heroin. Of the 161 patients, 20 results were positive for opioids, 5 for methadone, 39 for heroin and 2 for cocaine. Analysis at the UDS level demonstrated that, of the 2588 test results, 38 (1.5%) results did not have buprenorphine. Of the 2588, 28 (1.1%) test results were positive for opioids, 8 (0.3%) were positive for methadone, 39 (1.5%) for cocaine and 2 (0.1%) for heroin.. Given that the majority of patients in our study had expected urine results, it may be reasonable for less frequent urine testing in certain patients.

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

Medications for opioid use disorder such as opioid agonist treatment (OAT, including methadone, buprenorphine) are the gold standard intervention for opioid use disorder (OUD). Persons with OUD have high rates of neurocognitive impairment and psychiatric and substance use disorders, but few studies have examined these characteristics in diverse patients initiating OAT in opioid treatment programs (OTPs). Additionally, in these individuals, poor neurocognitive functioning and psychiatric/other substance use disorders are associated with poor OUD treatment outcomes. Given rapid changes in the opioid epidemic, we sought to replicate findings from our pilot study by examining these characteristics in a large diverse sample of persons with OUD starting OTP-based OAT.. Ninety-seven adults with OUD (M age = 42.2 years [SD = 10.3]; M education = 11.4 years [SD = 2.3]; 27% female; 22% non-Hispanic white) were enrolled in a randomized longitudinal trial evaluating methadone versus buprenorphine/naloxone on neurocognitive functioning. All participants completed a comprehensive neurocognitive, psychiatric, and substance use evaluation within one week of initiating OAT.. Most of the sample met criteria for learning (79%) or memory (69%) impairment. Half exhibited symptoms of current depression, and comorbid substance use was highly prevalent. Lifetime cannabis and cocaine use disorders were associated with better neurocognitive functioning, while depression was associated with worse neurocognitive functioning.. Learning and memory impairment are highly prevalent in persons with OUD starting treatment with either methadone or buprenorphine/naloxone in OTPs. Depression and comorbid substance use are prevalent among these individuals, but neither impact learning or memory. However, depression is associated with neurocognitive impairment in other domains. These findings might allow clinicians to help persons with OUD starting OAT to develop compensatory strategies for learning and memory, while providing adjunctive treatment for depression. Trial Registration NCT, NCT01733693. Registered November 4, 2012, https://clinicaltrials.gov/ct2/show/NCT01733693 .

Topics: Adult; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Female; Humans; Longitudinal Studies; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Pilot Projects

The comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT) trial showed that following induction, treatment with the sublingual agonist (buprenorphine-naloxone, BUP-NX) or injected antagonist (extended release naltrexone, XR-NTX) produced similar reductions in opioid relapse in injection users with opioid use disorder (OUD). Because XR-NTX reduces drinking in alcohol use disorder (AUD), we conducted a secondary analysis of the X:BOT sample of patients successfully inducted onto treatment to determine whether XR-NTX (n = 204) was superior to BUP-NX (n = 270) in reducing drinking or heavy drinking in patients with OUD.. Standard drink units consumed were measured using the Timeline Follow-back method. Mixed-models regression was used to examine the monthly frequency of any drinking and heavy drinking over 6 months of treatment. We used a proportional hazard survival analysis to examine the time to first drink.. Both treatment groups reduced drinking from baseline to posttreatment (small to medium effect), but no differences between groups were detected. However, only 29% (n = 136) of the sample had AUD and 19% (n = 26/136) of those were abstinent before treatment. Analysis of a subsample enriched for possible drinking included 136 individuals with an AUD diagnosis plus 43 who did not have AUD, but reported at least one day of heavy drinking prior to the study. However, this subsample reported only 32% of days of any drinking with a median of only 13% of days designated as "heavy." Within this subsample, at baseline, the BUP-NX group reported more mean drinks per drinking day than the XR-NTX group (p = 0.03); however, there were no other significant group differences on drinking observed before, during, or at the end of treatment.. There was an overall reduction in drinking during treatment of OUD using both agonist and antagonist medications, so that the hypothesis that XR-NTX would be superior to BUP-NX was not supported. The study is limited by low levels of comorbid AUD or heavy drinking observed in X:BOT trial participants seeking treatment for OUD.

Topics: Alcoholism; Buprenorphine, Naloxone Drug Combination; Clinical Trials as Topic; Delayed-Action Preparations; Humans; Narcotic Antagonists; Opioid-Related Disorders; Outpatients; Research Design

Opioid use disorder (OUD) is an important comorbidity in individuals with advanced cancer, in whom pain is common. Full-agonist opioid medications are the cornerstone of cancer pain management, but the existing literature does not address how to manage cancer pain in patients with OUD.. To conduct an expert panel to develop consensus on the appropriateness of management of cancer pain in individuals with co-occurring advanced cancer and OUD.. A 3-round modified Delphi process was completed from August to October 2020 with 2 cases: patient with advanced cancer, pain, and OUD treated with buprenorphine-naloxone or methadone. Participants rated management strategies in round 1, discussed results in round 2, and provided final responses in round 3. ExpertLens, an online approach to conducting modified Delphi panels, was used. Participants were experts in palliative care, addiction, or both, recruited by email from palliative care and addiction-focused professional groups, lists from prior studies, and snowball sampling. Data analysis was performed from November 2020 to July 2021.. Of 120 experts (median age, 40-49 years), most were White (78 participants [94%]), female (74 participants [62%]), and held MD or DO degrees (115 participants [96%]); 84 (70%) participated in all rounds. For a patient with OUD taking buprenorphine-naloxone, it was deemed appropriate to continue buprenorphine-naloxone with thrice-daily dosing. Continuing buprenorphine-naloxone and adding a full-agonist opioid was deemed to be appropriate for patients with a prognosis of weeks to months and of uncertain appropriateness for patients with a prognosis of months to years. For a patient with OUD taking methadone dispensed at a methadone clinic, it was deemed appropriate to take over prescribing and dose twice or thrice daily. Continuing methadone daily while adding another full-agonist opioid was deemed appropriate for patients with a prognosis of weeks to months and of uncertain appropriateness for those with a prognosis of months to years.. The findings of this qualitative study provide urgently needed, consensus-based guidance for clinicians and highlight critical research and policy gaps needed to facilitate implementation.

Topics: Adult; Buprenorphine, Naloxone Drug Combination; Cancer Pain; Delphi Technique; Female; Humans; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Prognosis; Qualitative Research

Topics: Buprenorphine, Naloxone Drug Combination; COVID-19; Humans; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Pandemics; Primary Health Care; Rural Health Services; SARS-CoV-2; Telemedicine; United States

To estimate incidence and predictors of opioid agonist therapy (OAT) discontinuation in a national cohort of people who inject drugs (PWID).. Annually repeated cross-sectional serosurveillance among PWID attending ~50 needle-syringe programmes across Australia.. Between 1995 and 2018, 2651 PWID who reported current OAT and had subsequent survey participation completed 6739 surveys. Respondents were followed over 11 984 person-years of observation (PYO). Respondents were predominantly male (60%), and the median age was 34 years. Heroin was the most commonly reported drug last injected (46%), and methadone was the most commonly prescribed OAT (77%).. The primary outcome was discontinuation of OAT (methadone, buprenorphine or buprenorphine-naloxone). Among respondents who reported current OAT, those who did not report current OAT in all subsequent records were defined as discontinued, and those with current OAT at all subsequent records were defined as retained. Predictors of discontinuation included self-reported demographic (sex, location, Indigenous status) and drug use characteristics (drug last injected, frequency of injection).. Just fewer than one-third of respondents (29%) reported an OAT discontinuation event. The crude discontinuation rate was 6.3 [95% confidence intervals (CI) = 5.9-6.8] per 100 PYO. Discontinuation was significantly higher among respondents who reported last injecting pharmaceutical opioids [adjusted hazard ratio (aHR) = 1.75, 95% CI = 1.41-2.17, P < 0.001], being prescribed buprenorphine (aHR = 1.44, 95% CI = 1.18-1.76, P = 0.001) or buprenorphine-naloxone (aHR = 1.68, 95% CI = 1.20-2.34, P = 0.002), daily or more frequent injection (aHR = 1.51, 95% CI = 1.23-1.85, P < 0.001), recent public injecting (aHR = 1.37, 95% CI = 1.17-1.60, P < 0.001), incarceration in the previous 12 months (aHR = 1.31, 95% CI = 1.05-1.64, P = 0.017), recent receptive syringe or injection equipment sharing (aHR = 1.28, 95% CI = 1.10-1.48, P = 0.001) and male sex (aHR = 1.27, 95% CI = 1.09-1.47, P = 0.002).. People who inject drugs attending needle-syringe programmes in Australia appear to be significantly more likely to discontinue opioid agonist treatment if they were prescribed buprenorphine or buprenorphine-naloxone compared with methadone, are male or report injection risk behaviours and recent incarceration.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cross-Sectional Studies; Humans; Incidence; Infant, Newborn; Male; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Substance Abuse, Intravenous

Individuals exposed to fentanyl are at risk of precipitated withdrawal using typical buprenorphine/naloxone induction procedures.. This case series describes buprenorphine/naloxone inductions of four individuals who tested positive for fentanyl.. Buprenorphine-precipitated withdrawal was observed in two individuals who completed a conventional buprenorphine/naloxone induction strategy. Two more individuals completed a revised buprenorphine/naloxone induction strategy that did not precipitate withdrawal.. Using multiple 2 mg doses of buprenorphine/naloxone in patients already in mild/moderate withdrawal improved outcomes.. Persons who use illicit fentanyl might be less likely to experience precipitated withdrawal from this revised buprenorphine/naloxone induction strategy. (Am J Addict 2021;30:83-87).

Topics: Adult; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Female; Fentanyl; Humans; Male; Middle Aged; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Substance Withdrawal Syndrome; Young Adult

Buprenorphine is commonly used to manage opioid use disorder; however, the literature describes its potential role in treating treatment-resistant depression.. We present a patient with bipolar disorder and opioid use disorder, who presented status post-suicide attempt.. After initiating buprenorphine-naloxone, the patient reported rapid improvement in depressive symptoms, pain, and suicidal ideation.. This case demonstrates buprenorphine's antisuicidal and mood-stabilizing capabilities, potentially via antagonizing κ-opioid receptors as well as reinstating the balance between reward and antireward circuitry.. This case highlights buprenorphine-naloxone as a treatment for both treatment-resistant depression and opioid use disorder, as well as buprenorphine's rapid antidepressant, analgesic, and antisuicidal effects. (Am J Addict 2021;30:80-82).

Topics: Adult; Analgesics, Opioid; Bipolar Disorder; Buprenorphine, Naloxone Drug Combination; Burns; Depression; Humans; Male; Opioid-Related Disorders; Pain; Receptors, Opioid, kappa; Suicidal Ideation; Suicide, Attempted

Despite increased public awareness and use of opioid agonist therapy (OAT), there is little published data on contraception among women on methadone or buprenorphine/naloxone. This study aimed to characterize patterns of contraception use among this population.. We conducted a cross-sectional survey between May 2014 and October 2015 at 6 medical clinics, pharmacies, and community organizations in British Columbia. Trained surveyors used the Canadian Sexual Health Survey (CSHS) to collect information on contraceptive practices and barriers to health care access. Descriptive analysis was performed on the subset of women on OAT who were at risk for unintended pregnancy.. Of the 133 survey respondents, 80 (60.2%) were at risk for unintended pregnancy. Among the 46 respondents with a recent pregnancy, 44 (95.7%) reported it as unintended. Of those at risk for unintended pregnancy, the most common contraceptive methods used were "no method," male condom, and depo-medroxyprogesterone at 28.8%, 16.3%, and 12.5%, respectively. Only 5% reported dual protection with a barrier and hormonal or intrauterine method. Barriers to contraception access included difficulty booking appointments with providers and cost, although 97% of all respondents reported feeling comfortable speaking with a physician about contraception.. We found that most respondents using OAT reported prior pregnancies that were unintended, and used less effective contraceptive methods. Health care professionals who provide addiction care are uniquely positioned to address their patients' concerns about contraception. Incorporating family planning discussions into OAT services may improve understanding and use of effective contraceptive methods. Addressing unmet contraceptive needs may enable women on OAT to achieve their reproductive goals.

Topics: Adult; British Columbia; Buprenorphine, Naloxone Drug Combination; Contraception; Contraception Behavior; Cross-Sectional Studies; Family Planning Services; Female; Health Services Accessibility; Humans; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy, Unplanned; Substance-Related Disorders

Topics: Buprenorphine, Naloxone Drug Combination; Humans; Naloxone; Nasal Sprays; Opioid-Related Disorders; Pharmacies; Texas

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Harm Reduction; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Philadelphia

Buprenorphine is an essential medication for the treatment of opioid use disorder (OUD), but studies show it has been underused over the last 2 decades. We sought to evaluate utilization of and spending on buprenorphine formulations in Medicaid and to evaluate the impact of key market and regulatory factors affecting availability of different formulations and generic versions.. We first identified all buprenorphine formulations approved by the Food and Drug Administration for OUD using Drugs@FDA. We then used National Drug Codes to identify each drug in the Medicaid State Drug Utilization Data and extracted annual utilization rates and spending between 2002 and 2018 by drug and according to whether a brand-name or generic version was dispensed. We compared these trends to market and regulatory factors that affected competition, which we identified through searching the Federal Register, Westlaw, PubMed, and Google News.. Brand-name buprenorphine-naloxone sublingual tablet and film formulations (Suboxone) were dispensed 2.7 times more (n = 634 213 140) and reimbursed 4.4 times more (n = $4 440 556 473) than all other formulations combined (n = 237 769 689; $1 018 988 133). We identified numerous market and regulatory factors that contributed to an estimated 9-year delay in generic versions of the tablet formulation and 6-year delay for generic versions of the film formulation.. Brand-name buprenorphine formulations have been widely used in Medicaid, leading to substantial costs, in part because generic versions were delayed by multiple years owing to market and regulatory factors. Timely availability of low-cost generics could have helped encourage OUD treatment with buprenorphine during the height of the opioid crisis.

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Drug Utilization; Drugs, Generic; Economic Competition; Humans; Medicaid; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Patents as Topic; United States

Prescribing naloxone to patients at increased opioid overdose risk is a key component of opioid overdose prevention efforts, but little is known about naloxone fills among patients receiving buprenorphine for opioid use disorder, one such high risk group.. This retrospective cross-sectional study used de-identified pharmacy claims representing 90% of all prescriptions filled at retail pharmacies in 50 states and the District of Columbia. We performed a multivariable logistic regression to examine filled naloxone prescriptions among patients receiving buprenorphine treatment and assessed how filled naloxone prescriptions vary by patient, prescriber, and community characteristics.. Filled naloxone prescriptions occurred among 4.5% of buprenorphine treatment episodes. Episodes paid through Medicaid (aOR 2.40, 95%CI 2.33-2.47) and Medicare (aOR 1.53, 95%CI 1.46-1.60) had higher odds of filled naloxone prescriptions than commercial insurance episodes. Compared to episodes where the primary prescriber was an adult primary care physician, odds of filling a naloxone prescription were higher among episodes prescribed by addiction specialists (aOR 1.30, 95% CI 1.24-1.37) and physician assistants/nurse practitioners (aOR 1.57, 95% CI 1.53-1.61).. Prescribing naloxone to patients receiving buprenorphine represents a tangible clinical action that can be taken to help prevent opioid overdose deaths. However, despite recommendations to co-prescribe naloxone to patients at increased risk for opioid overdose, rates of filling naloxone prescriptions remain low among patients dispensed buprenorphine. States, insurers, and health systems should consider implementing strategies to facilitate increased co-prescribing of naloxone to at-risk individuals.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cross-Sectional Studies; District of Columbia; Female; Humans; Male; Medicaid; Medicare; Middle Aged; Naloxone; Opiate Overdose; Opioid-Related Disorders; Pharmacies; Prescriptions; Retrospective Studies; United States

Prescription opioid dependence remains a major source of morbidity and mortality in the United States. Patients previously on high-dose opioids may poorly tolerate opioid tapers. Current guidelines support the use of buprenorphine therapy in opioid-tapering protocols, even among patients without a diagnosis of opioid use disorder. Buprenorphine microinduction protocols can be used to transition patients to buprenorphine therapy without opioid withdrawal. From November 2019 to April 2020, we transitioned 8 patients on high-dose prescribed opioids for pain to sublingual buprenorphine-naloxone using a microdose protocol without any evidence of precipitated withdrawal. Six of these patients remain on buprenorphine-naloxone and report improved analgesia. Because of its simplicity, the buprenorphine microinduction protocol can be easily adapted for telemedicine and may help to prevent unnecessary clinic visits and opioid-related admissions in the setting of social distancing regulations during the coronavirus 2019 pandemic.

Topics: Administration, Sublingual; Aged; Buprenorphine, Naloxone Drug Combination; COVID-19; Female; Humans; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; SARS-CoV-2; Substance Withdrawal Syndrome; Telemedicine

Opioid use disorder has affected many lives across the US. Medications for opioid use disorder (MOUD), including buprenorphine, have been shown to decrease mortality in this patient population. Here we present a case of a 32-year-old woman on buprenorphine/naloxone undergoing multiple surgical operations, whose course included buprenorphine discontinuation, methadone initiation, and buprenorphine re-induction using a novel "microdosing" approach. This report includes a presentation of the case and a discussion of the clinical decision making and relevant literature to give hospitalbased providers a perspective on management of peri-operative patients on MOUD.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Female; Humans; Inpatients; Opiate Substitution Treatment; Opioid-Related Disorders

According to the latest medical evidence, Methadone and buprenorphine-naloxone (Suboxone. This study aimed to use Twitter to assess the public perceptions about methadone and buprenorphine-naloxone, and to compare their discussion contents based on themes/topics, subthemes, and sentiment.. We conducted a descriptive analysis of a small and automatic analysis of a large volume of microposts ("tweets") that mentioned ". We manually analyzed 900 tweets, most of which related to. Twitter content about methadone and Suboxone

Topics: Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Humans; Methadone; Narcotic Antagonists; Natural Language Processing; Opiate Substitution Treatment; Opioid-Related Disorders; Public Opinion; Social Media

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Female; Humans; Opioid-Related Disorders; Pregnancy

Research has shown buprenorphine/naloxone to be an effective medication for treating individuals with opioid use disorder. At the same time, treatment discontinuation rates are reportedly high though much of the extant evidence comes from studies of the Medicaid population.. To examine the pattern and determinants of buprenorphine/naloxone treatment discontinuation in a population of commercially insured individuals.. We performed a retrospective observational analysis of Massachusetts All Payer Claims Data (MA APCD) covering years 2013 through 2017. We defined treatment discontinuation as a gap of 60 consecutive days without a prescription for buprenorphine/naloxone within a time frame of 24 months from the initiation of treatment. A mixed-effect Cox proportional hazard model examined the associated risk of discontinuing treatment with baseline predictors.. A total of 5134 individuals who were commercially insured during the study period.. Buprenorphine/naloxone treatment discontinuation.. Overall 75% of individuals had discontinued treatment within two years of initiating treatment, and median time to discontinuation was 300 days. Patients aged between 18 and 24 years (HR = 1.436, 95%, CI = 1.240-1.663) and receiving treatment from prescribers with high panel-size (HR = 1.278, 95% CI = 1.112-1.468) had higher risk of discontinuing treatment. On the contrary, patients receiving treatment from multiple prescribers had lower associated risk of treatment discontinuation.. A substantial percentage of patients discontinue treatment well before they can typically meet criteria for sustained remission. Further investigations should assess the clinical outcomes following premature discontinuation and identify strategies for retaining patients in treatment.

Topics: Adolescent; Adult; Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Humans; Massachusetts; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Retrospective Studies; United States; Young Adult

Buprenorphine-naloxone is an evidence-based treatment for opioid use disorder (OUD). Despite its efficacy, nearly half of patients discontinue treatment prematurely. Novel intervention strategies that may be delivered outside of traditional treatment settings are needed to support buprenorphine uptake and maintenance. The goal of this study was to elucidate key elements surrounding the acceptability/feasibility and structure of an interactive computer- and text message-delivered personalized feedback intervention for adults initiating outpatient buprenorphine treatment.. Twenty-four adults engaged in treatment at two outpatient addiction treatment centers completed semistructured interviews exploring preferences around digital health interventions. Trained interviewers conducted interviews, the study audio-recorded them, and a professional agency transcribed them verbatim. The research team iteratively developed a coding structure using thematic and content analysis and entered it into a framework matrix. The team double coded each transcript.. The sample was balanced by gender, primary type of opioid use (prescription pills; heroin/fentanyl), and phase of recovery [early (≤8 weeks of treatment) vs. late (>8 weeks of treatment)]. The study reached saturation after 24 interviews (mean age = 38.9; 70.8% white; 8.3% Hispanic/Latino). (1) Acceptability/feasibility themes: A computer- and text message-based intervention that incorporates a motivational- and distress tolerance-based framework is highly acceptable. Presentation of material, including the length of the intervention, is effective in facilitating learning. The center should offer the intervention to individuals entering treatment and they should have the flexibility to complete the intervention at the center or in private from their own home. The use of technology for intervention delivery helps to overcome fears of judgment stemming from stigmatizing experiences. (2) Structural themes: The text message intervention should deliver both predetermined (automatic) and on demand messages. Two to three messages per day (morning and early evening), with the option to elicit additional messages as needed, would be ideal. The messages must be personalized. Incorporating multimedia such as emojis, gifs, and links to videos will increase interactivity.. Overall, adults engaged in outpatient buprenorphine treatment were receptive to an interactive computer- and text messaged-delivered personalized feedback intervention to support recovery. Incorporating thematic results on suggested structural changes may increase the usability of this intervention to improve treatment outcomes by reducing illicit opioid use, increasing adherence/retention, and preventing future overdose and other complications of illicit opioid use.

Topics: Adult; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Feasibility Studies; Humans; Medication Adherence; Opioid-Related Disorders

Topics: Adolescent; Adult; Attitude; Buprenorphine, Naloxone Drug Combination; Female; Humans; Male; Methadone; Middle Aged; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Prevalence; United States; Young Adult

Despite rising morbidity and mortality from the opioid epidemic and other addictions, people who inject drugs (PWID) remain understudied regarding pain outcomes. Data among PWID regarding chronic pain and drug use, including non-medical use of opioids, is largely unknown. We examined the prevalence of chronic pain and drug use for pain in this population.. Standardized surveys captured self-report of demographics, chronic pain, and non-prescription drug use in 203 PWID in an urban syringe services program between April and November 2016. Chronic pain was defined as self-report of chronic pain diagnosis or persistent pains over the past 6 months.. Overall, 47% (95% CI, 40%-54%) of PWID reported chronic pain, while 35% (95% CI, 29%-42%) reported non-prescription drug use of any type for pain. Among those with chronic pain, drug use to treat pain was commonly reported (76%; 95% CI, 66%-83%). Non-medical opioid use did not differ among PWID with or without chronic pain or drug use for pain. A multivariable logistic regression model showed chronic pain was more likely among non-Hispanic whites and those with arthritis, older age, and homelessness.. Chronic pain serves as an important factor in the persistence of drug use in more than one-third of PWID in this sample. The high prevalence of chronic pain with drug use for pain suggests that proper pain management is likely to be an essential component of preventing or regressing injection drug use in PWID, with data needed on effective interventions for this population.

Topics: Adolescent; Adult; Age Factors; Analgesics, Opioid; Arthritis; Baltimore; Black or African American; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Chronic Pain; Cocaine-Related Disorders; Female; Heroin Dependence; Humans; Ill-Housed Persons; Male; Middle Aged; Needle-Exchange Programs; Odds Ratio; Opioid-Related Disorders; Prevalence; Risk Factors; Substance Abuse, Intravenous; White People; Young Adult

A 29-year-old woman presented to detox for treatment of an opioid use disorder with illicit fentanyl. While in detox, she was started on opioid agonist treatment with buprenorphine/naloxone. Unfortunately, she continued to have withdrawal symptoms despite being optimised to a dose of 32 mg. She was given additional PRNs of buprenorphine/naloxone to a total daily dose of 40 mg, which helped to alleviate her symptoms of withdrawal and cravings. She was stabilised on buprenorphine/naloxone 40 mg daily without any side effects and was discharged to a rehabilitation centre.

Topics: Adult; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Dose-Response Relationship, Drug; Female; Fentanyl; Humans; Narcotic Antagonists; Opioid-Related Disorders; Substance Withdrawal Syndrome; Treatment Outcome

Studies assessing the comparative effectiveness of methadone versus buprenorphine/naloxone for opioid use disorder in real-world settings are rare - challenged by structural differences in delivery across settings and factors influencing treatment selection. We identified determinants of selection into buprenorphine/naloxone and quantified contributions of individual and provider-level covariates in a setting delivering both medications within the same healthcare settings.. Utilizing linked health administrative datasets, we conducted a retrospective cohort study of people with opioid use disorder (PWOUD) receiving opioid agonist treatment (OAT) in British Columbia, Canada, from 2008-2017. Determinants of buprenorphine/naloxone selection were identified using a generalized linear mixed model with random intercept terms for providers and individuals. We determined the influence of individual demographics, clinical history, measures of provider experience and preference, and dates of key policy changes.. A total of 39,605 individuals experienced 178,976 OAT episodes (methadone:139,439(77.9 %);buprenorphine/naloxone:39,537(22.1 %)). Male sex, less OAT experience, younger age, mental health conditions and chronic pain were associated with higher odds of buprenorphine/naloxone prescription. For providers, higher client-attachment, more complex OAT case-mixes, and higher buprenorphine/naloxone prescribing-preference were also associated with higher odds of buprenorphine/naloxone prescription. Observed individual-level covariates explained 9.7 % of variance in odds of buprenorphine/naloxone selection, while observed provider-level covariates explained 20.0 %. Controlling for covariates, residual unmeasured between-individual variance accounted for 18.5 % of the explained variation in the odds of buprenorphine/naloxone selection, while unmeasured between-provider variance accounted for 28.4 %.. Provider characteristics were more influential in selection of buprenorphine/naloxone over methadone informing subsequent analyses of comparative effectiveness of these regimens.

Topics: Adult; Age Factors; British Columbia; Buprenorphine, Naloxone Drug Combination; Female; Humans; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Acceptance of Health Care; Practice Patterns, Physicians'; Retrospective Studies; Sex Factors; Young Adult

The requirement for moderate withdrawal prior to initiation can be a barrier to buprenorphine/naloxone induction.. We aimed to use a microdosing regimen to initiate regular dosing of buprenorphine/naloxone in a high-risk patient with a history of failed initiations due, in part, to withdrawal symptoms. Using an assertive outreach model and a buprenorphine/naloxone microdosing schedule, we initiated treatment of an individual's opioid use disorder. There was a successful buprenorphine/naloxone microdosing induction as the team reached a therapeutic dose of buprenorphine/naloxone. Including the induction period, the medication was used consistently for 4 weeks.. A microdosing schedule can be used to induce a patient onto buprenorphine/naloxone with no apparent withdrawal; gradually reducing illicit substance use. This case report builds on previous literature, highlighting ways to minimize barriers to induction of buprenorphine/naloxone, using a microdosing schedule and assertive outreach. Given the safety profile of buprenorphine and its potential to be a lifesaving intervention, a larger study of microdosing is indicated.

Topics: Buprenorphine, Naloxone Drug Combination; Dose-Response Relationship, Drug; Humans; Male; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders

Urine drug monitoring for medications for opioid use disorder (MOUD) such as buprenorphine can help to support treatment adherence. The practice of introducing unconsumed medication directly into urine (known as "spiking" samples) has been increasingly recognized as a potential means to simulate treatment adherence. In the laboratory, examination of the ratios of buprenorphine and its metabolite, norbuprenorphine, has been identified as a mechanism to identify "spiked" samples. Urine levels of naloxone may also be a novel marker in cases where the combination buprenorphine-naloxone product has been administered. This case study, which encompasses one provider's practice spanning two sites, represents a preliminary report on the utility of using urinary naloxone as an indicator of "spiked" urine toxicology samples. Though only a case study, this represents the largest published evaluation of patients' naloxone levels to date.. Over a 3-month period across two practice sites, we identified 1,223 patient samples with recorded naloxone levels, spanning a range of 0 to 12,161 ng/ml. The average naloxone level was 633.65 ng/ml with the majority (54%) of samples < 300 ng/ml. 8.0% of samples demonstrated extreme values of naloxone (> 2000 ng/ml). One practice site, which had increased evidence of specimen tampering at collections, had a greater percent of extreme naloxone levels (>  2000 ng/ml) at 9.3% and higher average naloxone level (686.8 ng/ml), in contrast to a second site (570.9 ng/ml; 6.4% at > 2000 ng/ml) that did not have known reports of specimen tampering.. We postulate that naloxone may serve as an additional flag to identify patient "spiking" of urine samples with use of the combination product of buprenorphine-naloxone.

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Humans; Narcotic Antagonists; Opioid-Related Disorders; Substance Abuse Detection

Opioid use disorder (OUD) has become an increasingly consequential public health concern, especially in the United States where 47,600 opioid overdose deaths occurred in 2017 (Scholl, Seth, Kariisa, Wilson, & Baldwin, 2019). Medications for OUD (MOUD) are effective for decreasing opioid-related morbidity and mortality, including within the criminal justice system (Hedrich et al., 2012; Medications for Opioid Use Disorder Save Lives, 2019; Moore et al., 2019).While a stronger evidence base exists for agonist MOUD than for antagonist MOUD, a national study of drug courts found that half prohibited agonist MOUD (Matusow et al., 2013).Furthermore, recent media reports suggest that the pharmaceutical manufacturer of an antagonist MOUD has marketed its product towards drug court judges (Goodnough & Zernike, 2017; Harper, 2017). However, no study to date has systematically examined the relationship between MOUD marketing practices and drug courts. This ecological study examines the association at the county level between MOUD manufacturer payments to prescribers and drug court locations.. We extracted provider-directed payments from Centers for Medicare and Medicaid Services (CMS)'s Sunshine Act Open Payments data 2014-2017, isolating those records mentioning any MOUD. We compared provider-directed payments for two major MOUDs: buprenorphine and extended-release naltrexone, in counties with and without drug courts.. The presence of any adult drug courts in the county is associated with a 7.86 percentage-point increase in the likelihood of providers in that county receiving any MOUD-related payments (about 22.46% of the sample mean, p<0.001) and with a 10.70% increase in the amount of these payments per 1000 county residents (p<0.001). The association between other forms of drug courts such as juvenile drug courts and Driving-Under-the-Influence courts (DUI) courts are less significant and slightly smaller in magnitude compared to those of adult drug courts. We did not find significant difference between payments by the manufacturer of Vivitrol and manufacturers of Zubsolv, Bunavail, and Suboxone (oral forms of buprenorphine).. Our results show an ecological association at the county level between MOUD manufacturer payments to prescribers and drug court presence. However, we did not examine a causal association between these variables.

Topics: Adult; Aged; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Humans; Marketing; Medicare; Opioid-Related Disorders; United States

Topics: Buprenorphine, Naloxone Drug Combination; Humans; Naloxone; North America; Opioid-Related Disorders

Topics: Adult; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Humans; Internet; Male; Opioid-Related Disorders; Tapentadol

Buprenorphine is an opioid partial agonist used to treat opioid use disorder. While several policy changes have attempted to increase buprenorphine availability, access remains well below optimal levels. This study characterized how buprenorphine utilization in the United States has changed over time and whether there are regional disparities in distribution of the medication.. The amount of buprenorphine distributed from 2007 to 2017 was obtained from the Drug Enforcement Administration's Automated Reports and Consolidated Ordering System. Data were expressed as the percent change and milligrams per person in each state. The formulations and cost for prescriptions covered by Medicaid (2008 to 2018) were also examined.. Buprenorphine distributed to pharmacies increased about 7-fold (476.8 to 3179.9 kg) while the quantities distributed to hospitals grew 5-fold (18.6 to 97.6 kg) nationally from 2007 to 2017. Buprenorphine distribution per person was almost 20-fold higher in Vermont (40.4 mg/person) relative to South Dakota (2.1 mg/person). There was a strong association between the number of physicians authorized to prescribe buprenorphine and distribution per state (r[49] = +0.94, P < .0005). The buprenorphine/naloxone sublingual film (Suboxone) was the predominant formulation (92.6% of 0.31 million Medicaid prescriptions) in 2008 but accounted for less than three-fifth (57.3% of 6.56 million prescriptions) in 2018.. Although buprenorphine availability has substantially increased over the last decade, distribution was very nonhomogeneous across the United States.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Drug Compounding; Drug Prescriptions; Drug Utilization; Healthcare Disparities; Humans; Medicaid; Opioid-Related Disorders; Practice Patterns, Physicians'; Time Factors; United States

Opioid dependency is a major epidemiologic problem with profound morbidity and mortality. Despite the availability of effective treatments, there are often overwhelming barriers to those treatments.. We present a case series involving a novel approach to the induction phase of buprenorphine or buprenorphine-naloxone therapy using transdermal buprenorphine. This approach has been demonstrated in inpatient settings but has not been widely explored in the outpatient setting. We demonstrated that a range of patients, from the highly medically complex to relatively straightforward cases, benefited from this approach.. We believe that this approach can be used in a wide range of patients to transition from opioid use to buprenorphine therapy without the patient having to experience withdrawal or wait to start treatment. This should reduce the risk of lack of return for follow-up as well as decrease the dropout rate caused by patients being unable to tolerate withdrawal symptoms.

Topics: Adult; Aged; Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Female; Humans; Male; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Transdermal Patch

Topics: Adult; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Chronic Pain; Humans; Male; Opiate Substitution Treatment; Opioid-Related Disorders; Physician-Patient Relations; Surgeons

Buprenorphine extended-release (BUP-XR) is a monthly injectable form of opioid agonist therapy. Before its administration, a minimum 7-day induction period with a transmucosal buprenorphine-containing product is recommended.. Case report (n = 1).. A 16-year-old female with active, severe opioid use disorder (OUD) and stimulant use disorder, hepatitis C virus, co-occurring mental health disorders, and complex social stressors had five recent overdoses requiring naloxone. She had previously been treated with methadone and several trials of sublingual buprenorphine/naloxone, but would quickly discontinue the treatment. Using a rapid micro-induction protocol, buprenorphine/naloxone was administered for 3 days. On day 4, 300 mg BUP-XR was administered subcutaneously. Minimal withdrawal symptoms occurred, despite recent fentanyl use.. A rapid sublingual buprenorphine/naloxone micro-induction was successfully used to initiate BUP-XR, thereby eliminating the abstinence period prior to buprenorphine/naloxone administration, shortening the induction period, and minimizing withdrawal.. This is the first reported case of using rapid micro-induction as a bridge to initiate BUP-XR. By reducing the length of induction to 4 days and minimizing withdrawal, this induction method can make BUP-XR more accessible to patients who would otherwise refuse the medication due to concerns of enduring withdrawal. (Am J Addict 2020;29:531-535).

Topics: Administration, Sublingual; Adolescent; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Delayed-Action Preparations; Drug Administration Schedule; Female; Humans; Induction Chemotherapy; Narcotic Antagonists; Opioid-Related Disorders

Increasing capacity to provide buprenorphine, a treatment for opioid addiction, can help mitigate the opioid epidemic in the United States. This study models black-market pricing of buprenorphine to better understand supply and demand for opioid addiction treatment. A mixed effects linear model was used to quantify the effect of county-level racial composition, health insurance coverage, and drug characteristics on price variation. From November 2010 to June 2018, there were 2481 submissions for street buprenorphine transactions in the StreetRx dataset. The mean price was $3.95/mg (SD = $23.12/mg). Price decreased 3.05% each year and was highest in the summer and spring. Brand name buprenorphine was on average 11.18% more expensive than generic buprenorphine. Buprenorphine/naloxone combinations were on average 19.75% less expensive than pure buprenorphine. Purchases in bulk were on average 10.51% cheaper than purchases not in bulk. Street buprenorphine in film form was on average 14.34% more expensive than in pill/tablet form. Buprenorphine street price was 17.12% higher in spring and 22.26% higher in summer compared to fall. For every percentage point increase in percent white, buprenorphine sold for 0.88% higher price. For every percentage point increase in health insurance coverage, street buprenorphine sold for 0.02% lower price. Findings demonstrate that geographic, demographic, and socioeconomic factors shape the diversion of opioid addiction treatment to the black-market. Buprenorphine street pricing can help estimate public need, gaps in care and emerging public health priorities.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Costs and Cost Analysis; Humans; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; United States

Patients who present to the hospital for infectious complications of intravenous opioid use are at high risk for against-medical-advice discharge and readmissions. The role of medication-assisted treatment for inpatients is not clear. We aimed to assess outcomes prior to and after rollout of an inpatient buprenorphine-based opioid use disorder protocol, as well as to assess outcomes in general for medication-assisted therapy.. This was a retrospective observational cohort study at our community hospital in New Hampshire. The medical record was searched for inpatients with a complication of intravenous opioid use. We searched for admissions 11 months prior to and after the November 2018 buprenorphine protocol rollout.. Rates of medication-assisted therapy usage and buprenorphine linkage increased significantly after protocol rollout. Rates of against-medical-advice discharge did not decrease after protocol rollout, nor did readmissions. However, when evaluating the entire group of patients regardless of date of presentation or protocol use, against-medical-advice discharge rates were substantially lower for patients receiving medication-assisted therapy compared with those receiving supportive care only (30.0% vs 59.6%). Readmissions rates were lower for patients who were discharged with any form of ongoing medication-assisted therapy compared with those who were not (30-day all-cause readmissions 18.8% vs 35.1%; 30-day opioid-related readmissions 10.1% vs 29.9%; 90-day all-cause readmissions 27.3% vs 42.7%; 90-day opioid-related readmissions 15.1% vs 33.3%).. There is a strong association between medication-assisted therapy and reduced against-medical-advice discharge rates. Additionally, maintenance medication-assisted therapy at time of discharge is strongly associated with reduced readmissions rates.

Topics: Abscess; Acute Disease; Adult; Arthritis, Infectious; Bacteremia; Buprenorphine, Naloxone Drug Combination; Cellulitis; Cohort Studies; Discitis; Endocarditis; Female; Hepatitis C; HIV Infections; Hospitalization; Humans; Infections; Male; Myositis; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Osteomyelitis; Patient Discharge; Patient Readmission; Substance Abuse, Intravenous; Treatment Refusal

Buprenorphine/naloxone has been shown to be an effective treatment of opioid use disorder. According to the Canadian National clinical practice guideline on the management of opioid use disorders, given the superior safety profile of buprenorphine/naloxone and its potential for flexible take-home dosing in comparison to other opioid agonist medication it is strongly recommended to initiate opioid agonist treatment with buprenorphine/naloxone as the preferred first-line treatment when possible. Due to its pharmacological properties induction can be challenging, requiring the cessation of all opioids for a certain amount of time to avoid the risk of precipitated withdrawal symptoms. For this reason, buprenorphine/naloxone is not initiated for the treatment of opioid use disorder in critically ill patients where continuous infusion of opioids are required for maintenance of sedation resulting in a missed opportunity for first line treatment of that patient's opioid use disorder.. We present a case of a 29-year-old female with opioid use disorder admitted for infective endocarditis and septic shock requiring intubation for hypoxic respiratory failure secondary to bilateral lung septic emboli with a high opioid debt requiring higher than typical doses of fentanyl and dexmedetomidine infusions to maintain sedation with clinical objective sign of inadequate treatment of her pain and opioid withdrawal. She was successfully started on buprenorphine/naloxone using a rapid micro-induction technique that did not cause precipitated withdrawal or require cessation of her fentanyl infusion.. This case illustrates a new method for starting buprenorphine/naloxone in a critically ill intubated patient, where buprenorphine/naloxone was never a consideration in this specific patient population.. This method can be used to minimize barriers to opioid agonist therapy in intubated patients.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Canada; Critical Illness; Female; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders

Opioid use disorders (OUDs) have devastating effects on individuals, families, and communities. While medication treatments for OUD save lives and are increasingly utilized, rates of treatment dropout are very high. In addition, most existing medication treatments for OUD may often neglect the impact of untreated OUD on relationships and ignore the potential role support persons (SPs) could have on encouraging long-term recovery, which can also impact patient treatment retention.. The current study adapts Community Reinforcement and Family Training (CRAFT) for use with SPs (family member, spouse or friend) of patients using buprenorphine/naloxone (buprenorphine) in an outpatient community clinic setting. The study will evaluate whether the adapted intervention, also known as integrating support persons into recovery (INSPIRE), is effective in increasing patient retention on buprenorphine when compared to usual care. We will utilize a two-group randomized design where patients starting or restarting buprenorphine will be screened for support person status and recruited with their support person if eligible. Support persons will be randomly assigned to the INSPIRE intervention, which will consist of 10 rolling group sessions led by two facilitators. Patients and SPs will each be assessed at baseline, 3 months post-baseline, and 12 months post-baseline. Patient electronic medical record data will be collected at six and 12 months post-baseline. We will examine mechanisms of intervention effectiveness and also conduct pre/post-implementation surveys with clinic staff to assess issues that would affect sustainability.. Incorporating the patient's support system may be an important way to improve treatment retention in medication treatments for OUD. If SPs can serve to support patient retention, this study would significantly advance work to help support the delivery of effective treatments that prevent the devastating consequences associated with OUD. Trial registration This study was registered with ClinicalTrials.gov, NCT04239235. Registered 27 January 2020, https://clinicaltrials.gov/ct2/show/NCT04239235 .

Topics: Adult; Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; California; Community Health Centers; Family; Female; Humans; Opioid-Related Disorders; Psychotherapy, Group; Social Support

Buprenorphine/naloxone is an evidence-based treatment for opioid use disorder, but an identified limitation is the period of required opioid abstinence prior to induction on the medication. 'Micro-dosing', or using incrementally increasing doses of buprenorphine/naloxone over time, may be a way to overcome this challenge as it can be done in parallel with the ongoing use of other opioids (either illicit or prescribed).. A retrospective case series (January to December 2018) was completed of seven participants who underwent buprenorphine/naloxone induction using micro-dosing at two outpatient addiction clinics in Vancouver, Canada.. Seven participants completed a 7-day buprenorphine/naloxone micro-dosing protocol. Prior to and during the induction, one participant was prescribed methadone, three were prescribed slow release oral morphine and three used only illicit fentanyl. Participants were prescribed sublingual buprenorphine/naloxone: 0.5 mg once daily (day 1), 0.5 mg twice daily (BID; day 2), 1 mg BID (day 3), 2 mg BID (day 4), 3 mg BID (day 5), 4 mg BID (day 6) and 12 mg once daily (day 7). On day 7, all prescribed or illicit full opioid agonists were discontinued. Buprenorphine/naloxone was subsequently titrated to a daily dose of between 12 and 32 mg. All patients reported success with buprenorphine/naloxone induction with no precipitated withdrawal.. Buprenorphine/naloxone micro-dosing may offer a promising alternative approach for successful induction for individuals with opioid use disorder who desire treatment with buprenorphine/naloxone, and further research to determine effectiveness is warranted.

Topics: Adult; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Dose-Response Relationship, Drug; Drug Prescriptions; Female; Humans; Male; Middle Aged; Opioid-Related Disorders; Retrospective Studies; Treatment Outcome; Young Adult

Topics: Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Coproporphyria, Hereditary; Drug Substitution; Female; Humans; Opioid-Related Disorders; Young Adult

Buprenorphine is first-line opioid agonist therapy for opioid use disorder. Standard regimens require that patients be in opioid withdrawal prior to induction, which is a barrier for many. Micro-induction is a novel induction approach that does not require patients to be in withdrawal. Our primary objective is to synthesize available evidence on the effectiveness of micro-inductions on patient and clinical outcomes compared to standard dosing or other approaches, or evaluated without a comparator group. Secondary objectives are to synthesize evidence on clinical factors that influence micro-induction effectiveness, and to summarize micro-induction regimens described in the literature.. We will search MEDLINE, Embase, CINAHL, Psycinfo, Science Citation Index, and the grey literature for studies that include adolescents or adults with opioid use disorder who received a buprenorphine micro-induction regimen. We will consider any patient or clinical outcomes defined by study authors. We will include controlled and non-controlled interventional studies, observational studies, case reports/series and reports from relevant organizations or guidelines pertinent to our third objective. We will select studies, extract data and assess study quality (using the Downs and Black, and Cochrane Risk of Bias tools) in duplicate. We will narratively synthesize our results, and will meta-analyze outcome measures if multiple studies report common outcomes with acceptably low heterogeneity.. Our review will include the most up-to-date available data on buprenorphine micro-inductions. We anticipate limitations relating to study heterogeneity and quality. We will disseminate study results widely to inform updated guidelines for opioid agonist therapy prescribers.

Topics: Adolescent; Adult; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Humans; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Substance Withdrawal Syndrome

Although treatment of opioid use disorders (OUD) with medications is expanding, the extent to which practitioners are prescribing medications following best practices has received little attention.. The aim of this study was to determine the extent to which privately insured patients being treated for OUD with buprenorphine were treated in a manner consistent with practice guidelines.. Longitudinal analyses of a large commercial claims dataset from 2012 to 2016.. We analyzed data for 38,517 patients with an OUD diagnosis continuously enrolled for 3 months prior to and 6 months after an initial buprenorphine or buprenorphine-naloxone prescription fill.. We evaluated whether practitioners tested patients for hepatitis B, hepatitis C, HIV, and liver function; how often they received urine drug screens; the frequency of outpatient visits; and the extent to which they filled prescriptions for buprenorphine for at least 6 months.. Practitioners tested approximately 4.7% of patients for hepatitis B, 6.5% for hepatitis C, and 29.3% for HIV; they tested 8.0% for liver functioning; and gave 33.3% urine drug tests. Approximately 76% of patients had at least one outpatient visit for their OUD. Among those with at least one visit, the mean number of visits was 7.38. After the initial prescription, 47.5% stayed on buprenorphine for at least 6 months.. A large portion of privately insured patients receiving buprenorphine for OUD did not receive care consistent with guidelines.

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Humans; Insurance; Opiate Substitution Treatment; Opioid-Related Disorders

Although opioid withdrawal ratings are frequently used as primary outcomes for therapeutic trials, there has been limited empirical examination of opioid withdrawal symptom onset or etiology as an outcome, and also little examination of differences in outcomes between patient-reported and observer-ratings of withdrawal. Patient-reported (Subjective Opiate Withdrawal Scale, SOWS) and observer ratings (Clinical Opiate Withdrawal Scale, COWS) of opioid withdrawal collected as part of a randomized controlled residential clonidine, tramadol-extended release, and buprenorphine/naloxone 7-day taper for opioid withdrawal management were analyzed. Withdrawal ratings were collected seven times daily and primary outcomes were percent of participants (N = 103) endorsing symptoms, time of symptom onset, and relationship of scales to taper completion. Participants had variable endorsement of specific symptoms, ranging from 37 % ("feel like vomiting") to 97 % ("change in resting pulse"). Symptoms were more likely to be reported on the SOWS than COWS. Most symptoms began around 8 h after last dose, though comparison of like symptoms across the scales revealed patients reported symptoms on the SOWS > 10 h before they were observed on the COWS. SOWS peak severity score was more closely associated with taper completion than the COWS. Data suggest the patient-reported SOWS demonstrated a higher level of symptom endorsement, earlier detection of symptom onset, and better association with taper completion relative to the observer rated COWS. These data provide insight into the etiology of opioid withdrawal symptom expression and time course that can be used to inform treatment intervention timing and provide a baseline for other withdrawal evaluations.

Topics: Adult; Analgesics, Opioid; Animals; Buprenorphine, Naloxone Drug Combination; Clonidine; Female; Humans; Male; Middle Aged; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Patient Reported Outcome Measures; Substance Withdrawal Syndrome; Swine; Tramadol

Prenatal use of cannabis and opioids are increasing and very concerning. Engagement and retention in comprehensive, perinatal substance use disorder (PSUD) care are associated with better outcomes for mothers and babies. We compared the characteristics and engagement in care among women with opioid use disorder who used cannabis late in pregnancy versus those who didn't.. The primary outcome, "overall engagement and retention in PSUD care" included: utilization of substance use treatment prenatally, negative screening/toxicology at delivery (excluding cannabis), and attendance at expected prenatal and postpartum visits. Cannabis use late in pregnancy was objectively assessed at delivery via maternal urine drug screen and/or neonatal meconium/cord toxicology. Between-group comparisons utilized chi square, t-test or Mann-Whitney. Associations were assessed using Spearman Rho and two multivariate, binary logistic regressions for cannabis use and the primary outcome.. 18.0% (85/472) consumed cannabis late in pregnancy. Women of color, younger women, and those diagnosed with concurrent cannabis use disorder were more likely to consume cannabis. Engagement and retention in PSUD care was not associated with cannabis use, but rather, with prescribed pharmacotherapy for psychiatric disorders. The use of prescribed buprenorphine+naloxone was associated with cannabis avoidance late in pregnancy.. Cannabis use late in pregnancy, compared to none, did not impact engagement and retention in our PSUD program. Adjunctive psychotropic medication and/or buprenorphine+naloxone prescription were associated with cannabis avoidance suggesting the use and interactions of pharmacotherapies in an opioid dependent population is complex. A shared decision-making process during PSUD care is warranted.

Topics: Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Cannabis; Child; Female; Humans; Infant, Newborn; Opioid-Related Disorders; Perinatal Care; Pregnancy

Young adults are disproportionately affected by the current opioid crisis. Although medications for opioid use disorder are broadly effective, with reductions in morbidity and mortality, the particular effectiveness of medications for opioid use disorder among young adults is less well understood.. This secondary analysis compared young adults (aged 18-25 years) with older adults (aged ≥26 years) in a large comparative effectiveness trial ("XBOT") that randomized subjects to extended-release naltrexone or sublingual buprenorphine-naloxone for 6 months. Opioid relapse was defined by opioid use over four consecutive weeks or seven consecutive days, using urine testing and self-report.. Among subjects in the intention-to-treat sample (n = 570, all randomized participants), a main effect of age group was found, with higher relapse rates among young adults (70.3%) compared with older adults (58.2%), with an odds ratio of 1.72 (95% confidence interval = 1.08-2.70), p = .02. In the per-protocol sample (n = 474, only participants who started medication), relapse rates were higher among young adults (66.3%) compared with older adults (50.8%), with an odds ratio of 1.91 (95% confidence interval = 1.19-3.06). Among the intention-to-treat sample, survival analysis revealed a significant time-by-age group interaction (p = .01) with more relapse over time in young adults. No significant interactions between age and medication group were detected.. Young adults have increased rates of relapse compared with older adults, perhaps because of vulnerabilities that increase their risk for treatment dropout and medication nonadherence, regardless of medication assignment. These results suggest that specialized, developmentally informed interventions may be needed to improve retention and successful treatment of opioid use disorder among young adults.

Topics: Adolescent; Adult; Aged; Buprenorphine, Naloxone Drug Combination; Delayed-Action Preparations; Female; Humans; Male; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Young Adult

Despite a recent meta-analysis including 31 randomised controlled trials comparing methadone and buprenorphine for the treatment of opioid use disorder, important knowledge gaps remain regarding the long-term effectiveness of different treatment modalities across individuals, including rigorously collected data on retention rates and other treatment outcomes. Evidence from real-world data represents a valuable opportunity to improve personalised treatment and patient-centred guidelines for vulnerable populations and inform strategies to reduce opioid-related mortality. Our objective is to determine the comparative effectiveness of methadone versus buprenorphine/naloxone, both overall and within key populations, in a setting where both medications are simultaneously available in office-based practices and specialised clinics.. We propose a retrospective cohort study of all adults living in British Columbia receiving opioid agonist treatment (OAT) with methadone or buprenorphine/naloxone between 1 January 2008 and 30 September 2018. The study will draw on seven linked population-level administrative databases. The primary outcomes include retention in OAT and all-cause mortality. We will determine the effectiveness of buprenorphine/naloxone vs methadone using intention-to-treat and per-protocol analyses-the former emulating flexible-dose trials and the latter focusing on the comparison of the two medication regimens offered at the optimal dose. Sensitivity analyses will be used to assess the robustness of results to heterogeneity in the patient population and threats to internal validity.. The protocol, cohort creation and analysis plan have been approved and classified as a quality improvement initiative exempt from ethical review (Providence Health Care Research Institute and the Simon Fraser University Office of Research Ethics). Dissemination is planned via conferences and publications, and through direct engagement and collaboration with entities that issue clinical guidelines, such as professional medical societies and public health organisations.

Topics: Adult; Analgesics, Opioid; British Columbia; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Humans; Methadone; Observational Studies as Topic; Opiate Substitution Treatment; Opioid-Related Disorders; Retrospective Studies

Opioid use disorder is a major public health crisis, and evidence suggests ways of better serving patients who live with opioid use disorder in the emergency department (ED). A multi-disciplinary team developed a quality improvement project to implement this evidence.. The intervention was developed by an expert working group consisting of specialists and stakeholders. The group set goals of increasing prescribing of buprenorphine/naloxone and providing next day walk-in referrals to opioid use disorder treatment clinics. From May to September 2018, three Alberta ED sites and three opioid use disorder treatment clinics worked together to trial the intervention. We used administrative data to track the number of ED visits where patients were given buprenorphine/naloxone. Monthly ED prescribing rates before and after the intervention were considered and compared with eight nonintervention sites. We considered whether patients continued to fill opioid agonist treatment prescriptions at 30, 60, and 90 days after their index ED visit to measure continuity in treatment.. The intervention sites increased their prescribing of buprenorphine/naloxone during the intervention period and prescribed more buprenorphine/naloxone than the controls. Thirty-five of 47 patients (74.4%) discharged from the ED with buprenorphine/naloxone continued to fill opioid agonist treatment prescriptions 30 days and 60 days after their index ED visit. Thirty-four patients (72.3%) filled prescriptions at 90 days.. Emergency clinicians can effectively initiate patients on buprenorphine/naloxone when supports for this standardized evidence-based care are in place within their practice setting and timely follow-up in community is available.

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Emergency Service, Hospital; Humans; Narcotic Antagonists; Opioid-Related Disorders

To raise awareness of alternative techniques that can facilitate buprenorphine-naloxone treatment for opioid use disorder.. PubMed was searched for articles using the terms. Buprenorphine-naloxone is the first-line option for opioid agonist therapy owing to its superior safety profile compared with methadone. The uptake of this potentially life-saving drug has been limited by unfamiliarity and prescribing restrictions, but perhaps the biggest barrier is the prerequisite that patients be in moderate to severe withdrawal before initiation. An induction option that does not require withdrawal or immediate cessation of current opioid use, termed. Microdosing is a safe and easy-to-implement regimen that can be used in a variety of practice settings with the help of community pharmacists. This article provides an overview of microdosing and serves as a guide to starting and maintaining treatment.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Dose-Response Relationship, Drug; Humans; Naloxone; Opioid-Related Disorders; Substance Withdrawal Syndrome

YES. MONTHLY EXTENDED-RELEASE INJECTABLE NALTREXONE (XR-NTX) TREATS OPIOID USE DISORDER AS EFFECTIVELY AS DAILY SUBLINGUAL BUPRENORPHINE-NALOXONE (BUP-NX) WITHOUT CAUSING ANY INCREASE IN SERIOUS ADVERSE EVENTS OR FATAL OVERDOSES. (STRENGTH OF RECOMMENDATION: A, 2 GOOD-QUALITY RCTS).

Topics: Administration, Sublingual; Adult; Aged; Aged, 80 and over; Buprenorphine, Naloxone Drug Combination; Delayed-Action Preparations; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Narcotic Antagonists; Norway; Opioid-Related Disorders; United States

Topics: Buprenorphine, Naloxone Drug Combination; Emergency Service, Hospital; Humans; Opioid-Related Disorders

Research on how US physicians individualize buprenorphine-naloxone treatment is limited. The current study uses conjoint analysis to examine the importance of current dose, visit frequency, clinical indicators, and payment type on office visit and dose adjustments during buprenorphine-naloxone treatment.. A national random sample of 776 US buprenorphine-prescribing physicians participated in a mailed survey between October 2015 and July 2018. The survey contained 16 patient vignettes describing: (1) current dose, (2) urine drug test (UDT) results and opioid blockade, (3) recent intravenous use, (4) visit attendance, (5) counseling adherence, (6) payment, and (7) visit schedule. Physicians rated how they would adjust office visits (0=definitely decrease to 5=no change to 10=definitely increase) and the dose (0=definitely decrease to 5=no change to 10=definitely increase). Descriptive statistics were calculated for the vignette responses. Conjoint analysis was used to estimate relative importance scores and part-worth utilities.. Across the vignettes, the mean response for adjusting office visits was 7.43 (SD = 1.69), indicating a tendency to increase the frequency of visits. UDT results/opioid blockade, intravenous use, and current visit schedule had the greatest importance scores for office visit adjustments. The mean response for adjusting the dose was 5.48 (SD = 1.69), corresponding with a tendency toward not changing dose. Current dose, UDT results/opioid blockade, and intravenous use had the largest importance scores for dose adjustment.. Physicians individualized buprenorphine-naloxone treatment in response to hypothetical patient attributes by changing visit frequency and, to a lesser extent, modifying maintenance dose, in a manner generally consistent with current practice guidelines.

Topics: Buprenorphine, Naloxone Drug Combination; Clinical Decision-Making; Female; Humans; Male; Middle Aged; Narcotic Antagonists; Office Visits; Opioid-Related Disorders; Physicians; Precision Medicine

Although there have been supply-side efforts in response to the opioid crisis (e.g., prescription drug monitoring programs), little information exists on demand-side approaches related to patient cost sharing that may affect utilization of and adherence to pharmacotherapy by individuals with opioid use disorder. Among individuals who had initiated pharmacotherapy, we estimated the price elasticity of demand of prescription fills of buprenorphine/naloxone, a common pharmacotherapy drug, overall and by patient characteristics. Using the IBM MarketScan® Commercial Claims and Encounters Database for individuals with employer-sponsored private health insurance coverage, we examined the relationship between cost sharing and the number of buprenorphine/naloxone prescription fills using enrollee-level longitudinal fixed effects models. Cost sharing was expressed as a price index for each employer-plan. By including enrollee-level fixed effects, the identification of the effect of interest comes from longitudinal variation in prices across multiple time points for each enrollee. Overall, the demand for buprenorphine/naloxone was price inelastic (p = 0.191). However, some subgroups were responsive to price. A doubling of price was associated with a decrease in fills by 3.0% for enrollees aged 45-64 years (p = 0.029); 5.7% for those in rural areas (p = 0.033); 5.8% for residents of the South (p ≤0.001); and 3.0% for those enrolled in an HMO (p = 0.004). Insurers should consider the effects on these groups before increasing beneficiary out-of-pocket costs for pharmacotherapy and efforts to increase adherence should consider that price may be a barrier for some subgroups with OUD.

Topics: Adolescent; Adult; Buprenorphine, Naloxone Drug Combination; Child; Commerce; Cost Sharing; Female; Humans; Insurance, Health; Male; Medication Adherence; Middle Aged; Opiate Substitution Treatment; Opioid Epidemic; Opioid-Related Disorders; Young Adult

Buprenorphine/naloxone treatment is a highly effective treatment for opioid use disorder decreasing illicit opioid use and both all-cause and opioid-involved overdose mortality. The purpose of this study was to investigate the relationships between buprenorphine/naloxone prescribing and high-dose opioid analgesic prescribing (HDOAP) over time.. This longitudinal study used 2012-2017 Kentucky All Schedule Prescription Electronic Reporting data and cross-lagged structural equation analysis. For each quarter-county observation, HDOAP rate (per 1,000 residents with opioid analgesic prescriptions) was used to predict buprenorphine/naloxone prescribing rate at the next quarter, and simultaneously buprenorphine/naloxone prescribing rate was used to predict HDOAP at the next quarter, accounting for baseline socioeconomic status, medical needs for opioid analgesics, and heroin availability.. On average, HDOAP rates in Kentucky decreased by more than 10% (p < .0001) and buprenorphine/naloxone prescribing rates increased by more than 5% (p < .0001) per quarter over the study period. Every one-per-thousand higher HDOAP rate in an earlier quarter was associated with a 0.01/1,000 increase in the buprenorphine/naloxone prescribing rate in a later quarter (p = .009). Conversely, a one-unit higher buprenorphine/naloxone prescribing rate in an earlier quarter was associated with a 0.01/1,000 reduction in the HDOAP rate in a subsequent quarter (p = .017).. Our results indicate a significant reciprocal relationship between HDOAP and buprenorphine/naloxone prescribing and a clinically meaningful effect of buprenorphine/naloxone prescribing on reducing HDOAP. Future studies on buprenorphine/naloxone treatment expansion should take into account this bi-directional association in the context of longitudinal data and evaluate for public health benefits beyond the reduction of HDOAP.

Topics: Adult; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Drug Prescriptions; Female; Heroin; Humans; Kentucky; Latent Class Analysis; Longitudinal Studies; Male; Opiate Substitution Treatment; Opioid-Related Disorders

Opioid use disorder (OUD) constitutes a significant public health burden as opioid overdose deaths have continued to rise in the United States. Although treatment modalities are available to manage OUD, some patients experience challenges achieving their OUD management goals. Some of these challenges may be attributable to inherited genetic variations, or polymorphisms, on the genes that code for proteins impacting the pharmacokinetics or pharmacodynamics of medications used in OUD management. Clinical pharmacogenomics testing can elucidate these polymorphisms; however, a lack of real-world evidence for the use of pharmacogenomics in OUD management complicates the implementation process. We conducted a retrospective cohort study of 113 patients undergoing buprenorphine-based OUD management in Northeast Washington D.C. to determine if clinical pharmacogenomics testing for CYP3A4 and CYP3A5 would impact treatment outcomes. Data were collected from the electronic medical record (EMR) from December 30, 2015 to December 31, 2016. Study outcomes were based on presence of withdrawal symptoms, instances of unauthorized substances in urine drug tests (UDTs), and sublingual buprenorphine/naloxone (SBN) dose with standard-of-care (SOC) dosing versus pharmacogenomics (PGx)-based dosing. Pearson correlation tests, Wilcoxon signed rank tests, Wilcoxon rank sum tests, and one-way ANOVA tests were used. Linear and logistic regression analyses were used to assess predictors of withdrawal symptomatology. Kaplan-Meier survival analyses were used to assess time to first withdrawal. Our research suggests that patients with at least one copy of the CYP3A4*1B allele exhibit an accelerated rate of metabolism compared to the wild-type allele CYP3A4*1.

Topics: Alleles; Black or African American; Buprenorphine, Naloxone Drug Combination; Cohort Studies; Cytochrome P-450 CYP3A; Decision Support Systems, Clinical; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Pharmacogenetics; Phenotype; Retrospective Studies

Opioid agonist therapy is the cornerstone of treatment of opioid use disorder. In Canada, buprenorphine/naloxone has recently been adopted as the first line agonist therapy given its comparable effectiveness to methadone and superior safety profile. This study examines factors associated with willingness to take buprenorphine/naloxone among opioid users.. Data were derived from two prospective cohorts of high-risk individuals who use drugs in Vancouver, Canada. Multivariable logistic regression analyses were used to determine factors associated with willingness to use buprenorphine/naloxone among people who use opioids and were not currently accessing this treatment option. Participants who were unwilling to use buprenorphine/naloxone were invited to provide reason(s) and their responses were examined in a sub-analysis.. Between December 2014 and May 2018, 1103 participants were interviewed. Overall, 194 (17.6%) respondents indicated that they would be willing to take buprenorphine/naloxone. Variables independently associated with willingness were previous buprenorphine/naloxone treatment (adjusted odds ratio [AOR] = 2.04), having ever used methadone treatment (AOR = 1.87), and age (AOR = 0.98, per year older) (all p < 0.05). Satisfaction with current agonist therapy (25.4%), not knowing what buprenorphine/naloxone is (25.1%), and wanting more information about buprenorphine/naloxone (15.1%) were the most commonly cited reasons for unwillingness. A low rate of willingness to use buprenorphine/naloxone (15.1%) was also observed among the sub-set of participants not using methadone.. While an overall low level of willingness to take buprenorphine/naloxone was observed, this appeared to be largely driven by satisfaction with other agonists and a low prevalence of community knowledge about buprenorphine/naloxone.

Topics: Adult; Analgesics, Opioid; British Columbia; Buprenorphine, Naloxone Drug Combination; Cohort Studies; Female; Humans; Male; Methadone; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Patient Acceptance of Health Care; Prospective Studies

Despite some improvements in access to evidence-based medications for opioid use disorder, treatment rates remain low at under a quarter of those with need. High costs for brand name products in these medication markets have limited the volume of drugs purchased, particularly through public health insurance and grant programs. Brand firm anti-competitive practices around the leading buprenorphine product Suboxone - including product hops, citizen petitions and Risk Evaluation and Mitigation Strategy abuses - helped to maintain high prices by extending brand exclusivity periods and hindering generic drug entry. Remedies to address costly anti-competitive activities include adoption of the proposed CREATES Act and modernization of the Hatch-Waxman Act by the Congress, and implementation of substantive modifications to the Food and Drug Administration citizen petition filing procedures. Given the persistence of these abuses, prescriptive changes are favorable to the procedural and clarifying steps thus far favored by the federal government. Extrapolating from the 37% price declines attributable to generic entry for buprenorphine tablets in 2011, our calculations suggest that implementing these remedies to facilitate generic competition with Suboxone film would have resulted in savings of approximately $703 million overall and $203 million to Medicaid in 2017.

Topics: Buprenorphine, Naloxone Drug Combination; Drugs, Generic; Health Policy; Humans; Legislation, Drug; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; United States; United States Food and Drug Administration

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Pain Management; Pain, Postoperative; Perioperative Period

Therapeutic adherence is one of the most important determinants of the outcome with OST. There are no published studies that have explored the impact of change in tablet formulation of buprenorphine-naloxone from one brand to another among patients receiving OST.. The current study is aimed at evaluation of the impact of change in buprenorphine-naloxone formulation on prescription pattern, treatment adherence, and patient satisfaction with OST.. Our study was a cross sectional study based on a cohort of patients who were receiving OST at the study setting. Changes in prescription pattern, reports of subjective opioid withdrawal symptoms, or observation of objective opioid withdrawal symptoms were noted from the case records. The satisfaction and concerns of the patients with buprenorphine-naloxone formulations were assessed using a semi-structured proforma.. An increase in dose of buprenorphine-naloxone was noted in 22 participants, since formulation change. Twenty participants reported that the color of the formulation was different from the previous one, the intensity of effect was reported to be different by 87% participants. Seventy-three percent participants endorsed that increase in dose can be a possible solution to address the perceived differences in the effects of two formulations. Changes in physical attributes of the formulation, perception among treatment seeking peers regarding such changes in treatment, and lack of sense of autonomy regarding one's treatment play a more important role in determining response of the patients to changes in formulation of buprenorphine-naloxone.

Topics: Adult; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Cross-Sectional Studies; Drug Compounding; Humans; Male; Medication Adherence; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Satisfaction; Substance Withdrawal Syndrome

Topics: Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Cost-Benefit Analysis; Humans; Naltrexone; Opioid-Related Disorders; Recurrence

Opioid use disorder is a growing social problem. Different agents are used in the treatment of this disorder. One of these agents is buprenorphine / naloxone combination that includes buprenorphine and naloxone in a ratio of 4:1. Although used successfully in opiate maintenance treatment, buprenorphine / naloxone could have some side effects that might affect the treatment. The present study aimed to examine the effects of buprenorphine /naloxone opiate maintenance treatment on sexual dysfunction, sleep and bodyweight in patients diagnosed with opioid use disorder and to draw the attention of clinicians to the adverse effects of the treatment. The study group included 107 inpatients who were diagnosed based on The Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) and received treatment for opioid use disorder. On admission to the hospital and at the end of the 4th month, a Sociodemographic and Clinical Data Form, the Pittsburgh Sleep Quality Index (PSQI) and the Arizona Sexual Life Scale (ASEX) were applied to all patients. Patients were weighed, and their weight was recorded on the day of admission to the hospital and at the end of the 4th month. The data recorded at the beginning and during the treatment of the same group were compared. The mean age of 107 patients was 24.55 ± 4.27. Overall ASEX scores were 12.98 ± 4.33 before treatment and 15.03 ± 6.61 at 4 months (p < 0.001). The mean patient bodyweight was 63.86 ± 8.78 kg before the treatment and 68.49 ± 8.65 kg at the 4th month of the treatment (p < 0.001). Total PSQI scores were 8.87 ± 3.53 before the treatment and 6.85 ± 3.29 at the 4th month of the treatment (p < 0.001). The study findings demonstrated that after 4 months of buprenorphine /naloxone treatment, total ASEX scores and bodyweight of the patients increased and total PSQI scores decreased. These results demonstrated that sexual problems and bodyweight of the patients increased after the buprenorphine /naloxone treatment and sleep-related problems decreased, albeit still prevalent. These potential side effects should be included with other information about buprenorphine that is given to patients as they may influence interest in starting or continuing treatment.

Topics: Adolescent; Adult; Analgesics, Opioid; Body Weight; Buprenorphine, Naloxone Drug Combination; Diagnostic and Statistical Manual of Mental Disorders; Humans; Male; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Sexual Dysfunction, Physiological; Sleep; Sleep Wake Disorders; Weight Gain; Young Adult

The act of intravenous misuse is common in patients under opioid maintenance treatment (OMT), but information on associated factors is still limited.. To explore factors associated with (a) intravenous OMT misuse, (b) repeated misuse, (c) emergency room (ER) admission, (d) misuse of different OMT types and (e) concurrent benzodiazepine misuse.. We recruited 3,620 patients in 27 addiction units in Italy and collected data on the self-reported rate of intravenous injection of methadone (MET), buprenorphine (BUP), BUP-naloxone (NLX), OMT dosage and type, experience of and reason for misuse, concurrent intravenous benzodiazepine misuse, pattern of -misuse in relation to admission to the addiction unit and ER -admissions because of misuse. According to inclusion/exclusion criteria, 2,585 patients were included.. Intravenous misuse of OMT substances was found in 28% of patients with no difference between OMT types and was associated with gender, age, type of previous opioid abuse and intravenous benzodiazepine misuse. Repeated OMT misuse was reported by 20% (i.e., 71% of misusers) of patients and was associated with positive OMT misuse experience and intravenous benzodiazepine misuse. Admission to the ER because of misuse complications was reported by 34% of patients, this outcome being associated with gender, employment, type of previous opioid abuse and intravenous benzodiazepine misuse. OMT dosage was lower than the recommended maintenance dosage.. We offered new information on factors associated with intravenous OMT misuse, repeated misuse and ER admission in Italian patients under OMT. Our data indicate that BUP-NLX misuse is not different from that of BUP or MET. Choosing the more expensive BUP-NLX over MET will likely not lead to the expected reduction of the risk of injection misuse of the OMT. Instead of prescribing new and expensive OMT formulations, addiction unit physicians and medical personnel should better focus on patient's features that are associated with a higher likelihood of misuse. Care should be paid to concurrent benzodiazepine and OMT misuse.

Topics: Administration, Intravenous; Adolescent; Adult; Analgesics, Opioid; Benzodiazepines; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cross-Sectional Studies; Drug Misuse; Female; Hospitalization; Humans; Italy; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Risk Factors; Young Adult

Buprenorphine/naloxone has been shown to be effective in the treatment of opioid use disorder. Due to its pharmacological properties, induction can be challenging, time-consuming, and result in sudden onset of withdrawal symptoms.. Retrospective case series (n = 2).. Two patients with opioid use disorder were successfully started on buprenorphine/naloxone using a rapid micro-induction technique that did not cause precipitated withdrawal or require preceding cessation of other opioids.. These cases provide an alternative method for starting buprenorphine/naloxone that offers unique benefits compared to protocols previously described in the literature.. This method can be used to minimize barriers to opioid agonist therapy. (Am J Addict 2019;28:262-265).

Topics: Adult; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Drug Administration Schedule; Female; Hospitalization; Humans; Induction Chemotherapy; Male; Opiate Substitution Treatment; Opioid-Related Disorders; Substance Withdrawal Syndrome

The natural course of prescription opioid use disorder has not been examined in longitudinal studies. The current study examined correlates of opioid abstinence over time after completion of a treatment trial for prescription opioid dependence.. The multisite Prescription Opioid Addiction Treatment Study examined different durations of buprenorphine-naloxone treatment and different intensities of counseling to treat prescription opioid dependence, as assessed by DSM-IV; following the clinical trial, a longitudinal study was conducted from March 2009-January 2013. At 18, 30, and 42 months after treatment entry, telephone interviews were conducted (N = 375). In this exploratory, naturalistic study, logistic regression analyses examined the association between treatment modality (including formal treatment and mutual help) and opioid abstinence rates at the follow-up assessments.. At the 3 follow-up assessments, approximately half of the participants reported engaging in current substance use disorder treatment (47%-50%). The most common treatments were buprenorphine maintenance (27%-35%) and mutual-help group attendance (27%-30%), followed by outpatient counseling (18%-23%) and methadone maintenance (4%). In adjusted analyses, current opioid agonist treatment showed the strongest association with current opioid abstinence (odds ratios [ORs] = 5.4, 4.6, and 2.8 at the 3 assessments), followed by current mutual-help attendance (ORs = 2.2, 2.7, and 1.9); current outpatient counseling was not significantly associated with abstinence in the adjusted models.. While opioid agonist treatment was most strongly associated with opioid abstinence among patients with prescription opioid dependence over time, mutual-help group attendance was independently associated with opioid abstinence. Clinicians should consider recommending both of these interventions to patients with opioid use disorder.. ClinicalTrials.gov identifier: NCT00316277​.

Topics: Buprenorphine, Naloxone Drug Combination; Female; Follow-Up Studies; Humans; Longitudinal Studies; Male; Opiate Substitution Treatment; Opioid-Related Disorders; Prescription Drug Misuse; Randomized Controlled Trials as Topic; Treatment Outcome

Topics: Buprenorphine, Naloxone Drug Combination; Canada; Competency-Based Education; Education, Medical, Graduate; Emergency Service, Hospital; Humans; Narcotic Antagonists; Opioid Epidemic; Opioid-Related Disorders; Patient Education as Topic; Prescription Drug Monitoring Programs; Social Determinants of Health; Transitional Care

Opioid-related emergency department (ED) visits have increased significantly in recent years. Our objective was to evaluate an ED-initiated buprenorphine/naloxone program, which provided rapid access to an outpatient community-based addictions clinic, for patients in opioid withdrawal.. A retrospective chart review was completed within a health system encompassing four community EDs in Ontario, Canada. Patients were screened for opioid withdrawal between April 2017-December 2017 and offered buprenorphine/naloxone treatment and referral to outpatient addictions follow-up. The main outcome measure was treatment retention in the six-month period after the index visit.. The overall sample (N = 49) showed high healthcare utilization in the year prior to the index ED visit. 88% of patients (n = 43) consented to ED-initiated buprenorphine/naloxone and were referred to outpatient addictions follow-up, with 54% attending the initial follow-up visit. In the 6-month follow-up period from the index ED visit, 35% of patients were receiving ongoing buprenorphine/naloxone treatment and 2.3% were weaned off opioids. Patients with ongoing treatment had significantly lower number of ED visits at 3 and 6 months (3 and 10, respectively) compared to patients who did not show up for outpatient follow-up (28, 40) or started/stopped treatment (23, 41).. Screening for opioid use disorder in the ED and initiating buprenorphine/naloxone treatment with rapid referral to an outpatient community-based addictions clinic led to a 6-month treatment retention rate of 37% and a significant reduction in ED visits at 3 and 6 months. Buprenorphine/naloxone initiation in the ED appears to be an effective intervention, but further research is needed.. Le nombre de consultations aux services des urgences (SU) motivées par l'usage des opioïdes a augmenté de façon importante au cours des dernières années. L’étude visait à évaluer l'efficacité d'un programme de traitement des troubles afférents par la buprénorphine (BPN) et la naloxone, entrepris au SU et suivi d'un accès rapide à des services communautaires de consultation externe pour le traitement de la dépendance chez les patients présentant un syndrome de sevrage aux opioïdes.. Il s'agit d'un examen rétrospectif de dossiers médicaux, réalisé dans un réseau de santé constitué 4 SU communautaires, en Ontario, au Canada. Les patients présentant des symptômes de sevrage aux opioïdes ont d'abord été repérés entre avril 2017 et décembre 2017, puis se sont vu offrir un traitement par la BUP et la naloxone avec aiguillage vers un service de consultation externe pour le suivi. Le critère d’évaluation principal consistait en la poursuite du traitement au cours de la période de 6 mois suivant la consultation de référence.. L'analyse de l’échantillon global (n = 49) a révélé une forte utilisation des services de santé au cours de l'année précédant la consultation de référence au SU. Dans l'ensemble, 88% des patients (n = 43) ont accepté l'offre de traitement entrepris au SU, puis ont été dirigés vers un service de consultation externe pour le suivi; 54% de ces derniers sont allés à la première consultation. Durant le suivi de 6 mois après la consultation de référence au SU, 35% des patients étaient encore en traitement et 2,3% des participants étaient sevrés. Les patients encore fidèles au traitement ont connu un nombre significativement moins élevé de consultations au SU au bout de 3 mois et de 6 mois (3 et 10, respectivement) que les patients qui ne sont pas présentés au service de consultation externe (28, 40) ou qui ont entrepris le traitement mais qui ne l'ont pas poursuivi (23, 41).. Le dépistage des troubles liés à l'usage des opioïdes, au SU, et l'instauration du traitement par la BUP et la naloxone avec aiguillage rapide vers un service communautaire de consultation externe pour le traitement de la dépendance se sont traduits par un taux de rétention des patients de 37% au bout de 6 mois et par une réduction significative du nombre de consultations au SU au bout de 3 mois et de 6 mois. L'instauration du traitement au SU semble donc une intervention efficace, mais il faudrait poursuivre la recherche sur le sujet.

Topics: Adult; Buprenorphine, Naloxone Drug Combination; Canada; Emergency Service, Hospital; Female; Hospitalization; Humans; Male; Narcotic Antagonists; Opioid-Related Disorders; Referral and Consultation; Retrospective Studies; Substance Abuse Treatment Centers

Opioid substitution treatment (OST) with methadone or buprenorphine is the most effective means of treating opioid dependence. If these substances are used by people who are not undergoing OST, they can however carry serious risks. This article examines the lifetime prevalence, motives, and drug sources for such use, as well as geographical differences in these variables.. Structured interviews were conducted with 411 patients from 11 OST clinics in five Swedish cities. The researchers carried out 280 interviews on-site, while 131 interviews were conducted by specially trained patients through privileged access interviewing. Data were analyzed by frequency and average calculations, cross-tabulations, and χ. The lifetime prevalence of non-prescribed use was 87.8% for methadone, 80.5% for buprenorphine, and 50.6% for buprenorphine/naloxone. Pseudo-therapeutic motives-avoiding withdrawal symptoms, staying clean from heroin, detoxification, or taking care of one's own OST-were commonly cited as driving the use, while using the drugs for euphoric purposes was a less common motive. Most respondents had bought or received the substances from patients in OST, but dealers were also a significant source of non-prescribed methadone and buprenorphine. Geographical differences of use, motives, and sources suggest that prescription practices in OST have a great impact on which substances are used outside of the treatment.. Experiences of non-prescribed use of methadone and buprenorphine are extremely common among those in OST in southern Sweden. As the use is typically driven by pseudo-therapeutic motives, increased access to OST might decrease the illicit demand for these substances. Buprenorphine/naloxone has a lower abuse potential than buprenorphine and should therefore be prioritized as the prescribed drug. Supervised dosage and other control measures are important provisions in the prevention of drug diversion and non-prescribed use among people not undergoing OST.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cities; Drug Trafficking; Female; Humans; Male; Methadone; Motivation; Opiate Substitution Treatment; Opioid-Related Disorders; Prescription Drug Diversion; Prevalence; Self Medication; Substance Withdrawal Syndrome; Sweden

Despite a significant number of patients dependent on "poppy husk" in India, they are poorly characterized. Moreover, scarce data is available with respect to their treatment.. A cohort of 148 patients with "poppy husk" dependence receiving substitution treatment with buprenorphine/naloxone were followed up for 4 years, using a retrospective chart-based assessment. Baseline demographic and substance-related characteristics were described. Retention rates (operationally redefined as "6 months of uninterrupted contact anytime during their visits") over the next 4 years and their predictors were assessed.. Mean age of onset of "poppy husk" use was found to be 27.51 years, and mean duration of dependence was 18.25 years. Mean amount of poppy husk consumed per month was 3.7 kg. Commonest reasons for initiating and quitting its use were enhancing work efficiency and lack of availability, respectively. Retention rates were 25%. Significant predictors of retention were age more than 40 years (OR = 2.295; 95%CI = 1.015-5.19) and uninterrupted treatment duration for at least 1 month from first contact (for 1 month (OR = 5.625; 95%CI = 2.28-13.89), for 3 months (OR = 10.96; 95%CI = 4.65-25.85), and for 6 months (OR = 52.8; 95%CI:14.08-197.98).. Factors associated with occupation such as enhancing work efficiency and overcoming fatigue are related to use of "poppy husk." While the amount of intake is considerably large among treatment seekers who are dependent on it, their dependence duration is longer and retention rates lower than those reported for patients with prescription and injectable opioid dependence. Specific strategies to tap patients less than 40 years and to target uninterrupted contact in initial phases of maintenance should be developed.

Topics: Adult; Buprenorphine, Naloxone Drug Combination; Humans; Male; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Retrospective Studies; Treatment Outcome

Untreated opioid use disorder (OUD) affects the care of HIV/HCV co-infected people who inject opioids. Despite active injection opioid use, there is evidence of increasing engagement in HIV care and adherence to HIV medications among HIV/HCV co-infected persons. However, less than one-half of this population is offered HCV treatment onsite. Treatment for OUD is also rare and largely occurs offsite. Integrating buprenorphine-naloxone (BUP-NX) into onsite care for HIV/HCV co-infected persons may improve outcomes, but the clinical impact and costs are unknown. We evaluated the clinical impact, costs, and cost-effectiveness of integrating (BUP-NX) into onsite HIV/HCV treatment compared with the status quo of offsite referral for medications for OUD.. We used a Monte Carlo microsimulation of HCV to compare two strategies for people who inject opioids: 1) standard HIV care with onsite HCV treatment and referral to offsite OUD care (status quo) and 2) standard HIV care with onsite HCV and BUP-NX treatment (integrated care). Both strategies assume that all individuals are already in HIV care. Data from national databases, clinical trials, and cohorts informed model inputs. Outcomes included mortality, HCV reinfection, quality-adjusted life years (QALYs), costs (2017 US dollars), and incremental cost-effectiveness ratios.. Integrated care reduced HCV reinfections by 7%, cases of cirrhosis by 1%, and liver-related deaths by 3%. Compared to the status quo, this strategy also resulted in an estimated 11/1,000 fewer non-liver attributable deaths at one year and 28/1,000 fewer of these deaths at five years, at a cost-effectiveness ratio of $57,100/QALY. Integrated care remained cost-effective in sensitivity analyses that varied the proportion of the population actively injecting opioids, availability of BUP-NX, and quality of life weights.. Integrating BUP-NX for OUD into treatment for HIV/HCV co-infected adults who inject opioids increases life expectancy and is cost-effective at a $100,000/QALY threshold.

Topics: Adult; Buprenorphine, Naloxone Drug Combination; Coinfection; Cost-Benefit Analysis; Delivery of Health Care, Integrated; Female; Hepatitis C; HIV Infections; Humans; Male; Middle Aged; Monte Carlo Method; Opiate Substitution Treatment; Opioid-Related Disorders; Quality of Life; Quality-Adjusted Life Years; Substance Abuse, Intravenous

Adverse childhood experiences (ACE) are a public health concern and strong predictor of substance abuse, but no studies to date have explored the association between ACE and opioid relapse during medication-assisted treatment. Using an observational design, we examined this relationship using archived medical records of 87 patients who attended opioid use disorder treatment (buprenorphine-naloxone and group counseling) at a rural medical clinic. All variables were collected from medical files. ACE scores were derived from a 10-item screening questionnaire administered at intake, a regular procedure for this clinic. The primary outcome was opioid relapse observed at each visit, as indicated by self-reported opioid use, positive urine drug screen for opioids, or prescription drug database results for opioid acquisition. The sample was 100% Caucasian and 75% male. A total of 2052 visit observations from the 87 patients were extracted from the medical records. Patients had an average of 23.6 (SD = 22) treatment visits. Opioid relapse occurred in 54% of patients. Results indicated that for every unit increase in ACE score, there was an increase of 17% in the odds of relapse (95% CI: 1.05-1.30, p = .005). Additionally, each treatment visit was associated with a 2% reduction in the odds of opioid relapse (95% CI: 0.97-0.99, p = .008). We conclude that ACE may increase the risk for poor response to buprenorphine-naloxone treatment due to high rates of opioid relapse during the first treatment visits. However, consistent adherence to treatment is likely to reduce the odds of opioid relapse.

Topics: Adult; Adverse Childhood Experiences; Aged; Aged, 80 and over; Ambulatory Care; Buprenorphine, Naloxone Drug Combination; Female; Humans; Male; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Psychotherapy, Group; Recurrence; Risk Factors; Rural Population; Young Adult

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Perioperative Care

Opioid use disorder (OUD) is highly prevalent among justice-involved individuals. While risk for overdose and other adverse consequences of opioid use are heightened among this population, most justice-involved individuals and other high-risk groups experience multiple barriers to engagement in opioid agonist treatment.. This paper describes the development of Project Connections at Re-Entry (PCARE), a low-threshold buprenorphine treatment program that engages vulnerable patients in care through a mobile van parked directly outside the Baltimore City Jail. Patients are referred by jail staff or can walk in from the street. The clinical team includes an experienced primary care physician who prescribes buprenorphine, a nurse, and a peer recovery coach. The team initiates treatment for those with OUD and refers those with other needs to appropriate providers. Once stabilized, patients are transitioned to longer-term treatment programs or primary care for buprenorphine maintenance. This paper describes the process of developing this program, patient characteristics and initial outcomes for the first year of the program, and implications for public health practice.. From November 15, 2017 through November 30, 2018, 220 people inquired about treatment services and completed an intake interview, and 190 began treatment with a buprenorphine/naloxone prescription. Those who initiated buprenorphine were primarily male (80.1%), African American (85.1%), had a mean age of 44.1 (SD = 12.2), and a mean of 24.0 (SD = 13.6) years of opioid use. The majority of patients (94.4%) had previous criminal justice involvement, were unemployed (72.9%) and were unstably housed (70.8%). Over a third (32.1%) of patients had previously overdosed. Of those who began treatment, 67.9% returned for a second visit or more, and 31.6% percent were still involved in treatment after 30 days. Of those who initiated care, 20.5% have been transferred to continue buprenorphine treatment at a partnering site.. The PCARE program illustrates the potential for low-threshold buprenorphine treatment to engage populations who are justice-involved and largely disconnected from care. While more work is needed to improve treatment retention among vulnerable patients and engaging persons in care directly after release from detention, offering on-demand, flexible and de-stigmatizing treatment may serve as a first point to connect high-risk populations with the healthcare system and interventions that reduce risk for overdose and related harms.

Topics: Adult; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Criminal Law; Female; Harm Reduction; Humans; Male; Middle Aged; Mobile Health Units; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Prisoners; Vulnerable Populations

Opioid use disorder (OUD) remains a serious public health issue, and treating adults with OUD is a major priority in the United States. Little is known about trends in the diagnosis of OUD and in buprenorphine prescribing by physicians in office-based medical practices. We sought to characterize OUD diagnoses and buprenorphine prescribing among adults with OUD in the United States between 2006 and 2015.. We used a repeated cross-sectional design, based on data from the 2006-15 National Ambulatory Medical Care Surveys that surveyed nationally representative samples of office-based out-patient physician visits.. Adult patients aged 18 years or older with a diagnosis of OUD (n = 1034 unweighted) were included.. Buprenorphine prescribing was defined by whether visits involved buprenorphine or buprenorphine-naloxone, or not. We also examined other covariates (e.g. age, gender, race and psychiatric comorbidities).. We observed an almost tripling of the diagnosis of OUD from 0.14% in 2006-10 to 0.38% in 2011-15 in office-based medical practices (P < 0.001). Among adults diagnosed with OUD, buprenorphine prescribing increased from 56.1% in 2006-10 to 73.6% in 2011-15 (P = 0.126). Adults with OUD were less likely to receive buprenorphine prescriptions if they were Hispanic [adjusted odds ratio (aOR) = 0.26; 95% confidence interval (CI) = 0.11, 0.60], had Medicaid insurance (aOR = 0.27; 95% CI = 0.10, 0.74) or were diagnosed with other psychiatric disorders (aOR = 0.45; 95% CI = 0.25, 0.83) or substance use disorders (aOR = 0.19; 95% CI = 0.09, 0.41).. In office-based medical practices in the United States, diagnoses for opioid use disorder and buprenorphine prescriptions for adults with opioid use disorder increased from 0.14 and 56.1%, respectively, in 2006-10 to 0.38 and 73.6% in 2011-15.

Topics: Adolescent; Adult; Aged; Ambulatory Care; Black or African American; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Delivery of Health Care; Female; Healthcare Disparities; Hispanic or Latino; Humans; Insurance, Health; Male; Medicaid; Mental Disorders; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Opioid Epidemic; Opioid-Related Disorders; Practice Patterns, Physicians'; United States; White People; Young Adult

Opiate agonist therapy (OAT) prescribing rates by family physicians are low in the context of community-based, comprehensive primary care. Understanding the factors that support and/or inhibit OAT prescribing within primary care is needed. Our study objectives are to identify and synthesize documented barriers to, and facilitators of, primary care opioid agonist prescribing, and effective strategies to inform intervention planning and support increased primary care OAT prescribing.. We will systematically search EMBASE, CINAHL, PsycINFO, Cochrane Central Register of Controlled Trials, MEDLINE, and gray literature in three domains: primary care providers, opioid agonist therapy, and opioid abuse. We will retain and assess primary studies reporting documented participation, or self-reported willingness to participate, in OAT prescribing; and/or at least one determinant of OAT prescribing; and/or strategies to address determinants of OAT prescribing from the perspective of primary care providers in comprehensive, community-based practice settings. There will be no restrictions on study design or publication date. Studies limited to specialty clinics with specialist prescribers, lacking extractable data, or in languages other than English or French will be excluded. Two reviewers will perform abstract review and data extraction independently. We will assess the quality of included studies using the Joanna Briggs Institute Critical Appraisal Tool. We will use a framework method of analysis to deductively code barriers and facilitators and to characterize effective strategies to support prescribing using a combined, modified a priori framework comprising the Theoretical Domains Framework and the Consolidated Framework for Implementation Research.. To date, no synthesis has been undertaken of the barriers and facilitators or effective interventions promoting OAT prescribing by primary care clinicians in community-based comprehensive care settings. Enacting change in physician behaviors, community-based programming, and health services is complex and best informed by using theoretical frameworks that allow the analysis of the available data to assist in designing and implementing interventions. In light of the current opioid crisis, increasing the capacity of primary care clinicians to provide OAT is an important strategy to curb morbidity and mortality from opioid use disorder.. PROSPERO CRD86835.

Topics: Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Physicians, Family; Practice Patterns, Physicians'; Primary Health Care; Systematic Reviews as Topic

Treatment with opioid agonists is effective for opioid use disorder, but early discontinuation of treatment is a major obstacle to success. Intensive longitudinal methods - which take many repeated measurements over time, usually in the field- have provided unique insight into the effects of stress, mood and craving on drug use while people are being treated; these methods might also be useful for studying the processes that lead people to drop out of treatment.. Ecological momentary assessment (EMA) was conducted for up to 17 weeks by obtaining multiple electronic diary entries per day from 238 participants being treated with methadone or buprenorphine-naloxone. Survival analysis was used to study two outcomes: dropping out of treatment and noncompliance with EMA self-report requirements. Self-reports of stress, craving, and mood were used as time-varying predictors. Demographic and psychosocial variables measured with the Addiction Severity Index at the start of treatment were used as time-invariant predictors.. Dropping out of treatment was more likely in participants with more reported hassles (a measure of stress), higher levels of cocaine craving, lower levels of positive mood, a recent history of emotional abuse, a recent history of being bothered frequently by psychological problems, and with buprenorphine rather than methadone as their medication. In contrast, study noncompliance was not significantly associated with any of the variables analyzed.. Assessment of stress, craving and mood during treatment might identify people who are at greater risk of dropping out, and therapeutic interventions targeting these processes might increase retention.

Topics: Adult; Affect; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Craving; Ecological Momentary Assessment; Female; Humans; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Dropouts; Stress, Psychological; Withholding Treatment

Opioid overdose deaths and healthcare costs associated with opioid use disorder (OUD) continue to escalate while the majority of addiction treatment providers in the United States do not use medication-assisted treatment (MAT) in spite of proven efficacy. The primary resistance to the use of MAT has been associated with the philosophical conflict many 12-step based treatment programs have with the use of these medications.. This study sought to determine whether patients self-selecting into a treatment program based upon the 12-step philosophy would elect to use MAT and, if so, what initial outcomes might result.. This naturalistic, prospective study of patients (N = 253) with OUD included a combination of OUD-specific group therapy and the use of buprenorphine-naloxone, oral naltrexone, injectable naltrexone, or no medication with standard 12-step treatment initiated in a residential or day treatment setting with outpatient follow-up. Baseline assessment of subjects with OUD included level of craving and opioid withdrawal symptom severity. Post-residential treatment outcomes at 1- and 6-months included craving, opioid withdrawal, residential treatment completion, continuing care compliance, medication compliance, substance use frequency and 12-step meeting attendance.. Irrespective of medication condition, nearly all patients successfully completed residential treatment and the majority attended additional programming afterward. Among those who elected to take a medication (71%), differences were associated with medication compliance. Patients who reported compliance with their medication at 1 and 6 months following residential treatment had significantly higher abstinence rates than patients who reported noncompliance. Among those who relapsed post-discharge, neither medication use nor compliance was significantly related to a change in the frequency of alcohol use days or drug use days at 6 months.. These preliminary results suggest that it is feasible to administer medications, including partial opioid agonists like buprenorphine, within the context of 12-step based treatment and taking these medications as prescribed is associated with favorable outcomes.

Topics: Adult; Ambulatory Care; Behavior Therapy; Buprenorphine, Naloxone Drug Combination; Combined Modality Therapy; Day Care, Medical; Feasibility Studies; Female; Follow-Up Studies; Humans; Male; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Outcome Assessment, Health Care; Patient Compliance; Prospective Studies; Residential Treatment

Primary care providers are well positioned to respond to the opioid crisis by providing buprenorphine/naloxone (B/N) through shared medical appointments (SMAs). Although quantitative research has been previously conducted on SMAs with B/N, the authors conducted a qualitative assessment from the patients' point of view, considering whether and how group visits provide value for patients.. Twenty-five participants with opioid use disorder (OUD) who were enrolled in a weekly B/N group visit at a family medicine clinic participated in either of two 1-hour-long focus groups, which were conducted as actual group visits. Participants were prompted with the question "How has this group changed you as a person?" Data were audio-recorded and professionally transcribed and analyzed using a qualitative thematic approach, identifying common communication behaviors and resulting attitudes about the value of the group visit model.. Participants demonstrated several communication behaviors that support group members in their recovery, including offering direct emotional support to others struggling with difficult experiences, making an intentional effort to probe about others' lives, venting about heavy situations, joking to lighten the mood, and expressing feelings of gratitude to the entire group. These communication behaviors appear to act as mechanisms to foster a sense of accountability, a shared identity, and a supportive community. Other demonstrated group behaviors may detract from the value of the group experience, including side conversations, tangential comments, and individual participants disproportionately dominating group time.. The group visit format for delivering B/N promotes group-specific communication behaviors that may add unique value in supporting patients in their recovery. Future research should elucidate whether these benefits can be isolated from those achieved solely through medication treatment with B/N and if similar benefits could be achieved in non-primary care sites.

Topics: Adult; Appointments and Schedules; Buprenorphine, Naloxone Drug Combination; Female; Focus Groups; Humans; Male; Middle Aged; Opioid-Related Disorders; Primary Health Care; Qualitative Research; Self-Help Groups

We investigated prescribing patterns for four opioid use disorder (OUD) medications: 1) injectable naltrexone, 2) oral naltrexone, 3) sublingual or oralmucosal buprenorphine/naloxone, and 4) sublingual buprenorphine as well as transdermal buprenorphine (which is approved for treating pain, but not OUD) in a nationally representative claims-based database (Truven Health MarketScan®) of commercially insured individuals in the United States. We calculated the prevalence of OUD in the database for each year from 2010 to 2014 and the proportion of diagnosed patient months on OUD medication. We compared characteristics of individuals diagnosed with OUD who did and did not receive these medications with bivariate descriptive statistics. Finally, we fit a Cox proportional hazards model of time to discontinuation of therapy as a function of therapy type, controlling for relevant confounders. From 2010 to 2014, the proportion of commercially insured individuals diagnosed with OUD grew by fourfold (0.12% to 0.48%), but the proportion of diagnosed patient-months on medication decreased from 25% in 2010 (0.05% injectable naltrexone, 0.4% oral naltrexone, 23.1% sublingual or oralmucosal buprenorphine/naloxone, 1.5% sublingual buprenorphine, and 0% transdermal buprenorphine) to 16% in 2014 (0.2% injectable naltrexone, 0.4% oral naltrexone, 13.8% sublingual or oralmucosal buprenorphine/naloxone, 1.4% sublingual buprenorphine, and 0.3% transdermal buprenorphine). Individuals who received medication therapy were more likely to be male, younger, and have an additional substance use disorder compared with those diagnosed with OUD who did not receive medication therapy. Those prescribed injectable naltrexone were more often male, younger, and diagnosed with additional substance use disorders compared with those prescribed other medications for opioid use disorder (MOUDs). At 30 days after initiation, 52% for individuals treated with injectable naltrexone, 70% for individuals treated with oral naltrexone, 31% for individuals treated with sublingual or oralmucosal buprenorphine/naloxone, 58% for individuals treated with sublingual buprenorphine, and 51% for individuals treated with transdermal buprenorphine discontinued treatment. In the Cox proportional hazard model, use of injectable naltrexone, oral naltrexone, sublingual buprenorphine, and transdermal buprenorphine were all associated with significantly greater hazard of discontinuing therapy beginning >30days after MOUD in

Topics: Adult; Age Factors; Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Drug Administration Routes; Female; Humans; Insurance Claim Review; Male; Medication Adherence; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Practice Patterns, Physicians'; Prevalence; Sex Factors; United States

In the United States, buprenorphine products (namely buprenorphine/naloxone combination) and methadone are the primary forms of medication-assisted treatment (MAT) that are authorized for addressing opioid addiction. Although treatment ideologies differentiate MAT programs, much of the provision in the US reflects a model of "high threshold, low tolerance." This model is discussed with a focus on structural and programmatic barriers that shape access to and retention in MAT. The critique continues with a discussion of multifaceted stigma that reinforces spoiled identities and diffuses into treatment settings. The social control mechanisms that are imposed in MAT are strikingly similar to those reflected in criminal justice settings, namely probation, parole and community corrections more generally. Parallels are drawn between the "addict" and the "felon" and how they are monitored, tracked, and controlled. These factors have major implications for recovery.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Health Services Accessibility; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Compliance; Social Control, Formal; Social Stigma

The objectives were to examine the abuse prevalence and route-of-administration (ROA) profiles of sublingual buprenorphine/naloxone combination (BNX) film in comparison with the BNX tablet and to identify clinically-relevant subgroups of patients or geographic patterns.. Between Q1 2015 through Q3 2015, data were collected from two major surveillance systems: (1) assessment of individuals in substance use disorder (SUD) treatment collected from the National Addictions Vigilance Intervention and Prevention Program (NAVIPPRO®) ASI-MV® system and (2) intentional abuse/misuse exposures in the RADARS® System Poison Center Program. Poisson regression models were tailored to each system's data characteristics by population (all SUD treatment patients, US census) and adjusted for prescription volume. Effects of gender, race, age and US region as well as ROA profile were examined.. For the ASI-MV study, 45,695 assessments of unique adults evaluated for substance use problems were collected. The abuse rate unadjusted for prescription volume of BNX tablet formulation was 2.64 cases/100 ASI-MV respondents versus 7.01 cases for the film formulation (RR=0.390, p<0.001). Prescription-adjusted abuse, however, was greater for the tablet version (0.47 abuse cases/100 ASI-MV respondents/100,000 dosage units compared with 0.38 for the film) (RR=1.25, p<0.001). Results among the US population from the RADARS System Poison Center Program data revealed a similar pattern; population rates for film abuse (0.0364) were greater than for tablet (0.0161), while prescription-adjusted rates were greater for tablet (0.2114) than for film (0.1703) per 100,000 prescriptions. ASI-MV ROA analyses indicated less abuse of the film by any alternate route, insufflation or injection than the tablet. Poison center data found more injection of tablets than film, although insufflation was not significantly different.. On a prescription-adjusted basis, overall abuse of the BNX tablet is greater than that of the sublingual film formulation. For those who continue to abuse BNX, use by alternate ROAs was, in general, lower for the film.

Topics: Administration, Sublingual; Adult; Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Drug Administration Routes; Female; Humans; Male; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Poison Control Centers; Tablets; United States

The Opiate Dosage Adequacy Scale (ODAS) is a clinical tool to individually measure the "adequacy" of opioid doses in patients on maintenance treatment. The aim of this paper is to provide evidence for the validity and reliability of the ODAS in a sample of patients in buprenorphine/naloxone (B/N) maintenance treatment.. Cross-sectional study of a convenience sample of B/N-treated patients (n = 316) from four Autonomous Communities in Spain. Participants completed a battery of instruments to assess the following: buprenorphine dose adequacy; heroin dependence severity; psychological adjustment; and patient-desired adjustment of buprenorphine dose.. Exploratory Factor Analysis identified four factors from the ODAS that together account for 85.4% of the total variance: "Heroin craving and use"; "Overmedication"; "Objective opiate withdrawal symptoms (OWS)" and 'Subjective OWS'. Compared to patients with an "inadequate" B/N dose (ODAS), patients with "adequate" doses had less heroin use in the last week (0.01 vs. 0.40; t = -2.73; p < 0.01, 95% CI: -0.67, -0.10), less severe heroin dependence (2.20 vs. 5.26, t = -5.14, p < 0.001; 95% CI: -4.23, -1.88), less psychological distress (3.00 vs. 6.31, t = -4.37, p < 0.001; 95% CI: -4.80, -1.81), and greater satisfaction with their doses (42.1% vs. 13.6%, χ. These findings support the validity and reliability of the ODAS as a tool to measure and assess buprenorphine dose adequacy in the context of an opioid dependency treatment program.

Topics: Adult; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Cross-Sectional Studies; Dose-Response Relationship, Drug; Female; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Reproducibility of Results; Substance Withdrawal Syndrome; Treatment Outcome; Young Adult

Currently, no pharmacogenetic tests for selecting an opioid-dependence pharmacotherapy have been approved by the US Food and Drug Administration.. Determine the effects of variants in 11 genes on dropout rate and dose in patients receiving methadone or buprenorphine/naloxone (ClinicalTrials.gov Identifier: NCT00315341).. Variants in six pharmacokinetic genes (CYP1A2, CYP2B6, CYP2C19, CYP2C9, CYP2D6, CYP3A4) and five pharmacodynamic genes (HTR2A, OPRM1, ADRA2A, COMT, SLC6A4) were genotyped in samples from a 24-week, randomized, open-label trial of methadone and buprenorphine/naloxone for the treatment of opioid dependence (n = 764; 68.7% male). Genotypes were then used to determine the metabolism phenotype for each pharmacokinetic gene. Phenotypes or genotypes for each gene were analyzed for association with dropout rate and mean dose.. Genotype for 5-HTTLPR in the SLC6A4 gene was nominally associated with dropout rate when the methadone and buprenorphine/naloxone groups were combined. When the most significant variants associated with dropout rate were analyzed using pairwise analyses, SLC6A4 (5-HTTLPR) and COMT (Val158Met; rs4860) had nominally significant associations with dropout rate in methadone patients. None of the genes analyzed in the study was associated with mean dose of methadone or buprenorphine/naloxone.. This study suggests that functional polymorphisms related to synaptic dopamine or serotonin levels may predict dropout rates during methadone treatment. Patients with the S/S genotype at 5-HTTLPR in SLC6A4 or the Val/Val genotype at Val158Met in COMT may require additional treatment to improve their chances of completing addiction treatment. Replication in other methadone patient populations will be necessary to ensure the validity of these findings.

Topics: Adult; Buprenorphine, Naloxone Drug Combination; Female; Genotype; Humans; Male; Methadone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Dropouts; Pharmacogenetics; Pharmacogenomic Testing; Treatment Outcome

To address concerns regarding the intravenous diversion of buprenorphine, a combined buprenorphine-naloxone (BUP-NLX) preparation was developed. The aim of this study is to compare health outcomes in opioid dependent patients treated with BUP and BUP-NLX. All patients treated with BUP and/or BUP-NLX in Western Australia between 2001 and 2010 were included in the study ( N = 3455). Patients were identified via State prescribing records and matched against the State mortality, hospital, and emergency department records. Rates of health events were examined and compared using Cox Proportional Hazard Models and Generalized Estimating Equations. While on treatment there was no significant difference between mortality rates in the two groups, mortality rates following the cessation of treatment were significantly higher in patients treated with BUP-NLX (adjusted hazard ratio: 1.59). Rates of hospitalization were significantly elevated in BUP-NLX patients (adjusted odds ratio: 1.17) compared with BUP treated patients; however, rates of hospitalization with a skin/subcutaneous diagnosis were significantly lower in BUP-NLX treated patients (adjusted odds ratio: 0.65). Off-treatment rates of both all-cause hospital admissions (adjusted odds ratio: 1.53) and hospital admissions with an opioid poisoning diagnosis (adjusted odds ratio: 1.59) were significantly elevated in BUP-NLX treated patients compared with BUP treated patients. The addition of naloxone does not appear to improve the safety profile of buprenorphine.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Female; Humans; Male; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Treatment Outcome

Rising concerns regarding diversion and misuse of mono-buprenorphine for treatment of pregnant women with opioid use disorders have sparked interest in the use of buprenorphine + naloxone to reduce misuse and diversion rates. Examined the relationship of prenatal buprenorphine + naloxone exposure to neonatal outcomes.. This is a retrospective chart review of 26 mother infant dyads in comprehensive medication-assisted treatment with buprenorphine + naloxone during pregnancy.. All neonatal birth outcome parameters were within normal ranges, albeit on the lower side of normal for gestational age and birth weight. Only 19% of neonates required morphine pharmacology for NAS.. Use of buprenorphine + naloxone shows relative safety in pregnancy.. These findings can help better guide prescribing practices for pregnant patients at risk for misuse or diversion of buprenorphine. (Am J Addict 2018;27:92-96).

Topics: Adult; Appalachian Region; Birth Weight; Buprenorphine, Naloxone Drug Combination; Female; Humans; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnant Women; Retrospective Studies; Risk Adjustment

Topics: Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Canada; Drug Overdose; Humans; Opioid-Related Disorders; Psychotherapy; Societies, Medical; Vulnerable Populations

Topics: Adult; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Chronic Pain; Humans; Male; Opioid-Related Disorders

Urine adulteration is a concern among patients treated for opioid use disorder. Quantitative urine testing for buprenorphine (B) and norbuprenorphine (NB), and the appropriate interpretation of B and NB levels, can facilitate constructive conversations with patients that may lead to modifications in the treatment plan, and strengthening of the patient-provider relationship.. Three cases are presented in which discordant urine B and NB levels were recognized. Each patient was submerging buprenorphine/naloxone strips in their urine to mask ongoing illicit drug use. The authors used an approach to addressing intentional adulteration of urine samples that adheres to the principles of harm-reduction, the centrality of the patient-provider relationship, and the acknowledgment that ongoing illicit drug use and subsequent dishonesty about disclosure may be common among persons with substance use disorders. Each of the three patients ultimately endorsed diluting their urine, which allowed for strengthening of the patient-provider relationship and modifications to their treatment plans. Two of the three patients stabilized and achieved abstinence, while the third was eventually referred to a methadone treatment program.. Providers should routinely monitor B and NB levels, rather than qualitative screening alone, and discordant levels should elicit a timely conversation with the patient. The authors use of a nonjudgmental approach to address urine adulteration, including giving patients an opportunity to reflect on potential solutions, has been effective at helping patients and providers to reestablish a therapeutic alliance and maintain retention in treatment.

Topics: Adult; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cocaine-Related Disorders; Drug Contamination; Female; Humans; Male; Methadone; Middle Aged; Opioid-Related Disorders; Substance Abuse Detection

Topics: Buprenorphine, Naloxone Drug Combination; Counseling; Epidemics; Humans; Opioid-Related Disorders; Patient-Centered Care

For the period January 1, 2015 through December 31, 2016, two datasets were analyzed: prescriptions and associated costs for buprenorphine-naloxone (BN) products and urine toxicology test results for patients in the Medicaid plan. The dataset comprised 1370 unique providers ordering 643,225 prescriptions for opioid addiction therapy. Patient and order volumes, and the rate of monthly positive laboratory values for opioid molecules and cocaine were reviewed. A targeted survey of physicians treating opioid-dependent patients with state Medicaid plan coverage was also conducted.. Upon plan conversion to BBN, there was a rapid increase in monthly BBN prescriptions mirrored by a rapid decrease in SLBN prescriptions. Peak in BBN prescriptions (2633 in November 2015) was approximately 60% lower than peak in SLBN prescriptions (6531 in July 2015). An unexpected finding was a 68% reduction of the overall BN market, indicating that many BN prescriptions were abandoned. The reduction was associated with quarterly cost savings to the Medicaid plan of approximately $3.5 million. Toxicology results indicated a reduction in drug positivity (defined as positivity for cocaine and/or any opioids except buprenorphine and methadone) from 13-16% in 2015 to less than 10% in 2016. Heroin positivity decreased from approximately 9% in December 2015 to an average of less than 1% during the last quarter of 2016, while positivity for norbuprenorphine, the major metabolite of buprenorphine, showed a marked increase in 2016 vs 2015. Among physicians who responded to the targeted survey most rated BBN as more difficult to abuse or misuse than SLBN.. The rapid reduction in the overall BN market following a complete formulary switch from SLBN to BBN was associated with quarterly savings of $3.5 million for the state Medicaid plan. Toxicology data suggest that this cost saving was realized in the context of improved physician and patient adherence to treatment protocols. The changing market dynamics can potentially be explained by a number of contributory factors, including a reduction of diversion and illicit distribution of BN following formulary conversion. These results are considered hypothesis-generating and future research should systematically compare the propensity for diversion and abuse of BN products using various epidemiological tracking tools.. BioDelivery Sciences International, Inc.

Topics: Administration, Buccal; Administration, Sublingual; Buprenorphine, Naloxone Drug Combination; Drug Utilization; Humans; Insurance Claim Review; Medicaid; Narcotic Antagonists; Opioid-Related Disorders; Practice Patterns, Physicians'; Substance Abuse Detection; Treatment Outcome; United States

Drop-out is a core problem in opioid maintenance treatment (OMT), but patients' reactions to and acceptance of the various OMT medications are insufficiently investigated. In Norway, there has been vocal patient resistance to the newest medication, buprenorphine-naloxone (BNX), and complaints have focused on the side effect profile. There has been no comparison of patient satisfaction and side effects of the three most common OMT medications.. To compare patient satisfaction with OMT and side effects of BNX, buprenorphine monopreparate (BUP), and methadone (MET) as reported by patients.. Data were drawn from a national peer-to-peer survey developed by a patient advocacy group. The survey engaged more than 1000 OMT patients, corresponding to one seventh of OMT patients in Norway. The associations between side effects, treatment satisfaction, and patient characteristics were tested in multinomial logistic regressions.. High patient satisfaction with OMT overall was reported despite lower satisfaction with medication itself and widely prevalent side effects. Among each medication group, dissatisfaction with medications or OMT in general along with poor health status increased the relative risk ratio of reporting the heaviest side effect burden. MET users reported the highest side effect burden and BNX users the lightest, but BNX users were more dissatisfied with their medication.. Side effects are a concern for nearly all OMT patients, and they do not appear to accumulate with age or length of treatment. BNX users' dissatisfaction with their medication is of particular concern, and expectations and preferences of medication may be influencing their dissatisfaction.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Female; Humans; Maintenance Chemotherapy; Male; Methadone; Middle Aged; Norway; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Dropouts; Patient Satisfaction; Surveys and Questionnaires

Efficacious medications to treat opioid use disorders (OUDs) have been slow to diffuse into practice, and insurance coverage limits may be one important barrier.. To compare coverage for medications used to treat OUDs and opioids commonly prescribed for pain management in plans offered on the 2017 Health Insurance Marketplace exchanges.. We identified a sample of 100 plans offered in urban and in rural counties on the 2017 Marketplaces, weighting by population. We accessed publicly available plan coverage information on healthcare.gov for states with a federally facilitated exchange, the state exchange website for state-based exchanges, and insurer websites.. About 14% of plans do not cover any formulations of buprenorphine/naloxone. Plans were more likely to require prior authorization for any of the covered office-based buprenorphine or naltrexone formulations preferred for maintenance OUD treatment (ie, buprenorphine/naloxone, buprenorphine implants, injectable long-acting naltrexone) than of short-acting opioid pain medications (63.6% vs. 19.4%; P<0.0001). Only 10.6% of plans cover implantable buprenorphine, 26.1% cover injectable naltrexone, and 73.4% cover at least 1 abuse-deterrent opioid pain medication.. Many Marketplace plans either do not cover or require prior authorization for coverage of OUD medications, and these restrictions are often more common for OUD medications than for short-acting opioid pain medications. Regulators tasked with enforcement of the Mental Health Parity and Addiction Equity Act, which requires that standards for formulary design for mental health and substance use disorder drugs be comparable to those for other medications, should focus attention on formulary coverage of OUD medications.

Topics: Buprenorphine, Naloxone Drug Combination; Health Insurance Exchanges; Health Services Accessibility; Humans; Insurance Coverage; Insurance, Pharmaceutical Services; Opiate Substitution Treatment; Opioid-Related Disorders

Buprenorphine accounts for the most opioid-related pediatric hospital admissions when compared with other opioid analgesics. Since 2010, several manufacturers began distributing their buprenorphine products with unit-dose packaging (UDP). Our main objective in this study is to evaluate the impact of UDP on unintentional pediatric buprenorphine-naloxone poison center exposures.. This is an observational surveillance study in which the Researched Abuse, Diversion, and Addiction-Related Surveillance System Poison Center Program is used. The main outcome was cases of unintentional ingestions involving children <6 years old and buprenorphine-naloxone (combination) products. The study was split into 3 periods: pre-UDP (first quarter 2008 through fourth quarter 2010), transition to UDP (first quarter 2011 through fourth quarter 2012), and post-UDP (first quarter 2013 through fourth quarter 2016).. Overall, there were 6217 exposures to combination products. In the pre-UDP period, there were 20.57 pediatric unintentional exposures per 100 000 prescriptions dispensed; in the transition to UDP period, there were 8.77 pediatric unintentional exposures per 100 000 prescriptions dispensed; and in the post-UDP period, there were 4.36 pediatric unintentional exposures per 100 000 prescriptions dispensed. This represents a 78.8% (95% confidence interval: 76.1%-81.3%;. The shift from non-UDP to UDP in over 80% of buprenorphine-naloxone products was associated with a significant decrease in unintentional pediatric exposures reported to poison centers. Packaging controls should be a mainstay in the approach to the prevention of unintentional buprenorphine pediatric exposures as well as exposures to other prescription opioids.

Topics: Buprenorphine, Naloxone Drug Combination; Child, Preschool; Drug Overdose; Drug Packaging; Female; Humans; Infant; Male; Narcotic Antagonists; Opioid-Related Disorders; United States

This is a follow-up study of a previously published randomized clinical trial conducted in Norway that compared extended-release naltrexone (XR-NTX) to buprenorphine-naloxone (BP-NLX) over 3 months. At the conclusion of the trial, participants were offered their choice of study medication for an additional 9 months. While BP-NLX was available at no cost through opioid maintenance treatment programmes, XR-NTX was available only through study participation, accounting for why almost all participants chose XR-NTX in the follow-up. The aim of this follow-up study was to compare differences in outcome between adults with opioid dependence continuing XR-NTX and those inducted on XR-NTX for a 9-month period, on measures of effectiveness, safety and feasibility.. In this prospective cohort study, participants were either continuing XR-NTX, changed from BP-NLX to XR-NTX or re-included into the study and inducted on XR-NTX treatment.. Five urban, out-patient addiction clinics in Norway.. Opioid-dependent adults continuing (n = 54) or inducted on (n = 63) XR-NTX.. XR-NTX administrated as intramuscular injections (380 mg) every fourth week.. Data on retention, use of heroin and other illicit substances, opioid craving, treatment satisfaction, addiction-related problems and adverse events were reported every fourth week.. Nine-month follow-up completion rates were 51.9% among participants continuing XR-NTX in the follow-up and 47.6% among those inducted on XR-NTX. Opioid abstinence rates were, respectively, 53.7 and 44.4%. No significant group differences were found in use of heroin and other opioids.. Opioid-dependent individuals who elect to switch from buprenorphine-naltrexone treatment after 3 months to extended-release naltrexone treatment for 9 months appear to experience similar treatment completion and abstinence rates and similar adverse event profiles to individuals who had been on extended-release naltrexone from the start of treatment.

Topics: Adult; Buprenorphine, Naloxone Drug Combination; Cohort Studies; Delayed-Action Preparations; Feasibility Studies; Female; Humans; Injections, Intramuscular; Male; Naltrexone; Narcotic Antagonists; Norway; Opioid-Related Disorders; Prospective Studies; Randomized Controlled Trials as Topic; Treatment Outcome

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

There is limited information on the most commonly used opioid reported at the time of presentation for treatment with buprenorphine/naloxone and the extent to which state policy may impact type of opioid use reported.. Retrospective study, total N = of 595 from four different medical locations from January 1, 2009 to July 1, 2016 that provided buprenorphine/naloxone treatment in Louisville, Kentucky. Study aims included identifying the most commonly used opioid at the time of treatment before and after the creation of a state-wide opioid prescribing surveillance system (ie, the 2012 House Bill 1 [HB1]), and determine the extent to which clinical setting, sex, age, and insurance type impacted type of opioid reported during the intake appointment.. Non-heroin opioid use decreased in the academic and private practice settings following passage of HB1, while heroin use increased in all three settings. After controlling for clinical setting and demographic characteristics, there was a significant increase in patients who reported using heroin (vs. non-heroin opioid) (RR = 25.00, p ≤ .001, CI = 12.08-51.73) and a significant increase in patients who reported using opioid agonists (vs. non-heroin opioid) (RR = 6.56, p ≤ .001, CI = 4.10-10.50) following enactment of HB1.. After the passage of HB1, there was a significant increase in patients reporting heroin use and opioid agonists compared to non-heroin opioids when presenting for treatment.. There has been a notable shift in the opioid epidemic, which is evident in the outpatient treatment settings. (Am J Addict 2018;27:560-566).

Topics: Adult; Ambulatory Care; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Female; Health Policy; Humans; Kentucky; Male; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Practice Patterns, Physicians'; Retrospective Studies

Cannabis use is common among people on opioid agonist treatment (OAT), causing concern for some care providers. However, there is limited and conflicting evidence on the impact of cannabis use on OAT outcomes. Given the critical role of retention in OAT in reducing opioid-related morbidity and mortality, we aimed to estimate the association of at least daily cannabis use on the likelihood of retention in treatment among people initiating OAT. As a secondary aim we tested the impacts of less frequent cannabis use.. Data were drawn from two community-recruited prospective cohorts of people who use illicit drugs (PWUD). Participants were followed for a median of 81 months (interquartile range = 37-130).. Vancouver, Canada.. This study comprised a total of 820 PWUD (57.8% men, 59.4% of Caucasian ethnicity, 32.2% HIV-positive) initiating OAT between December 1996 and May 2016. The proportion of women was higher among HIV-negative participants, with no other significant differences.. The primary outcome was retention in OAT, defined as remaining in OAT (methadone or buprenorphine/naloxone-based) for two consecutive 6-month follow-up periods. The primary explanatory variable was cannabis use (at least daily versus less than daily) during the same 6-month period. Confounders assessed included: socio-demographic characteristics, substance use patterns and social-structural exposures.. In adjusted analysis, at least daily cannabis use was positively associated with retention in OAT [adjusted odds ratio (aOR) = 1.21, 95% confidence interval (CI) = 1.04-1.41]. Our secondary analysis showed that compared with non-cannabis users, at least daily users had increased odds of retention in OAT (aOR = 1.20, 95% CI = 1.02-1.43), but not less than daily users (aOR = 1.00, 95% CI = 0.87-1.14).. Among people who use illicit drugs initiating opioid agonist treatment in Vancouver, at least daily cannabis use was associated with approximately 21% greater odds of retention in treatment compared with less than daily consumption.

Topics: Adult; Analgesics, Opioid; British Columbia; Buprenorphine, Naloxone Drug Combination; Female; Humans; Longitudinal Studies; Male; Marijuana Use; Methadone; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Retention in Care

Inability to access opioid agonist therapy (OAT) in correctional settings has previously been reported in Vancouver, Canada, and is associated with harms among people with opioid use disorder (OUD), including overdose death. We investigated the prevalence and correlates of OAT utilization within correctional settings among incarcerated persons with OUD in Vancouver.. Data were derived from three prospective cohorts of people who use drugs in Vancouver between 2005 and 2016. Using multivariable generalized estimating equations, we examined factors associated with OAT utilization among participants with OUD reporting incarceration in the past six months.. Among 597 eligible participants, 207 (34.7%) contributed 325 reports of having utilized OAT while incarcerated. Of those, 295 (90.8%) were continuations and 30 (9.2%) were new initiations of OAT while incarcerated. For those currently on OAT (at the time of interview), in multivariable analyses, non-fatal overdose (adjusted odds ratio [AOR] = 0.49, 95% confidence interval [CI]: 0.29-0.82) and daily prescription opioid use (AOR = 0.42, 95% CI: 0.20-0.85) remained independently and negatively associated with having utilized OAT while incarcerated. For those not currently on OAT, none of the variables considered had significant associations with utilization of OAT while incarcerated.. Utilization of OAT in correctional settings was low in our sample. Utilization of OAT was significantly and negatively associated with overdose and ongoing prescription opioid misuse if OAT was continued upon release from correctional settings. Findings underscore the urgent need for improved utilization of OAT in correctional settings, and linkage to community care to prevent harms such as overdose.

Topics: Adult; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Canada; Case-Control Studies; Drug Overdose; Female; Humans; Male; Medication Adherence; Methadone; Opioid-Related Disorders; Prevalence; Prisoners; Prospective Studies

Although buprenorphine/naloxone is widely recognized as first-line therapy for opioid use disorder, the requirement for moderate withdrawal prior to initiation in efforts to avoid precipitated withdrawal can be a barrier to its initiation.. We present a case utilizing transdermal fentanyl as a bridging treatment to eliminate withdrawal during the transition from methadone to buprenorphine/naloxone in a patient who had ongoing significant intravenous heroin use while on methadone.. Patient was successfully transitioned from methadone to buprenorphine/naloxone without a period of withdrawal utilizing transdermal fentanyl as a bridge in an inpatient setting.. Our experience indicates a transdermal depot of fentanyl allows for slow release and elimination while buprenorphine doses are introduced during an induction without presence of withdrawal, as quantified by serial clinical opiate withdrawal score.. This case report highlights ways to minimize barriers to induction of first-line opioid substitution therapy, buprenorphine/naloxone, by eliminating withdrawal during induction phase utilizing a fentanyl bridge within the limitations of a transdermal fentanyl bridge in an inpatient setting. (Am J Addict 2018;XX:1-4).

Topics: Administration, Cutaneous; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Delayed-Action Preparations; Fentanyl; Humans; Inpatients; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Substance Withdrawal Syndrome; Treatment Outcome

Topics: Buprenorphine, Naloxone Drug Combination; Emergency Service, Hospital; Health Services Accessibility; Humans; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Primary Health Care; Prisons; Substance Withdrawal Syndrome

The μ-opioid receptor (MOR) is the primary target of methadone and buprenorphine. The primary neuronal transcript of the OPRM1 gene, MOR-1, contains a ~13 kb 3' untranslated region with five common haplotypes in European-Americans. We analyzed the effects of these haplotypes on the percentage of opioid positive urine tests in European-Americans (n=582) during a 24-week, randomized, open-label trial of methadone or buprenorphine/naloxone (Suboxone) for the treatment of opioid dependence. A single haplotype, tagged by rs10485058, was significantly associated with patient urinalysis data in the methadone treatment group. Methadone patients with the A/A genotype at rs10485058 were less likely to have opioid-positive urine drug screens than those in the combined A/G and G/G genotypes group (relative risk=0.76, 95% confidence intervals=0.73-0.80, P=0.0064). Genotype at rs10485058 also predicted self-reported relapse rates in an independent population of Australian patients of European descent (n=1215) who were receiving opioid substitution therapy (P=0.003). In silico analysis predicted that miR-95-3p would interact with the G, but not the A allele of rs10485058. Luciferase assays indicated miR-95-3p decreased reporter activity of constructs containing the G, but not the A allele of rs10485058, suggesting a potential mechanism for the observed pharmacogenetic effect. These findings suggest that selection of a medication for opioid dependence based on rs10485058 genotype might improve outcomes in this ethnic group.

Topics: 3' Untranslated Regions; Adult; Alleles; Analgesics, Opioid; Australia; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Female; Genotype; Humans; Male; Methadone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Polymorphism, Genetic; Receptors, Opioid, mu; White People

Buprenorphine-naloxone treatment for opioid use disorder has rapidly expanded, yet little is known about treatment outcomes among patients in the general population.. To examine predictors of treatment duration, dosage, and continuity in a diverse community setting.. We examined QuintilesIMS Real World Data, an all-payer, pharmacy claims database, to conduct an analysis of individuals age 18 years and above initiating buprenorphine-naloxone treatment between January 2010 and July 2012 in 11 states. We used logistic regression to assess treatment duration longer than 6 months. We used accelerated failure time models to assess risk of treatment discontinuation. We used ordinary least squares regression to assess mean daily dosage. For patients with ≥3 fills, we also used logistic regression to assess whether ;an individual had a medication possession ratio of <80% and/or gaps in treatment >14 days. Models adjusted for individual demographics, prescribing physician specialty, state, and county-level variables.. Overall, 41% of individuals were retained in treatment for at least 6 months and the mean treatment length was 266 days. Compared with individuals who paid primarily for treatment with cash, adjusted odds of 6 month retention were significantly lower for individuals with primary payment from Medicaid fee-for-service, Medicare part D, and third-party commercial. There were substantial differences in 6-month retention across states with the lowest in Arizona and highest in New York. Low-possession ratios occurred for 30% of individuals and 26% experienced treatment episodes with gaps >14 days. Odds of low-possession and treatment gaps were largely similar across demographic groups and geographic areas.. Current initiatives to improve access and quality of buprenorphine-naloxone treatment should examine geographic barriers as well as the potential role of insurance benefit design in restricting treatment length.

Topics: Adolescent; Adult; Buprenorphine, Naloxone Drug Combination; Databases, Factual; Female; Humans; Male; Middle Aged; Opioid-Related Disorders; Practice Patterns, Physicians'; United States; Young Adult

Topics: Attitude of Health Personnel; Buprenorphine, Naloxone Drug Combination; Humans; Opioid-Related Disorders; Physician's Role; Physicians, Family

Topics: Attitude of Health Personnel; Buprenorphine, Naloxone Drug Combination; Burnout, Professional; Comorbidity; Humans; Opioid-Related Disorders; Physician's Role; Physicians, Family

To measure the effect of buprenorphine-naloxone as opioid substitution therapy on glycemic control in patients with type 2 diabetes mellitus and opioid use disorder.. Retrospective cohort study and secondary data analysis.. Northwestern Ontario.. Patients with diabetes receiving opioid substitution therapy, as well as patients with diabetes only, who live in 6 remote First Nations communities.. Glycated hemoglobin A. Over a 2-year period, there was an absolute decrease of 1.20% in mean glycated hemoglobin A. Patients with diabetes who also suffer from opioid use disorder achieve significant (

Topics: Adult; Buprenorphine, Naloxone Drug Combination; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Male; Middle Aged; Ontario; Opiate Substitution Treatment; Opioid-Related Disorders; Retrospective Studies

North America is currently in the grips of a crisis rooted in the use of licit and illicit opioid-based analgesics. Drug overdose is the leading cause of accidental death in Canada and the US, and the growing toll of opioid-related morbidity and mortality requires a diversity of novel therapeutic and harm reduction-based interventions. Research suggests that increasing adult access to both medical and recreational cannabis has significant positive impacts on public health and safety as a result of substitution effect. Observational and epidemiological studies have found that medical cannabis programs are associated with a reduction in the use of opioids and associated morbidity and mortality.. This paper presents an evidence-based rationale for cannabis-based interventions in the opioid overdose crisis informed by research on substitution effect, proposing three important windows of opportunity for cannabis for therapeutic purposes (CTP) to play a role in reducing opioid use and interrupting the cycle towards opioid use disorder: 1) prior to opioid introduction in the treatment of chronic pain; 2) as an opioid reduction strategy for those patients already using opioids; and 3) as an adjunct therapy to methadone or suboxone treatment in order to increase treatment success rates. The commentary explores potential obstacles and limitations to these proposed interventions, and as well as strategies to monitor their impact on public health and safety.. The growing body of research supporting the medical use of cannabis as an adjunct or substitute for opioids creates an evidence-based rationale for governments, health care providers, and academic researchers to consider the implementation and assessment of cannabis-based interventions in the opioid crisis.

Topics: Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Drug Overdose; Evidence-Based Medicine; Harm Reduction; Humans; Medical Marijuana; Methadone; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Public Health; Public Policy

Sublingual buprenorphine/naloxone, a common treatment for opioid dependence, is frequently abused by intravenous injection. Inadvertent intra-arterial injection of buprenorphine/naloxone can produce acute ischemic insult to the hand due to gelatin embolism. Our purpose was to review a series of these patients in order to describe the clinical entity, review the outcomes, and propose a rational treatment algorithm.. Clinical records of all patients evaluated by the hand surgery team between 2011 and 2015 for ischemia of the hand after buprenorphine/naloxone injection were reviewed. Treatment, complications, and amount of tissue loss were recorded. Patients presenting within 48 hours of the injection were treated with intravenous heparin for 5 days, followed by oral aspirin and clopidogrel for 30 days. Those presenting after 48 hours were treated with aspirin and clopidogrel only.. Ten patients presented during the review period. Average follow-up time was 13 weeks. Eight had ischemia of the radial side of the hand, 1 of the ulnar side, and 1 had bilateral ischemia. Three patients were treated with intravenous heparin and 5 with oral agents. Two presented with dry gangrene and did not receive anticoagulation. All patients experienced tissue loss. There was no difference in outcome regardless of treatment.. With the increasing use of sublingual buprenorphine/naloxone in opioid dependency, ischemic hand injuries will be seen with greater frequency. Whereas outcomes did not vary with treatment modality in this series, further study is needed to determine the most effective treatment of these injuries.

Topics: Adult; Aspirin; Buprenorphine, Naloxone Drug Combination; Clopidogrel; Female; Fibrinolytic Agents; Hand; Heparin; Humans; Injections, Intra-Arterial; Ischemia; Male; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Platelet Aggregation Inhibitors; Retrospective Studies; Young Adult

This study sought to determine the relative importance of a range of Bup/Nx doses compared to Bup alone in producing subjective and reinforcing effects.. Heroin-using volunteers (n=13) were transitioned onto daily oral hydromorphone (40mg). Laboratory sessions assessed the reinforcing and subjective effects of intravenous (IV) doses of Bup (1.51, 2.16, 6.15, and 8.64mg) and Bup/Nx (1.51/0.44, 2.16/0.61, 6.15/1.71, and 8.64/2.44mg). Placebo (Pbo), heroin (25mg) and Nx (0.3mg) were tested as neutral, positive, and negative controls, respectively.. IV Bup alone was self-administered substantially less than IV heroin, though the two largest doses of Bup produced positive subjective effects, drug "Liking" (0-100mm), which were comparable to heroin (mean difference: Heroin vs Bup 6.15mg: -3.4mm, Heroin vs Bup 8.64mg: -11.3mm). All indicators of abuse potential seen with IV Bup alone were substantially decreased with the addition of Nx. All Bup/Nx combinations produced ratings of aversive effects, "Bad", which were comparable to, or greater than IV, Nx. On three of the four measures of aversive effects, the largest difference is seen with the 8.64 vs 8.64/2.44 condition.. This study further demonstrates the ability of the Bup/Nx combination to deter IV use. Although none of the Bup/Nx combinations showed indications of abuse potential, formulations with larger absolute Nx, may be less abusable as they precipitate a greater degree of withdrawal.

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Heroin; Humans; Injections, Intravenous; Naloxone; Opioid-Related Disorders; Reinforcement, Psychology

Buprenorphine maintenance therapy patients frequently have severe postoperative pain due to buprenorphine-induced hyperalgesia and provider use of opioids with limited efficacy in the presence of buprenorphine. The authors report good-to-excellent pain management in 4 obstetric patients using nonopioid analgesics, regional anesthesia, continuation of buprenorphine, and use of opioids with high μ receptor affinity.

Topics: Adult; Analgesia, Obstetrical; Analgesia, Patient-Controlled; Analgesics, Non-Narcotic; Analgesics, Opioid; Anesthetics, Local; Buprenorphine, Naloxone Drug Combination; Cesarean Section, Repeat; Drug Administration Schedule; Female; Humans; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Pain Management; Pain Measurement; Pain Perception; Pain Threshold; Pain, Postoperative; Pregnancy; Sterilization, Tubal; Treatment Outcome; Young Adult

Combination buprenorphine-naloxone is a cornerstone of outpatient treatment for substance use disorder, and is more widely accessible in primary care. Because oral buprenorphine has been diverted and abused for its euphoric properties, a combination formulation was developed and will trigger withdrawal symptoms if injected IV.

Topics: Buprenorphine, Naloxone Drug Combination; Drug Combinations; Humans; Narcotic Antagonists; Opioid-Related Disorders; Substance Withdrawal Syndrome

This study investigated a 51-year-old married man with a history of heroin dependence who underwent methadone maintenance treatment for 7 years. He received traditional Chinese medicine (TCM)-facilitated treatments and switched from methadone to buprenorphine/naloxone. Strong anxiety symptoms were observed during the initial stage; therefore, we prescribed a combination of Chaihu-Shugan-San, Zhi Bai Di Huang and Chin-Gin-Kuan-Ming decoction as the major herbal synergic regimen to relieve the symptoms of opioid withdrawal, anxiety and insomnia. During the treatment course, no precipitating withdrawal syndromes were noted, and the subject was gradually relieved of his anxiety symptoms through continual TCM treatments. In conclusion, TCM is effective in facilitating the switch from methadone to buprenorphine/naloxone and relieving anxiety symptoms. Therefore, focus on TCM-facilitated treatments for heroin dependence should be increased.

Topics: Anxiety; Buprenorphine, Naloxone Drug Combination; Drug Substitution; Drugs, Chinese Herbal; Humans; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders

Opioid use disorder among young adults is rising sharply with an increase in morbidity and mortality. This study examined differences in treatment response to a fixed dose of buprenorphine-naloxone between heroin (HU) and prescriptions opioids (POU) users.. Eighty opioid dependent young adults (M = 22 years) were treated with buprenorphine-naloxone 16-4 mg/day for 8 weeks. Differences between HU (N = 17) and POU (N = 63) on changes in weekly opioid use, opioid craving, withdrawal, and depression symptoms were analyzed with mixed-effects regression models.. The HU had an overall mean proportion of weekly opioid use of .32 (SD = .14) compared to POU's weekly mean of .24 (SD = .15) showing a significant main effect (Z = 2.21, p = .02). Depressive symptoms (CES-D scores) were elevated at baseline for both groups (HU: M = 23.1, SD = 11.9; PO: M = 22.2, SD = 9.4), but only POU improved significantly to a score of 9.88 (SD = 7.4) compared to HU's score of 18.58 (SD = 10.3) at week 8 (Z = 2.24, p = .02). There were no significant differences in treatment retention, craving, or withdrawal symptoms.. Treatment response to 16-4 mg/day of buprenorphine-naloxone was significantly diminished for heroin users relative to opioid prescription users in weekly opioid use. Heroin users also had persistent depressive symptoms suggesting the need for close monitoring.. These data suggest that young heroin users might require higher doses of buprenorphine. (Am J Addict 2017;26:838-844).

Topics: Adolescent; Age Factors; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Cognitive Behavioral Therapy; Combined Modality Therapy; Craving; Drug Therapy, Combination; Female; Heroin Dependence; Humans; Male; Memantine; Opiate Substitution Treatment; Opioid-Related Disorders; Psychotherapy, Group; Substance Withdrawal Syndrome; Substance-Related Disorders; Young Adult

Topics: Analgesics, Opioid; Arkansas; Buprenorphine, Naloxone Drug Combination; Humans; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Organizational Case Studies

Opioid use disorders are common, chronic relapsing disorders. Buprenorphine (BUP) is an FDA approved medication in the treatment of opioid use disorders, but patient adherence to this medication remains a challenge. To identify risk factors for non-adherence, this chart review study examined the association between DSM-IV Axis I psychiatric disorders, substance use, demographics, and adherence to BUP-naloxone in African-American patients.. Charts were selected of patients who had ≥5 visits and completed psychometric screens (Patient Health Questionnaire, Mood Disorder Questionnaire, and a posttraumatic stress disorder questionnaire) at the time of the initial visit (N = 50). Urine drug screens (UDS) were also obtained. Treatment adherence was defined as BUP presence in UDS for ≥80% of the visits.. A total of 48% of patients were adherent to treatment. Non-adherent patients had higher rates of use for not only opioids, but also cocaine, and alcohol. Cocaine use was associated with BUP-naloxone non-adherence even after controlling for opioid use. Attendance in cognitive behavioral group therapy sessions (CBT) was significantly associated with adherence. Patients endorsing PTSD symptoms showed higher adherence to treatment compared to those who did not endorse these symptoms.. Our results indicate that alcohol and illicit substance use is associated with non-adherence to BUP-naloxone treatment, and suggests that CBT and efforts to promote abstinence from non-opioid substance use may improve adherence among African-Americans. These findings contribute to growing literature on understanding adherence to BUP-naloxone, which is critical to reduce morbidity and mortality.

Topics: Black or African American; Buprenorphine, Naloxone Drug Combination; Cognitive Behavioral Therapy; Combined Modality Therapy; Female; Humans; Male; Medication Adherence; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Patient Compliance; Retrospective Studies; Risk Factors; Treatment Outcome; United States

At present, polydrug abuse comprises, besides traditional illicit drugs, new psychoactive substances (NPS) and non-prescribed psychotropic medicines (N-PPM). Polydrug abuse was comprehensively evaluated among opioid-dependent patients undergoing opioid maintenance treatment (OMT).. Two hundred consecutively collected urine samples from 82 OMT patients (52 male) treated with methadone or buprenorphine-naloxone medication were studied using a liquid chromatography/time-of-flight mass spectrometry screening method. The method enables simultaneous detection of hundreds of abused substances covering the traditional drugs of abuse and many NPS as well as N-PPM.. Ninety-two (45.8%) samples were positive for the abused substances. Benzodiazepines (29.0%), amphetamines (19.5%), cannabinoids (17.0%), NPS (13.0%), N-PPM (9.0%), and opioids (9.0%) were detected in different combinations. The simultaneous occurrence of up to three groups of abused substances was common (40.0%), and in one sample, all six groups were found. The stimulant NPS alpha-pyrrolidinovalerophenone was found in 10.0% and the sedative N-PPM pregabalin in 4.0% of the samples. The patients were seldom aware of what particular NPS they had abused.. A widespread occurrence of abused substances beyond the ordinary was revealed. Identifying these patients is essential as polydrug abuse is a safety risk to the patient and may cause attrition from OMT.

Topics: Adult; Buprenorphine, Naloxone Drug Combination; Chromatography, Liquid; Female; Humans; Illicit Drugs; Male; Mass Spectrometry; Methadone; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Psychotropic Drugs; Retrospective Studies; Substance Abuse Detection; Substance-Related Disorders; Young Adult

Patients, providers, communities and health systems have struggled to achieve balance between access to opioid treatment for chronic pain and its potential harmful consequences: especially misuse, addiction and overdose. We developed an interdisciplinary clinic embedded within primary care (the Opioid Reassessment Clinic-ORC) with the goal of improving the quality of care of patients with co-occurring chronic pain and issues related to opioid safety, efficacy and/or misuse.. We present three cases referred to the ORC that highlight complex clinical scenarios related to assessment and treatment of patients with chronic pain and issues related to opioid safety, efficacy and misuse.. In the context of the three cases, with respect to assessment, we discuss: making the diagnosis of opioid use disorder; allowing the patient space to endorse lack of efficacy; identification of co-occurring hazardous alcohol use; and recognizing barriers to multimodal pain care. With respect to treatment, we discuss: making a change in treatment with which the patient may not agree; effectiveness of buprenorphine/naloxone for the treatment of chronic pain; responding to low efficacy; and making continued opioid therapy contingent on engagement with substance abuse treatment.. The core components of our approach-biopsychosocial assessment and multimodal treatment planning with an emphasis on promoting functional goals and safety using clear communication and a patient-centered stance-should guide providers in the management of similar clinical scenarios. More evidence is needed to definitively guide specific interventions and points of clinical equipoise.

Topics: Alcoholism; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Chronic Pain; Humans; Opioid-Related Disorders; Pain Management; Primary Health Care; Quality Improvement

To test if polysubstance use profiles and drug-related outcomes differ between those receiving and not receiving opioid substitution therapies (OST) among people who inject drugs (PWID).. An annual cross-sectional, sentinel sample of PWID across Australia.. Data came from 3 years (2011-13) of the Illicit Drug Reporting System (IDRS).. A total of 2673 participants who injected drugs from the combined national IDRS samples of 2011 (n = 868), 2012 (n = 922) and 2013 (n = 883).. Latent class analysis (LCA) was used to summarize participants' self-reported use of 18 types of substances, with the resulting polysubstance use profiles then associated with participant experience of a number of drug-related outcomes.. Polysubstance use profiles exhibiting a broad range of substance use were generally at increased risk of negative drug-related outcomes, whether or not participants were receiving OST, including thrombosis among OST receivers [odds ratio (OR) = 2.13, 95% confidence intervals (CI) = 1.09-4.17], injecting with used needles among OST receivers and non-receivers, respectively (OR = 2.78, 95% CI = 1.50-5.13; OR = 2.15, 95% CI = 1.34-3.45) and violent criminal offences among OST receivers and non-receivers, respectively (OR =2.30, 95% CI = 1.16-4.58; OR = 1.87, 95% CI = 1.14-3.07). An important exception was non-fatal overdose which was related specifically to a class of PWID who were not receiving OST and used morphine frequently (OR = 1.83, 95% CI = 1.06-3.17) CONCLUSION: Regardless of opioid substitution therapies usage, people who inject drugs who use a broad-range of substances experience greater levels of injecting-related injuries and poorer health outcomes and are more likely to engage in criminal activity than other groups of people who inject drugs.

Topics: Abscess; Adolescent; Adult; Alcoholism; Amphetamine-Related Disorders; Analgesics, Opioid; Australia; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cocaine-Related Disorders; Cross-Sectional Studies; Drug Overdose; Female; Heroin Dependence; Humans; Male; Marijuana Abuse; Methadone; Middle Aged; Needle Sharing; Odds Ratio; Opiate Substitution Treatment; Opioid-Related Disorders; Substance Abuse, Intravenous; Substance-Related Disorders; Thrombosis; Violence; Young Adult

The intravenous (IV) use of opioid maintenance treatment (OMT) medications and other intoxicating drugs among OMT patients is a challenge for many OMT units and affects treatment outcomes. The aim of this study is to examine factors associated with IV use of OMT medications and other intoxicating drugs among Finnish OMT patients.. A cross-sectional study was conducted among all Finnish OMT patients of whom 60% (n=1508) participated. The data were collected by anonymous questionnaire. Binominal regression analysis with unadjusted and adjusted ORs was conducted to evaluate predictors for IV use.. Factors associated with the injection of a patient's own OMT medication were: being treated with buprenorphine-naloxone (BNX) (OR 2.60, p=0.005) with a low dose (<9.0mg/day; OR 5.70, p<0.001) and being treated in a health-care centre (OR 2.03, p=0.029). Factors associated with the injection of illicit OMT medications were: being treated with BNX (OR 5.25, p<0.001) with a low dose (<9.0mg/day; OR 2.89, p=0.017), lack of psychosocial support (OR 2.62, p<0.001) and concurrent use of psychotropic medications from illicit sources (OR 4.28, p<0.001). Associated factors for the injection of other intoxicating drugs were: concurrent use of illicit drugs (OR 1.72, p=0.015), psychotropic medications from illicit sources (OR 4.78, p<0.001) and from a doctor (OR 1.93, p=0.004).. More effort should be made to reduce concurrent injecting use during OMT. This may be done by addressing concurrent substance use orders more effectively, by ensuring that patients receive an optimal BNX dose and by providing more psychosocial support.

Topics: Administration, Intravenous; Adult; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Cross-Sectional Studies; Female; Finland; Humans; Male; Medication Adherence; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Regression Analysis; Surveys and Questionnaires

Topics: Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Drug Prescriptions; Humans; Medicare Part D; Opioid-Related Disorders; Practice Patterns, Physicians'; United States

Identifying predictors of early drop out from outpatient treatment of opioid use disorder (OUD) with buprenorphine/naloxone (BN) may improve care for subgroups requiring more intensive engagement to achieve stabilization. However, previous research on predictors of dropout among this population has yielded mixed results. The aim of the present study was to elucidate these mixed findings by simultaneously evaluating a range of putative risk factors that may predict dropout in BN maintenance treatment.. Outpatient medical records and weekly supervised urine toxicology results were retrospectively reviewed for patients at two community psychiatric clinics (n = 202): a private hospital clinic (n = 84) and a federally qualified health center (n = 118). A forward stepwise logistic regression was utilized to investigate the association between early dropout (i.e., discontinuing treatment or buprenorphine non-adherence within the first 3 months of clinic entry) and extracted sociodemographic, clinical, substance use, and treatment history variables.. Overall, 56 of 202 participants (27.7%) dropped out of treatment. The multivariable analysis indicated that age under 25 (B = 1.47, SEB = .52, p < .01) and opioid use in month 1 (B = 1.50, SEB = .41, p < .001) were significantly associated with early dropout; those with a history of suicide attempt were significantly less likely to drop out (B = -1.44, SEB = .67, p < .05).. Consistent with previous research, younger age and use of opioids during the first month of treatment predicted early dropout. Having a history of prior suicide attempt was associated with 3-month BN treatment retention, which has not been previously reported. (Am J Addict 2016;25:472-477).

Topics: Adult; Buprenorphine, Naloxone Drug Combination; Female; Humans; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Outpatients; Patient Dropouts; Prognosis; Risk Assessment; Risk Factors

Attention must be focused on needed changes to the current United States law that restricts physicians who prescribe buprenorphine for the detoxification or treatment of Opioid Use Disorder, to accepting no more than 100 patients. The current system does not provide comprehensive treatment as defined by the American Society of Addiction Medicine (ASAM) criteria. In addition, it suffers from both fragmentation and stigma and will require a significant change to comply with ASAM's call for integrated delivery of comprehensive addiction treatment. This commentary calls for the development and implementation of "best practice," by recommending caution in lifting the 100 patient limit until substantial achievement of this goal occurs. The authors call for an increase to 200 in the patient limit to be restricted to those physicians who are Board Certified in Addiction Medicine by the American Board of Addiction Medicine (ABAM) or in Addiction Psychiatry by the American Board of Psychiatry and Neurology (ABPN), or other responsible medical organizations. Any additional restriction lifting should follow a systemic evolution that rewards and documents competency. Such a system would involve the integration of treatment, treatment systems, and recovery with prescription medication. In addition, it should monitor emotional blunting, treatment progress and initiation of genetic addiction risk testing.

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

We examine ethical challenges encountered in the design of an effectiveness trial (CTN-0051; X:BOT), comparing sublingual buprenorphine-naloxone (BUP-NX), an established treatment for opioid dependence, to the newer extended-release injectable naltrexone (XR-NTX). Ethical issues surrounded: 1) known poor effectiveness of one possible, commonly used treatment as usual control condition-detoxification followed by counseling without medication; 2) the role of patients' preferences for treatments, given that treatments were clinically approved and available to the population; 3) differences between the optimal "usual treatment" clinical settings for different treatments making it challenging to design a fair comparison; 4) vested interest groups favoring different treatments exerting potential influence on the design process; 5) potentially vulnerable populations of substance users and prisoners; 6) potential therapeutic misconception in the implementation of safety procedures; and 7) high cost of a large trial limiting questions that could be addressed. We examine how the design features underlying these ethical issues are characteristic of effectiveness trials, which are often large trials that compare treatments with varying degrees of existing effectiveness data and familiarity to patients and clinicians, in community-based treatment settings, with minimal exclusion criteria that could involve vulnerable populations. Hence, investigators designing effectiveness trials may wish to remain alert to the possibility of similar ethical issues.

Topics: Administration, Sublingual; Buprenorphine, Naloxone Drug Combination; Comparative Effectiveness Research; Counseling; Delayed-Action Preparations; Ethics, Research; Humans; Informed Consent; Injections, Intramuscular; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Patient Preference; Patient Safety; Prisoners; Randomized Controlled Trials as Topic; Vulnerable Populations

Tropicamide is an antimuscarinic ophthalmic solution used to produce short-acting mydriasis and cycloplegia. Topical abuse of ophthalmic solutions has been reported, but intravenous (IV) abuse of tropicamide seems to be a new phenomenon.. The authors present 2 patients with concomitant IV tropicamide abuse and opioid use disorder. Patients were hospitalized and started on buprenorphine/naloxone treatment for opioid withdrawal. Patients' reports about tropicamide effects are remarkable, as they claimed that tropicamide increased the efficacy of heroin while decreasing and delaying the withdrawal symptoms.. Although anticholinergics have been known to be abused for their euphoric effects, these cases' motivation to use tropicamide seemed to extend beyond its euphoric effect and was also based on its interaction with heroin. It is feared that tropicamide abuse may become more frequent. Health professionals should be aware of this trend so that symptoms of misuse and intoxication can be recognized, and ophthalmologists should consider the abuse potential of anticholinergic eye drops when prescribing them.

Topics: Adult; Buprenorphine, Naloxone Drug Combination; Humans; Male; Muscarinic Antagonists; Opioid-Related Disorders; Substance Abuse, Intravenous; Substance Withdrawal Syndrome; Tropicamide

To compare three missing data strategies: (i) the latent growth model that assumes the data are missing at random (MAR) model; (ii) the Diggle-Kenward missing not at random (MNAR) model, where dropout is a function of previous/concurrent urinalysis (UA) submissions; and (iii) the Wu-Carroll MNAR model where dropout is a function of the growth factors. DESIGN : Secondary data analysis of a National Drug Abuse Treatment Clinical Trials Network trial that examined a 7-day versus 28-day taper (i.e. stepwise decrease in buprenorphine/naloxone) on the likelihood of submitting an opioid-positive UA during treatment.. 11 out-patient treatment settings in 10 US cities.. A total of 516 opioid-dependent participants.. Opioid UAs provided across the 4-week treatment period.. The MAR model showed a significant effect (B = -0.45, P < 0.05) of trial arm on the opioid-positive UA slope (i.e. 28-day taper participants were less likely to submit a positive UA over time) with a small effect size (d = 0.20). The MNAR Diggle-Kenward model demonstrated a significant (B = -0.64, P < 0.01) effect of trial arm on the slope with a large effect size (d = 0.82). The MNAR Wu-Carroll model showed a significant (B = -0.41, P < 0.05) effect of trial arm on the UA slope that was relatively small (d = 0.31).. This performance comparison of three missing data strategies (latent growth model, Diggle-Kenward selection model, Wu-Carrol selection model) on sample data indicates a need for increased use of sensitivity analyses in clinical trial research. Given the potential sensitivity of the trial arm effect to missing data assumptions, it is critical for researchers to consider whether the assumptions associated with each model are defensible.

Topics: Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Data Collection; Female; Humans; Male; Models, Biological; Multicenter Studies as Topic; Opioid-Related Disorders; Randomized Controlled Trials as Topic; Substance Abuse Detection

Substance abuse and gambling problems are associated, however, studies on gambling problems among opioid substitution treatment (OST) patients are scarce. The aims of this study are to explore the association of gender, age, treatment medication and treatment program with gambling behaviour, including gambling participation and gambling problems, among OST patients.. All OST patients (n = 244) in three Finnish outpatient clinics were recruited in March - April 2014. The response rate was 64.3%. OST programs included two choices of orientation (rehabilitative/harm reduction) and two choices for treatment medication (methadone/buprenorphine-naloxone). Of 144 respondents, 70.1% had gambled during the past year and 12.5% were identified as potential past-year problem gamblers. Gambling was statistically significant more commonly among males (79.8%) compared with females (53.7%). Similarly patients in the rehabilitative program gambled (75.9%) more than those in the harm reduction program (50.0%). Gender, age, treatment medication or treatment program was not associated with past-year gambling problems.. Gambling participation of the OST patients seemed to be somewhat similar compared with the Finnish general population, but gambling problems were more common among OST patients. Gender and age may not be very strong indicators of risk while screening problem gamblers among OST patients. Institution of a problem gambling screening program is recommended, and additional intervention for gambling problems should be implemented for that need as a part of OST.

Topics: Adult; Age Factors; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cross-Sectional Studies; Drug Combinations; Female; Finland; Gambling; Humans; Male; Methadone; Middle Aged; Narcotic Antagonists; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Sex Factors

Topics: Buprenorphine, Naloxone Drug Combination; Humans; Nurses; Opioid-Related Disorders; Physician Impairment

Despite buprenorphine's promise as a novel therapy for opioid dependence, little is known about its clinical adoption. We characterized trends in ambulatory use of buprenorphine in the United States.. Cross-sectional, descriptive analyses of buprenorphine utilization from 2003 to 2013 using the IMS Health National Disease and Therapeutic Index, a nationally representative audit of ambulatory care. The primary unit of analysis was an office visit where buprenorphine was used for opioid dependence (treatment visit).. Between 2003 and 2013, there was significant uptake of buprenorphine in ambulatory treatment visits, from 0.16 million [M] (95% confidence interval [CI] 0.10-0.20) visits in 2003 to 2.1M (CI 1.9-2.3M) treatment visits during 2013. Approximately 90% involved the use of brand name combination buprenorphine/naloxone (Suboxone), although this percentage decreased modestly to 80% by the last quarter of 2013. Buprenorphine prescribing increased among all specialties, but the proportion accounted for by primary care physicians increased significantly from 6.0% in 2003 to 63.5% in 2013 and decreased among psychiatrists from 92.2% to 32.8% over the same time period.. The use of buprenorphine products to treat opioid dependence has increased significantly in the past 10 years and has shifted to greater use by primary care physicians, indicating a rapidly changing face of opioid maintenance therapy in the United States.

Topics: Ambulatory Care; Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cross-Sectional Studies; Drug Utilization; Female; Humans; Opioid-Related Disorders; United States

The buprenorphine/naloxone combination for the treatment of opioid dependence is available in a film or tablet formulation. Recent retrospective studies demonstrated that treatment with the sublingual film formulation is associated with improved treatment retention and lower healthcare costs. In March 2013, generic buprenorphine/naloxone tablets were approved in the US. A budget impact model was built to compare healthcare expenditures for different market shares of sublingual film and tablet.. A Markov model was developed to track a cohort of opioid dependent patients treated with sublingual film or tablet through the following treatment phases: initiation, maintenance, discontinuation, off-treatment and reinitiation. Transition probabilities and costs for each phase were estimated from the MarketScan Medicaid database for the period between 1 March 2010 and 30 June 2012. The total expenditure for the plan and expenditure per plan member per month were predicted over 5 years. Two market share scenarios were considered: 1) sublingual film is progressively replaced by generic tablet (current situation) and 2) the sublingual film holds a market share of 100%.. Predicted total costs over 5 years were $6400 million when the sublingual film holds a market share of 100% (as per Scenario 2) which is lower than when sublingual film is progressively replaced by generic tablet (current situation as per Scenario 1) by $64 million. These savings were mostly driven by inpatient care ($56 million saved over 5 years), followed by emergency room care ($27 million) and pharmaceutical costs ($24 million). Costs of outpatient care attenuated the difference as they were predicted to be higher by $44 million in Scenario 2. The reduction in total cost per member per month reached $0.027 in the fifth year. Results were most sensitive to price rebates and to the probability of non-psychiatric hospitalization.. While using the sublingual film formulation for more patients treated with buprenorphine/naloxone is predicted to increase outpatient care costs, it would generate savings in emergency care and hospitalizations. In the treatment of opioid dependence, total direct medical costs for Medicaid would be lower for sublingual film treated patients, at current drug prices.

Topics: Administration, Sublingual; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Health Expenditures; Health Services; Humans; Markov Chains; Medicaid; Narcotic Antagonists; Opioid-Related Disorders; Reproducibility of Results; Retrospective Studies; Tablets; Time Factors; United States

The Clinical Opiate Withdrawal Scale (COWS) is used to assess withdrawal in clinical trials and practice. The aims of this study were to examine the inter-item correlations and factor structure of the COWS in opioid-dependent men and women.. This is a secondary data analysis of the National Drug Abuse Treatment Clinical Trials Network 0003, a randomized clinical trial that compared buprenorphine/naloxone tapering strategies. The trial included 11 sites in 10 US cities. Participants were opioid-dependent individuals (n=516) that had data on the COWS. The COWS at study baseline was analyzed in this study.. Inter-item correlations showed weak to moderate relationships among the items. A 1-factor model did not fit the data for men (comparative fit index (CFI)=.801, root mean square error of approximation (RMSEA)=.073, weighted root mean square residual (WRMR)=1.132) or women (CFI=.694, RMSEA=.071, WRMR=.933), where resting pulse rate was not related to withdrawal for men, and yawning and gooseflesh skin was not related to withdrawal for women. A reduced model comprised of only the 8 items that were significantly related to the construct of withdrawal in both men and women, and an exploratory 2-factor model, were also assessed but not retained due to inconsistencies across gender.. When traditional psychometric models are applied to the COWS, it appears that the scale may not relate to a single underlying construct of withdrawal. Further research testing the hypothesized factor structure in other opioid-dependent samples is needed.

Topics: Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Female; Humans; Male; Middle Aged; Opioid-Related Disorders; Psychometrics; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome; United States

Substance use disorders affect 12% of Medicaid beneficiaries. The prescription drug epidemic and growing need for treatment of alcohol and opioid dependence have refocused states' attention on their provision of substance use disorder treatment services, including medications. This study characterized how Medicaid programs cover these treatment medications. Data were from 2013 Medicaid pharmacy documents, 2011 and 2012 Medicaid state drug utilization records, and a 2013 American Society of Addiction Medicine survey. Results showed that only 13 state Medicaid programs included all medications approved for alcohol and opioid dependence on their preferred drug lists. The most commonly excluded were extended-release naltrexone (19 programs), acamprosate (19 programs), and methadone (20 programs). For combined buprenorphine-naloxone, 48 Medicaid programs required prior authorization, and 11 programs used 1- to 3-year lifetime treatment limits. Given the chronic nature of substance use disorders and the overwhelming evidence supporting ongoing coverage for many of these medications, states may want to reexamine substance use disorder benefits.

Topics: Acamprosate; Alcohol Deterrents; Alcohol-Related Disorders; Buprenorphine, Naloxone Drug Combination; Humans; Insurance Coverage; Medicaid; Methadone; Naltrexone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Taurine; United States

Diversion (i.e. selling or giving away) of opioid maintenance treatment (OMT) medications is a challenge that concerns many units providing OMT worldwide and tools for prevention are needed. The object of this study was to examine the prevalence and predictors for diversion of the OMT medications buprenorphine-naloxone (BNX) and methadone (MET) among Finnish OMT patients.. A cross-sectional study was conducted among all Finnish OMT patients of whom 60% (n=1508) participated. The data were collected by anonymous questionnaires distributed through all OMT units in Finland. To evaluate predictors for diversion, we used binominal regression analysis with unadjusted and adjusted ORs. Selling and/or giving away of OMT medication was used as a dependent variable and explanatory variables were gender, age, duration of OMT, type of OMT medication and dose, dispensation method of OMT medication, place of residence and intravenous use of any intoxicating drugs during the past six months.. Of all 1508 respondents, 7% (n=100) had sold and 12% (n=169) had given their OMT medication to others, 57% for money and 23% in exchange for other drugs. In multivariate analysis, predictors associated with diversion were BNX as OMT medication (OR 2.76, 95% CI 1.76-4.33), low (<9.0mg/day) BNX dose (OR 1.74, 95% CI 1.01-2.98), intravenous use of intoxicating drugs during the past six months (OR 4.48, 95% CI 3.13-6.43) and increasing length of OMT (OR 1.01, 95% CI 1.01-1.02). Age, place of residence or unsupervised pharmacy distribution of BNX were not associated with diversion.. In order to reduce diversion, more interventions are needed to support patients to stop concurrent substance abuse. Increasing control measures, for example, increased supervision, are unlikely to prevent diversion. Given that sub-optimal dosing of BNX increases the risk of diversion, more attention should be paid to providing patients with an optimal medical dose.

Topics: Adult; Buprenorphine, Naloxone Drug Combination; Cross-Sectional Studies; Female; Finland; Humans; Male; Methadone; Middle Aged; Multivariate Analysis; Opiate Substitution Treatment; Opioid-Related Disorders; Prescription Drug Diversion; Regression Analysis; Surveys and Questionnaires; Young Adult

Medication assisted treatment with buprenorphine/naloxone (Bup/Nx), including prescribing and dispensing practices of general practitioners (GPs) in Malaysia and their patients' experiences with this treatment have not been systematically examined. The current study surveyed GPs providing Bup/Nx treatment and patients receiving office-based Bup/Nx treatment in Malaysia.. Two cross-sectional surveys of GPs (N=115) providing outpatient Bup/Nx maintenance treatment and of patients (N=253) currently receiving Bup/Nx treatment throughout peninsular Malaysia.. Physicians prescribed Bup/Nx dosages in the range of 2-4mg daily for 70% of patients and conducted urine testing in the past month on approximately 16% of their patients. In the patient survey, 79% reported taking daily Bup/Nx doses of 2mg or less; 82% reported that no urine toxicology testing had been conducted on them in the past month, 36% had an opiate positive urine test at the time of the survey, 43% reported illicit opiate use, 15% reported injection of heroin and 22% reported injection of Bup/Nx in the past month.. Low daily Bup/Nx doses, lack of behavioral monitoring or counseling, and high rates of continued drug use, including injection of drugs and medications during Bup/Nx treatment in Malaysia, indicate continuing problems with implementation and less than optimal treatment effectiveness. High cost of Bup/Nx in Malaysia may deter patients from seeking treatment and contribute to taking low Bup/Nx dosages. Improved training of physicians and establishing standards for Bup/Nx dosing, routine toxicology testing, and counseling may be needed to improve care and treatment response.

Topics: Adult; Attitude of Health Personnel; Buprenorphine, Naloxone Drug Combination; Cross-Sectional Studies; Female; Humans; Malaysia; Male; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Satisfaction; Surveys and Questionnaires

Illicit use of buprenorphine has increased in the U.S., but our understanding of its use remains limited. This study aims to explore Web-forum discussions about the use of buprenorphine to self-treat opioid withdrawal symptoms.. PREDOSE, a novel Semantic Web platform, was used to extract relevant posts from a Web-forum that allows free discussions on illicit drugs. First, we extract information about the total number of buprenorphine-related posts per year between 2005 and 2013. Second, PREDOSE was used to identify all posts that potentially contained discussions about buprenorphine and opioid withdrawal. A total number of 1,217 posts that contained these terms were extracted and entered into NVivo data base. A random sample of 404 (33%) posts was selected and content analyzed.. Buprenorphine-related posts increased over time, peaking in 2011. The posts were about equally divided between those that expressed positive and negative views about the effectiveness of buprenorphine in relieving withdrawal symptoms. Web-forum participants emphasized that buprenorphine's effectiveness may become compromised because of the "size of a person habit," and/or when users repeatedly switch back and forth between buprenorphine and other illicit opioids. Most posts reported use of significantly lower amounts of buprenorphine (≤2 mg) than doses used in standard treatment. Concomitant use of other psychoactive substances was also commonly reported, which may present significant health risks.. Our findings highlight the usefulness of Web-based data in drug abuse research and add new information about lay beliefs about buprenorphine that may help inform prevention and policy measures.

Topics: Adult; Attitude to Health; Buprenorphine, Naloxone Drug Combination; Cross-Sectional Studies; Female; Health Surveys; Humans; Hydrocodone; Internet; Middle Aged; Opioid-Related Disorders; Oxycodone; Self Medication; Substance Withdrawal Syndrome; Treatment Outcome

While the risk of opioid overdose is widely accepted, the dangers of opioid withdrawal are far less clearly defined. The purpose of this publication is to provide evidence against the erroneous clinical dictum that opioid withdrawal is never life-threatening.. This case report (N = 1) illustrates an unfortunate, common scenario of a man abusing prescription opioids and heroin. His attempt at self-detoxification with buprenorphine-naloxone resulted in life-threatening opioid withdrawal. A detailed account of each day of his withdrawal period was documented by patient and family report and review of all medical records. The patient was contacted three months after hospitalization to verify information and determine progress in treatment and abstinence from drugs and alcohol.. A review of the literature was completed on severe cases of precipitated and spontaneous opioid withdrawal followed by a discussion of the significance as it relates to this case.. Given the widespread use of prescription opioids and opioid maintenance treatment, physicians should be aware of the complications of acute opioid withdrawal and should be equipped to treat these complications.

Topics: Acute Kidney Injury; Administration, Intranasal; Administration, Oral; Administration, Sublingual; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Intensive Care Units; Male; Opioid-Related Disorders; Oxycodone; Oxymorphone; Prescription Drugs; Rhabdomyolysis; Self Medication; Substance Withdrawal Syndrome; Young Adult

Topics: Animals; Behavior, Addictive; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Clinical Trials as Topic; Cocaine-Related Disorders; Counseling; Dopamine; Drug Discovery; Drug Industry; Humans; Ibogaine; Lobeline; Molecular Targeted Therapy; Naloxone; Naltrexone; Oligopeptides; Opioid-Related Disorders; Pleasure; Rats; Receptors, Nicotinic; Reward; Substance-Related Disorders; Tobacco Use Disorder; Vaccines; Vesicular Monoamine Transport Proteins

Experiences of buprenorphine-naloxone (BNX) sublingual film injection are not well documented or understood. We examined how people who inject BNX film seek and share information about this practice, document the methods used to prepare BNX film for injection, and report participants' experiences of this practice.. Interviews were (n = 16) conducted with people who indicated that they had injected BNX film since its introduction onto the Australian market. Semistructured interviews were recorded and transcribed. NVivo10 program (QSR International) was used to analyse the data using qualitative description methodology.. Participants largely reported similar BNX film preparation techniques, although the texture of BNX film during preparation to inject was reported to be unusual (gluggy), and there were many varied accounts associated with the amount of water used. Physical harms reported as associated with injecting BNX film were described (including local and systemic issues); participants reported injecting the film to enhance its immediate effects, yet generally reported that sublingual administration provided longer-lasting effects.. Understanding knowledge acquisition about injecting new formulations of opioid substitution therapy is crucial in developing more effective harm-reduction strategies. Dissemination by peer networks to those who are currently or planning to inject BNX film regarding the 'gelatine like' texture when mixing, using only cold water and double filtering is important to ensure safer injecting practices. Findings from this study highlight the importance of peer networks for the dissemination of harm-reduction information. Introduction of new formulations internationally requires more qualitative studies to inform safer practices.

Topics: Administration, Sublingual; Adult; Australia; Buprenorphine, Naloxone Drug Combination; Female; Humans; Interviews as Topic; Male; Middle Aged; Opioid-Related Disorders; Prescription Drug Misuse; Qualitative Research; Substance Abuse, Intravenous; Young Adult

Opioid dependency currently affects over 2.5 million patients in the United States and is increasing in incidence. Office-based opioid therapy with buprenorphine-naloxone provides greater patient access to treatment and has significantly improved therapeutic outcomes.. We conducted a study of 100 consecutive patients treated for opioid dependence with buprenorphine-naloxone in a single provider's community-based internal medicine practice. The primary outcome measures were retention in therapy, wellness, and abstinence from ongoing drug use. Data were obtained from frequent physical examinations, self-report data, and periodic urine drug screening.. The retention rate in therapy was 75%. A multidimensional evaluation of wellness improved in 75% of the patients. Eighty-five percent reported no opiate relapse during therapy.. Office-based opioid therapy with buprenorphine-naloxone has provided greater access to therapy with improved therapeutic outcomes. Our findings support the mounting literature that more patients should be offered office-based opioid therapy for opioid dependency.

Topics: Adult; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Community Health Services; Drug Combinations; Female; Humans; Internal Medicine; Male; Middle Aged; Naloxone; Narcotic Antagonists; Oklahoma; Opioid-Related Disorders; Treatment Outcome; Young Adult

Perinatal opioid use disorders negatively impact maternal and neonatal outcomes and are a public health problem of increasing severity. More than half of women with a substance use disorder have a history of posttraumatic stress disorder that, if not adequately addressed, can impede substance use disorder treatment. This case report describes complexities in the treatment of a pregnant woman with opioid use disorder and posttraumatic stress disorder and reviews the psychotherapeutic and pharmacologic approaches available to treat these co-occurring disorders in pregnancy. This case demonstrates the importance of early screening and intervention for co-occurring posttraumatic stress disorder in pregnant women who use substances in a closely coordinated, multidisciplinary approach to improve outcomes for women and their infants.

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Counseling; Female; Humans; Infant, Newborn; Narcotics; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Smoking; Smoking Cessation; Stress Disorders, Post-Traumatic; Treatment Outcome; Young Adult

Injection drug users (IDUs) are at increased risk of various medical conditions, including bacterial skin and soft tissue infections (SSTIs). SSTIs, which are painful and can lead to life-threatening complications, are common but scarcely studied.. To investigate life time, past 12 month and past 30-day prevalence for SSTI related to injection drug use, in IDUs at Malmö syringe exchange program (Malmö SEP). To investigate factors associated with having ever had an SSTI.. IDUs were recruited from Malmö SEP (N = 80). They participated in a survey with questions about demographics, drug use, and experience of SSTIs. Factors independently associated with self-reported SSTI ever were assessed using logistic regression analysis.. The lifetime reported prevalence of SSTI was 58%, past 12 months 30%, and past 30 days 14%. Factors independently associated with SSTI ever were age (adjusted odds ratio [AOR] = 1.09; 95% confidence interval [CI] = 1.01-1.18), female sex (AOR = 6.75; 95% CI = 1.40-32.47), having ever injected prescribed drugs (AOR = 52.15; 95% CI = 5.17-525.67), and having ever injected in the neck (AOR = 8.08; 95% CI = 1.16-56.08).. SSTI is common among IDUs in Malmö. Women and those injecting in the neck or injecting prescribed drugs (crushed tablets/liquids), are more likely to have had an SSTI.

Topics: Adult; Amphetamine-Related Disorders; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Drug Users; Female; Heroin Dependence; Housing; Humans; Ill-Housed Persons; Logistic Models; Male; Methadone; Methylphenidate; Middle Aged; Neck; Needle-Exchange Programs; Odds Ratio; Opioid-Related Disorders; Prescription Drugs; Prevalence; Sex Factors; Skin Diseases, Bacterial; Soft Tissue Infections; Substance Abuse, Intravenous; Surveys and Questionnaires; Sweden; Young Adult

Drug overdose is the leading cause of injury death in the United States, and most deaths are related to prescription drugs. A substantial proportion of these deaths involve opioid or benzodiazepine drugs, and many overdoses include a combination of both drug classes. Buprenorphine/naloxone has an unusual pharmacology that distinguishes it from other opioid drugs. Animal and human studies have found that buprenorphine is associated with a ceiling to its cardio-respiratory depressant effect at higher doses, such that it may have a wider safety margin compared to other opioid drugs. Compared to buprenorphine alone, buprenorphine/naloxone is associated with less cardiorespiratory depression. Drug safety data from the National Poison Data System, Drug Abuse Warning Network, and other sources suggest that the safety of buprenorphine/naloxone is favorable compared to the morbidity and mortality associated with other opioid drugs and other classes of psychotropic drugs.

Topics: Benzodiazepines; Buprenorphine, Naloxone Drug Combination; Drug Interactions; Drug Overdose; Humans; Opioid-Related Disorders; United States

Attention-deficit hyperactivity disorder (ADHD) is a risk factor for the development of substance use disorders. Treatment of ADHD with psychostimulants in patients on opioid maintenance treatment (OMT) has been restricted in Norway. We examined the use of prescribed drugs for ADHD in OMT patients and assessed co-medication with other psychotropics.. Data were drawn from the nationwide Norwegian Prescription Database (NorPD), which includes all prescriptions filled at pharmacies. The study population included subjects ≥18 years on OMT during 2008-2010.. In 2010, 6,116 patients received OMT and 2.8% of these also received ADHD drugs. This percentage is seven times greater than that in the gender- and age-specific general population of Norway. The prevalence was higher in the youngest patients, while there was no gender difference. Methylphenidate was the most commonly used drug for ADHD in OMT patients, followed by atomoxetine. 60% of OMT patients filled at least one prescription for antidepressants, anxiolytics or hypnotics, and percentages were similar for users and non-users of ADHD drugs.. Treatment with ADHD drugs was higher in OMT patients than expected from the general population, but was relatively low compared to the prevalence of ADHD in patients with substance use disorders reported in the literature.

Topics: Adolescent; Adult; Analgesics, Opioid; Attention Deficit Disorder with Hyperactivity; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Central Nervous System Stimulants; Databases, Factual; Female; Humans; Male; Methadone; Naloxone; Norway; Opiate Substitution Treatment; Opioid-Related Disorders; Prescription Drugs; Treatment Outcome; Young Adult

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

Buprenorphine/naloxone film was developed to improve retention in treatment and reduce public health risks over the tablet formulation for opioid dependence.. To compare patient persistence and resource utilization between formulations for the treatment of opioid dependence.. A longitudinal, retrospective cohort analysis was conducted to compare persistence and healthcare costs in a private US insurance claims database. Previously untreated patients, who initiated treatment with buprenorphine/naloxone following the introduction of the film, were classified in two groups according to the initial prescription. Persistence was defined as the proportion of patients continuing treatment for at least 6 months. Resource utilization and related costs were calculated over the 6- and 12-month periods after treatment initiation.. Film and tablet groups included 2796 and 1510 patients enrolled over 9.76 and 13.76 months on average, respectively, from initiation of treatment. Patient characteristics were similar between groups. Mean prescribed doses were 14.62 and 14.26 mg/day in film and tablet groups. Among patients enrolled for at least 6 months from the initial treatment, persistence rates were 63.78% with film vs 58.13% with tablet. Time to treatment discontinuation was longer in the film group, with a hazard ratio of 0.818 (p = 0.0005, 95% CI = [0.730;0.916]) adjusted for baseline characteristics. Patients treated with film had significantly more outpatient visits (+4%, p = 0.0185) and lower probability to be hospitalized (-17%, p = 0.0158), resulting in lower total healthcare costs over the 12-month period after initiation (-27%, p < 0.0001).. Patients treated with the film formulation of buprenorphine/naloxone appeared to stay longer on treatment, have a lower probability of hospital admission, and lower health care costs compared to patients treated with the tablet. This study, based on insurance claims data, has the advantage of reflecting real-world practice, but one cannot rule out the existence of bias due to differences in patient or prescriber profiles, despite adjustments made for observed characteristics at treatment initiation.

Topics: Adult; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Comorbidity; Drug Combinations; Female; Health Services; Humans; Insurance Claim Review; Male; Medication Adherence; Middle Aged; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Retrospective Studies; Tablets

I have a patient recently confirmed to be 6 weeks pregnant. For the past 6 months she has been treated for an opioid addiction with buprenorphine-naloxone combination. Should I be concerned about her exposure to this drug combination up to this point of the pregnancy? Should I switch her medication to methadone now that she is pregnant?. The limited data on buprenorphine exposure during pregnancy show no increased risk of adverse outcomes in the newborn. There are limited data on naloxone exposure during pregnancy; however, oral use is not expected to be associated with an increased risk of adverse pregnancy outcomes. Physicians treating pregnant women or women who become pregnant while they are stable taking buprenorphine-naloxone treatment are advised to continue this treatment but to consider transition to buprenorphine monotherapy.

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Contraindications; Drug Combinations; Female; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Pregnancy; Pregnancy Complications

Interviews with fourteen opioid retail pill sellers provides an exploration into the diversion and diffusion of Suboxone to recreational ("week-end warriors") drug users. The use of social media and electronic devices enables the diffusion of Suboxone to dependent and non-dependent opiate/opioid drug abusers. Overprescribing by physicians and prescribing in drug treatment settings fuels the diversion of Suboxone. The diversion and the diffusion of Suboxone have the potential to delay entrance into drug treatment and promote the misuse of the drug by both dependent opiate/opioid drug abusers and recreational users. The dilemma posed by Suboxone maintenance treatment will not be easily addressed or mitigated in the near future.

Topics: Adult; Attitude to Health; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Commerce; Crime; Female; Humans; Illicit Drugs; Male; Middle Aged; Naloxone; Narcotic Antagonists; New York City; Opioid-Related Disorders; Prescription Drug Diversion; Young Adult

Opioids are psychoactive analgesic drugs prescribed for pain relief and palliative care. Due to their addictive potential, effort and vigilance in controlling prescriptions is needed to avoid misuse and dependence. Despite the effort, the prevalence of opioid use disorder continues to rise. Opioid substitution therapies are commonly used to treat opioid dependence; however, there is minimal consensus as to which therapy is most effective. Available treatments include methadone, heroin, buprenorphine, as well as naltrexone. This systematic review aims to assess and compare the effect of all available opioid substitution therapies on the treatment of opioid dependence.. The authors will search Medline, EMBASE, PubMed, PsycINFO, Web of Science, Cochrane Library, Cochrane Clinical Trials Registry, World Health Organization International Clinical Trials Registry Platform Search Portal, and the National Institutes for Health Clinical Trials Registry. The title, abstract, and full-text screening will be completed in duplicate. When appropriate, multiple treatment comparison Bayesian meta-analytic methods will be performed to deduce summary statistics estimating the effectiveness of all opioid substitution therapies in terms of retention and response to treatment (as measured through continued opioid abuse).. Using evidence gained from this systematic review, we anticipate disseminating an objective review of the current available literature on the effectiveness of all opioid substitution therapies for the treatment of opioid use disorder. The results of this systematic review are imperative to the further enhancement of clinical practice in addiction medicine.. PROSPERO CRD42013006507.

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Heroin; Humans; Methadone; Naloxone; Naltrexone; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Research Design; Systematic Reviews as Topic

The buprenorphine/naloxone combination is used to treat the chronic relapsing disorder of opioid dependence. Adequate dosing levels are important to control cravings, prevent withdrawal syndrome, and maintain patients in treatment. The objective of this study was to estimate the impact of dosing on treatment persistence, resource utilization, and total direct health care costs.. A retrospective cohort analysis was performed using administrative claims extracted from the MarketScan and Clinformatics databases from January 2007 to June and November 2012. Patients initiating treatment with buprenorphine/naloxone were classified into 2 groups based on the prescribed average dose over the entire treatment period and matched by multiple criteria. The threshold for differentiating the dosing groups was set at 15 and 15.7 mg/day for publicly and privately insured patients, respectively. Resource utilization and related costs were calculated over the 12-month period after the treatment initiation.. Patient characteristics at baseline were considerably different between the privately and publicly insured patients. Publicly insured patients were slightly younger (33.1 vs 34.3 years old for privately insured) and had a higher prevalence of mental disorders (70.9% vs 64.9%). In both groups, patients treated with higher doses (> 15 mg and > 15.7 mg per day for publicly and privately insured patients, respectively) had lower risk of discontinuation (public: 11% lower; private: 9% lower) and lower probability of a psychiatric hospitalization than patients treated with lower doses (public: 17% lower; private: 41% lower). Total costs were comparable between the 2 groups (public: $14 600; private: $21 000) despite the expected higher cost of pharmacy in the higher-dose group.. Treatment with higher doses of buprenorphine/naloxone was associated with a longer time to treatment discontinuation, less resource use, and lower total medical costs despite higher pharmacy acquisition cost.

Topics: Adult; Age Factors; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Comorbidity; Dose-Response Relationship, Drug; Female; Health Expenditures; Health Services; Humans; Insurance Claim Review; Insurance, Health; Kaplan-Meier Estimate; Male; Medication Adherence; Mental Disorders; Naloxone; Opiate Substitution Treatment; Opioid-Related Disorders; Recurrence; Retrospective Studies

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; France; Humans; Naloxone; Opiate Substitution Treatment; Opioid-Related Disorders; Prescription Drug Misuse

We report here on a feasibility study of initiating buprenorphine/naloxone prior to release from incarceration and linking participants to community treatment providers upon release. The study consisted of a small number of Rhode Island (RI) prisoners (N = 44) diagnosed with opioid dependence. The study design is a single arm, open-label pilot study with a 6-month follow up interview conducted in the community. However, a natural experiment arose during the study comparing pre-release initiation of buprenorphone/naloxone to initiation post-release. Time to post-release prescriber appointment (mean days) for initiation of treatment outside Rhode Island Department of Corrections (RIDOC) versus inside RIDOC was 8.8 and 3.9, respectively (p = .1). Median post release treatment duration (weeks) for outside RIDOC versus inside RIDOC was 9 and 24, respectively (p = .007). We conclude that initiating buprenorphine/naloxone prior to release from incarceration may increase engagement and retention in community-based treatment.

Topics: Adult; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Community Health Services; Feasibility Studies; Female; Follow-Up Studies; Humans; Male; Middle Aged; Naloxone; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Compliance; Pilot Projects; Prisoners; Rhode Island; Time Factors

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Female; Humans; Indians, North American; Male; Naloxone; Narcotic Antagonists; Ontario; Opiate Substitution Treatment; Opioid-Related Disorders; Oxycodone; Prescription Drug Misuse

Topics: Adolescent; Adult; Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Canada; Drug Combinations; Humans; Naloxone; Opioid-Related Disorders; Population Groups; Prescription Drug Misuse; Rural Health; Treatment Outcome

Addictions to illicit drugs are among the nation's most critical public health and societal problems. The current opioid prescription epidemic and the need for buprenorphine/naloxone (Suboxone®; SUBX) as an opioid maintenance substance, and its growing street diversion provided impetus to determine affective states ("true ground emotionality") in long-term SUBX patients. Toward the goal of effective monitoring, we utilized emotion-detection in speech as a measure of "true" emotionality in 36 SUBX patients compared to 44 individuals from the general population (GP) and 33 members of Alcoholics Anonymous (AA). Other less objective studies have investigated emotional reactivity of heroin, methadone and opioid abstinent patients. These studies indicate that current opioid users have abnormal emotional experience, characterized by heightened response to unpleasant stimuli and blunted response to pleasant stimuli. However, this is the first study to our knowledge to evaluate "true ground" emotionality in long-term buprenorphine/naloxone combination (Suboxone™). We found in long-term SUBX patients a significantly flat affect (p<0.01), and they had less self-awareness of being happy, sad, and anxious compared to both the GP and AA groups. We caution definitive interpretation of these seemingly important results until we compare the emotional reactivity of an opioid abstinent control using automatic detection in speech. These findings encourage continued research strategies in SUBX patients to target the specific brain regions responsible for relapse prevention of opioid addiction.

Topics: Behavior, Addictive; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Emotions; Female; Humans; Male; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Speech

Buprenorphine is associated with enhanced human immunodeficiency virus (HIV) treatment outcomes including increased antiretroviral therapy initiation rates, adherence, and CD4 cell counts among HIV-infected opioid-dependent individuals. Buprenorphine facilitates hepatitis C virus (HCV) treatment in opioid-dependent patients with HCV monoinfection. Less is known about buprenorphine's role in HIV/HCV coinfection.. We conducted a retrospective chart review to evaluate HCV care for HIV-infected buprenorphine patients in the first 4 years of buprenorphine's integration into a Rhode Island HIV clinic.. Sixty-one patients initiated buprenorphine. All had HCV antibody testing; 57 (93%) were antibody-positive. All antibody-positive patients underwent HCV RNA testing; 48 (84%) were RNA-positive. Of these, 15 (31%) were not referred to HCV care. Among chronically infected patients, 3 received HCV treatment after buprenorphine; all had cirrhosis and none achieved viral eradication. At buprenorphine induction, most patients had inadequately controlled HIV infection, with detectable HIV RNA (59%) or CD4 cell count less than or equal to 350/μL (38%).. Buprenorphine has shown limited success to date as a bridge to HCV treatment within an HIV clinic. Buprenorphine's stabilization of opioid dependence and HIV disease may permit the use of HCV therapy over time.

Topics: Adult; Antiretroviral Therapy, Highly Active; Antiviral Agents; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Comorbidity; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Hepatitis C, Chronic; HIV Infections; Humans; Male; Middle Aged; Naloxone; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Retrospective Studies; Substance Withdrawal Syndrome

Abuse of opioids has become a public health crisis. The historic separation between the addiction and pain communities and a lack of training in medical education have made treatment difficult to provide, especially in primary care. The Co-occurring Disorders Clinic (COD) was established to treat patients with co-morbid chronic pain and addiction. This retrospective chart review reports results of a quality improvement project using buprenorphine/naloxone to treat co-occurring chronic non-cancer pain (CNCP) and opioid dependence in a primary care setting. Data were collected for 143 patients who were induced with buprenorphine/naloxone (BUP/NLX) between June 2009 and November 2011. Ninety-three patients (65%) continued to be maintained on the medication and seven completed treatment and were no longer taking any opioid (5%). Pain scores showed a modest, but statistically significant improvement on BUP/NLX, which was contrary to our expectations and may be an important factor in treatment retention for this challenging population.

Topics: Adult; Aged; Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Chronic Pain; Female; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Pain Measurement; Prescription Drugs; Primary Health Care; Quality Improvement; Retrospective Studies; Treatment Outcome

Previous studies have not examined patterns of pain treatment use among patients seeking office-based buprenorphine-naloxone treatment (BNT) for opioid dependence.. To examine, among individuals with pain seeking BNT for opioid dependence, the use of pain treatment modalities, perceived efficacy of prior pain treatment, and interest in pursuing pain treatment while in BNT.. A total of 244 patients seeking office-based BNT for opioid dependence completed measures of demographics, pain status (ie, "chronic pain (CP)" [pain lasting at least 3 months] vs "some pain (SP)" [pain in the past week not meeting the duration criteria for chronic pain]), pain treatment use, perceived efficacy of prior pain treatment, and interest in receiving pain treatment while in BNT.. In comparison with the SP group (N = 87), the CP group (N = 88) was more likely to report past-week medical use of opioid medication (adjusted odds ratio [AOR] = 3.2; 95% CI, 1.2-8.4), lifetime medical use of nonopioid prescribed medication (AOR = 2.2; 95% CI, 1.1-4.7), and lifetime use of prayer (AOR = 2.8; 95% CI, 1.2-6.5) and was less likely to report lifetime use of yoga (AOR = 0.2; 95% CI, 0.1-0.7) to treat pain. Although the 2 pain groups did not differ on levels of perceived efficacy of prior lifetime pain treatments, in comparison with the SP group, the CP group was more likely to report interest in receiving pain treatment while in BNT (P < 0.001).. Individuals with pain seeking BNT for opioid dependence report a wide range of conventional, complementary, and alternative pain-related treatments and are interested (especially those with CP) in receiving pain management services along with BNT.

Topics: Adult; Analgesics; Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Chronic Pain; Combined Modality Therapy; Comorbidity; Complementary Therapies; Female; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Primary Health Care; Treatment Outcome; Utilization Review

Chronology of important historical events in Bosnia and Herzegovina during past two centuries indirectly influenced the incidence and prevalence of different psychoactive substances use and thus the organization of services for the treatment of persons who develop addiction symptoms. The organization of health system in the last war, 1992-1995, suffered enormous damage and the reform process which inevitably followed, included the area of mental health care services and the establishment of network of centers for mental health in the community (CMHC). The centers are functioning within the primary health care almost in whole country, with specialized centers for the prevention and treatment of addicts and the therapeutic communities, which today represents the basic organizational units to help people who have drug related issues. In this paper we will present the possibility of treatment of drug addicts in Bosnia and Herzegovina, from consulting services, psycho-education and early detection of disease, detoxification and substitution programs with Methadone and Suboxone, as well as programs of rehabilitation and resocialization. Although a very complicated political and administrative structure of the country, insufficient financial support, pronounced stigmatization of addicts, insufficient staffing and number of treatment centers are objective obstacles for progress in treatment of addicts, we believe that, with existing resources, these constraints can be converted into new opportunities in terms of improvement of treatment options in the future.

Topics: Adult; Analgesics, Opioid; Bosnia and Herzegovina; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Community Mental Health Centers; Humans; Mental Health Services; Methadone; Naloxone; Opiate Substitution Treatment; Opioid-Related Disorders; Treatment Outcome

To present medically assisted treatment for opiate addiction with substitution medicament Suboxone and prevention of social exclusion of young opiate addicts in Bosnia and Herzegovina.. Until recently there was no solution for long-term and comprehensive treatment of young persons who suffer from opiate addiction. This is not an illness that impairs only psychological and physical health of addicts with possible fatal aftermaths, but serious societal problem due to its consequences such as delinquency, crimes and violence that lead young people to social exclusion. There are no capacities within the existing health facilities for long-term stationary treatment, which is necessary for drug addiction. In addition, far less adequate solution is placement of young addicts into penal and correctional institutions, which are stigmatizing and contribute to their exclusion from normal social life. Hence, the latest medically assisted method of substitution treatment with a combination of buprenorphine and naloxone (Suboxone) is introduced. This medicament, with its characteristics, offers possibility for outpatient treatment, and prompt and effective results of detoxification and weaning of opiates is to be achieved. Opiate addicts that undergo this treatment benefit from "clear mind" and capability for occupational and social activities, which significantly improves the quality of their family and social relations. With Suboxone substitution method, the institutional (inpatient) treatment is to be avoided and social exclusion of young addicts treated with Suboxone prevented.. Medically assisted treatment for opiate addiction with Suboxone is conducted in outpatient setting with the involvement of close relatives who are not addicted. It brings back "clear mind" to previous addicts, does not stigmatize but contribute to re-socialization and prevention of social exclusion of young opiate addicts.

Topics: Adult; Analgesics, Opioid; Bosnia and Herzegovina; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Humans; Naloxone; Opiate Substitution Treatment; Opioid-Related Disorders; Outpatients; Social Isolation; Treatment Outcome; Young Adult

Although many in the addiction treatment field use the term "medication-assisted treatment" to describe a combination of pharmacotherapy and counseling to address substance dependence, research has demonstrated that opioid agonist treatment alone is effective in patients with opioid dependence, regardless of whether they receive counseling. The time has come to call pharmacotherapy for such patients just "treatment". An explicit acknowledgment that medication is an essential first-line component in the successful management of opioid dependence.

Topics: Behavior, Addictive; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Counseling; Humans; Methadone; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Substance-Related Disorders

Diversion and injection of buprenorphine (Subutex(®)) and buprenorphine-naloxone (Suboxone(®)) have been well documented. Recent international research and local anecdotal evidence suggest that these medications are also used by other routes of administration, including smoking and snorting.. A cross-sectional sample of 440 opioid substitution treatment (OST) clients was recruited through pharmacies and clinics in three Australian jurisdictions, and interviewed face-to-face using a structured questionnaire. Eligible participants were those aged 18 or over, who had resided in their home state for at least six months, and had been in their current treatment episode for at least 4 weeks. We compared differences in characteristics between clients who had ever inhaled (smoked or snorted) buprenorphine (including buprenorphine-naloxone) and other OST clients. Logistic regression was used to identify correlates of buprenorphine inhalation. Sixty-eight clients who had never used buprenorphine were excluded from analysis.. Sixty-five clients (18%) reported having ever inhaled buprenorphine, with Subutex(®) smoking being most common, reported by 50 clients (77%). In multivariable logistic regression, those who reported ever inhaling buprenorphine were significantly more likely to: be aged 35 or younger, have ever been in prison and have ever injected buprenorphine. Clients from New South Wales and Victoria were significantly less likely to have ever inhaled buprenorphine than those from South Australia.. Our data indicates that the inhalation of buprenorphine has occurred in a significant minority of Australian OST clients. The motivations, contexts and potential health consequences of buprenorphine use by these atypical routes of administration, particularly in a correctional setting, warrant further exploration.

Topics: Administration, Inhalation; Administration, Intranasal; Adult; Age Factors; Analgesics, Opioid; Australia; Behavior, Addictive; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cross-Sectional Studies; Drug Users; Female; Humans; Interviews as Topic; Logistic Models; Male; Methadone; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Prevalence; Prisons; Product Surveillance, Postmarketing; Risk Assessment; Risk Factors; Smoking; Substance Abuse Treatment Centers

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

This study was part of a national, multisite demonstration project evaluating the impact of integrated buprenorphine/naloxone treatment and HIV care. The goals of this study were to describe the baseline demographic, clinical, and substance use characteristics of the participants and to explore HIV transmission risk behaviors in this group.. Nine sites across the United States participated. Data obtained by interview and chart review included demographic information, medical history, substance use, and risk behaviors.We performed a descriptive analysis of patient characteristics at entry and used logistic regression to evaluate factors associated with 1) unprotected anal or vaginal sex; and 2) needle-sharing within the previous 90 days.. Three hundred eighty-six individuals were included in the study: 303 (78.5%) received buprenorphine/naloxone; 41 (10.6%) received methadone; and 42 (10.9%) received another form of treatment. The analysis of risk behaviors was limited to those in the buprenorphine group (n = 303). Among those reporting vaginal or anal sex in the previous 90 days, 24% had sex without a condom. Factors significantly associated with unprotected sex were: having a partner; female gender; and alcohol use in previous 30 days. A total of 8.9% of participants shared needles in the previous 90 days. Factors significantly associated with needle-sharing were: amphetamine use; marijuana use; homelessness; and anxiety.. Addressing transmission risk behaviors is an important secondary HIV prevention strategy. In addition to treatment for opioid dependence, addressing other substance use, social issues, particularly housing, and mental health may have important implications for reducing HIV transmission in HIV-infected opioid-dependent patients.

Topics: Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cross-Sectional Studies; Female; HIV Infections; Humans; Male; Methadone; Middle Aged; Naloxone; Narcotic Antagonists; Needle Sharing; Odds Ratio; Opiate Substitution Treatment; Opioid-Related Disorders; Risk-Taking; Unsafe Sex

Opioid dependence and HIV infection are associated with poor health-related quality of life (HRQOL). Buprenorphine/naloxone (bup/nx) provided in HIV care settings may improve HRQOL.. We surveyed 289 HIV-infected opioid-dependent persons treated with clinic-based bup/nx about HRQOL using the Short Form Health Survey (SF-12) administered at baseline, 3, 6, 9, and 12 months. We used normalized SF-12 scores, which correspond to a mean HRQOL of 50 for the general US population (SD 10, possible range 0-100). We compared mean normalized mental and physical composite and component scores in quarters 1, 2, 3, and 4 with baseline scores using generalized estimating equation models. We assessed the effect of clinic-based bup/nx prescription on HRQOL composite scores using mixed effects regression with site as random effect and time as repeated effect.. Baseline normalized SF-12 scores were lower than the general US population for all HRQOL domains. Average composite mental HRQOL improved from 38.3 (SE 12.5) to 43.4 (SE 13.2) [β 1.13 (95% CI: 0.72 to 1.54)] and composite physical HRQOL remained unchanged [β 0.21 (95% CI: -0.16 to 0.57)] over 12 months follow-up. Continued bup/nx treatment across all 4 quarters was associated with improvements in both physical [β 2.38 (95% CI: 0.63 to 4.12)] and mental [β 2.51 (95% CI: 0.42 to 4.60)] HRQOL after adjusting for other contributors to HRQOL.. Clinic-based bup/nx maintenance therapy is potentially effective in ameliorating some of the adverse effects of opioid dependence on HRQOL for HIV-infected populations.

Topics: Adult; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Female; HIV Infections; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Quality of Life

Research has shown that buprenorphine/naloxone (bup/nx) is a safe and effective treatment for opioid dependence. Few reports, however, describe the patient perspective on bup/nx treatment and its integration into HIV care settings.. We conducted qualitative interviews with 33 patients to further investigate patient satisfaction and experience with bup/nx treatment and integrated care. Interviews focused on drug use/cessation history; attitudes toward and satisfaction with bup/nx treatment; and perspectives on integrated bup/nx treatment and HIV care.. Patients were overwhelmingly satisfied with the pharmacologic effects and treatment outcomes of bup/nx, including effectiveness in blocking cravings and controlling opioid use; decreased fear of withdrawal and/or missing doses; and an overall improvement in quality of life. Patients also described being more engaged with both their substance abuse treatment and HIV care, including greater ability to manage their own treatment, keep, appointments, and adhere to antiretroviral medication regimes. Counseling was seen by some patients as an important component of bup/nx treatment. Nearly all were positive about their experience with integrated care, appreciative of an improved drug treatment environment, convenience, and quality of care.. Findings suggest that patients report bup/nx to be a viable treatment and many prefer it to other opioid replacement therapies.

Topics: Adult; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Counseling; Data Collection; Female; HIV Infections; Humans; Interviews as Topic; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Satisfaction

The safety of buprenorphine/naloxone (bup/nx) in HIV-infected patients has not been established. Prior reports raise concern about hepatotoxicity and interactions with atazanavir.. We conducted a prospective cohort study of 303 opioid-dependent HIV-infected patients initiating bup/nx treatment. We assessed changes in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) over time. We compared bup/nx doses in patients receiving the antiretroviral atazanavir to those not receiving atazanavir. We conducted surveillance for pharmacodynamic interactions.. Median AST [37.0 vs. 37.0 units/liter (U/L) respective interquartile ranges (IQRs) 26-53 and 26-59] and ALT (33.0 vs. 33.0 U/L, respective IQRs 19-50 and 18-50) values did not change over time among 141 patients comparing pre-bup/nx exposure with post-bup/nx exposure measures. During bup/nx exposure, 207 subjects demonstrated no significant change in median AST (36.0 vs. 35.0 U/L, respective IQRs 25-57 and 25-61) and ALT (29.0 vs. 31.0 U/L, respective IQRs 19-50 and 18-50) values collected a median of 6 months apart. Analyses restricted to patients with hepatitis C and HIV co-infection yielded similar results, except a small but significant decrease in first to last AST, during treatment with bup/nx (P = 0.048). Mean bup/nx dose, ranging 16.0-17.8 mg, did not differ over time or with co-administration of atazanavir. No pharmacodynamic interactions were noted.. Buprenorphine/naloxone did not produce measurable hepatic toxicity or pharmacodynamic interaction with atazanavir in HIV-infected opioid-dependent patients.

Topics: Anti-HIV Agents; Atazanavir Sulfate; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Chemical and Drug Induced Liver Injury; Cohort Studies; Dose-Response Relationship, Drug; Drug Interactions; HIV Infections; Humans; Naloxone; Oligopeptides; Opioid-Related Disorders; Pyridines

Cocaine use is common in opioid-dependent HIV-infected patients, but its impact on treatment outcomes in these patients receiving buprenorphine/naloxone is not known.. We conducted a prospective study in 299 patients receiving buprenorphine/naloxone who provided baseline cocaine data and a subset of 266 patients who remained in treatment for greater than or equal to one quarter. Assessments were conducted at baseline and quarterly for 1 year. We evaluated the association between baseline and in-treatment cocaine use on buprenorphine/naloxone retention, illicit opioid use, antiretroviral adherence, CD4 counts, HIV RNA, and risk behaviors.. Sixty-six percent (197 of 299) of patients reported baseline cocaine use and 65% (173 of 266) of patients with follow-up data reported in-treatment cocaine use. Baseline and in-treatment cocaine use did not impact buprenorphine/naloxone retention, antiretroviral adherence, CD4 lymphocytes, or HIV risk behaviors. However, baseline cocaine use was associated with a 14.8 (95% confidence interval [CI], 9.0-24.2) times greater likelihood of subsequent cocaine use (95% CI, 9.0-24.2), a 1.4 (95% CI, 1.02-2.00) times greater likelihood of subsequent opioid use, and higher log10 HIV RNA (P < 0.016) over time. In-treatment cocaine use was associated with a 1.4 (95% CI, 1.01-2.00) times greater likelihood of concurrent opioid use.. Given cocaine use negatively impacts opioid and HIV treatment outcomes, interventions to address cocaine use in HIV-infected patients receiving buprenorphine/naloxone treatment are warranted.

Topics: Adult; Anti-HIV Agents; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cocaine-Related Disorders; Female; HIV Infections; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Needle Sharing; Opiate Substitution Treatment; Opioid-Related Disorders; Prospective Studies; Risk Factors; Treatment Outcome; Unsafe Sex

Replication of effective practices requires detailed descriptions of implementation processes, barriers and facilitators, and lessons learned. The experiences of physicians leading the Buprenorphine HIV Evaluation and Support initiative provides valuable information for other HIV providers seeking to integrate medication-assisted treatment services into HIV clinical care.. Evaluation staff conduced site visits to the 10 funded Buprenorphine HIV Evaluation and Support programs to better understand buprenorphine/naloxone (bup/nx) integration practices; services offered; staffing; provider experiences with and perceptions of bup/nx; perceived barriers, facilitators, and sustainability; and recommendations regarding replication of integrated care program components. Interviews with site principal investigators conducted during the last year of program implementation were transcribed, coded, and analyzed according to both pre-identified and emerging themes.. Integrated bup/nx and HIV treatment was successfully introduced to community and hospital-based clinics under the direction of infectious disease, psychiatry, and general internal medicine physicians. All but 1 of the principal investigators interviewed were highly satisfied with integrated HIV and bup/nx treatment, and all anticipated continued provision of the service. Multiple prescribers were necessary to ensure sufficient coverage and a bup/nx coordinator (eg, nurse, counselor) was seen as essential to the provision of quality care. Ongoing challenges included multisubstance use and mental health issues among patients; limited adoption of bup/nx treatment among colleagues; and the necessity of incorporating new procedures, including urine toxicology testing into established practice.. Findings suggest that integrated bup/nx treatment and HIV care is acceptable to providers and feasible in a variety of practice settings.

Topics: Ambulatory Care; Anti-HIV Agents; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Delivery of Health Care, Integrated; Health Resources; Health Services Needs and Demand; HIV Infections; Humans; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Primary Health Care; Substance Abuse Treatment Centers; United States

Opioid-dependent HIV-infected patients are less likely to receive HIV quality of care indicators (QIs) compared with nondependent patients. Buprenorphine/naloxone maintenance therapy (bup/nx) could affect the quality of HIV care for opioid-dependent patients.. We abstracted 16 QIs from medical records at nine HIV clinics 12 months before and after initiation of bup/nx versus other treatment for opioid dependence. Summary quality scores (number of QIs received/number eligible × 100) were calculated. We compared change in QIs and summary quality scores in patients receiving bup/nx versus other participants.. One hundred ninety-four of 268 participants (72%) received bup/nx and 74 (28%) received other treatment. Mean summary quality scores increased over 12 months for participants receiving bup/nx (45.6% to 51.6%, P < 0.001) but not other treatment (48.6% to 47.8%, P = 0.788). Bup/nx participants experienced improvements in six of 16 HIV QIs versus three of 16 QIs in other participants. Improvements were mostly in preventive and monitoring care domains. In multivariable analysis, bup/nx was associated with improved summary quality score (β 8.55; 95% confidence interval, 2.06-15.0).. In this observational cohort study, HIV-infected patients with opioid dependence received approximately half of HIV QIs at baseline. Buprenorphine treatment was associated with improvement in HIV QIs at 12 months. Integration of bup/nx into HIV clinics may increase receipt of high-quality HIV care. Further research is required to assess the effect of improved quality of HIV care on clinical outcomes.

Topics: Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cohort Studies; Female; Guideline Adherence; HIV Infections; Humans; Male; Middle Aged; Multivariate Analysis; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Practice Guidelines as Topic; Quality of Health Care

Implementing integrated HIV and buprenorphine/naloxone treatment requires cost estimates to plan and obtain funding.. We identified costs incurred at HIV clinical sites participating in a cross-site evaluation of integrated care that followed patients for 1 year. Costs include labor, overhead, and urine toxicology analyses (clinic perspective), buprenorphine/naloxone (payer perspective) and patient time and transportation (patient perspective). Sites provided resource utilization quarterly, and providers estimated time required for each activity. With site as the unit of analysis, results are reported as median (range) of average site costs in 2008 US dollars.. The median number of monthly provider encounters for integrated care patients was 3.2 (1.5-13.3) compared with 1.7 (1.1-4.2) for similar patients not in integrated care, but integrated care patients had fewer physician encounters. Median monthly clinic costs per integrated care patient were $136 ($67-$677) for labor and overhead and $8 ($2-$23) for toxicology analyses, $22 higher than clinic costs for patients not in integrated care. Median monthly costs for buprenorphine/naloxone were $209 ($165-$272), and monthly patient costs in integrated care were $11 ($1-$54) higher.. Integrated HIV and buprenorphine/naloxone treatment requires different resources, including costs that are not third-party reimbursed. Implementing integrated care will require funding for training and for new staff such as buprenorphine coordinators, in addition to reimbursement for buprenorphine/naloxone. Further research is needed to identify potential cost offsets outside of the clinic setting.

Topics: Anti-HIV Agents; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Delivery of Health Care, Integrated; Health Care Costs; HIV Infections; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders

Physicians' adoption of buprenorphine/naloxone treatment is hindered by concerns over feasibility, cost, and lack of comfort treating patients with addiction. We examined the use of buprenorphine/naloxone in a community practice by two generalist physicians without addiction training, employing a retrospective chart review. From 2006-2010, 228 patients with opiate abuse/dependence were treated with buprenorphine/naloxone using a home-induction protocol. Multiple co-morbidities including diabetes (23% of patients), hypertension (36%), Hepatitis C (43%), and depression (74%) were concurrently managed. In this diverse sample, 1/228 experienced precipitated withdrawal during induction. Of the convenience subsample analyzed (n = 28), 82% (+/-10%) had negative urine drug tests for opioids; 92% (+/-11%) were negative for cocaine; 88% (+/-12%) were positive for buprenorphine. This case series demonstrated feasibility and safety of a low-cost buprenorphine/naloxone home induction protocol employed by generalists. Concurrent treatment of multiple comorbidities conforms with the patient-centered medical home ideal. Randomized trials of this promising approach are needed.

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Comorbidity; Drug Combinations; Humans; Naloxone; Opioid-Related Disorders; Primary Health Care; Retrospective Studies; Self Administration

Opiate dependence (OD) and borderline personality disorder (BPD), separately and together, are significant public health problems with poor treatment outcomes. BPD is associated with difficulties in emotion regulation, and brain-imaging studies in BPD individuals indicate differential activation in prefrontal cingulate cortices and their interactions with limbic regions. Likewise, a similar network is implicated in drug cue responsivity in substance abusers. The present, preliminary study used functional MRI to examine activation of this network in comorbid OD/BPD participants when engaged in an "oddball" task that required attention to a target in the context of emotionally negative distractors. Twelve male OD/BPD participants and 12 male healthy controls participated. All OD/BPD participants were taking the opiate replacement medication Suboxone, and a subset of participants was positive for substances of abuse on scan day. Relative to controls, OD/BPD participants demonstrated reduced activation to negative stimuli in the amygdala and anterior cingulate. Unlike previous studies that demonstrated hyperresponsivity in neural regions associated with affective processing in individuals with BPD versus healthy controls, comorbid OD/BPD participants were hyporesponsive to emotional cues. Future studies that also include BPD-only and OD-only groups are necessary to help clarify the individual and potentially synergistic effects of these two conditions.

Topics: Adult; Analysis of Variance; Arousal; Borderline Personality Disorder; Brain Mapping; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Case-Control Studies; Comorbidity; Cues; Drug Combinations; Emotions; Functional Laterality; Humans; Limbic System; Magnetic Resonance Imaging; Male; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Reaction Time; Self Report

To evaluate the economic impact of buprenorphine/naloxone (B/N) as an agonist opioid treatment for opiate dependence.. A budgetary impact analysis model was designed to calculate the annual costs (drugs and associated costs) to the Spanish National Healthcare System of methadone versus B/N. Data for the model were obtained from official databases and expert panel opinion.. It was estimated that 86,017 patients would be in an agonist opioid treatment program each of the 3 years of the study. No increase in the number of patients is expected with the introduction of B/N combination. The budgetary impact (drugs and associated costs) for agonist opiate treatment in the first year of the study would be 89.53 million EUR. In the first year of B/N use, the budgetary impact would rise by 4.39 million EUR (4.6% of the total impact), with an incremental cost of 0.79 million EUR (0.9% of the total impact). The budgetary increase would be 0.6% (0.48 million EUR increase) and 0.6% (0.49 million EUR increase) in the second and third years of use, respectively. The mean cost per patient in the first year with and without B/N would be EUR 1,050 and 1,041, respectively. The most influential variables in the sensitivity analysis were logistics and production costs of methadone and the percentage use of B/N.. With an additional cost of only EUR 9 per patient, B/N is an efficient addition to the therapeutic arsenal in the drug treatment of opiate dependence, particularly when considering clinical aspects of novel pharmacotherapy.

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

The National Institute on Drug Abuse (NIDA) established the National Drug Abuse Treatment Clinical Trials Network (CTN) in 1999 to bring researchers and treatment providers together to develop a clinically relevant research agenda. Initial CTN efforts addressed the use of buprenorphine, a mu-opioid partial agonist, as treatment for opioid dependence. Strong evidence of buprenorphine's therapeutic efficacy was demonstrated in clinical trials involving several thousand opioid-dependent participants, and in 2002, the Food and Drug Administration approved buprenorphine for the treatment of opioid dependence. With the advent of a sublingual tablet containing both buprenorphine and naloxone to mitigate abuse and diversion (Suboxone), buprenorphine appeared poised to be the first-line treatment for opioid addiction. Notwithstanding its many attributes, certain implementation barriers remained to be addressed in CTN studies, and these efforts have brought a body of knowledge on buprenorphine to frontline clinicians. The purpose of this article is to review CTN-based buprenorphine research and related efforts to overcome challenges to the implementation of buprenorphine therapy in mainstream practice. Furthermore, this article explores current issues and future challenges that may require additional CTN efforts.

Topics: Administration, Sublingual; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Clinical Trials as Topic; Community Health Services; Drug Combinations; Humans; Naloxone; Narcotic Antagonists; Narcotics; National Institute on Drug Abuse (U.S.); Opioid-Related Disorders; Receptors, Opioid, mu; United States

Pain complaints are common among individuals with opioid dependence. However, few studies investigate pain during opioid detoxification or the impact this pain has on continued opioid use. This secondary analysis utilized data from two Clinical Trials Network randomized controlled trials of buprenorphine-naloxone for short-term opioid detoxification to examine the extent to which pain was associated with continued opioid use during and immediately following a 13-day detoxification protocol. At follow-up, more severe pain was associated with a greater number of self-reported days of opioid use during the prior 30 days (p < .05) but was not associated with urine toxicology results collected at follow-up. These results, although mixed, have potentially important clinical implications for assessing and addressing pain during opioid detoxification. Pain that is experienced during and immediately following medically monitored detoxification may be associated with continued opioid use. These findings lend further support for continued research on pain among patients with opioid dependence.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Drug Combinations; Female; Follow-Up Studies; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Pain; Randomized Controlled Trials as Topic; Severity of Illness Index; Substance Withdrawal Syndrome

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Drug Tolerance; Humans; Methadone; Naloxone; Opioid-Related Disorders; Pain; Pain Measurement

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Documentation; Humans; Naloxone; Opioid-Related Disorders; Pain; Patient Compliance; Practice Guidelines as Topic; Prescription Drugs

Diversion of buprenorphine (BPN) has been described in settings where it is legally prescribed and has resulted in increasing concern. To address this concern, co-formulation of buprenorphine/naloxone (BPN/NLX) replaced buprenorphine alone in Malaysia in December 2006.. To assess the significance of BPN/NLX introduction, 41 BPN/NLX injectors in Kuala Lumpur, Malaysia were recruited using a modified snowball recruitment technique.. In January 2007, all subjects had previously injected BPN alone. During the transition from injecting BPN alone to co-formulated BPN/NLX, the mean daily BPN injection dose increased from 1.88 mg (range 1.0-4.0 mg) to 2.49 mg/day (p < .001). Overall, 18 (44%) subjects increased their daily amount of injection while 22 (54%) had no change in dose; only one subject reduced the amount of injection. Development of opioid withdrawal symptoms was the primary outcome, however the only symptom that was significantly associated with BPN/NLX dosage was the report of "stomach pains" (p = .01). In logistic regression analysis, the development of opioid withdrawal symptoms was associated with increased benzodiazepine injection and increased syringe sharing.. These data suggests that the introduction of BPN/NLX did not reduce injection related risk behaviors such as syringe sharing and was associated with increased benzodiazepine use. Evidence-based approaches to treat BPN injection are urgently needed.

Topics: Adult; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Drug Combinations; Humans; Logistic Models; Malaysia; Male; Middle Aged; Naloxone; Narcotic Antagonists; Needle Sharing; Opioid-Related Disorders; Risk-Taking; Substance Abuse, Intravenous; Substance Withdrawal Syndrome; Young Adult

Assessing social risks has proven difficult for IRBs. We undertook a novel effort to empirically investigate social risks before an HIV prevention trial among drug users in Thailand and China. The assessment investigated whether law, policies and enforcement strategies would place research subjects at significantly elevated risk of arrest, incarceration, physical harm, breach of confidentiality, or loss of access to health care relative to drug users not participating in the research. The study validated the investigator's concern that drug users were subject to serious social risks in the site localities, but also suggested that participation in research posed little or no marginal increase in risk and might even have a protective effect. Our experience shows that it is feasible to inform IRB deliberations with actual data on social risks, but also raises the question of whether and when such research is an appropriate use of scare research resources.

Topics: Adult; Buprenorphine; Buprenorphine, Naloxone Drug Combination; China; Confidentiality; Conflict of Interest; Counseling; Ethics Committees, Research; Ethics, Research; Female; Financing, Government; Health Services Accessibility; HIV Infections; Human Rights; Humans; Informed Consent; International Cooperation; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Patient Selection; Randomized Controlled Trials as Topic; Research Design; Research Subjects; Risk Assessment; Risk Reduction Behavior; Social Environment; Thailand; United States; Vulnerable Populations

Suboxone (Buprenorphine/naloxone) is a novel drug used in opiate substitution therapy. In Hungary, it was introduced in November 2007. Suboxone is a product for sublingual administration containing the partial mu-receptor agonist buprenorphine and antagonist naloxone in a 4:1 ratio.. Objectives of our study were to monitor and evaluate the effects of Suboxone treatment.. 6 outpatient centers participated in the study, 3 from Budapest and 3 from smaller cities in Hungary. At these centers, all patients entering Suboxone maintenance therapy between November 2007 and March 2008, altogether 80 persons (55 males, 35 females, mean age = 30.2 years, SD=5.48) were included in the study sample. During the 6-month period of treatment, data were collected 4 times; when entering treatment, 1 month, 3 months, and 6 months after entering treatment. Applied measures were the Addiction Severity Index, SCID-I, SCID-II, Hamilton Depression Scale, Hamilton Anxiety Scale, STAI-S State Anxiety Inventory, Beck Depression Inventory, Heroin Craving Questionnaire, WHO Well-being Inventory, Perceived Stress Scale, ADHD retrospective questionnaire, TCI short version, and Ways of Coping questionnaire.. Nearly fourth of the altogether 80 heroin dependent patients (18 persons, 22.5%) dropped out of treatment during the first month (the majority, 12 persons [15%] during the first week) or chose methadone substitution instead. Following this period however, dropout rate decreased and the six-month treatment period was completed by 32 patients (40%). During the first month of treatment significant positive changes were experienced in all studied psychological and behavioral dimensions that proved to be stabile throughout the studied period.. According to the early experience with Suboxone treatment, it is a well tolerable and successfully applicable drug in the substitution therapy of opiate addicts. A critical phase seems to be the first one or two weeks of treatment. Dropout rate is high during this early period, while after a successful conversion clients presumably remain in therapy for a long period. At the beginning of administration special emphasis must be put on informing patients, especially concerning withdrawal symptoms that might be present during the first week, which highly contributes to better retention in treatment.

Topics: Adult; Anxiety; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Depression; Drug Combinations; Female; Humans; Hungary; Irritable Mood; Male; Naloxone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Psychiatric Status Rating Scales; Stress, Psychological; Substance Abuse Treatment Centers; Surveys and Questionnaires; Treatment Outcome

The purpose of this article was to characterize practices of buprenorphine/naloxone (B/N) diversion in a region with a high prescribing prevalence. A cross-sectional, open-ended survey was administered to individuals entering opioid addiction treatment programs in two New England states. The authors obtained formative information about the knowledge, attitudes, beliefs, practices, and street economy of B/N diversion. The authors interviewed 51 individuals, 49 of which were aware of B/N medication. Of that number, 100% had diverted B/N to modulate opiate withdrawal symptoms arising from attempted "self-detoxification," insufficient funds to purchase preferred illicit opioids, or inability to find a preferred source of drugs. Thirty of 49 (61%) participants obtained the illicit drug from an individual holding a legitimate prescription for B/N. A high proportion of individuals in the study locations who sought treatment for opioid addiction self-reported the purchase and use of diverted B/N. The diversion of B/N may be minimized by modifying educational, treatment, monitoring, and dispensing practices.

Topics: Adult; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cross-Sectional Studies; Demography; Drug Costs; Female; Health Knowledge, Attitudes, Practice; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Practice Patterns, Physicians'; Self Administration; Self Medication

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

Buprenorphine (Subutex) is widely abused in Finland. A combination of buprenorphine plus naloxone (Suboxone) has been available since late 2004, permitting a comparison of the abuse of the two products among untreated intravenous (IV) users. A survey was distributed to attendees at a Helsinki needle exchange program over 2-weeks in April, 2005, At least 30% were returned anonymously. Survey variables included: years of prior IV opioid abuse, years of buprenorphine abuse, frequency, dosage, route of administration and reasons for use, concomitant IV abuse of other substances and amount paid on the street for both buprenorphine and buprenorphine+naloxone. Buprenorphine was the most frequently used IV drug for 73% of the respondents. More than 75% said they used IV buprenorphine to self-treat addiction or withdrawal. Most (68%) had tried the buprenorphine+naloxone combination IV, but 80% said they had a "bad" experience. Its street price was less than half that of buprenorphine alone. The buprenorphine+naloxone combination appears to be a feasible tool, along with easier access to addiction treatment, for decreasing IV abuse of buprenorphine.

Topics: Adolescent; Adult; Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Drug Combinations; Female; Finland; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Self Medication; Substance Abuse, Intravenous

Topics: Adaptation, Psychological; Analgesics, Opioid; Attitude of Health Personnel; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Drug and Narcotic Control; Humans; Male; Naloxone; Nursing Staff, Hospital; Occupational Health; Opioid-Related Disorders; Professional Impairment; Self-Help Groups; Shame; Substance Abuse Treatment Centers; Substance Withdrawal Syndrome; Theft

Drugs used for treatment of narcotic addicts (buprenorphin at high concentration or methadone) have different advantages and disadvantages. The author has tried to insist on what can be complementary between both treatments. Two new formulations of buprenorphin at high concentration (Suboxone and Subutex NF) are described and proposed to replace Subutex.

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Drug Combinations; Humans; Methadone; Naloxone; Narcotics; Opioid-Related Disorders

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Drug Combinations; Humans; Naloxone; Narcotic Antagonists; Office Visits; Opioid-Related Disorders