buprenorphine and Substance-Withdrawal-Syndrome

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

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

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

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

Medicine's acceptance of addiction as a medical concept has waxed and waned over time. Addiction, as a disease, fits with modern disease definitions and scientific advances in elucidating the interactions between neurobiology and environment. Definitions of addiction need to acknowledge the complex interactions of brain circuits, genetics, environmental factors, and individual life experiences. Addiction aligns with diagnostic categories of substance use disorders that do not rely on tolerance and withdrawal as defining characteristics. Shifts in social and political views of addiction continue to propel and mirror changes in addiction treatment approaches and terminology within the medical community.

Topics: Adolescent; Analgesics, Opioid; Behavior; Behavior, Addictive; Buprenorphine; Comprehensive Health Care; Environment; Female; History, 20th Century; Humans; Life Change Events; Male; Methadone; Neurobiology; Social Stigma; Substance Withdrawal Syndrome; Substance-Related Disorders; Terminology as Topic; Transgender Persons; Young Adult

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

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

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

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

Buprenorphine and naloxone (Suboxone) is a combination medication-assisted treatment (MAT) for opioid use disorder. MAT withdrawal-induced psychosis is a rare clinical presentation. To our best knowledge, only three reports have summarized the characteristic manifestations of buprenorphine withdrawal psychosis, yet all of them were male. In this case report, we present a 41-year-old female patient with bipolar disorder and comorbid substance use disorder who developed new-onset psychosis and relapse of manic symptoms following abrupt discontinuation of Suboxone. Manic and psychotic symptoms remitted after a short-term hospitalization with the treatment of an antipsychotic and a mood stabilizer. In addition to discussing this case presentation and treatment approach, we review existing literature and discuss possible underlying mechanisms to enhance understanding of this clinical phenomenon.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Female; Humans; Male; Naloxone; Psychotic Disorders; Substance Withdrawal Syndrome

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

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

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

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

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

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

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

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

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

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

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

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

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

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

This study's main objective is to carry out a systematic review of the onset of psychotic symptoms after opioid withdrawal. The opiate dependence correlated to psychiatric symptoms has been well described.. Following the PRISMA methodology. The consecutive search strategy was applied: (morphine OR buprenorphine OR oxycodone OR tramadol OR fentanyl OR remifentanil OR opioids OR heroin OR methadone) AND (Psychosis OR psychotic symptoms OR schizophrenia).. 12 case reports, 3 series of cases, 2 clinical studies, and 2 reviews were found. It seems that the time association is present in all of them; symptoms appear days after the interruption of the opioid. Most of the articles reported are case reports that describe symptoms that appear after the suspension of the opioid substance; in most cases, the reintroduction of the opioid had therapeutic effects and provoked a remission of these symptoms. These preliminary findings indicate that opiates could have an antipsychotic effect; however, the literature is scarce. It is critical to consider, if needed, in opioid-dependent patients who start with psychosis after the opioid withdrawal the possible replacement or reintroduction of opioids to prevent further deterioration in the patient's mental status.. This study encompasses a comprehensive description of the literature concerning the possible not well-studied outcome of opioid withdrawal. There are some reports of temporal association between withdrawal and psychotic symptoms that improved after the reintroduction of the opioid; it could be taken into consideration in the clinical practice.

Topics: Analgesics, Opioid; Buprenorphine; Heroin; Humans; Methadone; Morphine; Oxycodone; Psychotic Disorders; Substance Withdrawal Syndrome; Tramadol

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

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

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

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

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

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

An increasing number of patients with opioid use disorder (OUD) are treated with opioid agonist-antagonists such as buprenorphine/naloxone. Perioperative management of patients on buprenorphine/naloxone is inconsistent and remains a controversial topic with mismanagement posing a significant risk to the long-term health of these patients.. We performed a systematic literature search involving Medline, Medline In-Process, Embase, Cochrane Central, Cochrane Database of Systematic Reviews, PsycINFO, Web of Science (Clarivate), Scopus (Elsevier), CINAHL (EbscoHosst), and PubMed (NLM).. Eighteen studies were included in the final sample, including one controlled study and four observational studies . Neither the controlled study nor the observational studies assessed addiction treatment retention, harm reduction, or long-term mortality rates as primary or secondary outcomes. Of the observational studies, authors showed equivalent peri- and postoperative pain control among buprenorphine continued patients. All but one authors described adequate analgesia among the case reports in which buprenorphine ≤ 16 mg sublingually (SL) daily was continued during the perioperative period. Long-term harm reduction was not reported with only three case reports including any long-term abstinence or relapse rates.. The current understanding of the risks and benefits of continuing or stopping buprenorphine perioperatively is limited by a lack of high-quality evidence. Observational studies and case reports indicate no evidence against continuing buprenorphine perioperatively, especially when the dose is < 16 mg SL daily. In patients with significant potential for relapse, such as those with a recent history of OUD, the discontinuation of buprenorphine should have a strong rationale supported by patient and surgical preferences. Future studies require standardized reporting of median doses, details on the route of delivery, dosing schedules and any dosing changes, and rates of addiction relapse, including long-term morbidity and mortality where possible.. RéSUMé: CONTEXTE: Un nombre croissant de patients présentant un trouble d’utilisation des opioïdes (TUO) sont traités avec des agonistes/antagonistes des opioïdes, tels que la buprénorphine et la naloxone. La gestion périopératoire des patients sous buprénorphine/naloxone n’est pas constante et reste un sujet de controverses; de plus une mauvaise gestion pose un risque significatif pour la santé à long terme de ces patients. MéTHODES: Nous avons effectué une recherche systématique de la littérature dans les bases de données suivantes : Medline, Medline In-Process, Embase, Cochrane Central, Cochrane Database of Systematic Reviews, PsycINFO, Web of Science (Clarivate), Scopus (Elsevier), CINAHL (EbscoHosst) et PubMed (NLM). RéSULTATS: Dix-huit études ont été incluses dans l’échantillon final, y compris une étude contrôlée et quatre études observationnelles. Ni l’étude contrôlée ni les études observationnelles n’ont évalué la continuation du traitement de l’addiction, la réduction des préjudices infligés ou les taux de mortalité à long terme parmi les critères d’évaluation principaux ou secondaires. Dans les études observationnelles, les auteurs ont montré qu’il y avait un contrôle équivalent de la douleur en péri- et postopératoire chez les patients continuant à recevoir de la buprénorphine. Tous les auteurs sauf un ont décrit une analgésie satisfaisante dans les rapports de cas où la buprénorphine sublinguale avec une dose ≤ 16 mg par jour était maintenue pendant la période périopératoire. La réduction des préjudices à long terme n’était pas décrite; seulement trois rapports de cas indiquaient le taux d’abstinence à long terme ou les taux de rechute. CONCLUSIONS: Les connaissances actuelles des risques et avantages de la poursuite ou de l’arrêt de la buprénorphine en période périopératoire sont limitées par le manque de données probantes de grande qualité. Les études observationnelles et les rapports de cas ne fournissent pas de données probantes à l’encontre de la poursuite de la buprénorphine dans la période périopératoire, en particulier quand la dose journalière par voie sublinguale est < 16 mg. Chez les patients présentant un risque significatif de rechute, comme ceux ayant des antécédents récents de TUO, l’arrêt de la buprénorphine devrait être solidement justifié avec le soutien des préférences des patients et des équipes chirurgicales. Les futures études nécessitent une normalisation du rapport des doses médianes, des détails sur les voies d’admini

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Humans; Perioperative Care; Substance Withdrawal Syndrome; Treatment Outcome

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

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

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

Opioid neonatal abstinence syndrome (NAS) refers to signs of withdrawal observed in infants experiencing intrauterine opioid exposures. Early identification of at-risk infants allows for the prompt initiation of nonpharmacologic supportive care. When withdrawal symptoms are severe despite these interventions, pharmacologic therapy including opioid weaning is initiated. Consistency with standardized nonpharmacologic approaches as well as stringent weaning protocols are important in minimizing the length of stay and length of pharmacologic treatment for these vulnerable patients.

Topics: Buprenorphine; Clinical Protocols; Humans; Infant, Newborn; Length of Stay; Morphine; Neonatal Abstinence Syndrome; Risk Assessment; Substance Withdrawal Syndrome

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

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

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

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

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

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

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

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

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

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

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

Substance use disorders are common in primary care settings, but detection, assessment, and management are seldom undertaken. Substantial evidence supports alcohol screening and brief intervention for risky drinking, and pharmacotherapy is effective for alcohol use disorders. Substance use disorders can complicate the management of chronic noncancer pain, making routine monitoring and assessment for substance use disorders an important aspect of long-term opioid prescribing. Patients with opioid use disorders can be effectively treated with methadone in opioid treatment programs or with buprenorphine in the primary care setting.

Topics: Alcohol Deterrents; Analgesics, Opioid; Buprenorphine; Cognitive Behavioral Therapy; Comorbidity; Harm Reduction; Humans; Mass Screening; Methadone; Motivational Interviewing; Narcotic Antagonists; Narcotics; Opiate Substitution Treatment; Physician-Patient Relations; Primary Health Care; Secondary Prevention; Self-Help Groups; Substance Abuse Detection; Substance Withdrawal Syndrome; Substance-Related Disorders; Surveys and Questionnaires

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

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

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

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

In this article, the authors briefly review the pharmacotherapeutic agents that are currently available for the treatment of substance use disorders. Nicotine replacement therapies are most effective for tobacco cessation. Naltrexone, acamprosate, and disulfiram are effective for reducing alcohol use. The most effective pharmacotherapies for opiate use disorders are agonist therapies, including methadone and buprenorphine. The authors also examine recent advances in medication development for other substance use disorders such as stimulant addiction. The role of medication adherence and behavioral treatments and the integration of behavioral and pharmacotherapeutic interventions are also discussed.

Topics: Alcohol Deterrents; Alcoholism; Analgesics, Opioid; Behavior Therapy; Behavior, Addictive; Buprenorphine; Disulfiram; Humans; Naltrexone; Narcotic Antagonists; Secondary Prevention; Smoking Cessation; Substance Withdrawal Syndrome; Substance-Related Disorders; Tobacco Use Disorder

This review will summarize the symptoms, evaluation, and treatment of neonatal and iatrogenic withdrawal syndromes.. Buprenorphine is emerging as the drug of choice for maintaining opioid-dependent women during pregnancy, because of its association with less severe withdrawal symptoms. Recent findings suggest it may be the drug of choice for treating the opioid-exposed neonate as well.. Healthcare workers should be cognizant of the risk factors for neonatal abstinence syndrome (NAS), as well as its symptoms, so that nonpharmalogic and pharmacologic therapies can be initiated. With increased emphasis on pain control in children, it is likely that iatrogenic withdrawal will continue to be a concern, and healthcare workers should understand the similarities and differences between this and NAS.

Topics: Analgesics, Opioid; Buprenorphine; Diagnosis, Differential; Evidence-Based Medicine; Humans; Infant, Newborn; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Risk Factors; Substance Withdrawal Syndrome

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

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

An intrauterine abstinence syndrome (IAS) is a potentially fatal consequence of maternal opiate withdrawal. This study reviews the evidence for this syndrome. Withdrawal also creates an adverse environment for the developing fetal brain that can have long-term health effects. Effective methadone treatment eliminates risks of fetal withdrawal. However, concerns about neonatal abstinence syndrome (NAS) in methadone-exposed neonates have resulted in efforts to withdraw women from methadone during pregnancy or to use buprenorphine, a mixed agonist/antagonist opiate in place of methadone. Both approaches necessarily expose the fetus to either acute or chronic withdrawal. Routine fetal monitoring is not able to detect such symptoms, unless they are life-threatening. Therefore, the safety of the fetus during buprenorphine inductions or methadone tapers cannot be assured and the fetus should be protected from such procedures. Further research into methods of diagnosing IAS and its developmental consequences is needed to assure that attempts to reduce NAS do not harm the fetus.

Topics: Buprenorphine; Epigenesis, Genetic; Female; Fetal Diseases; Humans; Methadone; Narcotics; Pregnancy; Substance Withdrawal Syndrome

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

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

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

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

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

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

The transdermal therapeutic system (TTS) with buprenorphine is currently being used 'off-label' to treat chronic pediatric pain. We compiled available pharmacokinetic (PK), pharmacodynamic (PD), and clinical pediatric data on buprenorphine to rationalize treatment regimens.. We conducted a systematic biomedical literature review focusing on pediatric buprenorphine data.. There are few relevant pediatric buprenorphine data, particularly in children suffering chronic pain. There are no pediatric PK and PD data for children with chronic pain given sublingual or TTS formulations. Children given single dose buprenorphine have increased drug clearance referenced to bodyweight with a possible paradoxical longer duration of action. Buprenorphine metabolism is independent of renal function, which is advantageous in renal insufficiency. The risk of respiratory depression after buprenorphine is difficult to quantify. A concentration-response relationship for respiratory effects has not been described and it is unknown whether children have a ceiling effect similar to that described in healthy adult volunteers.. Buprenorphine is of interest in pediatric postoperative pain and cancer pain control because of its multiple administration routes, long duration of action, and metabolism largely independent of renal function. There is little reason to expect buprenorphine effects in children out of infancy are fundamentally different to those in adults. From the limited pediatric data available, it appears that buprenorphine has no higher adverse potential than the more commonly used opioids. There is an urgent need for focused PK, PD, and safety studies in children before use in children becomes more widespread.

Topics: Administration, Cutaneous; Adolescent; Adult; Analgesics, Opioid; Buprenorphine; Child; Drug Delivery Systems; Drug Eruptions; Female; Humans; Male; Pain; Pain, Postoperative; Receptors, Opioid, mu; Respiratory Insufficiency; Substance Withdrawal Syndrome; Young Adult

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Topics: Analgesics, Opioid; Buprenorphine; Female; Fetus; Humans; Infant, Low Birth Weight; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Pregnancy; Pregnancy Complications; Prenatal Care; Substance Withdrawal Syndrome; Substance-Related Disorders

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Topics: Adrenergic beta-Antagonists; Alcohol Deterrents; Anti-Anxiety Agents; Benzodiazepines; Buprenorphine; Disulfiram; Humans; Methadone; Naltrexone; Narcotic Antagonists; Narcotics; Neurobiology; Neuropharmacology; Psychopharmacology; Substance Withdrawal Syndrome; Substance-Related Disorders

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

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

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

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

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

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

Patients with heroin dependence frequently present to internists and other physicians for heroin-related medical, psychiatric, and behavioral health problems and often seek help with reducing their heroin use. Thus, physicians should be familiar with the identification and diagnosis of heroin dependence in their patients and be able to initiate treatment of heroin dependence both directly and by referral. Recent research has provided much information concerning effective pharmacologically based treatment approaches for managing opioid withdrawal and helping patients to remain abstinent Methadone maintenance and newer approaches using L-alpha acetylmethadol and buprenorphine seem to be particularly effective in promoting relapse prevention. Although these treatments are currently provided in special drug treatment settings, recent and ongoing research indicates that the physician's office may be an effective alternative site for these treatments.

Topics: Analgesics, Opioid; Buprenorphine; Counseling; Heroin Dependence; Humans; Mental Disorders; Methadone; Methadyl Acetate; Naltrexone; Narcotic Antagonists; Physician's Role; Substance Withdrawal Syndrome

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

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

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

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

Topics: Ambulatory Care; Buprenorphine; Combined Modality Therapy; Drug Administration Schedule; Humans; Methadone; Neurologic Examination; Patient Admission; Patient Care Team; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Buprenorphine; Clonidine; Humans; Methadone; Naltrexone; Narcotic Antagonists; Substance Withdrawal Syndrome; Substance-Related Disorders; United Kingdom

Topics: Behavior Therapy; Buprenorphine; Clonidine; Humans; Lithium; Methadone; Narcotics; Nicotine; Psychotherapy; Substance Withdrawal Syndrome; Thiamine

Detoxification from opiate addiction has been a medical problem for as long as opiate drugs have been available. Treatment before the discovery of clonidine involved giving another opioid drug with less dangerous consequences of chronic use, such as the long-acting and orally administered once a day methadone, for another opioid mu agonist like heroin, which must be taken intravenously many times a day, thus making rehabilitation, work, and avoidance of hepatitis, HIV, and other illnesses difficult. Although methadone has proved to be very beneficial, it still has significant abuse potential. Naltrexone, because it blocks the effects of all opiates, has facilitated the transformation from addiction to a drug-free state for many recovering addicts. By alleviating withdrawal symptoms and by lessening the detoxification period, clonidine similarly has improved the prospect of recovery from opiate addiction. Relapse, whether withdrawal is treated with clonidine or other new agents or not, occurs with great regularity because repeated opiate use can induce a new acquired drive state--the drive for opiates. In addition, with powerful withdrawal symptoms during abstinence, opiate relapse is difficult to prevent without an adequate treatment program. The efficacy of clonidine and other medical magic bullets for withdrawal distress needs to be given as part of a long-term recovery program which not only allows the brain to re-establish normal homeostatic changes in the drug-free state but also provides sufficient motivation for new approaches to achieving and sustaining pleasurable existence.

Topics: Animals; Buprenorphine; Clonidine; Humans; Locus Coeruleus; Methadone; Naltrexone; Opioid-Related Disorders; Substance Withdrawal Syndrome

Topics: Analgesics, Opioid; Animals; Buprenorphine; Heroin Dependence; Humans; Nausea; Opioid-Related Disorders; Substance Withdrawal Syndrome

Topics: Analgesics; Analgesics, Opioid; Buprenorphine; Buspirone; Double-Blind Method; Humans; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Substance Withdrawal Syndrome; Treatment Outcome

Conflictual evidence exists regarding the effects of cannabis use on the outcomes of opioid agonist therapy (OAT). In this exploratory analysis, we examined the effect of recent cannabis use on opioid use, craving, and withdrawal symptoms, in individuals participating in a trial comparing flexible buprenorphine/naloxone (BUP/NX) take-home dosing model to witnessed ingestion of methadone.. We analyzed data from a multi-centric, pragmatic, 24-week, open label, randomized controlled trial in individuals with prescription-type opioid use disorder (n = 272), randomly assigned to BUP/NX (n = 138) or methadone (n = 134). The study measured last week cannabis and opioid use via timeline-follow back, recorded at baseline and every two weeks during the study. Craving symptoms were measured using the Brief Substance Craving Scale at baseline, and weeks 2, 6, 10, 14, 18 and 22. The study measured opioid withdrawal symptoms via Clinical Opiate Withdrawal Scale at treatment initiation and weeks 2, 4, and 6.. The mean maximum dose taken during the study was 17.3 mg/day (range = 0.5-32 mg/day) for BUP/NX group and 67.7 mg/day (range = 10-170 mg/day) in the methadone group. Repeated measures generalized linear mixed models demonstrated that cannabis use in the last week (mean of 2.3 days) was not significantly associated with last week opioid use (aβ ± standard error (SE) = -0.06 ± 0.04; p = 0.15), craving (aβ ± SE = -0.05 ± 0.08, p = 0.49), or withdrawal symptoms (aβ ± SE = 0.09 ± 0.1, p = 0.36). Bayes factor (BF) for each of the tested models supported the null hypothesis (BF < 0.3).. The current study did not demonstrate a statistically significant effect of cannabis use on outcomes of interest in the context of a pragmatic randomized-controlled trial. These findings replicated previous results reporting no effect of cannabis use on opioid-related outcomes.

Topics: Analgesics, Opioid; Bayes Theorem; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cannabis; Humans; Methadone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Substance Withdrawal Syndrome

Despite the evidence in support of the use of buprenorphine in the treatment of OUD and increasing ability of emergency medicine (EM) clinicians to prescribe it, emergency department (ED)-initiated buprenorphine is uncommon. Many EM clinicians lack training on how to manage acute opioid withdrawal or initiate treatment with buprenorphine. We developed a brief buprenorphine training program and assessed the impact of the training on subsequent buprenorphine initiation and knowledge retention.. We conducted a pilot randomized control trial enrolling EM clinicians to receive either a 30-min didactic intervention about buprenorphine (standard arm) or the didactic plus weekly messaging and a monetary inducement to administer and report buprenorphine use (enhanced arm). All participants were incentivized to complete baseline, immediate post-didactic, and 90-day knowledge and attitude assessment surveys. Our objective was to achieve first time ED buprenorphine prescribing events in clinicians who had not previously prescribed buprenorphine in the ED and to improve EM-clinician knowledge and perceptions about ED-initiated buprenorphine. We also assessed whether the incentives and reminder messaging in the enhanced arm led to more clinicians administering buprenorphine than those in the standard arm following the training; we measured changes in knowledge of and attitudes toward ED-initiated buprenorphine.. Of 104 EM clinicians enrolled, 51 were randomized to the standard arm and 53 to the enhanced arm. Clinical knowledge about buprenorphine improved for all clinicians immediately after the didactic intervention (difference 19.4%, 95% CI 14.4% to 24.5%). In the 90 days following the intervention, one-third (33%) of all participants reported administering buprenorphine for the first time. Clinicians administered buprenorphine more frequently in the enhanced arm compared to the standard arm (40% vs. 26.3%, p = 0.319), but the difference was not statistically significant. The post-session knowledge improvement was not sustained at 90 days in the enhanced (difference 9.6%, 95% CI - 0.37% to 19.5%) or in the standard arm (difference 3.7%, 95% CI - 5.8% to 13.2%). All the participants reported an increased ability to recognize patients with opioid withdrawal at 90 days (enhanced arm difference .55, 95% CI .01-1.09, standard arm difference .85 95% CI .34-1.37).. A brief educational intervention targeting EM clinicians can be utilized to achieve first-time prescribing and improve knowledge around buprenorphine and opioid withdrawal. The use of weekly messaging and gain-framed incentivization conferred no additional benefit to the educational intervention alone. In order to further expand evidence-based ED treatment of OUD, focused initiatives that improve clinician competence with buprenorphine should be explored.. ClinicalTrials.gov Identifier: NCT03821103.

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

Topics: Analgesics, Opioid; Azepines; Buprenorphine; Craving; Double-Blind Method; Humans; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Sleep; Substance Withdrawal Syndrome; Treatment Outcome; Triazoles

Opioid Use Disorder (OUD) is a significant public health problem associated with severe morbidity and mortality. While effective pharmacotherapies are available, limitations exist with each. Induction onto extended-release naltrexone (XR-NTX) is more difficult than initiation of buprenorphine or methadone, even in inpatient settings, as it is recommended that patients remain abstinent for at least 7 days prior to initiating XR-NTX. The purpose of this trial was to determine if lorcaserin, a 5HT2c agonist, improves outpatient XR-NTX induction rates.. An 8-week trial beginning with a brief detoxification period and induction onto XR-NTX. Sixty participants with OUD were enrolled in the trial, with 49 participants at the initiation of detoxification randomized to lorcaserin or placebo for 39 days. Additionally, ancillary medications were provided. The primary outcome was the proportion of participants inducted onto the first XR-NTX injection. Secondary outcomes were withdrawal severity (measured by COWS and SOWS) prior to the first injection and the proportion of participants receiving the second XR-NTX injection.. The proportion of participants inducted onto the first (lorcaserin: 36 %; placebo: 44 %; p = .67) and the second XR-NTX injection (lorcaserin: 27 %; placebo: 31 %; p = .77) was not significantly different between treatment arms. Prior to the first injection, withdrawal scores did not significantly differ between treatment arms over time (treatment*time interaction COWS: p = .11; SOWS: p = .39).. Lorcaserin failed to improve outpatient XR-NTX induction rates. Although this study is small, the findings do not support the use of lorcaserin in promoting induction onto XR-NTX or in mitigating withdrawal symptoms.

Topics: Adult; Animals; Benzazepines; Buprenorphine; Delayed-Action Preparations; Female; Humans; Injections; Male; Methadone; Middle Aged; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Outpatients; Substance Withdrawal Syndrome; Swine

Opioid withdrawal symptoms are widely understood to contribute to health risk but have rarely been measured in community samples of opioid using people who inject drugs (PWID).. Using targeted sampling methods, 814 PWID who reported regular opioid use (at least 12 uses in the last 30 days) were recruited and interviewed about demographics, drug use, health risk, and withdrawal symptoms, frequency, and pain. Multivariable regression models were developed to examine factors associated with any opioid withdrawal, withdrawal frequency, pain severity, and two important health risks (receptive syringe sharing and non-fatal overdose).. Opioid withdrawal symptoms were reported by 85 % of participants in the last 6 months, with 29 % reporting at least monthly withdrawal symptoms and 35 % reporting at least weekly withdrawal symptoms. Very or extremely painful symptoms were reported by 57 %. In separate models, we found any opioid withdrawal (adjusted odds ratio [AOR] = 2.75, 95 % confidence interval [CI] = 1.52, 5.00) and weekly or more opioid withdrawal frequency (AOR = 1.94; 95 % CI = 1.26, 3.00) (as compared to less than monthly) to be independently associated with receptive syringe sharing while controlling for confounders. Any opioid withdrawal (AOR = 1.71; 95 % CI = 1.04, 2.81) was independently associated with nonfatal overdose while controlling for confounders. In a separate model, weekly or more withdrawal frequency (AOR = 1.69; 95 % CI = 1.12, 2.55) and extreme or very painful withdrawal symptoms (AOR = 1.53; 95 % CI = 1.08, 2.16) were associated with nonfatal overdose as well.. Withdrawal symptoms among PWID increase health risk. Treatment of withdrawal symptoms is urgently needed and should include buprenorphine dispensing.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Cross-Sectional Studies; Drug Overdose; Female; Health Status; Humans; Male; Middle Aged; Needle Sharing; Opioid-Related Disorders; Pain; Risk Factors; Substance Abuse, Intravenous; Substance Withdrawal Syndrome

When patients seek to discontinue buprenorphine (BUP) treatment, monthly injectable extended-release naltrexone (XR-NTX) may help them avoid relapse. The efficacy of low ascending doses of oral NTX vs placebo for patients transitioning from BUP to XR-NTX is evaluated in this study.. In a phase 3, hybrid residential/outpatient study, clinically stable participants with opioid use disorder (N = 101), receiving BUP for more than or equal to 3 months and seeking antagonist treatment, were randomized (1:1) to 7 residential days of descending doses of BUP and low ascending doses of oral NTX (NTX/BUP, n = 50) or placebo (PBO-N/BUP, n = 51). Both groups received standing ancillary medications and psychoeducational counseling. Following negative naloxone challenge, participants received XR-NTX (day 8). The primary endpoint was the proportion of participants who received and tolerated XR-NTX.. There was no statistical difference between groups for participants receiving a first dose of XR-NTX: 68.6% (NTX/BUP) vs 76.0% (PBO-N/BUP; P = .407). The mean number of days with peak Clinical Opiate Withdrawal Scale (COWS) score less than or equal to 12 during the treatment period (days 1-7) was similar for NTX/BUP and PBO-N/BUP groups (5.8 vs 6.3; P = .511). Opioid withdrawal symptoms during XR-NTX induction and post-XR-NTX observation period (days 8-11) were mild and similar between groups (mean peak COWS score: NTX/BUP, 5.1 vs PBO-N/BUP, 5.4; P = .464). Adverse events were mostly mild/moderate.. Low ascending doses of oral NTX did not increase induction rates onto XR-NTX compared with placebo. The overall rate of successful induction across treatment groups supports a brief BUP taper with standing ancillary medications as a well-tolerated approach for patients seeking transition from BUP to XR-NTX. (Am J Addict 2020;00:00-00).

Topics: Adult; Buprenorphine; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Monitoring; Drug Substitution; Female; Humans; Male; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Substance Withdrawal Syndrome; Treatment Outcome

Opioid use disorder (OUD) is a public health crisis. Differences in opioid withdrawal severity that predict treatment outcome could facilitate the process of matching patients to treatments. This is a secondary analysis of a randomized controlled trial (RCT) that enrolled treatment seeking heroin-users (N = 89, males = 78) into a residential study. Participants maintained on morphine (30 mg, subcutaneous, four-times daily) underwent a naloxone (0.4 mg, IM = intramuscular) challenge session to precipitate withdrawal. Area-under-the-curve (AUC) values from self-reported withdrawal ratings during the challenge session were analyzed using K-means clustering, revealing two phenotype groups. Withdrawal and retention from the subsequent 14-day double-blind, double-dummy RCT comparing three study medications (clonidine, tramadol-ER, and buprenorphine) were evaluated as a function of phenotype. Cluster analyses suggested HIGH (N = 37; mean [SD] subjective opiate withdrawal scale [SOWS]-AUC 123.7 [65.8]) and LOW (N = 52; SOWS-AUC 68.0 [47.7]) withdrawal phenotype groups. HIGH participants were significantly more female and had lower body mass indices than LOW participants; no drug-use variables were significant. Regarding RCT outcomes, HIGH phenotype participants were less likely to be retained in the study (P = 0.02) and had higher mean self-reported withdrawal (P = 0.05) than LOW phenotype participants. A significant interaction in RCT retention was observed between phenotype (P = 0.02) and study medication (P < 0.01). Self-reported withdrawal was significant for phenotype (P = 0.02); study medication trended towards significance (P = 0.07). Results suggest patients have meaningfully different experiences of opioid withdrawal that may predict differential response to opioid pharmacotherapies during supervised withdrawal. Additional prospective research to replicate and more thoroughly evaluate withdrawal phenotype correlates and sex differences is warranted.

Topics: Adult; Analgesics; Buprenorphine; Clonidine; Cluster Analysis; Double-Blind Method; Female; Humans; Male; Morphine; Naloxone; Narcotic Antagonists; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Phenotype; Severity of Illness Index; Substance Withdrawal Syndrome; Tramadol; Treatment Outcome

To compare buprenorphine to clonidine for the treatment of opioid withdrawal in the emergency department (ED) and to study the effect assigned treatment medication had on longer-term addiction treatment outcomes.. Randomized controlled trial.. Toronto, Ont.. Twenty-six patients presenting to the ED while in opioid withdrawal or soon to be in opioid withdrawal.. Patients were randomized to receive either clonidine or buprenorphine treatment. Both groups also received a corresponding discharge prescription and information on how to follow up in the addictions rapid access clinic (RAC) within a few days. Participants were followed for 1 month with respect to attendance at the RAC and to opioid agonist treatment status. Outcome measures included attendance at the RAC within 5 days of the initial ED visit and opioid agonist treatment status at 1 month (as determined by clinic attendance or self-report during a follow-up telephone interview).. Participants who received buprenorphine in the ED were more likely to be receiving opioid agonist treatment at the 1-month mark compared with those participants who received clonidine to treat their withdrawal (. When opioid withdrawal is treated with buprenorphine in the ED, patients are more likely to be receiving opioid agonist treatment and connected with addiction treatment 1 month later.. NCT03174067 (ClinicalTrials.gov).

Topics: Adult; Buprenorphine; Clonidine; Emergency Service, Hospital; Female; Humans; Male; Narcotic Antagonists; Ontario; Opiate Substitution Treatment; Opioid-Related Disorders; Prospective Studies; Substance Withdrawal Syndrome; Treatment Outcome

The purpose of this study was to compare the effect of 300 mg of bupropion and 8 mg of buprenorphine per day on the treatment of methamphetamine withdrawal cravings over a 2-week treatment interval.. Sixty-five methamphetamine-dependent men who met the DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision) criteria for methamphetamine dependence and withdrawal were randomly divided into two groups. Subjects randomly received 300 mg of bupropion or 8 mg of buprenorphine per day in a psychiatric ward. Of the 65 subjects, 35 (53.8%) received buprenorphine and 30 (46.2%) received bupropion. The subjects were assessed by using methamphetamine craving score, interview, and negative urine drug test.. There were no statistically significant differences between the two groups in regard to age, education, duration of methamphetamine dependency, marital status, employment, and income. The mean ages were 32.8 years (standard deviation (SD) = 7.26, range = 22 to 59) for the buprenorphine group and 32.21 years (SD = 8.45, range = 17 to 51) for the bupropion group. All 65 patients completed the 2-week study. Both medications were effective in the reduction of methamphetamine cravings. Reduction of craving in the buprenorphine group was significantly more than the bupropion group (P = 0.011). Overall, a significant main effect of day (P <0.001) and group (P = 0.011) and a non-significant group-by-day interaction (P >0.05) were detected.. The results support the safety and effectiveness of buprenorphine and bupropion in the treatment of methamphetamine withdrawal craving. Administration of 8 mg of buprenorphine per day can be recommended for the treatment of methamphetamine withdrawal cravings. We should note that it is to be expected that craving decreases over time without any medication. So the conclusion may not be that bupropion and buprenorphine both lower the craving. As the buprenorphine is superior to bupropion, only buprenorphine does so for sure.. Iranian Registry of Clinical Trials (IRCT) registration number: IRCT2015010320540N1 . Date registered: April 10, 2015.

Topics: Adolescent; Adult; Amphetamine-Related Disorders; Analgesics, Opioid; Behavior, Addictive; Buprenorphine; Bupropion; Central Nervous System Stimulants; Craving; Dopamine Uptake Inhibitors; Double-Blind Method; Humans; Iran; Male; Methamphetamine; Middle Aged; Substance Withdrawal Syndrome; Time Factors; Treatment Outcome; Young Adult

Injectable extended-release naltrexone (XR-NTX), approved to prevent relapse to opioid dependence, requires initial abstinence. This multisite outpatient clinical trial examined the efficacy and safety of low-dose oral naltrexone (NTX), combined with a brief buprenorphine (BUP) taper and standing ancillary medications, for detoxification and induction onto XR-NTX.. Patients (N = 378) were randomized, stratified by primary short-acting opioid-of-use, to one of three regimens: NTX + BUP; NTX + placebo BUP (PBO-B); placebo NTX (PBO-N) + PBO-B. Patients received 7 days of ascending NTX or placebo, concurrent with a 3-day BUP or placebo taper, and ancillary medications in an outpatient setting. Daily psychoeducational counseling was provided. On Day 8, patients passing a naloxone challenge received XR-NTX.. Rates of transition to XR-NTX were comparable across groups: NTX/BUP (46.0%) vs. NTX/PBO-B (40.5%) vs. PBO-N/PBO-B (46.0%). Thus, the study did not meet its primary endpoint. Adverse events, reported by 32.5% of all patients, were mild to moderate in severity and consistent with opioid withdrawal. A first, second, and third XR-NTX injection was received by 44.4%, 29.9%, and 22.5% of patients, respectively. Compared with the PBO-N/PBO-B group, the NTX/BUP group demonstrated higher opioid abstinence during the transition and lower post-XR-NTX subjective opioid withdrawal scores.. A 7-day detoxification protocol with NTX alone or NTX + BUP provided similar rates of induction to XR-NTX as placebo. For those inducted onto XR-NTX, management of opioid withdrawal symptoms prior to induction was achieved in a structured outpatient setting using a well-tolerated, fixed-dose ancillary medication regimen common to all three groups.

Topics: Adult; Ambulatory Care; Buprenorphine; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Outpatients; Patient Transfer; Substance Withdrawal Syndrome

Long acting naltrexone has improved the therapy of opioid use disorder (OUD), and safe and effective withdrawal management during naltrexone induction may help advance treatment. Despite the uncertain role of opioid withdrawal in predicting successful outcomes, early symptom control may favor detoxification completion.. We explored withdrawal severity and early response to treatment, safety, and clinical measures in 35 adult patients with DSM-5 OUD during a 7-day office-based buprenorphine-naltrexone and ancillary medications transition to extended-release naltrexone (XR-NTX).. Subjective and objective measures of withdrawal intensity improved consistently throughout treatment in the whole sample. Participants who went on to receive XR-NTX (n = 27, 77%) reported a greater attenuation of symptoms by treatment day 2 (r = .595, p = .001), and were less likely to be injection drug users (r = -.501, p = .004). Adverse events (AEs) were recorded in 20% of participants: the majority (n = 6, 85.7%) consisted of single episodes of increased withdrawal which were well controlled using ancillary medications. One serious AE was unrelated to treatment.. Early opioid withdrawal changes may be a useful indicator of treatment response, helping adjust the transition protocol to the individual patients' need and gather valuable information for a better understanding of the relationship between initiating and remaining in treatment. (Am J Addict 2018;27:471-476).

Topics: Adult; Buprenorphine; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Monitoring; Female; Humans; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Outcome Assessment, Health Care; Outpatients; Severity of Illness Index; Substance Withdrawal Syndrome; Symptom Assessment

Preliminary evidence suggested that the PPARγ agonist pioglitazone reduces opioid-withdrawal symptoms, possibly by inhibiting increases in proinflammatory cytokines.. A randomized, placebo-controlled clinical trial was conducted utilizing two different study designs (entirely outpatient, and a combination of inpatient and outpatient) to evaluate the safety and efficacy of pioglitazone as an adjunct medication for people with opioid physical dependence undergoing a buprenorphine taper. Participants were stabilized on buprenorphine/naloxone (sublingual, up to 16/4 mg/day), then randomized to receive oral pioglitazone (up to 45 mg/day) or placebo before, during, and after buprenorphine taper. Outcome measures included the Subjective Opiate Withdrawal Scale (SOWS) and Clinical Opiate Withdrawal Scale, use of rescue medications to alleviate opioid withdrawal symptoms, and opioid-positive urine specimens. Cerebrospinal fluid (CSF) and plasma were collected during the taper in a subset of participants for measurement of proinflammatory cytokines.. The clinical trial was prematurely terminated due to slow enrollment; 40 participants per group were required for adequate statistical power to test study hypotheses. Twenty-four participants enrolled; 17 received at least one dose of study medication (6 pioglitazone, 11 placebo). SOWS scores were higher in the pioglitazone arm than in the placebo arm after adjusting for use of rescue medications; participants in the pioglitazone arm needed more rescue medications than the placebo arm during the post-taper phase. SOWS scores were positively correlated with monocyte chemoattractant protein-1 (MCP-1) in CSF (r = 0.70, p = 0.038) and plasma (r = 0.77, p = 0.015). Participants having higher levels of plasma MCP-1 reported higher SOWS, most notably after the buprenorphine taper ended.. Results from this study provide no evidence that pioglitazone reduces opioid withdrawal symptoms during buprenorphine taper. High correlations between MCP-1 and opioid withdrawal symptoms support a role of proinflammatory processes in opioid withdrawal.. clinicaltrials.gov identifier: NCT01517165.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Cytokines; Double-Blind Method; Female; Humans; Male; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Pioglitazone; Substance Withdrawal Syndrome

Buprenorphine is usually administered to treat opioid use disorder and pain syndromes. This research presents the first study regarding the effectiveness of different singly administered high doses of buprenorphine (a partial opioid agonist (of μ-opioid receptors), a potent opioid antagonist (of κ-receptors) and a partial agonist of nociception receptors) in reducing suicidal ideation in acutely depressed people with co-morbid opiate dependence. It follows small studies that suggest that ultra-low-dose buprenorphine may be useful in reducing suicidal ideation. The goal of this study was to describe the outcome of different doses of buprenorphine on suicidal opioid-dependent patients over a 3-day interval, by conducting a randomized clinical trial.. Fifty-one suicidal male inpatients who fulfilled the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for both opioid dependence and major depressive disorder were randomized to three groups (n = 17 per group) to receive a single, sublingual dose of buprenorphine (32 mg, 64 mg, or 96 mg). Out of 51 participants, there were 47 patients; 16 (34.04%) received 32 mg, 17 (36.17%) received 64 mg, and 14 (29.78%) received 96 mg of sublingual buprenorphine. They were evaluated by using psychometric assessment of the Beck Scale for Suicidal Ideation (BSSI) and interviews based on DSM-5 criteria. A placebo group was not included because of the high probability of severe withdrawal without active pharmacological treatment. The study was conducted with appropriate precautions and monitoring of respiratory and cardiovascular measures. The medication was administered while the patients were in moderate opiate withdrawal, as indicated by the presence of four to five withdrawal symptoms. A structured clinical interview was conducted, and urine toxicology testing was performed.. Patients completed the 3-day trial course. The outcomes illustrated a significant reduction in BSSI scores within each of the three groups, p < 0.01., but no difference in results between the groups, p = 0.408.. The results suggest that a single high dose of buprenorphine could rapidly treat suicidal ideations. A single high dose of buprenorphine may be a main-mechanism medication that gives a rapid treatment for suicidal opioid-dependent patients. Placebo-controlled trials are required to measure the safety and the physiological and psychological effects of this medication.

Topics: Administration, Sublingual; Adult; Analgesics, Opioid; Antidepressive Agents; Buprenorphine; Comorbidity; Depressive Disorder, Major; Double-Blind Method; Humans; Iran; Male; Opioid-Related Disorders; Substance Withdrawal Syndrome; Suicidal Ideation; Time Factors; Treatment Outcome

Opioid use disorder is one of the most prevalent addiction problems worldwide. Buprenorphine is used as a medication to treat this disorder, but in countries where buprenorphine is unavailable in combination with naloxone, diversion can be a problem if the medication is given outside a hospital setting.. The objective of this research is to evaluate the effect of a single, high dose of buprenorphine on craving in opioid-dependent patients over 5 days of abstinence from use of other opioids. The primary goal was to determine the safety and efficacy of buprenorphine during withdrawal in a hospital setting.. Ninety men who used opium, heroin, or prescribed opioids and met DSM-5 criteria for opioid use disorder (severe form) were randomized to three groups (n = 30 per group) to receive a single, sublingual dose of buprenorphine (32, 64, or 96 mg). The study was conducted in an inpatient psychiatric ward, with appropriate precautions and monitoring of respiratory and cardiovascular measures. Buprenorphine was administered when the patients were in moderate opiate withdrawal, as indicated by the presence of four to five symptoms. A structured clinical interview was conducted, and urine toxicology testing was performed at baseline. Self-reports of craving were obtained at baseline and on each of the 5 days after buprenorphine administration.. Craving decreased from baseline in each of the three groups (p < 0.0001), with a significant interaction between group and time (p < 0.038), indicating that groups with higher doses of buprenorphine had greater reduction.. A single, high dose of buprenorphine can reduce craving during opioid withdrawal; additional studies with follow-up are warranted to evaluate safety.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Craving; Double-Blind Method; Humans; Inpatients; Iran; Male; Opiate Substitution Treatment; Opioid-Related Disorders; Substance Withdrawal Syndrome; Time Factors; Treatment Outcome

We sought to test the effectiveness of methadone and buprenorphine in the treatment of methamphetamine withdrawal craving over a 17-day treatment period.. Patients were randomized into one of two groups. The study sample comprised 40 male subjects dependent on methamphetamine who met criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, for methamphetamine dependence and withdrawal and were seeking treatment. Furthermore, they should have a history of daily methamphetamine use for at least 6 months and should have discontinued their use just before starting the protocol. Patients received 40 mg of methadone or 8 mg of buprenorphine per day and were treated in an inpatient psychiatric hospital. We used methamphetamine craving score, negative urine drug screening test (thin-layer chromatography) during the study, and retention in treatment.. All 40 patients completed the study. Both drugs were effective in decreasing methamphetamine craving during methamphetamine withdrawal. Reduction of craving in the buprenorphine group was significantly more than in the methadone group (P < 0.05).. The results favor the efficacy and safety of buprenorphine as a short-term treatment for methamphetamine withdrawal craving. We should mention that it is to be expected that craving declines over time without any medication. Therefore, the conclusion may not be that methadone and buprenorphine both reduce the craving. Because buprenorphine is superior to methadone, only buprenorphine surely reduces craving.. Iranian Registry of Clinical Trials identifier: IRCT2015112125160N1 . Registered on 4 June 2016.

Topics: Adult; Amphetamine-Related Disorders; Analgesics, Opioid; Behavior, Addictive; Buprenorphine; Central Nervous System Stimulants; Craving; Double-Blind Method; Humans; Iran; Male; Methadone; Methamphetamine; Substance Withdrawal Syndrome; Time Factors; Treatment Outcome; Young Adult

Buprenorphine is an efficacious, widely used treatment for opioid use disorder (OUD). Daily oral transmucosal formulations can be associated with misuse, diversion, and nonadherence; these limitations may be obviated by a sustained release formulation.. To evaluate the ability of a novel, weekly, subcutaneous buprenorphine depot formulation, CAM2038, to block euphorigenic opioid effects and suppress opioid withdrawal in non-treatment-seeking individuals with OUD.. This multisite, double-blind, randomized within-patient study was conducted at 3 controlled inpatient research facilities. It involved 47 adults with DSM-V moderate-to-severe OUD. The study was conducted from October 12, 2015 (first patient enrolled), to April 21, 2016 (last patient visit).. A total of five 3-day test sessions evaluated the response to hydromorphone (0, 6, and 18 mg intramuscular in random order; 1 dose/session/day). After the first 3-day session (ie, qualification phase), participants were randomized to either CAM2038 weekly at 24 mg (n = 22) or 32 mg (n = 25); the assigned CAM2038 dose was given twice, 1 week apart (day 0 and 7). Four sets of sessions were conducted after randomization (days 1-3, 4-6, 8-10, and 11-13).. The primary end point was maximum rating on the visual analog scale for drug liking. Secondary end points included other visual analog scale (eg, high and desire to use), opioid withdrawal scales, and physiological and pharmacokinetic outcomes.. A total of 46 of 47 randomized participants (mean [SD] age, 35.5 [9] years; 76% male [n = 35]) completed the study. Both weekly CAM2038 doses produced immediate and sustained blockade of hydromorphone effects (liking maximum effect, CAM2038, 24 mg: effect size, 0.813; P < .001, and CAM2038, 32 mg: effect size, 0.753; P < .001) and suppression of withdrawal (Clinical Opiate Withdrawal Scale, CAM2038, 24 mg: effect size, 0.617; P < .001, and CAM2038, 32 mg: effect size, 0.751; P < .001). CAM2038 produces a rapid initial rise of buprenorphine in plasma with maximum concentration around 24 hours, with an apparent half-life of 4 to 5 days and approximately 50% accumulation of trough concentration from first to second dose (trough concentration = 0.822 and 1.23 ng/mL for weeks 1 and 2, respectively, with 24 mg; trough concentration = 0.993 and 1.47 ng/mL for weeks 1 and 2, respectively, with 32 mg).. CAM2038 weekly, 24 and 32 mg, was safely tolerated and produced immediate and sustained opioid blockade and withdrawal suppression. The results support the use of this depot formulation for treatment initiation and stabilization of patients with OUD, with the further benefit of obviating the risk for misuse and diversion of daily buprenorphine while retaining its therapeutic benefits.. Clinicaltrials.gov Identifier: NCT02611752.

Topics: Adolescent; Adult; Analgesics, Opioid; Buprenorphine; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Hydromorphone; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Substance Withdrawal Syndrome; Treatment Outcome; Young Adult

Opioid use disorder (OUD) is a significant public health problem. Supervised withdrawal (ie, detoxification) from opioids using clonidine or buprenorphine hydrochloride is a widely used treatment.. To evaluate whether tramadol hydrochloride extended-release (ER), an approved analgesic with opioid and nonopioid mechanisms of action and low abuse potential, is effective for use in supervised withdrawal settings.. A randomized clinical trial was conducted in a residential research setting with 103 participants with OUD. Participants' treatment was stabilized with morphine, 30 mg, administered subcutaneously 4 times daily. A 7-day taper using clonidine (n = 36), tramadol ER (n = 36), or buprenorphine (n = 31) was then instituted, and patients were crossed-over to double-blind placebo during a post-taper period. The study was conducted from October 25, 2010, to June 23, 2015.. Retention, withdrawal symptom management, concomitant medication utilization, and naltrexone induction. Results were analyzed over time and using area under the curve for the intention-to-treat and completer groups.. Of the 103 participants, 88 (85.4%) were men and 43 (41.7%) were white; mean (SD) age was 28.9 (10.4) years. Buprenorphine participants (28 [90.3%]) were significantly more likely to be retained at the end of the taper compared with clonidine participants (22 [61.1%]); tramadol ER retention was intermediate and did not differ significantly from that of the other groups (26 [72.2%]; χ2 = 8.5, P = .01). Time-course analyses of withdrawal revealed significant effects of phase (taper, post taper) for the Clinical Opiate Withdrawal Scale (COWS) score (taper mean, 5.19 [SE, .26]; post-taper mean, 3.97 [SE, .23]; F2,170 = 3.6, P = .03) and Subjective Opiate Withdrawal Scale (SOWS) score (taper mean,8.81 [SE, .40]; post-taper mean, 4.14 [SE, .30]; F2,170 = 15.7, P < .001), but no group effects or group × phase interactions. Analyses of area under the curve of SOWS total scores showed significant reductions (F2,159 = 17.7, P < .001) in withdrawal severity between the taper and post-taper periods for clonidine (taper mean, 13.1; post-taper mean, 3.2; P < .001) and tramadol ER (taper mean, 7.4; post-taper mean, 2.8; P = .03), but not buprenorphine (taper mean, 6.4; post-taper mean, 7.4). Use of concomitant medication increased significantly (F2,159 = 30.7,  P < .001) from stabilization to taper in the clonidine (stabilization mean, 0.64 [SE, .05]; taper mean, 1.54 [SE, .10]; P < .001) and tramadol ER (stabilization mean, 0.53 [SE, .05]; taper mean, 1.19 [SE, .09]; P = .003) groups and from stabilization to post taper in the buprenorphine group (stabilization mean, 0.46 [SE, .05] post-taper mean, 1.17 [SE, .09]; P = .006), suggesting higher withdrawal for those groups during those periods. Naltrexone initiation was voluntary and the percentage of participants choosing naltrexone therapy within the clonidine (8 [22.2%]), tramadol ER (7 [19.4%]), or buprenorphine (3 [9.7%]) groups did not differ significantly (χ2 = 2.5, P = .29).. The results of this trial suggest that tramadol ER is more effective than clonidine and comparable to buprenorphine in reducing opioid withdrawal symptoms during a residential tapering program. Data support further examination of tramadol ER as a method to manage opioid withdrawal symptoms.. Clinicaltrials.gov Identifier: NCT01188421.

Topics: Adult; Analgesics; Analgesics, Opioid; Buprenorphine; Clonidine; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Male; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Substance Withdrawal Syndrome; Tramadol; Treatment Outcome; Young Adult

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

Most patients relapse to opioids within one month of opioid agonist detoxification, making the antecedents and parallel processes of first use critical for investigation. Craving and withdrawal are often studied in relationship to opioid outcomes, and a novel analytic strategy applied to these two phenomena may indicate targeted intervention strategies.. Specifically, this secondary data analysis of the Prescription Opioid Addiction Treatment Study used a discrete-time mixture analysis with time-to-first opioid use (survival) simultaneously predicted by craving and withdrawal growth trajectories. This analysis characterized heterogeneity among prescription opioid-dependent individuals (N=653) into latent classes (i.e., latent class analysis [LCA]) during and after buprenorphine/naloxone stabilization and taper.. A 4-latent class solution was selected for overall model fit and clinical parsimony. In order of shortest to longest time-to-first use, the 4 classes were characterized as 1) high craving and withdrawal, 2) intermediate craving and withdrawal, 3) high initial craving with low craving and withdrawal trajectories and 4) a low initial craving with low craving and withdrawal trajectories. Odds ratio calculations showed statistically significant differences in time-to-first use across classes.. Generally, participants with lower baseline levels and greater decreases in craving and withdrawal during stabilization combined with slower craving and withdrawal rebound during buprenorphine taper remained opioid-free longer. This exploratory work expanded on the importance of monitoring craving and withdrawal during buprenorphine induction, stabilization, and taper. Future research may allow individually tailored and timely interventions to be developed to extend time-to-first opioid use.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Craving; Disease-Free Survival; Female; Humans; Male; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Outpatients; Recurrence; Substance Withdrawal Syndrome; Treatment Outcome

The effects of steady-state faldaprevir on the safety, pharmacokinetics, and pharmacodynamics of steady-state methadone and buprenorphine-naloxone were assessed in 34 healthy male and female subjects receiving stable addiction management therapy. Subjects continued receiving a stable oral dose of either methadone (up to a maximum dose of 180 mg per day) or buprenorphine-naloxone (up to a maximum dose of 24 mg-6 mg per day) and also received oral faldaprevir (240 mg) once daily (QD) for 8 days following a 480-mg loading dose. Serial blood samples were taken for pharmacokinetic analysis. The pharmacodynamics of the opioid maintenance regimens were evaluated by the objective and subjective opioid withdrawal scales. Coadministration of faldaprevir with methadone or buprenorphine-naloxone resulted in geometric mean ratios for the steady-state area under the concentration-time curve from 0 to 24 h (AUC(0-24,ss)), the steady-state maximum concentration of the drug in plasma (C(max,ss)), and the steady-state concentration of the drug in plasma at 24 h (C(24,ss)) of 0.92 to 1.18 for (R)-methadone, (S)-methadone, buprenorphine, norbuprenorphine, and naloxone, with 90% confidence intervals including, or very close to including, 1.00 (no effect), suggesting a limited overall effect of faldaprevir. Although individual data showed moderate variability in the exposures between subjects and treatments, there was no evidence of symptoms of opiate overdose or withdrawal either during the coadministration of faldaprevir with methadone or buprenorphine-naloxone or after faldaprevir dosing was stopped. Similar faldaprevir exposures were observed in the methadone- and buprenorphine-naloxone-treated subjects. In conclusion, faldaprevir at 240 mg QD can be coadministered with methadone or buprenorphine-naloxone without dose adjustment, although given the relatively narrow therapeutic windows of these agents, monitoring for opiate overdose and withdrawal may still be appropriate. (This study has been registered at ClinicalTrials.gov under registration no. NCT01637922.).

Topics: Administration, Oral; Adult; Aminoisobutyric Acids; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Drug Interactions; Female; Humans; Leucine; Male; Methadone; Middle Aged; Oligopeptides; Proline; Quinolines; Substance Withdrawal Syndrome; Substance-Related Disorders; Thiazoles; Young Adult

To investigate the efficacy and safety of Ji-Tai tablet and Ji-Tai tablet combined with buprenorphine in the treatment of patients with acute withdrawal syndrome of mild heroin dependence.. A total of 150 patients with mild heroin dependence were recruited, and were randomly assigned to a Ji-Tai tablet group (n=50), a Ji-Tai tablet combined with buprenorphine group (n=50) and a control group (n=50) during a 10-day clinical trial. Opiate withdrawal scale (OWS) was used to measure the severity of withdrawal symptoms. Anxiety symptoms assessments were made at 0 day (baseline), the day 5 (middle), and the day 10 (end) by the Hamilton anxiety scale (HAMA). Symptoms were assessed before and 1 h or 2 h after medication each day. The total withdrawal symptoms scores and the daily reduction rate were used to measure the effect of Ji-Tai tablet vs Ji- Tai tablet plus buprenorphine. Safety evaluation was carried out by the following measures: baseline of treatment, drug side effects after the treatment, vital signs (blood pressure, heart rate, and respiration rate), laboratory examination (routine blood and urine tests and the liver and kidney function tests), and electrocardiograms.. A total of 142 mild heroin dependence patients performed the experiments (including 48 in the Ji-Tai tablet group, 48 in the Ji-Tai tablet with buprenorphine group and 46 in the control group). The scores of baseline withdrawal symptoms were 43.520±19.786, 42.640±17.648 and 47.100±24.450, respectively, with no significant differences among the 3 groups (all P>0.05 ). During the 10-day treatment, the reduction rate of acute withdrawal symptoms scores increased daily, the acute withdrawal syndrome scores and the anxiety symptoms scores declined from day 0 to day 10, there was also no significant difference among the 3 groups (all P>0.05). Ji-Tai tablet did not affect vital signs such as blood pressure, heart rate, and respiration rate.. Ji-Tai tablet or Ji-Tai tablet combined with buprenorphine had no effect on acute withdrawal symptoms of mild heroin dependence.

Topics: Anxiety; Buprenorphine; Double-Blind Method; Drugs, Chinese Herbal; Heroin Dependence; Humans; Substance Withdrawal Syndrome; Tablets

The authors tested whether clonidine blocks stress-induced seeking of heroin and cocaine. The study was also intended to confirm translational findings from a rat model of drug relapse by using ecological momentary assessment of patients' stress to test hypotheses about clonidine's behavioral mechanism of action.. The authors conducted a randomized double-blind placebo-controlled clinical trial with 208 opioid-dependent patients at an outpatient buprenorphine clinic. The 118 participants (57%) who maintained abstinence during weeks 5-6 were continued on buprenorphine and randomly assigned to receive clonidine (N=61) or placebo (N=57) for 14 weeks. Urine was tested thrice weekly. Lapse was defined as any opioid-positive or missed urine test, and relapse as two or more consecutive lapses. Time to lapse and relapse were examined with Cox regressions; longest period of abstinence was examined with a t test, and ecological momentary assessment data were examined with generalized linear mixed models.. In an intent-to-treat analysis, clonidine produced the longest duration (in consecutive days) of abstinence from opioids during the intervention phase (34.8 days [SD=3.7] compared with 25.5 days [SD=2.7]; Cohen's d=0.38). There was no group difference in time to relapse, but the clonidine group took longer to lapse (hazard ratio=0.67, 95% CI=0.45-1.00). Ecological momentary assessment showed that daily-life stress was partly decoupled from opioid craving in the clonidine group, supporting the authors' hypothesized mechanism for clonidine's benefits.. Clonidine, a readily available medication, is useful in opioid dependence not just for reduction of withdrawal signs, but also as an adjunctive maintenance treatment that increases duration of abstinence. Even in the absence of physical withdrawal, it decouples stress from craving in everyday life.

Topics: Adult; Analgesics; Buprenorphine; Clonidine; Craving; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Maintenance Chemotherapy; Male; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Proportional Hazards Models; Substance Withdrawal Syndrome; Treatment Outcome

Buprenorphine is an effective and popular treatment for opioid dependence. It remains unclear, however, when or how to transition stable buprenorphine-maintained individuals to complete abstinence. This trial investigates the feasibility of using naltrexone to facilitate buprenorphine discontinuation in stable individuals who had tolerated a taper to 2mg or less but were unable to terminate entirely due to withdrawal-related distress.. The sample consisted of 6 buprenorphine-maintained individuals in sustained full remission, and who had tolerated a taper but were unable to discontinue altogether. A rapid induction procedure was performed, which included supervised buprenorphine discontinuation, oral naltrexone titration with a starting dose of 6.25mg, and administration of long-acting injectable naltrexone. Participants were followed weekly for 5weeks after the injection, with telephone follow-up occurring at 6months.. The rapid induction procedure was well tolerated. There was no observed or reported clinical worsening over the course of study participation. Notably, no participants experienced an increase in Subjective Opioid Withdrawal Scale (SOWS) scores after the first oral dose of NTX as compared to day 1 (24hours after last dose of buprenorphine); instead, SOWS scores decreased between days 1 and 7 (p=0.043). All participants were able to discontinue buprenorphine and to remain opioid free during the trial and at follow-up.. This preliminary trial represented for all participants the first successful attempt at buprenorphine discontinuation. Further research is needed to better understand if naltrexone is effective at facilitating buprenorphine discontinuation, as well as the feasibility of a sequential approach (buprenorphine stabilization to naltrexone) for opioid use disorders.

Topics: Administration, Oral; Adult; Buprenorphine; Drug Administration Schedule; Feasibility Studies; Female; Humans; Injections; Male; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Substance Withdrawal Syndrome; Treatment Outcome

Prescription opioid (PO) abuse has become an urgent public health issue in the United States. Detoxification is one important treatment option, yet relatively little is known about the time course and severity of opioid withdrawal during buprenorphine detoxification.. This is a secondary analysis of data from a randomized, placebo-controlled, double-blind evaluation of 1, 2, and 4-week outpatient buprenorphine tapers among primary prescription opioid (PO) abusers. The aim is to characterize the time course and severity of buprenorphine withdrawal under rigorous, double-blind conditions, across multiple taper durations, and using multiple withdrawal-related measures (i.e., self-report and observer ratings, pupil diameter, ancillary medication utilization). Participants were PO-dependent adults undergoing buprenorphine detoxification and biochemically-verified to be continuously abstinent from opioids during their taper (N = 28).. Participants randomly assigned to the 4-week taper regimen experienced a relatively mild and stable course of withdrawal, with few peaks in severity. In contrast, the 1- and 2-week taper groups experienced stark increases in withdrawal severity during the week following the last buprenorphine dose, followed by declines in withdrawal severity thereafter. The 4-week taper group also reported significantly fewer disruptions in sleep compared to the other experimental groups. When predictors of withdrawal were examined, baseline ratings of "Expected Withdrawal Severity" was the most robust predictor of withdrawal experienced during the taper.. Data from this trial may inform clinicians about the expected time course, magnitude, and pattern of buprenorphine withdrawal and aid efforts to identify patients who may need additional clinical support during outpatient buprenorphine detoxification.

Topics: Adult; Buprenorphine; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Acuity; Prescription Drug Misuse; Substance Withdrawal Syndrome; Treatment Outcome; United States

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 approval of extended release injectable naltrexone (XR-NTX; Vivitrol(®)) has introduced a new option for treating opioid addiction, but studies are needed to identify its place within the spectrum of available therapies. The absence of physiological opioid dependence is a necessary and challenging first step for starting XR-NTX. Outpatient detoxification gives poor results and inpatient detoxification is either unavailable or too brief for the physiological effects of opioids to resolve. Here we present findings from an open label study that tested whether the transition from opioid addiction to XR-NTX can be safely and effectively performed in an outpatient setting using very low dose naltrexone and buprenorphine.. Twenty treatment seeking opioid addicted individuals were given increasing doses of naltrexone starting at 0.25mg with decreasing doses of buprenorphine starting at 4 mg during a 7-day outpatient XR-NTX induction procedure. Withdrawal discomfort, craving, drug use, and adverse events were assessed daily until the XR-NTX injection, then weekly over the next month.. Fourteen of the 20 participants received XR-NTX and 13 completed weekly assessments. Withdrawal, craving, and opioid or other drug use were significantly lower during induction and after XR-NTX administration compared with baseline, and no serious adverse events were recorded.. Outpatient transition to XR-NTX combining upward titration of very low dose naltrexone with downward titration of low dose buprenorphine was safe, well tolerated, and completed by most participants. Further studies with larger numbers of subjects are needed to see if this approach is useful for naltrexone induction.

Topics: Adult; Buprenorphine; Craving; Delayed-Action Preparations; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Outpatients; Substance Withdrawal Syndrome; Young Adult

Prescription opioid dependence is increasing and creates a significant public health burden, but primary care physicians lack evidence-based guidelines to decide between tapering doses followed by discontinuation of buprenorphine hydrochloride and naloxone hydrochloride therapy (hereinafter referred to as buprenorphine therapy) or ongoing maintenance therapy.. To determine the efficacy of buprenorphine taper vs ongoing maintenance therapy in primary care-based treatment for prescription opioid dependence.. We conducted a 14-week randomized clinical trial that enrolled 113 patients with prescription opioid dependence from February 17, 2009, through February 1, 2013, in a single primary care site.. Patients were randomized to buprenorphine taper (taper condition) or ongoing buprenorphine maintenance therapy (maintenance condition). The buprenorphine taper was initiated after 6 weeks of stabilization, lasted for 3 weeks, and included medications for opioid withdrawal, after which patients were offered naltrexone treatment. The maintenance group received ongoing buprenorphine therapy. All patients received physician and nurse support and drug counseling.. Illicit opioid use via results of urinanalysis and patient report, treatment retention, and reinitiation of buprenorphine therapy (taper group only).. During the trial, the mean percentage of urine samples negative for opioids was lower for patients in the taper group (35.2% [95% CI, 26.2%-44.2%]) compared with those in the maintenance group (53.2% [95% CI, 44.3%-62.0%]). Patients in the taper group reported more days per week of illicit opioid use than those in the maintenance group once they were no longer receiving buprenorphine (mean use, 1.27 [95% CI, 0.60-1.94] vs 0.47 [95% CI, 0.19-0.74] days). Patients in the taper group had fewer maximum consecutive weeks of opioid abstinence compared with those in the maintenance group (mean abstinence, 2.70 [95% CI, 1.72-3.75] vs 5.20 [95% CI, 4.16-6.20] weeks). Patients in the taper group were less likely to complete the trial (6 of 57 [11%] vs 37 of 56 [66%]; P < .001). Sixteen patients in the taper group reinitiated buprenorphine treatment after the taper owing to relapse.. Tapering is less efficacious than ongoing maintenance treatment in patients with prescription opioid dependence who receive buprenorphine therapy in primary care.. clinicaltrials.gov Identifier: NCT00555425.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Drug Administration Schedule; Female; Humans; Male; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Prescription Drugs; Primary Health Care; Recurrence; Substance Withdrawal Syndrome; Treatment Outcome; Urinalysis

We aim to examine predictors of opiate abstinence status 3 months after the end of buprenorphine/naloxone treatment for opioid-dependent participants.. Participants (n= 516, age > 15 years) received buprenorphine/ naloxone treatment for 4 weeks and then randomly assigned to undergo dose tapering over either 7 days or 28 days. Bivariate analysis was performed to identify possible predictors of successful opiate abstinence outome (p-value < 0.10). Logistic regression analysis with backward stepwise selection was, then, performed to produce final model containing independent predictors at p-value < 0.05.. Bivariate analysis identified several possible predictors including: opioid and drug urine tests result at the end taper; employment status, family problems, and alcohol use domains of addiction severity index (ASI) score; and clinical opiate withdrawal scale (COWS) at the end of stabilization. Final predictor list identified by logistic regression include: ASI score for family and alcohol problems, COWS at the end of stabilization and opiate urine test at the end of taper.. Participants presenting with a negative urine test for opiate, more severe alcohol, more severe family problems, or more symptoms of opiate withdrawal at the end of stabilization were more likely to have a successful opiate abstinence.

Topics: Adolescent; Adult; Aged; Analgesics, Opioid; Buprenorphine; Female; Humans; Logistic Models; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Substance Withdrawal Syndrome; Treatment Outcome; Young Adult

Interactions between human immuno-deficiency virus (HIV) and opioid-dependence therapies can occur.. We sought to determine whether such interactions occurred between buprenorphine/naloxone and raltegravir.. We performed a within-subject open-labeled pharmacokinetic and pharmacodynamic study in 12 HIV-seronegative subjects stabilized on at least 3 weeks of buprenorphine/naloxone therapy. Subjects underwent baseline and steady-state evaluation of the effect of raltegravir 400 mg BID on buprenorphine/naloxone parameters.. Compared with baseline values, buprenorphine AUC(0-24 h) (58.2 vs. 56.0 hr*ng/mL) and C(max) (7.37 vs. 6.60 ng/mL) did not differ significantly after achieving steady-state raltegravir. Similar analyses of norbuprenorphine, the primary metabolite of buprenorphine, demonstrated no significant difference after raltegravir administration. Naloxone concentrations were unchanged for AUC(0-24 h) (.595 vs. .581 hr*ng/mL), C(max) (.251 vs. .243 ng/mL) and T(max) (.75 vs.1.08 h). Objective opioid withdrawal was not observed. The AUC(0-12 h) and C(max) of raltegravir did not significantly differ from historical controls (5543 vs. 4428 h*ng/mL and 1070 vs. 1266 ng/mL), respectively.. The addition of raltegravir to stabilized patients receiving buprenorphine/naloxone does not significantly affect buprenorphine/naloxone or raltegravir pharmacokinetic or pharmacodynamic parameters.

Topics: Adult; Antiviral Agents; Buprenorphine; Drug Combinations; Drug Interactions; Female; Glucuronosyltransferase; HIV Seronegativity; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Pyrrolidinones; Raltegravir Potassium; Substance Withdrawal Syndrome

Induction onto buprenorphine during pregnancy may be more challenging than induction onto methadone. This study explores factors predicting withdrawal intensities and compares trajectories of withdrawal during the induction phase between opioid-dependent women randomly assigned to methadone or buprenorphine.. A secondary analysis was conducted on data from 175 opioid-dependent pregnant women inducted onto buprenorphine or methadone subsequent to stabilization on morphine sulfate. ANOVA analyses were conducted to determine differences between mean peak CINA scores by medication and completion status. General linear mixed models were fitted to compare trajectories of CINA scores between methadone and buprenorphine conditions, and between study dropouts and completers within the buprenorphine condition.. Both buprenorphine and methadone patients experienced withdrawal categorized as minimal by the CINA scoring system. Significant differences in mean peak CINA scores for the first 72 hours of induction were found between the methadone (4.5; SD=0.4) and buprenorphine conditions (6.9; SD=0.4), with buprenorphine patients exhibiting higher mean peak CINA scores [F (3, 165)=9.70, p<0.001]. The trajectory of CINA scores showed buprenorphine patients exhibiting a sharper increase in mean CINA scores than methadone patients [F (1, 233)=8.70, p=0.004]. There were no differences in mean peak CINA scores [F (3, 77)=0.08, p=0.52] or in trajectory of CINA scores [F (1, 166)=0.42, p=0.52] between buprenorphine study dropouts and completers.. While mean peak CINA score was significantly higher in the buprenorphine condition than the methadone condition, neither medication condition experienced substantial withdrawal symptoms. Further research on factors related to successful induction to buprenorphine treatment in pregnant women is needed.

Topics: Adult; Analysis of Variance; Buprenorphine; Confidence Intervals; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Educational Status; Ethnicity; Female; Humans; Linear Models; Methadone; Morphine; Narcotics; Patient Dropouts; Pregnancy; Pregnancy Complications; Socioeconomic Factors; Substance Withdrawal Syndrome

The Controlled Substances Act requires physicians in the United States to provide or refer to behavioral treatment when treating opioid-dependent individuals with buprenorphine; however, no research has examined the combination of buprenorphine with different types of behavioral treatments. This randomized controlled trial compared the effectiveness of four behavioral treatment conditions provided with buprenorphine and medical management (MM) for the treatment of opioid dependence.. After a 2-week buprenorphine induction/stabilization phase, participants were randomized to one of four behavioral treatment conditions provided for 16 weeks: cognitive behavioral therapy (CBT = 53); contingency management (CM = 49); both CBT and CM (CBT + CM = 49); and no additional behavioral treatment (NT = 51).. Study activities occurred at an out-patient clinical research center in Los Angeles, California, USA.. Included were 202 male and female opioid-dependent participants.. Primary outcome was opioid use, measured as a proportion of opioid-negative urine results over the number of tests possible. Secondary outcomes include retention, withdrawal symptoms, craving, other drug use and adverse events.. No group differences in opioid use were found for the behavioral treatment phase (χ2  = 1.25, P = 0.75), for a second medication-only treatment phase, or at weeks 40 and 52 follow-ups. Analyses revealed no differences across groups for any secondary outcome.. There remains no clear evidence that cognitive behavioural therapy and contingency management reduce opiate use when added to buprenorphine and medical management in opiate users seeking treatment.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Cognitive Behavioral Therapy; Combined Modality Therapy; Female; Humans; Los Angeles; Male; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Outpatients; Substance Withdrawal Syndrome; Treatment Outcome; Young Adult

This pilot study examined the efficacy of the N-type calcium channel blocker gabapentin to improve outcomes during a brief detoxification protocol with buprenorphine. Treatment-seeking opioid-dependent individuals were enrolled in a 5-week, double-blind, placebo-controlled trial examining the effects of gabapentin during a 10-day outpatient detoxification from buprenorphine. Participants were inducted onto buprenorphine sublingual tablets during Week 1, were randomized and inducted onto gabapentin or placebo during Week 2, underwent a 10-day buprenorphine taper during Weeks 3 and 4, and then were tapered off gabapentin/placebo during Week 5. Assessments included thrice-weekly opioid withdrawal scales, vitals, and urine drug screens. Twenty-four individuals (13 male; 17 Caucasian, 3 African American, 4 Latino; mean age 29.7 years) participated in the detoxification portion of the study (gabapentin, n = 11; placebo, n = 13). Baseline characteristics did not differ significantly between groups. Self-reported and observer-rated opioid withdrawal ratings were relatively low and did not differ between groups during the buprenorphine taper. Urine results showed a Drug × Time interaction, such that the probability of opioid-positive urines significantly decreased over time in the gabapentin versus placebo groups during Weeks 3 and 4 (OR = 0.73, p = .004). These results suggest that gabapentin reduces opioid use during a 10-day buprenorphine detoxification procedure.

Topics: Adult; Amines; Buprenorphine; Cyclohexanecarboxylic Acids; Diagnostic and Statistical Manual of Mental Disorders; Directly Observed Therapy; Double-Blind Method; Excitatory Amino Acid Antagonists; Female; Gabapentin; gamma-Aminobutyric Acid; Humans; Induction Chemotherapy; Maintenance Chemotherapy; Male; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Dropouts; Pilot Projects; Secondary Prevention; Severity of Illness Index; Substance Withdrawal Syndrome

Using buprenorphine as a medication to treat opioid dependence is becoming more prevalent as illicit opiate use increases. Identifying the characteristics of opiate dependent individuals best suited to benefit from buprenorphine would improve guidelines for its administration. This study evaluates baseline and treatment participation variables for predicting positive response to short-term stabilization with buprenorphine. Data include demographic, drug use, and other variables collected from participants undergoing stabilization over a 4-week period before being tapered off buprenorphine in a short-term detoxification process. Outcome variables include opioid use and retention. Logistic regression results indicate several characteristics associated with opioid use at the end of the stabilization period. These include being older, having no criminal history, and less opiate use. Criminal activity and opioid use in the last 30 days were significantly associated with shorter treatment stays. The benefits of identifying individual characteristics that may predict treatment response are discussed.

Topics: Age Factors; Buprenorphine; Crime; Female; Humans; Logistic Models; Male; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Psychiatric Status Rating Scales; Substance Withdrawal Syndrome; Time Factors; Treatment Outcome

To provide controlled data on direct induction with buprenorphine/naloxone (BNX) versus indirect buprenorphine (BPN)-to-BNX induction.. Phase 4, prospective, randomized, active-drug controlled, parallel-group trial consisting of a 2-day, double-blind, double-dummy induction phase followed by 26 days of open-label treatment with BNX.. Nineteen sites in 10 European countries from March 2008 to December 2009.. A total of 187 opioid-dependent men and women ≥ 15 years of age.. The primary objective was assessment of patient response to direct and indirect BNX induction [proportion of patients receiving the scheduled 16-mg BNX dose on day 3 (i.e. first day post-induction)]. Secondary assessments included illicit drug use, treatment retention and compliance, withdrawal scale scores, and safety.. Patient response to direct- versus indirect-BNX induction was similar [direct 91.4% (85/93) versus indirect 90.4% (85/94); 95% confidence interval (CI): -7.3%, 9.2%]. Rapid dose induction (16 mg of BPN equivalent on day 2) was acceptable and 72% of patients completed treatment (day 28). There were no significant differences in secondary measures across groups. An average BNX maintenance dose of 15.3 mg across groups was associated with substantial reductions in illicit opioid use and no self-reported intravenous misuse. Treatment compliance and retention rates were similar (98.5% and 81.3%, respectively). Treatment-emergent adverse event rates were comparable: 75% versus 74% for direct- versus indirect-induction groups, respectively.. Direct buprenorphine/naloxone induction was a safe and effective strategy for maintenance treatment of opioid dependence. Response to high-dose direct buprenorphine/naloxone induction appears to be similar to indirect buprenorphine-to-buprenorphine/naloxone induction and was not associated with reports of intravenous buprenorphine/naloxone misuse.

Topics: Administration, Sublingual; Adolescent; Adult; Buprenorphine; Drug Combinations; Europe; Female; Heroin Dependence; Humans; Induction Chemotherapy; Intention to Treat Analysis; Maintenance Chemotherapy; Male; Middle Aged; Naloxone; Narcotic Antagonists; Patient Compliance; Prospective Studies; Substance Abuse, Intravenous; Substance Withdrawal Syndrome; 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

Prescription opioid (PO)-dependent treatment presentations are becoming increasingly common; however, most research on the treatment of opioid-dependent populations has been conducted in heroin users. The aim of this secondary data analysis was to compare the buprenorphine induction experience of 167 heroin and 61 PO users. Results demonstrate that although the groups differed on some baseline characteristics, many of the key induction experience variables were comparable between the groups. Heroin users were found to have significantly higher preinduction Clinical Opiate Withdrawal Scale (COWS) scores (p = .014) and postinduction COWS score (p = .008) compared with the PO users. No differences between groups were found for self-reported craving and withdrawal scores, mean buprenorphine dose on Day 1, or retention at the end of the first week. The findings of this study suggest that existing buprenorphine induction practices developed for heroin users appear to be equally effective with PO users.

Topics: Adult; Aged; Buprenorphine; Female; Follow-Up Studies; Heroin Dependence; Humans; Male; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Prescription Drugs; Substance Withdrawal Syndrome; Treatment Outcome

Lapse to opiate use after initiation of buprenorphine treatment is common and is a strong predictor of poor treatment retention and increased risk of long-term opiate use. Drug cues and situations or events associated with distress are known to provoke craving and increase risk for lapse. This study evaluated the predictive validity of a behavioral index of persistence during a stress challenge among opiate users identified as affectively vulnerable to lapse risk due to elevated depressive symptoms.. Patients from an ongoing clinical trial (n = 48) completed a stress-challenge task before receiving their first dose of buprenorphine.. After controlling for levels of craving on their induction day, persistence on the stress-challenge task before initiating buprenorphine treatment was associated with successful transition to early abstinence, and lower rates of opiate use during the initial 3 months of buprenorphine treatment across antidepressant and placebo groups.. Results from this preliminary study suggest the promise of laboratory-based behavioral paradigms in facilitating an understanding of important mechanisms of early lapse. Identifying individual behavioral responses to drug and stress cues before attempts at abstinence may facilitate delivery of adjunctive behavioral treatments to prevent early lapse.

Topics: Adult; Antidepressive Agents, Second-Generation; Buprenorphine; Citalopram; Comorbidity; Depressive Disorder; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Medication Adherence; Middle Aged; Motivation; Narcotics; Opioid-Related Disorders; Patient Dropouts; Probability; Risk Assessment; Stress, Psychological; Substance Abuse Detection; Substance Withdrawal Syndrome

A sublingual soluble-film formulation of buprenorphine/naloxone (B/N) has been approved by the US Food and Drug Administration for the treatment of opioid dependency. This preparation provides unit-dose, child-resistant packaging amenable to tracking and accountability, offers more rapid dissolution, and has a potentially preferred taste vs. tablets. This study compared the ability of buprenorphine (B) and B/N films to suppress spontaneous withdrawal in opioid-dependent volunteers. Participants were maintained on morphine and underwent challenge sessions to confirm sensitivity to naloxone-induced opioid withdrawal. Subjects were randomized to receive either B (16 mg, n = 18) or B/N (16/4 mg, n = 16) soluble films for 5 days. The primary outcome measure was the Clinical Opiate Withdrawal Scale (COWS) score. Thirty-four subjects completed induction onto soluble films. There was a significant decrease in COWS scores but no significant differences between the groups. The results support the use of B and B/N soluble films as safe and effective delivery methods for opioid induction.

Topics: Administration, Sublingual; Adult; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Double-Blind Method; Drug Approval; Drug Packaging; Female; Humans; Male; Medication Systems; Middle Aged; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Solubility; Substance Withdrawal Syndrome; Tablets; Taste; United States; United States Food and Drug Administration

Despite findings that opioid detoxification serves little more than a palliative function, few patients who enter detoxification subsequently transition to long-term treatment. The current study evaluated intensive role induction (IRI), a strategy adapted from a single-session intervention previously shown to facilitate engagement of substance-dependent patients in drug-free treatment. IRI was delivered either alone or combined with case management (IRI+CM) to determine the capacity of each condition to enhance transition and engagement in long-term treatment of detoxification patients. Study participants were 240 individuals admitted to a 30-day buprenorphine detoxification delivered at a publicly funded outpatient drug treatment clinic. Following clinic intake, participants were randomly assigned to IRI, IRI+CM, or standard clinic treatment (ST). Outcomes were assessed in terms of adherence and satisfaction with the detoxification program, detoxification completion, and transition and retention in treatment following detoxification. Participants who received IRI and IRI+CM attended more counseling sessions during detoxification than those who received ST (both ps<.001). IRI, but not IRI+CM participants, were more likely to complete detoxification (p=.017), rated their counselors more favorably (p=.01), and were retained in long-term treatment for more days following detoxification (p=.005), than ST participants. The current study demonstrated that an easily administered psychosocial intervention can be effective for enhancing patient involvement in detoxification and for enabling their engagement in long-term treatment following detoxification.

Topics: Adult; Ambulatory Care Facilities; Buprenorphine; Case Management; Certification; Counseling; Female; Humans; Male; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Satisfaction; Psychometrics; Psychotherapy; Standard of Care; Substance Withdrawal Syndrome; Tape Recording; Time Factors; Treatment Outcome

Previous work suggests that opioid users have lower health-related quality of life (HRQOL) than patients with more prevalent chronic illnesses such as hypertension or diabetes. Although comparisons with population norms are informative, studies of the correlates of HRQOL for opioid users are needed to plan clinical services.. We tested a conceptual model of the pathways between physiologic factors and symptoms in relation to HRQOL among 344 opioid users in a clinical trial. Physical and mental HRQOL were measured by the Short-Form (SF)-36; withdrawal signs, symptoms, and functioning were also measured with validated instruments. Using structural equation modeling, we tested hypotheses that medical history directly predicts withdrawal signs and symptoms, and that medical history, withdrawal signs and symptoms, and functioning predict the physical and mental HRQOL latent variables of the SF-36.. Most hypothesized relationships were significant, and model fit was good. The model explained 36% of the variance in mental HRQOL and 34% of the variance in physical HRQOL.. The conceptual framework appears valid for explaining variation in the physical and mental HRQOL of opioid users undergoing medically managed withdrawal. Analysis of longitudinal data would help to evaluate more rigorously the adequacy of the model for explaining HRQOL in opioid withdrawal.

Topics: Adolescent; Adult; Analgesics, Opioid; Body Mass Index; Buprenorphine; Humans; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Quality of Life; Severity of Illness Index; Sickness Impact Profile; Substance Withdrawal Syndrome; Young Adult

This pilot study tested the effectiveness of transcutaneous electric acupoint stimulation (TEAS) as an adjunctive treatment for inpatients receiving opioid detoxification with buprenorphine-naloxone at a private psychiatric hospital. Participants (N = 48) were randomly assigned to active or sham TEAS and received three 30-minute treatments daily for 3 to 4 days. In active TEAS, current was set to maximal tolerable intensity (8-15 mA); in sham TEAS, it was set to 1 mA. By 2 weeks postdischarge, participants in active TEAS were less likely to have used any drugs (35% vs. 77%, p < .05). They also reported greater improvements in pain interference (F = 4.52, p < .05) and physical health (F = 4.84, p < .01) over time. TEAS is an acceptable, inexpensive adjunctive treatment that is feasible to implement on an inpatient unit and may be a beneficial adjunct to pharmacological treatments for opioid detoxification.

Topics: Acupuncture Points; Adolescent; Adult; Analgesics, Opioid; Analysis of Variance; Buprenorphine; Chi-Square Distribution; Combined Modality Therapy; Drug Administration Schedule; Female; Health Status; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Pain; Patient Selection; Substance Withdrawal Syndrome; Survival Analysis; Time Factors; Transcutaneous Electric Nerve Stimulation

The present investigation examines baseline patient characteristics to predict dosing of buprenorphine-naloxone, a promising treatment for opioid addiction in youths.. This study of 69 opioid-dependent youths is a secondary analysis of data collected during a National Institute on Drug Abuse (NIDA) Clinical Trials Network study. Outpatients aged 15-21 were randomized to a 12-week buprenorphine-naloxone dosing condition (including 4 weeks of taper). Predictors of dosing included sociodemographic characteristics (gender, race, age, and education), substance use (alcohol, cannabis, cocaine, and nicotine use), and clinical characteristics (pain and withdrawal severity).. Most (75.4%) reported having either "some" (n=40, 58.0%) or "extreme" (n=12, 17.4%) pain on enrollment. Maximum daily dose of buprenorphine-naloxone (19.7 mg) received by patients reporting "extreme" pain at baseline was significantly higher than the dose received by patients reporting "some" pain (15.0mg) and those without pain (12.8 mg). In the adjusted analysis, only severity of pain and withdrawal significantly predicted dose. During the dosing period, there were no significant differences in opioid use, as measured by urinalysis, by level of pain.. These data suggest that the presence of pain predicts buprenorphine-naloxone dose levels in opioid-dependent youth, and that patients with pain have comparable opioid use outcomes to those without pain, but require higher buprenorphine-naloxone doses.

Topics: Adolescent; Age Factors; Buprenorphine; Data Interpretation, Statistical; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Male; Naloxone; Narcotic Antagonists; Narcotics; National Institute on Drug Abuse (U.S.); Opioid-Related Disorders; Outpatients; Pain; Pain Measurement; Socioeconomic Factors; Substance Withdrawal Syndrome; Time Factors; Treatment Outcome; United States; Young Adult

Physician adoption of buprenorphine treatment of opioid dependence may be limited in part by concerns regarding the induction process. Although national guidelines recommend observed induction, some physicians utilize unobserved induction outside the office. The aim of this pilot randomized clinical trial was to assess preliminary safety and effectiveness of unobserved versus observed office buprenorphine/naloxone induction among patients entering a 12-week primary care maintenance study. Participants (N=20) with DSM-IV opioid dependence were randomly assigned to unobserved or office induction, stratifying by past buprenorphine use. All patients received verbal and written instructions. A withdrawal scale was used during initiation and to monitor treatment response. Clinic visits occurred weekly for 4 weeks then decreased to monthly. The primary outcome, successful induction one week after the initial clinic visit, was defined as retention in buprenorphine/naloxone treatment and being withdrawal free. Secondary outcomes included prolonged withdrawal beyond 2 days after medication initiation and stabilization at week 4, defined as being in treatment without illicit opioid use for the preceding 2 weeks. Outcome results were similar in the two groups: 6/10 (60%) successfully inducted in each group, 3/10 (30%) experienced prolonged withdrawal, and 4/10 (40%) stabilized by week 4. These pilot study results suggest comparable safety and effectiveness of unobserved and office induction and point toward utilization of non-inferiority design during future definitive protocol development. By addressing an important barrier for physician adoption, further validation of the unobserved buprenorphine induction method will hopefully lead to increased availability of effective opioid dependence treatment.

Topics: Adolescent; Adult; Aged; Ambulatory Care; Buprenorphine; Directly Observed Therapy; Female; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; New York; Opioid-Related Disorders; Pilot Projects; Practice Patterns, Physicians'; Primary Health Care; Substance Withdrawal Syndrome; Treatment Outcome; Young Adult

Buprenorphine (Subutex) is the most abused opioid in Finland. In order to curb the abuse potential of this drug, many treatment centers and prisons crush Subutex tablets before administering them to patients. To date, there are no published studies comparing the efficacy and bioavailability of crushed and whole Subutex tablets.. A total of 16 opioid-dependent patients stabilized on 24 mg of buprenorphine were enrolled in a double-blind, double-dummy, randomized cross-over study comparing crushed and whole buprenorphine tablets on a range of pharmacokinetic and pharmacodynamic variables. Buprenorphine tablets (either crushed or whole) and placebo tablets (either crushed or whole) were administered to subjects simultaneously. Buprenorphine and norbuprenorphine serum levels were measured at 30, 60, 90, 120, 180, 240 and 360 min, as well as 24 h, after tablet administration. After 1 week, the experiment was repeated in a cross-over design so that, by the end of the study, each patient had received the active drug (buprenorphine) as both crushed and whole tablets.. Pharmacokinetic parameters (mean serum levels, C(max), T(max), AUC) of buprenorphine or norbuprenorphine did not differ significantly between crushed and whole tablets, although serum levels were slightly higher after administration of the crushed tablets. There were also no significant differences in dissolution/absorption time, withdrawal signs or opiate craving.. We conclude that crushing Subutex tablets does not significantly alter serum buprenorphine or norbuprenorphine levels or the drug's clinical effect. Our results indicate that crushing Subutex tablets may be used as an alternative method to counter the risk of buprenorphine diversion.

Topics: Adult; Area Under Curve; Biological Availability; Buprenorphine; Cross-Over Studies; Double-Blind Method; Female; Humans; Male; Narcotic Antagonists; Opioid-Related Disorders; Powders; Substance Withdrawal Syndrome; Tablets; Time Factors; Young Adult

For individuals dependent on opioids, recovery efforts begin with a period of withdrawal that typically includes discomfort from symptoms, possibly precipitating a return to drug use. The study described here investigated whether the provision of ancillary medications for opioid withdrawal symptoms affected treatment outcomes in 139 participants receiving buprenorphine in a 13-day detoxification trial. Outcome measures include the number of opioid-free urine samples collected and retention in treatment. Ancillary medications were provided to 70% of participants: 59% received medication for insomnia, 45% for anxiety, 40% for bone pain, 35% for nausea, and 28% for diarrhea. Findings indicate no difference in the number of opioid-free urine samples between the group receiving ancillary medication and the group who did not, although tests of specific ancillary medications indicate that those who received diarrhea medication had fewer opioid-free urines than those who did not (P = .004). Results also indicate that participants attended fewer days of treatment if they received anxiety, nausea, or diarrhea medication compared to no medication (all P values < .05).

Topics: Adult; Analgesics, Opioid; Anxiety; Buprenorphine; Diarrhea; Female; Humans; Inactivation, Metabolic; Male; Middle Aged; Narcotics; Nausea; Opioid-Related Disorders; Pain; Receptors, Opioid, delta; Sleep Initiation and Maintenance Disorders; Substance Withdrawal Syndrome; Treatment Outcome

Sublingual buprenorphine is an effective maintenance treatment for opioid dependence, yet intravenous buprenorphine misuse occurs. A buprenorphine/naloxone formulation was developed to mitigate this misuse risk. This randomized, double-blind, cross-over study was conducted to assess the intravenous abuse potential of buprenorphine/naloxone compared with buprenorphine in buprenorphine-maintained injection drug users (IDUs).. Intravenous heroin users (n = 12) lived in the hospital for 8-9 weeks and were maintained on each of three different sublingual buprenorphine doses (2 mg, 8 mg, 24 mg). Under each maintenance dose, participants completed laboratory sessions during which the reinforcing and subjective effects of intravenous placebo, naloxone, heroin and low and high doses of buprenorphine and buprenorphine/naloxone were examined. Every participant received each test dose under the three buprenorphine maintenance dose conditions.. Intravenous buprenorphine/naloxone was self-administered less frequently than buprenorphine or heroin (P < 0.0005). Participants were most likely to self-administer drug intravenously when maintained on the lowest sublingual buprenorphine dose. Subjective ratings of 'drug liking' and 'desire to take the drug again' were lower for buprenorphine/naloxone than for buprenorphine or heroin (P = 0.0001). Participants reported that they would pay significantly less money for buprenorphine/naloxone than for buprenorphine or heroin (P < 0.05). Seven adverse events were reported; most were mild and transient.. These data suggest that although the buprenorphine/naloxone combination has intravenous abuse potential, that potential is lower than it is for buprenorphine alone, particularly when participants received higher maintenance doses and lower buprenorphine/naloxone challenge doses. Buprenorphine/naloxone may be a reasonable option for managing the risk for buprenorphine misuse during opioid dependence treatment.

Topics: Administration, Sublingual; Adult; Analysis of Variance; Behavior, Addictive; Buprenorphine; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Female; Heroin Dependence; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Narcotics; Patient Preference; Self Administration; Substance Abuse, Intravenous; Substance Withdrawal Syndrome; Young Adult

The aim of this study was to determine whether oral sustained release d-amphetamine (SR-AMP) reduces cocaine and opioid/cocaine combination ('speedball'-like) seeking in volunteers with current opioid dependence and cocaine dependence. Following outpatient buprenorphine (BUP) 8 mg/day stabilization without SR-AMP, eight participants completed a 3-week in-patient study with continued BUP 8 mg/day maintenance and double-blind ascending SR-AMP weekly doses of 0, 30, and 60 mg/day, respectively. After 3 days (Saturday-Monday) stabilization at each SR-AMP weekly dose (0, 15, or 30 mg administered at 0700 and 1225 each day), on Tuesday-Friday mornings (0900-1200 hours), participants sampled four drug combinations in randomized, counterbalanced order under double-blind, double-dummy (intranasal cocaine and intramuscular hydromorphone) conditions: cocaine (COC 100 mg+saline); hydromorphone (COC 4 mg+HYD 24 mg); 'speedball' (COC 100 mg+HYD 24 mg); and placebo (COC 4 mg+saline). Subjective and physiological effects of these drug combinations were measured. From 1230 to 1530 hours, participants could respond on a choice, 12-trial progressive ratio schedule to earn drug units (1/12th of total morning dose) or money units (US$2). SR-AMP significantly reduced COC, but not HYD or speedball, choices and breakpoints. SR-AMP also significantly reduced COC subjective (eg, abuse-related) effects and did not potentiate COC-induced cardiovascular responses. This study shows the ability of SR-AMP to attenuate COC self-administration, as well as its selectivity, in cocaine/heroin polydrug abusers. Further research is warranted to ascertain whether SR-AMP combined with BUP could be a useful dual-agonist pharmacotherapy.

Topics: Adolescent; Adult; Buprenorphine; Choice Behavior; Cocaine; Cocaine-Related Disorders; Delayed-Action Preparations; Dextroamphetamine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Drug-Seeking Behavior; Female; Humans; Hydromorphone; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Reinforcement Schedule; Reward; Substance Withdrawal Syndrome

Few studies in community settings have evaluated predictors, mediators, and moderators of treatment success for medically supervised opioid withdrawal treatment. This report presents new findings about these factors from a study of 344 opioid-dependent men and women prospectively randomized to either buprenorphine-naloxone or clonidine in an open-label 13-day medically supervised withdrawal study. Subjects were either inpatient or outpatient in community treatment settings; however not randomized by treatment setting. Medication type (buprenorphine-naloxone versus clonidine) was the single best predictor of treatment retention and treatment success, regardless of treatment setting. Compared to the outpatient setting, the inpatient setting was associated with higher abstinence rates but similar retention rates when adjusting for medication type. Early opioid withdrawal severity mediated the relationship between medication type and treatment outcome with buprenorphine-naloxone being superior to clonidine at relieving early withdrawal symptoms. Inpatient subjects on clonidine with lower withdrawal scores at baseline did better than those with higher withdrawal scores; inpatient subjects receiving buprenorphine-naloxone did better with higher withdrawal scores at baseline than those with lower withdrawal scores. No relationship was found between treatment outcome and age, gender, race, education, employment, marital status, legal problems, baseline depression, or length/severity of drug use. Tobacco use was associated with worse opioid treatment outcomes. Severe baseline anxiety symptoms doubled treatment success. Medication type (buprenorphine-naloxone) was the most important predictor of positive outcome; however the paper also considers other clinical and policy implications of other results, including that inpatient setting predicted better outcomes and moderated medication outcomes.

Topics: Adrenergic alpha-Agonists; Adult; Aged; Anxiety; Buprenorphine; Clonidine; Data Interpretation, Statistical; Depression; Drug Therapy, Combination; Female; Heroin Dependence; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; National Institute on Alcohol Abuse and Alcoholism (U.S.); Opioid-Related Disorders; Prognosis; Smoking; Socioeconomic Factors; Substance Abuse Detection; Substance Withdrawal Syndrome; Treatment Outcome; United States; Young Adult

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

Buprenorphine, a mu-opioid receptor partial agonist, has been shown to be safe and effective for treatment of opioid dependence. A novel implantable formulation of buprenorphine (Probuphine), using a polymer matrix sustained-release technology, has been developed to offer treatment for opioid dependence while minimizing risks of patient noncompliance and illicit diversion. The goal of the current study was to conduct an initial, open-label, evaluation of the safety, pharmacokinetics, and efficacy of two doses of Probuphine in subjects with opioid dependence maintained on sublingual buprenorphine. Two doses of Probuphine were evaluated in 12 heroin-dependent volunteers switched from daily sublingual buprenorphine dosing to either two or four Probuphine implants based upon their buprenorphine daily maintenance dose of 8 mg or 16 mg respectively, and were monitored for 6 months. Probuphine implants provided continuous steady state delivery of buprenorphine until their removal at 6 months. Withdrawal symptoms and craving remained low throughout the 6 months. For the 12 subjects, an average of 59% of urines were opioid-negative across the 6 month treatment period. Injection site reactions were present in half of patients, but none were serious. No safety concerns were evident. These results suggest that Probuphine implants offer significant promise for enhancing delivery of effective opioid substitution treatment while minimizing risk for abuse of medication.

Topics: Administration, Sublingual; Adolescent; Adult; Buprenorphine; Drug Implants; Female; Heroin Dependence; Humans; Male; Middle Aged; Narcotic Antagonists; Patient Selection; Safety; Substance Withdrawal Syndrome; Young Adult

Cognitive impairment in drug-dependent patients receiving methadone (MMP) maintenance treatment has been reported previously. We assessed cognitive functioning after at least 14 days of stable substitution treatment with buprenorphine (BUP) or MMP and after 8 to 10 weeks. We performed a randomized, nonblinded clinical trial in 59 drug-dependent patients receiving either BUP or MMP maintenance treatment and healthy normal controls (n = 24) matched for sex, age, and educational level. Thirteen patients dropped out of the study before the second testing was performed (BUP, n = 22; MMP, n = 24). A neuropsychological test battery was used to measure selective attention, verbal memory, motor/cognitive speed, and cognitive flexibility. In addition, subjective perceived stress was assessed with a questionnaire. Patients in both treatment groups performed equally well in all of the cognitive domains tested. Both BUP and MMP patients showed significantly improved concentration and executive functions after 8 to 10 weeks of stable substitution treatment. The control group achieved better results than the BUP and MMP groups in most cognitive domains, indicating cognitive impairment in the patients. Perceived stress did not show any significant change after 8 to 10 weeks of treatment, and no major differences were detected between the 3 groups. No effects of perceived stress on cognitive function were found. Our results indicate a cognitive impairment in patients receiving maintenance treatment with BUP or MMP compared with healthy controls. Selective attention improved in both patient groups during treatment. We propose that the improvement of attention may facilitate rehabilitation of drug-dependent patients.

Topics: Analgesics, Opioid; Attention; Buprenorphine; Cognition; Humans; Memory; Methadone; Neuropsychological Tests; Opioid-Related Disorders; Patient Dropouts; Perception; Psychomotor Performance; Stress, Psychological; Substance Withdrawal Syndrome; Surveys and Questionnaires; Time Factors; Treatment Outcome

This was a 6-month, randomized, flexible-dose study comparing the effects of methadone (Meth) and buprenorphine (Bup) on retention rate and substance use in a sample of 140 opioid-dependent, primarily heroin-addicted, patients who had been without opioid substitution therapy in the 4 weeks prior to the study. The major aims were to compare the efficacy of Bup and Meth in a flexible dosing regimen and to identify possible predictors of outcome. There were no major inhomogeneities between treatment groups. All patients also received standardized psychosocial interventions. Mean daily dosages after the induction phase were 44-50 mg for Meth and 9-12 mg for Bup. Results from this study indicate a favourable outcome, with an overall retention rate of 52.1% and no significant differences between treatment groups (55.3% vs. 48.4%). Substance use decreased significantly over time in both groups and was non-significantly lower in the Bup group. Predictors of outcome were length of continuous opioid use and age at onset of opioid use, although these were only significant in the Bup group. Mean dosage and other parameters were not significant predictors of outcome. Overall, the results of this study give further evidence that substitution treatment is a safe and effective treatment for drug dependence. Meth and Bup are equally effective. Duration of continuous opioid use and age at onset were found to have predictive value for negative outcome. The intensity of withdrawal symptoms showed the strongest correlation with drop-out. Future studies are warranted to further address patient profiles and outcome under different substitution regimens.

Topics: Adult; Analysis of Variance; Buprenorphine; Chi-Square Distribution; Double-Blind Method; Female; Humans; Male; Methadone; Narcotics; Opioid-Related Disorders; Predictive Value of Tests; Prospective Studies; Substance Withdrawal Syndrome; Survival Analysis; Time Factors; Treatment Outcome

The study is a preliminary investigation to compare the effectiveness of buprenorphine and methadone as opiate detoxification treatments. The sample comprised 123 drug misusers who were dependent upon opiates only or who were codependent upon opiates and benzodiazepines. Drug misusers dependent upon methadone doses up to 70 mg were eligible for the study. Detoxification took place within a specialist inpatient drug-dependence unit. Withdrawal symptom severity was assessed on a daily basis by means of the Short Opiate Withdrawal Scale. Outcome was assessed for reductions in severity of withdrawal symptoms, treatment retention, and treatment completion. Buprenorphine detoxification was associated with less severe opiate withdrawal symptoms than methadone. Opiate/Benzodiazepine codependent patients reported less severe withdrawal symptoms during treatment with buprenorphine than with methadone and were also more likely to complete detoxification when treated with buprenorphine.

Topics: Adult; Anti-Anxiety Agents; Benzodiazepines; Buprenorphine; Diazepam; Female; Humans; Male; Methadone; Narcotic Antagonists; Opioid Peptides; Opioid-Related Disorders; Severity of Illness Index; Sex Factors; Substance Withdrawal Syndrome

Acute doses of buprenorphine can precipitate withdrawal in opioid dependent persons. The likelihood of this withdrawal increases as a function of the level of physical dependence.. To test the acute effects of sublingual buprenorphine/naloxone tablets in volunteers with a higher level of physical dependence. The goal was to identify a dose that would precipitate withdrawal (Phase 1), then determine if withdrawal could be attenuated by splitting this dose (Phase 2).. Residential laboratory study; subjects (N=16) maintained on 100mg per day of methadone. Phase 1: randomized, double blind, triple dummy, within subject study. Conditions were sublingual buprenorphine/naloxone (4/1, 8/2, 16/4, 32mg/8mg), intramuscular naloxone (0.2mg), oral methadone (100mg), or placebo. Medication conditions were randomized, but buprenorphine/naloxone doses were ascending within the randomization. Phase 2: Conditions were methadone, placebo, naloxone, 100% of the buprenorphine/naloxone dose that precipitated withdrawal in Phase 1 (full dose), and 50% of this dose administered twice in a session (split dose). Analyses covaried by trough methadone serum levels.. Six subjects did not complete the study. Of the 10 who completed, 3 tolerated up to 32mg/8mg of buprenorphine/naloxone without evidence of precipitated withdrawal. For the seven completing both phases, split doses generally produced less precipitated withdrawal compared to full doses.. There is considerable between subject variability in sensitivity to buprenorphine's antagonist effects. Low, repeated doses of buprenorphine/naloxone (e.g., 2mg/0.5mg) may be an effective mechanism for safely dosing this medication in persons with higher levels of physical dependence.

Topics: Administration, Sublingual; Adult; Buprenorphine; Cognition Disorders; Double-Blind Method; Drug Combinations; Female; Humans; Male; Methadone; Middle Aged; Naloxone; Neuropsychological Tests; Opioid-Related Disorders; Psychomotor Disorders; Substance Withdrawal Syndrome

Buprenorphine is marketed in a sublingual formulation for treatment of opioid dependence. A transdermal formulation has been developed that may provide extended relief from opioid withdrawal, reduce required clinic visits and improve adherence, while having less potential for diversion and abuse. This study evaluated the safety and biodelivery (blood levels) of this transdermal buprenorphine formulation (i.e. buprenorphine patch), and its apparent efficacy in suppressing the opioid withdrawal syndrome.. Open-label, first-in-humans trial.. A residential research facility.. Nine physically dependent opioid-users completed the 10-day opioid detoxification study.. Each volunteer received a single patch application that remained in place for 3 days. The formulation has shown an average delivery of 1.9 mg/day of buprenorphine over 3 days in pre-clinical evaluation.. Physiological, behavioral, subjective and observer ratings of opioid withdrawal and opioid agonist effects were collected.. Overall, the patch appeared safe and well tolerated. There were no serious adverse events, and no opioid intoxication following patch application. Oxygen saturation, heart rate, blood pressure, skin temperature and pupil diameter remained well within normal ranges. Buprenorphine blood levels peaked 48 hours after patch application at a concentration of 0.60 ng/ml. Volunteers' self-reports of the presence and severity of withdrawal symptoms were reduced by approximately 50% on the 3 days of patch application. Withdrawal symptoms increased marginally upon patch removal. Administration of opioid rescue medication was eliminated within 6 hours of patch application, and increased slightly upon patch removal.. The significant biodelivery of buprenorphine and the suppression of the opioid withdrawal syndrome during patch application and its reappearance after patch removal indicate clinically useful pharmacodynamic activity. Transdermal buprenorphine may be a useful opioid detoxification treatment that reduces compliance concerns, and delivers buprenorphine in a formulation less likely to be diverted to illicit use.

Topics: Administration, Cutaneous; Adult; Buprenorphine; Dose-Response Relationship, Drug; Female; Heroin Dependence; Humans; Inactivation, Metabolic; Male; Middle Aged; Narcotic Antagonists; Substance Withdrawal Syndrome

Previous studies comparing buprenorphine and clonidine provided little information about subjective factors associated with the effective management of opioid withdrawal. This study sought to compare detoxification programs using these medications with regard to side-effects and related distress, general well-being, perceived self-efficacy and social support. A total of 200 treatment-seeking heroin-dependent patients, aged 18-50, were randomly assigned to buprenorphine or clonidine inpatient withdrawal treatments over 10days followed by 11days of relapse prevention measures. A semi-structured interview and a battery of self-rating scales assessing parameters of the interest were administered to the patients who completed the 10-day detoxification protocol with buprenorphine (n=90) and clonidine (n=50). Chi-square statistics and analysis of covariance were performed to examine between-group differences. Compared with patients treated with clonidine, patients who received buprenorphine developed significantly less side-effects and related distress, and had higher senses of well-being, self-efficacy and social support. The findings suggest that buprenorphine is preferable for inpatient detoxification due to its side-effects profile and positive effects on well-being and psychosocial variables. These early benefits of buprenorphine could enable consequent maintenance treatment.

Topics: Adolescent; Adult; Analgesics; Analgesics, Opioid; Buprenorphine; Clonidine; Cross-Sectional Studies; Female; Health Status; Heroin Dependence; Humans; Male; Middle Aged; Self Efficacy; Social Support; Substance Withdrawal Syndrome

This study assessed treatment retention, compliance and completion of a 9-month buprenorphine replacement programme. In addition, changes in drug use and other relevant variables, as well as predictors of completion, were examined. Seventy-five opioid-dependent out-patients (mean age 26 years; 33% females) who aimed for opioid abstinence were enrolled into the study. Assessments were undertaken prior to buprenorphine induction and again at 3, 6 and 9 months. Forty patients (53%) completed the buprenorphine programme. At 9 months, 67 patients (87%) were still in counselling. Mean attendance rates for buprenorphine dosing and counselling sessions were 0.91 and 0.74, respectively. There were significant and persistent reductions in drug use during treatment with, however, a reversed tendency in the 9th month. Psychiatric problems escalated at 9 months, and three patients died during the detoxification phase. Completion was predicted by fewer previous treatment episodes. Detoxification from buprenorphine is associated with substantial psychological distress and an increased death risk. Buprenorphine replacement therapy should be continued until the patient chooses to leave, and close monitoring during the detoxification phase is essential.

Topics: Adult; Ambulatory Care Facilities; Buprenorphine; Counseling; Drug Administration Schedule; Female; Humans; Male; Narcotic Antagonists; Norway; Opioid-Related Disorders; Outpatients; Patient Compliance; Risk Factors; Stress, Psychological; Substance Withdrawal Syndrome; Treatment Outcome

Twelve-month treatment of heroin addicts with methadone or buprenorphine normalized plasma cortisol levels, and controlled withdrawal symptoms as well as craving. During treatment, the time course of plasma cortisol levels and craving was not strictly correlated: heroin craving was more elevated at 12 than at 3 months. The results suggest a correlation between hypercortisolism, withdrawal symptoms and heroin use and suppose a more complex role for craving and its components in drug-taking behaviour. The main goal of the pharmacological treatment of opioid-dependence should be addressed at the normalization of hypothalamic-pituitary-adrenocortical (HPA) axis more than at the control of craving.

Topics: Adult; Buprenorphine; Female; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Methadone; Motivation; Narcotics; Pituitary-Adrenal System; Statistics as Topic; Substance Withdrawal Syndrome

Buprenorphine has a long duration of action that allows less than daily dosing for opioid dependence, but pharmacologic characterization of buprenorphine's duration of effects over multiple days is incomplete.. This study assessed opioid blockade and spontaneous withdrawal effects of buprenorphine/naloxone (B/N) over a 98-h period.. Residential opioid-dependent volunteers (n = 8) were maintained, in randomized sequence, on each of three different daily sublingual B/N doses (8/2, 16/4, 32/8 mg). After 2 weeks on each maintenance dose, participants underwent challenge sessions on each weekday for 1 week. Challenges consisted of within-session, ascending dose administration of IM hydromorphone (H: 0, 6, and 12 mg). During that week, active B/N dose was given only on Monday; double-blind placebo was administered on the remaining weekdays. Thus, these sessions assessed the extent of both opioid blockade and spontaneous withdrawal at 2, 26, 50, 74, and 98 h after the last active B/N dose.. All three maintenance doses provided substantial but incomplete blockade against opioid agonist effects for 98 h. The extent of blockade diminished steadily but modestly over this time and did not differ as a function of B/N maintenance dose. In general, participants did not report marked spontaneous opioid withdrawal, although mild withdrawal effects were observed as time since the last active B/N dose increased. However, withdrawal did not differ as a function of B/N maintenance dose.. These findings suggest that B/N doses greater than 8/2 mg provide minimal incremental value in terms of opioid blockade and withdrawal suppression.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Hydromorphone; Naloxone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Substance Withdrawal Syndrome

The growing tendency among opioid addicts to misuse multiple other drugs should lead clinicians and researchers to search for new pharmacological strategies in order to prevent life-threatening complications and minimize withdrawal symptoms during polydrug detoxification.. A non-randomised, open-label in-patient detoxification study was used to compare the short-time efficacy of a standardised regimen comprising 6 days Buprenorphine and 10 days Valproate (BPN/VPA) (n = 12) to a control group (n = 50) who took a 10-day traditional Clonidine/Carbamazepine (CLN/CBZ) regimen. Sixty-two dependent subjects admitted to a detoxification unit were included, all dependent on at least opioids and benzodiazepines. Other dependencies were not excluded.. In the BPN/VPA group, 8 out of 12 patients (67%) completed treatment compared with 25 of 50 patients (50%) in the CLN/CBZ group; this difference between the groups was non-significant (p = 0.15). Withdrawal symptoms were reduced in both groups, but only the BPN/VPA group achieved a reduction in withdrawal symptoms from day one. The difference between the two groups was significantly in favour of the BPN/VPA group for days 2 (p < 0.001), 3 (p < 0.05), 4 (p < 0.001), 5 (p < 0.01), 7 (p < 0.01) and 8 (p < 0.05). The BPN/VPA combination did not affect blood pressure, pulse or liver function, and the total burden of side-effects was experienced as modest. There appeared to be no pharmacological interactions of clinical concern, based on measurement of Buprenorphine and Valproate serum levels. Both the patients and the staff were satisfied with the standardised treatment combination.. Overall, the combination of Buprenorphine and Valproate seems to be a safe and promising method for treating multiple drug withdrawal symptoms. The results of this study suggest that the BPN/VPA combination is potentially a better detoxification treatment for polydrug withdrawal than the traditional treatment with Clonidine and Carbamazepine. However, a randomised, double-blind study with a larger sample size to confirm our results is recommended.

Topics: Adult; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Buprenorphine; Carbamazepine; Clonidine; Comorbidity; Drug Therapy, Combination; Female; Hospitalization; Humans; Male; Opioid-Related Disorders; Substance Withdrawal Syndrome; Substance-Related Disorders; Treatment Outcome; Valproic Acid

This study compared the safety and withdrawal discomfort associated with transitioning pregnant opioid-dependent women from short-acting morphine onto buprenorphine or methadone under well-controlled double-blind conditions. Participants (n=18) were patients in a comprehensive treatment setting and were part of a larger randomized controlled trial comparing the neonatal abstinence syndrome in mothers treated with individualized doses of sublingual buprenorphine or oral methadone. Methadone was first given to all patients within 24h of treatment admission. After written informed consent was signed (3-5 days post-admission), methadone was discontinued and Immediate Release Morphine (IRM) was initiated. The initial total daily dose of IRM was six times the last daily methadone dose. The daily dose of IRM was divided in four daily doses. Induction onto double-blind, double dummy (i.e., two medications were administered with only one being active) methadone or buprenorphine was accomplished over 3 days (i.e., induction). Withdrawal scores during the IRM and induction onto randomized medication were judged mild and not statistically different for both methadone (mean dose 53.5 mg) and buprenorphine (mean dose 10.9 mg). No significant differences between medication groups were observed when individual withdrawal items were examined. No observed differences in safety measures including fetal movement, maternal physiological parameters of body temperature, heart rate and blood pressure were observed between groups. Transitioning opioid-dependent pregnant women from IRM to methadone or buprenorphine during the second trimester of pregnancy can be conducted with similar comfort and safety.

Topics: Adult; Buprenorphine; Double-Blind Method; Female; Humans; Methadone; Morphine; Opioid-Related Disorders; Pregnancy; Substance Withdrawal Syndrome

Although buprenorphine is effective in treating opioid dependence, optimal maintenance doses of buprenorphine or the buprenorphine/naloxone combination have not yet been established.. The present study was designed to evaluate the effects of buprenorphine/naloxone maintenance (2/0.5, 8/2, 32/8 mg sublingual) on the reinforcing and subjective effects of heroin (0, 12.5, 25, 50, and 100 mg intranasal) in heroin-dependent individuals.. During test weeks, participants (N=7) first sampled a dose of heroin and 20 dollars. During subsequent choice sessions, participants could choose to self-administer heroin and/or money. Participants responded under a modified progressive-ratio schedule (PR 50, ..., 2,800) during a ten-trial self-administration task.. Heroin break point values and subjective responses were significantly lower under 8/2 and 32/8 mg buprenorphine/naloxone compared to 2/0.5 mg. The self-administration and subjective effects data for heroin in the presence of buprenorphine/naloxone were compared to a separate control group of recently detoxified participants (N=8) in order to obtain estimates for the apparent in vivo dissociation constant (K(A)), the efficacy estimate (tau), and the estimated fraction of receptors remaining after buprenorphine/naloxone treatment (q). The apparent in vivo dissociation constant for heroin ranged from 50 to 126 mg (K(A)) and the efficacy estimate ranged from 13 to 20 (tau). In addition, 2/0.5, 8/2, and 32/8 mg buprenorphine/naloxone dose-dependently reduced the receptor population by 74, 83, and 91%, respectively.. These data demonstrate that both 8/2 and 32/8 mg buprenorphine/naloxone were well tolerated and effective in reducing the reinforcing and subjective effects of heroin, relative to the 2/0.5-mg dose. The data also show for the first time in humans that it is possible to quantify the efficacy and affinity of heroin for mu opioid receptors, and that 80-90% of mu receptors need to be inactivated in order to obtain significant reductions in heroin-induced effects. These results have important implications for future studies in which it will be possible to obtain estimates of relative affinity and efficacy of different agonists at mu opioid receptors.

Topics: Adult; Buprenorphine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Motivation; Naloxone; Narcotics; Reinforcement, Psychology; Substance Withdrawal Syndrome; Treatment Outcome

Rapid opioid detoxification with opioid antagonist induction using general anesthesia has emerged as an expensive, potentially dangerous, unproven approach to treat opioid dependence.. To determine how anesthesia-assisted detoxification with rapid antagonist induction for heroin dependence compared with 2 alternative detoxification and antagonist induction methods.. A total of 106 treatment-seeking heroin-dependent patients, aged 21 through 50 years, were randomly assigned to 1 of 3 inpatient withdrawal treatments over 72 hours followed by 12 weeks of outpatient naltrexone maintenance with relapse prevention psychotherapy. This randomized trial was conducted between 2000 and 2003 at Columbia University Medical Center's Clinical Research Center. Outpatient treatment occurred at the Columbia University research service for substance use disorders. Patients were included if they had an American Society of Anesthesiologists physical status of I or II, were without major comorbid psychiatric illness, and were not dependent on other drugs or alcohol.. Anesthesia-assisted rapid opioid detoxification with naltrexone induction, buprenorphine-assisted rapid opioid detoxification with naltrexone induction, and clonidine-assisted opioid detoxification with delayed naltrexone induction.. Withdrawal severity scores on objective and subjective scales; proportions of patients receiving naltrexone, completing inpatient detoxification, and retained in treatment; proportion of opioid-positive urine specimens.. Mean withdrawal severities were comparable across the 3 treatments. Compared with clonidine-assisted detoxification, the anesthesia- and buprenorphine-assisted detoxification interventions had significantly greater rates of naltrexone induction (94% anesthesia, 97% buprenorphine, and 21% clonidine), but the groups did not differ in rates of completion of inpatient detoxification. Treatment retention over 12 weeks was not significantly different among groups with 7 of 35 (20%) retained in the anesthesia-assisted group, 9 of 37 (24%) in the buprenorphine-assisted group, and 3 of 34 (9%) in the clonidine-assisted group. Induction with 50 mg of naltrexone significantly reduced the risk of dropping out (odds ratio, 0.28; 95% confidence interval, 0.15-0.51). There were no significant group differences in proportions of opioid-positive urine specimens. The anesthesia procedure was associated with 3 potentially life-threatening adverse events.. These data do not support the use of general anesthesia for heroin detoxification and rapid opioid antagonist induction.

Topics: Adult; Anesthesia, General; Buprenorphine; Clonidine; Drug Therapy, Combination; Female; Heroin Dependence; Humans; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Substance Withdrawal Syndrome

The prevalence of heroin and other opioid use has markedly increased among adolescents in the last decade; however, virtually no research has been conducted to identify effective treatments for this population.. To evaluate the relative efficacy of 2 pharmacotherapies, the partial opioid agonist buprenorphine hydrochloride and the centrally active alpha(2)-adrenergic blocker clonidine hydrochloride, in the detoxification of opioid-dependent adolescents.. A double-blind, double-dummy, parallel-groups randomized controlled trial conducted in a university-based research clinic from October 2001 to December 2003. Patients were a volunteer sample of 36 adolescents who met DSM-IV criteria for opioid dependence (ages 13-18 years eligible).. Participants were randomly assigned to a 28-day, outpatient, medication-assisted withdrawal treatment with either buprenorphine or clonidine. Both medications were provided along with thrice weekly behavioral counseling and incentives contingent on opiate abstinence. Postdetoxification, all participants were offered the opportunity for continued treatment with the opiate antagonist, naltrexone hydrochloride.. Treatment retention, opiate abstinence, and human immunodeficiency virus risk behavior, along with measures of withdrawal and medication effects.. A significantly greater percentage of adolescents who received buprenorphine were retained in treatment (72%) relative to those who received clonidine (39%) (P<.05). For those in the buprenorphine group, a significantly higher percentage of scheduled urine test results were opiate negative (64% vs 32%; P = .01). Participants in both groups reported relief of withdrawal symptoms and drug-related human immunodeficiency virus risk behavior. Those in the buprenorphine condition generally reported more positive effects of the medication. No evidence of opioid intoxication or psychomotor impairment was observed. Sixty-one percent of participants in the buprenorphine condition and 5% of those in the clonidine group initiated treatment with naltrexone.. Combining buprenorphine with behavioral interventions is significantly more efficacious in the treatment of opioid-dependent adolescents relative to combining clonidine and behavioral interventions.

Topics: Administration, Cutaneous; Adolescent; Adrenergic alpha-Agonists; Adrenergic alpha-Antagonists; Behavior Therapy; Buprenorphine; Clonidine; Combined Modality Therapy; Double-Blind Method; HIV Infections; Humans; Narcotic Antagonists; Opioid-Related Disorders; Psychomotor Performance; Risk-Taking; Substance Withdrawal Syndrome; Treatment Outcome

We evaluated peak plasma concentrations, trough concentrations, and the 24-hour area under the concentration curve (AUC(0-24 h)) during maintenance with sublingual (SL) liquid or tablet formulations in 57 opiate-dependent volunteers. Study participants were assigned randomly to one of three SL daily buprenorphine dose pairs and maintained for 2 weeks with the liquid formulation followed by 2 weeks with the corresponding tablet dose. Plasma samples were obtained after at least 10 days of maintenance with the liquid formulation and after at least 10 days of that with the tablet formulation. The bioequivalence of the tablet compared with the liquid doses ranged from 57% to 75% based on peak concentrations, from 102% to 108% based on trough concentrations, and from 66% to 86% based on 24-hour AUC, but there was a large intersubject and intrasubject variability in plasma concentrations, with greater variability following tablets than liquid. Measures of withdrawal symptoms or illicit opioid use were not associated with buprenorphine dose, formulation, or plasma buprenorphine levels.

Topics: Administration, Sublingual; Adult; Buprenorphine; Female; Humans; Male; Metabolic Clearance Rate; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Pharmaceutical Solutions; Substance Withdrawal Syndrome; Tablets; Treatment Outcome

This is the first trial to compare the relationship of opioid plasma concentrations in methadone-versus buprenorphine-maintained subjects. Sixty subjects (19 females and 41 males) seeking treatment who met Diagnostic and Statistical Manual version IV (DSM-IV) criteria for opioid dependence were recruited and treated at the Drug Addiction Outpatient Clinic at the University of Vienna. Of these, 44 (11 female and 33 male) were included in the analyses of plasma concentrations. Subjects received either daily sublingual buprenorphine (2 mg or 8 mg tablets; maximum daily dose: 8 mg) or oral methadone (racemic R-/S-methadone) and were maintained on a stable dose after an induction period of 2 weeks. Mean dose and mean plasma concentrations were correlated on an individual and collective basis. Correlation was 0.51 for buprenorphine, whereas the score for methadone was 0.69. Intra-individual variation was much higher for buprenorphine (p<0.0001), while the concentration-to-dose ratio was very small. Based on the differences of the pharmacokinetics of blood plasma of the two agents, we tried to explain the differences in the acceptance of treatment, which was significantly lower in the buprenorphine-maintained group. No such differences could be evaluated between completers and dropouts in buprenorphine-maintained subjects, neither concerning withdrawal scores nor dose, plasma concentration, concentration-to-dose ratios or intra-individual variation.

Topics: Administration, Oral; Administration, Sublingual; Adolescent; Adult; Buprenorphine; Dose-Response Relationship, Drug; Female; Humans; Long-Term Care; Male; Methadone; Middle Aged; Opioid-Related Disorders; Patient Acceptance of Health Care; Patient Dropouts; Statistics as Topic; Substance Withdrawal Syndrome

Buprenorphine, a partial mu-opioid agonist, has been shown effective for treatment of opioid dependence but also has some abuse potential. A novel formulation of buprenorphine, using a polymer microcapsule depot sustained-release technology, has been developed which may offer effective treatment of opioid dependence while also minimizing risks of patient noncompliance and illicit diversion. This open-label, first-in-human study evaluated the safety and pharmacokinetics of a single-dose buprenorphine depot in physically dependent opioid abusers. The present study also examined the efficacy of depot buprenorphine in suppressing symptoms of opioid withdrawal, attenuating the effects of exogenous opioid challenge, and providing clinical detoxification. Five opioid-dependent volunteers each received a single subcutaneous depot injection containing 58 mg of buprenorphine and were assessed for at least four weeks for signs and symptoms of opioid withdrawal, first residentially and then as outpatients. Depot buprenorphine appeared to provide effective relief from opioid withdrawal, with no participant requiring additional medication for withdrawal relief following depot administration. The depot was safe and well-tolerated, with no significant side effects, signs of intoxication, or respiratory depression. In the opioid challenge sessions, depot buprenorphine appeared to produce substantial opioid blockade that persisted for 6 weeks post-depot administration. Results from the present study suggest that depot buprenorphine offers significant promise for enhancing the delivery of effective opioid agonist treatment while minimizing risk for abuse of the medication.

Topics: Administration, Oral; Adult; Ambulatory Care; Buprenorphine; Delayed-Action Preparations; Dose-Response Relationship, Drug; Double-Blind Method; Female; Heroin Dependence; Humans; Hydromorphone; Injections, Subcutaneous; Male; Metabolic Clearance Rate; Narcotics; Neurologic Examination; Patient Acceptance of Health Care; Rehabilitation Centers; Substance Withdrawal Syndrome

The purpose of this study was to conduct a cost-effectiveness analysis of detoxification from heroin using buprenorphine in a specialist clinic versus a shared care setting. A randomized controlled trial was conducted with a total of 115 heroin-dependent patients receiving a 5-day treatment regime of buprenorphine. The specialist clinic was a community-based treatment agency in inner-city Sydney. Shared care involved treatment by a general practitioner supplemented by weekend dispensing and some concurrent counselling at the specialist clinic. Quantification of resource use was limited to inputs for treatment provision. The primary outcome measure used in the economic analysis was the proportion of each group that completed detoxification and achieved an initial 7-day period of abstinence. Buprenorphine detoxification in the shared care setting was estimated to be 24 dollars more expensive per patient than treatment at the clinic, which had an average treatment cost of 332 dollars per patient. Twenty-three per cent of the shared care patients and 22% of the clinic patients reported no opiate use during the withdrawal period. These results suggest that the provision of buprenorphine treatment for heroin dependence in shared care and clinic appear to be equally cost-effective.

Topics: Adolescent; Adult; Aged; Buprenorphine; Community Mental Health Services; Cost-Benefit Analysis; Female; Heroin; Humans; Inactivation, Metabolic; Male; Middle Aged; Narcotic Antagonists; Substance Withdrawal Syndrome; Urban Population

Topics: Adolescent; Adult; Buprenorphine; Capsules; Drug Therapy, Combination; Drugs, Chinese Herbal; Female; Heroin; Humans; Male; Middle Aged; Phytotherapy; Substance Withdrawal Syndrome

With the growing role of intravenous drug use in the transmission of HIV infection, HIV-infected patients frequently present with comorbid opioid dependence. Yet, few empirical evaluations of the efficacy and consequences of opioid detoxification medications in medically ill HIV-infected patients have been reported. In a randomized, double-blind clinical trial, we evaluated the impact of three medications on the signs and symptoms of withdrawal and on the pain severity in heroin-dependent HIV-infected patients (N=55) hospitalized for medical reasons on an inpatient AIDS service. Patients received a 3-day pharmacologic taper with intramuscular buprenorphine (n=21), oral clonidine (n=16), or oral methadone (n=18), followed by a clonidine transdermal patch on the fourth day. Observed and self-reported measures of opioid withdrawal and pain were taken 1-3 times daily for up to 4 days. Opiate administration used as medically indicated for pain was also recorded. Observer- and subject-rated opiate withdrawal scores decreased significantly following the first dose of medication and overall during treatment. Among all 55 subjects, self-reported and observer-reported pain decreased after treatment (on average observer-rated opioid withdrawal scale (OOWS) scores declined 5.6 units and short opioid withdrawal scale (SOWS) declined 4.8 units, P<0.001, for both) with no indication of increased pain during medication taper. There were no significant differences of pain decline and other measures of withdrawal between the three treatment groups. During the intervention period, supplemental opiates were administered as medically indicated for pain to 45% of the patients; only 34% of men versus 62% of women received morphine (P<0.05). These findings suggest buprenorphine, clonidine, and methadone regimens each decrease opioid withdrawal in medically ill HIV-infected patients.

Topics: Administration, Oral; Adrenergic alpha-Agonists; Adult; Buprenorphine; Clonidine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Heroin Dependence; HIV Infections; Hospitalization; Humans; Injections, Intramuscular; Male; Methadone; Middle Aged; Narcotics; Pain Measurement; Receptors, Opioid; Substance Abuse, Intravenous; Substance Withdrawal Syndrome; Treatment Outcome

In maintenance patients methadone has been shown to produce considerable changes in opioid effects and withdrawal over the dosing interval. As a partial agonist buprenorphine may be expected to produce smaller changes, but the nature and magnitude of these changes have only been described for single doses. In the present study opioid effects and withdrawal were described in patients maintained on buprenorphine. Twenty four opioid dependent subjects were administered 16 mg buprenorphine tablets sublingually for 10 days. On day 10 plasma samples were collected and physiological, subjective and observer-rated measures collected pre-dose and at 14 time points during the dosing interval. No significant respiratory depression was observed. Consistent with the partial agonist properties of buprenorphine, other physiological and subjective changes were also of small magnitude. However, even at a once daily dose of 16 mg some patients experienced significant opioid withdrawal that was maximal at the end of the dosing interval. Buprenorphine maintenance should be associated with a high level of safety and a low level of disruption caused by changing opioid effects over the dosing interval, but some patients may require high doses or other strategies to completely suppress withdrawal.

Topics: Administration, Sublingual; Adult; Buprenorphine; Cross-Over Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Narcotics; Neurologic Examination; Opioid-Related Disorders; Substance Withdrawal Syndrome

The study aimed to identify the range of buprenorphine doses required to comfortably alleviate symptoms in patients undergoing inpatient heroin withdrawal using a symptom-triggered titration dosing regime, and to identify the patient characteristics that impact upon the buprenorphine dose requirements. The study was conducted in two Australian inpatient withdrawal units, recruiting 63 dependent, injecting heroin users with no recent methadone treatment, dependence on other drugs, or other active medical or psychiatric conditions. In a single (patient) blinded case series, placebo or 2 mg sublingual buprenorphine tablets was administered four times a day according to severity of withdrawal (assessed with Subjective Opiate Withdrawal Scale). Up to 16 mg buprenorphine was available over the first 4 days of the admission, up to 8 mg on day 5, and placebo continued until day 6. Thirty-two subjects completed the dosing regime, with mean (+/-S.D.) daily doses of 3.8+/-2.8 on day 1, 5.8+/-3.2 on day 2, 4.8+/-3.3 on day 3, 2.3+/-2.6 on day 4, 0.8+/-1.3 on day 5, and a total dose of 17.4+/-9.7. Higher buprenorphine doses were required by those patients with more severe psychosocial dysfunction, women, those with more frequent heroin use, and those with more severe dependence on heroin at intake. A dosing regime using sublingual buprenorphine tablets for short inpatient heroin withdrawal is proposed.

Topics: Adolescent; Adult; Buprenorphine; Dose-Response Relationship, Drug; Female; Heroin; Humans; Male; Middle Aged; Narcotic Antagonists; Substance Abuse, Intravenous; Substance Withdrawal Syndrome; Titrimetry

Buprenorphine is used in the treatment of opioid dependence. Due to its pharmacology, the transfer from methadone to buprenorphine may precipitate withdrawal symptoms.. Methadone maintained patients with clinical indicators of stability who were seeking withdrawal from methadone were recruited from three Australian states. Patients on methadone doses between 30 and 40 mg were randomised to transfer to buprenorphine by a fixed dose (transfer at 30 mg methadone) or by a variable dose induction (transfer when 'uncomfortable'). A third group of patients with methadone doses less than 30 mg were transferred to buprenorphine at their entry methadone dose. Fifty-one patients were inducted onto buprenorphine using the same dosing protocol with the first dose of 4 mg buprenorphine. Following stabilisation on buprenorphine, patients gradually reduced the buprenorphine dose to 0 mg. Withdrawal severity and drug use was monitored.. There were no significant difference between the transfer at 30 mg and transfer when 'uncomfortable' dosing protocols in severity of withdrawal on transfer from methadone to buprenorphine. Those on doses less than 30 mg reported significantly less withdrawal discomfort at transfer. All but one patient stabilised on buprenorphine. Thirty-eight of the 51 patients inducted onto buprenorphine reached 0 mg.. Transfer from methadone to buprenorphine can safely occur from doses of around 30 mg of methadone. Buprenorphine dose reductions were well tolerated. Thirty-one percent of patients were not using heroin or methadone at 1-month follow-up.

Topics: Adult; Buprenorphine; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Methadone; Pilot Projects; Substance Withdrawal Syndrome; Treatment Outcome

Fifty-two heroin addicts were inducted onto buprenorphine under the care of psychiatric residents in a setting modeled on office practice. Subjects were maintained on a protocol of six weeks of 16 mg daily dosing, then tapered to zero dose up to week 16, and maintained on placebo through week 18. Of 44 subjects who continued after the first induction dose, 11 terminated during maintenance, 17 during taper; and 16 while on zero dose. Twice weekly urine toxicologies showed significant successive declines in samples positive for heroin use across these three periods: 70%, 41%, and 20%, respectively. Among historical variables, only prior AA attendance distinguished subjects who achieved zero dose from those who did not. A comparison with recent studies suggests that relatively inexperienced office-based physicians can maintain patients on buprenorphine at a level comparable to that reported for research clinic settings, but with comparable rates of heroin abstinence. These findings are discussed in light of potential options for office-based opioid maintenance.

Topics: Adult; Alcoholics Anonymous; Appointments and Schedules; Buprenorphine; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Heroin Dependence; Humans; Internship and Residency; Male; Naloxone; Narcotic Antagonists; Narcotics; Outcome and Process Assessment, Health Care; Patient Dropouts; Substance Abuse Detection; Substance Withdrawal Syndrome; Treatment Outcome

Various drugs have been used for the treatment of opioid withdrawal, e.g., methadone, buprenorphine, and clonidine. Tramadol is a centrally acting synthetic analgesic agent with opiate activity due to low affinity binding of the parent compound and higher affinity binding of the O-demethylated metabolite M1 to mu opioid receptors. As a consequence, there may be a role for the use of tramadol in the treatment of opiate withdrawal. We attempt to assess the efficacy of tramadol in treating moderate heroin withdrawal through a retrospective cohort control study, conducted in a detoxification unit in a community teaching hospital. Out of 100 heroin abusers admitted for detoxification during the review period, 64 patients who were treated either with buprenorphine or tramadol, were included in this study, with 20 participants in the buprenorphine group and 44 in the tramadol group. Both groups were matched for age, sex, and self-reported average quantity of heroin used per day. In the tramadol group, the average CINA maximum was 9.0, and in the buprenorphine group it was 11.2 (P = 0.07). The use of oral clonidine per patient in the tramadol group was 1.6 tablets, and in the buprenorphine group 0.1 tablets (P = 0.002). The length of stay was 3.7 days in the tramadol group and 4.1 days in the buprenorphine group (P = 0.5). Four participants in the tramadol group received three or more doses of buprenorphine because their symptoms were not controlled, and were considered as treatment failures. These preliminary data suggest that tramadol may be comparable to buprenorphine in the management of mild to moderately severe heroin withdrawal. These findings, if reproduced in larger studies with stronger research designs, have potentially great implications for the management of opioid withdrawal in both the inpatient and outpatient setting.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Cohort Studies; Female; Heroin Dependence; Humans; Male; Narcotic Antagonists; Retrospective Studies; Substance Withdrawal Syndrome; Tramadol

The purpose of this open-label, uncontrolled study was to evaluate the feasibility of administering off-label buprenorphine in combination with ancillary medications for inpatient short-term detoxification of heroin-dependent patients at a psychiatric facility. A sample of 20 heroin-dependent patients admitted to an urban psychiatric hospital was administered buprenorphine 6, 4, and 2 mg/day during the first, second, and third day of detoxification, respectively, and then observed during the fourth and fifth day. Eighty-five percent of the subjects abused other substances, 75% reported cocaine abuse/dependence, 75% had comorbid mood disorders. All subjects completed the medication phase of the study. No clinically significant adverse events were reported. There was a significant decrease in the Clinical Investigation Narcotic Assessment (CINA) total score between baseline and days 2 through 5. The results suggest that buprenorphine is well tolerated and may be beneficial for medically supervised short-term withdrawal from heroin for hospitalized psychiatric patients.

Topics: Adult; Analgesics, Opioid; Baltimore; Buprenorphine; Cocaine-Related Disorders; Comorbidity; Emergency Services, Psychiatric; Female; Heroin Dependence; Humans; Male; Middle Aged; Mood Disorders; Narcotic Antagonists; Patient Satisfaction; Pilot Projects; Substance Withdrawal Syndrome

To determine whether buprenorphine is more effective than clonidine and other symptomatic medications in managing ambulatory heroin withdrawal.. Open label, prospective randomized controlled trial examining withdrawal and 4-week postwithdrawal outcomes on intention-to-treat.. Two specialist, out-patient drug treatment centres in inner city Melbourne and Sydney, Australia.. One hundred and fourteen dependent heroin users were recruited. Participants were 18 years or over, and with no significant other drug dependence, medical or psychiatric conditions or recent methadone treatment. One hundred and one (89%) participants completed a day 8 research interview examining withdrawal outcomes, and 92 (81%) completed day 35 research interview examining postwithdrawal outcomes.. Participants randomized to control (n = 56) (up to 8 days of clonidine and other symptomatic medications) or experimental (n = 58) (up to 5 days of buprenorphine) withdrawal groups. Following the 8-day withdrawal episode, participants could self-select from range of postwithdrawal options (naltrexone, substitution maintenance, or counselling).. Retention in withdrawal; heroin use during withdrawal; and retention in drug treatment 4 weeks after withdrawal.. Withdrawal severity; adverse events, and heroin use in the postwithdrawal period.. The experimental group had better treatment retention at day 8 (86% versus 57%, P = 0.001, 95% CI for numbers needed to treat (NNT) = 3-8) and day 35 (62% versus 39%, P = 0.02, 95% CI for NNT = 4-18); used heroin on fewer days during the withdrawal programme (2.6 +/- 2.5 versus 4.5 +/- 2.3, P < 0.001, 95% CI = 1-2.5 days) and in the postwithdrawal period (9.0 +/- 8.2 versus 14.6 +/- 10, P < 0.01, 95% CI = 1.8-9.4); and reported less withdrawal severity. No severe adverse events reported.. Buprenorphine is effective for short-term ambulatory heroin withdrawal, with greater retention, less heroin use and less withdrawal discomfort during withdrawal; and increased postwithdrawal treatment retention than symptomatic medications.

Topics: Adult; Ambulatory Care; Buprenorphine; Clonidine; Female; Heroin Dependence; Humans; Male; Narcotics; Patient Compliance; Substance Abuse Treatment Centers; Substance Withdrawal Syndrome; Sympatholytics

The aim of this study was to assess the safety of buprenorphine administered intravenously for the treatment of opioid withdrawal in medically ill hospitalized patients. Data regarding demographic information, number of doses of buprenorphine, and measures of buprenorphine's effects were collected via chart reviews for 30 heroin-dependent patients who received buprenorphine intravenously during their hospitalization for an acute medical problem. No respiratory depression was observed, and no patients reported feeling "high." All patients reported that buprenorphine decreased withdrawal symptoms. Thus, intravenous administration of buprenorphine appears to be safe for the treatment of opioid withdrawal.

Topics: Acute Disease; Adult; Buprenorphine; Female; Heroin; Heroin Dependence; Humans; Injections, Intravenous; Male; Middle Aged; Narcotic Antagonists; Substance Withdrawal Syndrome

Buprenorphine is a partial mu opioid agonist under development as a sublingual (SL) medication for opioid dependence treatment in the United States. Because buprenorphine may be abused, tablets combining buprenorphine with naloxone in a 4:1 ratio have been developed to reduce that risk. Low doses of injected buprenorphine/naloxone have been tested in opioid-dependent subjects, but higher doses (more than 2 mg of either medication) and direct comparisons to SL buprenorphine/naloxone have not been examined.. To assess and compare the effects of intramuscular (i.m.) versus SL buprenorphine/naloxone in opioid-dependent volunteers.. Opioid-dependent volunteers were maintained on 40 mg per day of oral hydromorphone while on a residential research ward. After safety testing in two pilot subjects, participants (n = 8) were tested with both i.m. and SL buprenorphine/naloxone (1/0.25, 2/0.5, 4/1, 8/2, 16/4 mg); i.m. hydromorphone (10 mg) and naloxone (0.25 mg); both i.m. and SL buprenorphine alone (8 mg); and placebo. Test sessions were twice per week; dosing was double-blind.. Intramuscular buprenorphine/naloxone produced dose-related increases on indices of opioid antagonist effects. Effects were consistent with naloxone-precipitated withdrawal, and were short-lived. As withdrawal effects dissipated, euphoric opioid agonist effects from buprenorphine did not appear. Sublingual buprenorphine/naloxone produced neither opioid agonist nor antagonist effects.. Intramuscular injection of buprenorphine/naloxone precipitates withdrawal in opioid dependent persons; therefore, the combination has a low abuse potential by the injection route in this population. Sublingual buprenorphine/naloxone by tablet is well tolerated in opioid dependent subjects, and shows neither adverse effects (i.e., precipitated withdrawal) nor a high abuse potential (i.e., opioid agonist effects).

Topics: Administration, Sublingual; Adolescent; Adult; Affect; Buprenorphine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Hydromorphone; Injections, Intramuscular; Male; Middle Aged; Naloxone; Narcotic Antagonists; Narcotics; Observer Variation; Opioid-Related Disorders; Psychomotor Performance; Substance Withdrawal Syndrome

Opioid-dependent outpatients may be more likely to present for pharmacological treatment if less than daily dosing can be arranged. These studies compared opioid withdrawal symptoms during 24-, 72-, and 120-hour buprenorphine dosing regimens and evaluated participants' preferences for these different dosing regimens.. Thirty-three opioid-dependent participants received daily sublingual maintenance doses of 4 mg/70 kg (n = 14) or 8 mg/70 kg (n = 19) of liquid buprenorphine.. In Study I participants received, in a random order, three dosing regimens for five repetitions of each: daily maintenance doses every 24 hours (4 or 8 mg/70 kg), triple the daily maintenance dose every 72 hours (12 or 24 mg/70 kg) and quintuple the daily maintenance dose every 120 hours (20 or 40 mg/70 kg). Doses were administered under double-blind procedures, and placebos were administered on the interposed days during the latter two regimens. Subjective and observer ratings of opioid withdrawal symptoms were assessed daily prior to receipt of each dose. In Study II, a new group of participants received each of the three dosing regimens under open-dosing procedures and then chose between the different dosing regimens.. Opioid withdrawal symptoms increased significantly during the every-fifth-day dosing regimen in both the blind- and open-dosing studies. In the choice phase of Study II, only one participant (7%) chose quintuple-every-fifth-day dosing over all other dosing options.. These results suggest that the maximum duration of action of buprenorphine is less than 5 days when five times the daily maintenance dose is provided.

Topics: Adult; Analysis of Variance; Appointments and Schedules; Buprenorphine; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Narcotics; Opioid-Related Disorders; Patient Compliance; Patient Satisfaction; Substance Withdrawal Syndrome; Treatment Outcome

The relative efficacy of quintuple and sextuple buprenorphine dosing in abating withdrawal symptoms for 120 h was compared in opioid-dependent outpatients. Fourteen subjects received buprenorphine in a double-blind, placebo-controlled, cross-over design. Daily sublingual maintenance doses were 4 mg/70 kg (n=4) and 8 mg/70 kg (n=10). After a stabilization period of daily maintenance administration, subjects received quintuple (5x daily maintenance dose) and sextuple (6x daily maintenance dose) doses every 120 h. Measures of opioid agonist and withdrawal effects were assessed daily. Subjective ratings of withdrawal were significantly greater than baseline ratings beyond 96-h post dosing under both regimens. There was no evidence, however, that those subjective ratings of withdrawal differed between the two regimens. Thus, these data suggest that sextuple buprenorphine dosing, administered every 5 days, does not abate opioid-withdrawal beyond 96 hours.

Topics: Adult; Analysis of Variance; Buprenorphine; Female; Humans; Male; Middle Aged; Outcome Assessment, Health Care; Substance Withdrawal Syndrome

To compare opioid withdrawal symptoms during 24-, 48-, 72- and 96-hour buprenorphine dosing regimens and to evaluate subjects' preferences for these different dosing schedules.. Fourteen opioid-dependent subjects participated in this study. They received daily sublingual maintenance doses of 4 mg/70 kg (n = 4) or 8 mg/70 kg (n = 10) of buprenorphine.. In the first study subjects received, in a random order, four dosing regimens for five repetitions of each: daily maintenance doses every 24 hours (4 or 8 mg/70 kg), double the daily maintenance dose every 48 hours (8 or 16 mg/70 kg), triple the daily maintenance dose every 72 hours (12 or 24 mg/70 kg), and quadruple the daily maintenance dose every 96 hours (16 or 32 mg/70 kg). Measures of subjective and observer opioid withdrawal symptoms were assessed prior to receipt of each dose. In a second study, subjects chose between the different dosing regimens.. Some withdrawal ratings increased during the less frequent dosing schedules in the first study. In the second study, 46% of subjects preferred the quadruple-every-fourth-day dosing regimen over every other option, and only 14% preferred to be dosed daily.. These results suggest that some opioid-dependent outpatients are willing and able to endure the withdrawal symptoms associated with less than daily dosing, and a twice-weekly dosing regimen may be possible.

Topics: Adult; Analysis of Variance; Buprenorphine; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Narcotics; Opioid-Related Disorders; Substance Withdrawal Syndrome; Treatment Outcome

We used an open-labeled, 21-day inpatient detoxification treatment to compare the short-term effects of a 10-day buprenorphine plus 19-day carbamazepine regimen (n = 15) to a 14-day oxazepam plus 19-day carbamazepine regimen (n = 12) during rapid detoxification from opioids and other abused drugs. Somatic and psychopathological changes were assessed using the following rating scales: ASI, HAMD, SCL-90-R, and SOWS. Eighteen of 27 patients (67%) completed the study. Four dropouts (27%) were treated with buprenorphine/carbamazepine (BPN/CBZ) and the other five dropouts (42%) were treated with oxazepam/carbamazepine (OXA/CBZ). Repeated measures analysis of variance showed that SOWS scores were significantly less pronounced with BPN-CBZ than with OXA/CBZ. On the first day of admission, no significant difference in HAMD scores was detected (BPN/CBZ 11.6, BPN/CBZ 1.0). On day 14, HAMD was significantly less pronounced in BPN/CBZ (3.0) than in OXA/CBZ (6.1). BPN/CBZ showed a significant improvement in the ASI score on days 7 and 14 compared with OXA/CBZ. Three of nine items of the SCL-90-R showed a trend toward less pronounced outcome in BPN-CBZ. No severe side effects occurred during treatment in either group. The buprenorphine/carbamazepine regimen provided significantly more effective relief from affect disturbances and withdrawal syndromes than the oxazepam/carbamazepine regimen. The pharmacological basis of these effects of buprenorphine (kappa-antagonism activity,mu-agonism activity) are discussed.

Topics: Adult; Affect; Analgesics, Non-Narcotic; Analysis of Variance; Anti-Anxiety Agents; Anxiety; Buprenorphine; Carbamazepine; Clinical Protocols; Drug Therapy, Combination; Female; Humans; Male; Narcotic Antagonists; Opioid-Related Disorders; Oxazepam; Prospective Studies; Psychiatric Status Rating Scales; Substance Withdrawal Syndrome; Substance-Related Disorders; Treatment Outcome

Sublingual buprenorphine is a promising new treatment for opiate dependence, but its opioid agonist effects pose a risk for parenteral abuse. A formulation combining buprenorphine with the opiate antagonist naloxone could discourage such abuse. The effects of three intravenous (IV) buprenorphine and naloxone combinations on agonist effects and withdrawal signs and symptoms were examined in 12 opiate-dependent subjects. Following stabilization on a daily dose of 60 mg morphine intramuscularly, subjects were challenged with IV doses of buprenorphine alone (2 mg) or in combination with naloxone in ratios of 2:1, 4:1, and 8:1 (1, 0.5, or 0.25 mg naloxone), morphine alone (15 mg) or placebo. Buprenorphine alone did not precipitate withdrawal and had agonist effects similar to morphine. A naloxone dose-dependent increase in opiate withdrawal signs and symptoms and a decrease in opioid agonist effects occurred after all drug combinations. Buprenorphine with naloxone in ratios of 2:1 and 4:1 produced moderate to high increases in global opiate withdrawal, bad drug effect, and sickness. These dose ratios also decreased the pleasurable effects and estimated street value of buprenorphine, thereby suggesting a low abuse liability. The dose ratio of 8:1 produced only mild withdrawal symptoms. Dose combinations at 2:1 and 4:1 ratios may be useful in treating opiate dependence.

Topics: Adult; Affect; Buprenorphine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Morphine; Naloxone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Substance Withdrawal Syndrome

Buprenorphine (BUP)-maintained patients were first exposed to various BUP doses and then chose between BUP doses and money. In the choice phase, they had 10 units exchangeable for units of BUP (constant at 3 mg/unit) or money (varied from $0.30 to $20/unit). They chose BUP exclusively (30 mg) when the money alternative was low. As available money increased, they selected lower daily BUP doses (down to 3 mg). An economic analysis indicated demand for BUP was inelastic; changes in drug intake were proportionally lower than changes in price. Subjective reports of agonist and withdrawal effects increased > 200% when high and low BUP doses, respectively, were given during the exposure phase. In the choice phase, subjective drug effects were constant regardless of the BUP dose selected. Thus, BUP dose selection varies with the magnitude of alternative reinforcers, and subjective drug effects depend on whether doses are self- or experimenter-selected.

Topics: Adult; Analgesics, Opioid; Behavior; Buprenorphine; Humans; Male; Opioid-Related Disorders; Reinforcement, Psychology; Self Administration; Substance Withdrawal Syndrome

Buprenorphine is an effective new treatment for opiate dependence. This study compared the bioavailability of buprenorphine from a tablet to that from a reference solution. Six men experienced with, but not dependent on, opiates (DSM-III-R) were each administered 7.7 mg of buprenorphine in liquid form and 8 mg in tablet form 1 week apart in a balanced crossover design. Plasma levels were measured by electron capture capillary gas chromatography (GC), and concentration-time curves were constructed. Pharmacokinetic data were analyzed by analysis of variance. The bioavailability from the tablet was approximately 50% that from the liquid and was not affected by saliva pH. Lower bioavailability from the tablet may be due to slow dissolution.

Topics: Administration, Sublingual; Adult; Analgesics, Opioid; Area Under Curve; Biological Availability; Buprenorphine; Cross-Over Studies; Heart Rate; Humans; Male; Narcotics; Pharmaceutical Solutions; Substance Withdrawal Syndrome; Tablets

This study evaluated plasma buprenorphine concentrations 24-72 h following sublingual administration of a dose of buprenorphine solution, ranging from 16 mg/70 kg to 44 mg/70 kg, administered on a daily or thrice-weekly schedule. Additionally, this study evaluated the effects of different thrice-weekly buprenorphine dose schedules on opiate use and withdrawal symptoms.. Opiate dependent subjects (n = 10) were maintained in an outpatient clinic for two 3-week periods at each of three thrice-weekly buprenorphine dose schedules (providing a weekly total buprenorphine dose of 64, 84 and 112 mg) and for 1 week of a daily buprenorphine dose of 16 mg/70 kg. Plasma samples were obtained 24, 48 and 72 h following administration of buprenorphine. Urine samples were also collected and opiate withdrawal symptoms, agonist effects and the use of heroin, cocaine, alcohol and other drugs, were assessed.. Plasma levels showed a wide range of intra- and inter-subject variability. Nonetheless, higher doses of buprenorphine resulted in higher plasma concentrations at each time point and plasma concentration decreased with time. There were no significant differences in heroin use across dosing. Rates of withdrawal symptoms were low and did not differ across dosing schedules.. In the two highest dose schedules, plasma levels 72 h following the administration of the highest dose and at 48 h after the lower dose, were comparable to plasma concentrations at 24 h following daily administration of 16 mg/70 kg of buprenorphine.

Topics: Administration, Sublingual; Buprenorphine; Cocaine; Dose-Response Relationship, Drug; Double-Blind Method; Ethanol; Female; Heroin; Humans; Male; Narcotics; Opioid-Related Disorders; Substance Withdrawal Syndrome; Time Factors

This double-blind, randomized, placebo-controlled clinical trial evaluated the impact on withdrawal symptoms of (i) combining naltrexone with a 4-day buprenorphine taper for short opioid detoxification (NB Group), compared to (ii) using a 4-day buprenorphine taper alone, followed by naltrexone on day 8 (PB Group). Sublingual buprenorphine was administered on days 1-4 (26 mg total). For the NB Group (n = 32) escalating doses of oral naltrexone were given on days 2-8 (placebo day 1). For the PB Group (n = 28) placebo was given on days 1-7 and naltrexone on day 8. Main outcome measures were Observed Opioid Withdrawal scores (OOW, 0-30) and use of medications to treat opioid withdrawal. Of 32 patients in the NB group, 59% experienced clinically relevant withdrawal (defined as OOW > or = 5) on day 2, but, after day 5, none experienced withdrawal. In the PB group, the number of patients experiencing withdrawal increased over time. The first naltrexone dose induced comparable withdrawal in both groups: peak OOW scores were (mean +/- SD) 5.2 +/- 3.3 on day 2 for the NB group, and 4.0 +/- 3.9 on day 8 for the PB group (NS), though, on day 2, 7 patients dropped out in the NB group and none in the PB group, while only one patient dropped out in the PB group on day 8. Throughout the 8-day study, patients in both groups received similar amount of adjunct medication: 0.64 +/- 0.07 mg (NB group) of clonidine vs 0.73 +/- 0.15 mg (PB group; NS). Only 25% of patients required use of sedatives (up to 20 mg diazepam). Starting naltrexone on day 2 appeared to abolish withdrawal symptoms after day 5 and, thus, to shorten the duration of withdrawal symptoms. Peak withdrawal symptoms after naltrexone were of moderate intensity, suggesting that naltrexone combined with buprenorphine is an acceptable and safe treatment for shortened opioid detoxification and induction of naltrexone maintenance.

Topics: Adult; Analgesics; Area Under Curve; Buprenorphine; Clonidine; Double-Blind Method; Drug Interactions; Drug Therapy, Combination; Female; Heroin; Heroin Dependence; Humans; Male; Naltrexone; Narcotic Antagonists; Substance Withdrawal Syndrome

Alternate-day buprenorphine dosing was compared to daily dosing in opioid-dependent outpatients and choice of alternate-day versus daily dosing was assessed. Four dosing schedules were presented in random order under blind and open dosing conditions. Subjects received two exposures to each dosing schedule. During daily dosing, subjects received maintenance doses every 24 h. During blind alternate-day dosing, subjects received double maintenance doses every 48 h; placebo was interposed on intervening days. During open alternate-day dosing, subjects received twice their maintenance dose on Monday, Wednesday and Friday and maintenance doses on Sunday. After completing two exposures to each dosing schedule, subjects chose either daily or alternate-day schedules each week for 1 month. Study participation was contingent on daily attendance and opioid abstinence. Ten subjects were exposed to the four conditions once. Seven subjects repeated these conditions and participated in the choice phase. The effects of daily versus alternate-day dosing were not influenced by blind or open dosing conditions. Subjects' ratings of withdrawal, "sick" and sedation were lower during daily than during alternate-day dosing, but the difference between treatments was small. Nonetheless, subjects still chose alternate-day dosing on 96% of occasions, suggesting that the subject-rated differences between dosing schedules were not influential. These results extend prior findings to open-dosing conditions, and replicate the safety and acceptability of alternate-day buprenorphine treatment. Choice of alternate-day buprenorphine administration underscores the procedure's clinical utility and potential use as a positive reinforcer to enhance opioid treatment.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Double-Blind Method; Female; Humans; Male; Middle Aged; Opioid-Related Disorders; Patient Dropouts; Psychiatric Status Rating Scales; Substance Withdrawal Syndrome; Treatment Outcome

The present study, conducted as part of the development of a buprenorphine/naloxone combination product, was designed to evaluate the individual and combined effects of intravenously administered buprenorphine and naloxone. This in-patient trial used a randomized, double-blind, crossover design. Ten opioid-dependent male subjects were stabilized and maintained on morphine, 15 mg given intramuscularly four times daily. Then, at 48- to 72-h intervals, subjects received one of the following by intravenous injection: (1) placebo, (2) morphine 15 mg, (3) buprenorphine 2 mg, (4) buprenorphine 2 mg/naloxone 0.5 mg, and (5) naloxone 0.5 mg. Both naloxone and buprenorphine/naloxone produced significant (P < 0.005) opioid withdrawal effects compared to placebo as assessed with the CINA scale, an instrument which utilizes subject- and observer-reported, as well as physiological parameters. The combination of buprenorphine with naloxone in a 4:1 ratio produced opioid antagonist-like effects which should limit its potential for intravenous abuse by opioid addicts.

Topics: Adult; Analysis of Variance; Area Under Curve; Behavior, Addictive; Buprenorphine; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Humans; Injections, Intravenous; Male; Middle Aged; Morphine; Naloxone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Substance Withdrawal Syndrome; Time Factors; Veterans

Examine the relationship between buprenorphine and norbuprenorphine plasma concentrations with subject-reported withdrawal symptomatology during buprenorphine dose induction, maintenance treatments (daily and alternate-day dosing) and withdrawal.. Two groups of randomly assigned subjects inducted onto buprenorphine and maintained on 8 mg daily by the sublingual route for 18 days. Group 1 continued to receive daily buprenorphine to day 36. Group 2 subjects received alternate-day dosing of buprenorphine and placebo on days 19 to 36. Both groups received placebo on days 37 to 52.. Inpatient facilities at the Addiction Research Center, Intramural Research Center, NIDA, Baltimore, MD.. Eleven male, heroin-dependent volunteers participating in a research study.. Medications for treatment of withdrawal symptoms were prescribed as needed after day 39 (72 hours after the last dose of buprenorphine).. Plasma concentrations of buprenorphine and norbuprenorphine, withdrawal symptomatology and pupil diameter.. The mean steady-state buprenorphine plasma concentration (24 hours) after daily administrations of sublingual buprenorphine for study days 21-35 was 0.80 ng/ml, and the mean alternate day steady-state buprenorphine plasma concentration (24 hours) was 0.77 ng/ml. Daily and alternate day steady-state norbuprenorphine plasma concentrations were 1.10 and 0.90 ng/ml, respectively. Predicted alternate day steady-state buprenorphine and norbuprenorphine plasma concentrations at 48 hours were 0.49 ng/ml and 0.57 ng/ml, respectively. Withdrawal scores varied inversely with plasma concentration. There were no significant differences between Groups 1 and 2 during steady-state (days 21-35) with regard to withdrawal scale scores or pupillary diameter. The overall, mean terminal elimination half-lives for buprenorphine and norbuprenorphine were 42 and 57 hours, respectively.. during daily buprenorphine maintenance, plasma concentrations greater than 0.7 ng/ml of buprenorphine and norbuprenorphine were associated with minimal withdrawal symptoms. The long elimination half-life of buprenorphine suggested that increasing the buprenorphine dose with alternate-day administration may provide an effective, flexible therapy regimen for the treatment of opioid dependence.

Topics: Administration, Sublingual; Buprenorphine; Heroin Dependence; Humans; Male; Narcotic Antagonists; Substance Withdrawal Syndrome; Time Factors

Buprenorphine (BUP) is an alternative to methadone (METH) maintenance. However, there are few studies on the switching of patients from METH to BUP. Eighteen volunteers who had been maintained on METH for 1-19 years were recruited for a residential cocaine self-administration study. All subjects were maintained on 60 mg METH for up to 1 1/2 weeks before the 7-day changeover (60, 40, 30, 30, 0 mg METH; 4, 8 mg BUP). Fifteen subjects successfully completed the transfer from METH to BUP, experiencing moderate withdrawal symptoms, as measured by the Subjective Opiate Withdrawal Scale (SOWS). Withdrawal symptoms were the highest during the first assessment of the day, at the time of BUP administration. SOWS scores returned to baseline 4 days after the switchover. This study demonstrates that within a supportive inpatient setting, research volunteers can be rapidly switched from high-maintenance doses of METH to BUP with an acceptable degree of tolerability.

Topics: Adult; Anti-Anxiety Agents; Anxiety; Buprenorphine; Clonidine; Cocaine; Drug Administration Schedule; Female; Humans; Inpatients; Male; Methadone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Oxazepam; Substance Abuse Treatment Centers; Substance Withdrawal Syndrome; Sympatholytics; Treatment Outcome

Buprenorphine is undergoing clinical trials for the treatment of opiate addiction. Although the abuse liability of sublingual buprenorphine is low, reports of intravenous abuse have appeared. This study describes the physiologic and subjective effects of intravenously administered buprenorphine and naloxone given alone and in combination to methadone-maintained patients (40-60 mg/day). On four separate occasions at least 1 day apart, 6 subjects were administered either 0.2 mg buprenorphine, 0.1 mg naloxone, 0.2 mg buprenorphine and 0.1 mg naloxone in combination, or placebo. One male subject quit the experiment after three sessions because of excessive opiate withdrawal. Buprenorphine produced no significant physiologic or subjective effects. Naloxone produced marked opiate withdrawal symptoms. Buprenorphine in combination with naloxone produced characteristic physiologic and subjective opiate antagonist-like symptoms and signs. The parenteral abuse potential of the buprenorphine and naloxone combination is discussed.

Topics: Adult; Buprenorphine; Drug Interactions; Drug Therapy, Combination; Female; Humans; Male; Methadone; Middle Aged; Naloxone; Narcotic Antagonists; Narcotics; Substance Withdrawal Syndrome; Substance-Related Disorders

Buprenorphine's clinical utility as an opioid dependence pharmacotherapy may be enhanced with less-than-daily dosing. This study assessed opioid withdrawal after an acute 72 h dose omission in buprenorphine-maintained patients (8 mg/day s.l.). Eight outpatients required to remain free of opioids, cocaine and benzodiazepines completed four double-blind, double-dummy, Latin-square ordered conditions. Test conditions of 8 or 16 mg s.l. buprenorphine were followed by 2 days of placebo dosing. Control conditions were buprenorphine maintenance (8 mg/day), to provide a reference for evaluation of placebo test days and naloxone administration (10 mg 70 kg i.m.) during 8 mg buprenorphine maintenance to assess withdrawal measure sensitivity. Subjective measures and pupil diameter were significantly influenced only by naloxone. The lack of subjective symptoms and physiological signs of opioid withdrawal during 72 h of acute dose omission supports the feasibility of less-than-daily dosing at buprenorphine doses of 8 mg/day in patients who have demonstrated an ability to remain drug-free for an extended period.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Cocaine; Humans; Naloxone; Narcotic Antagonists; Narcotics; Psychiatric Status Rating Scales; Substance Withdrawal Syndrome; Substance-Related Disorders

Opioid detoxification in a primary care setting followed by ongoing substance abuse treatment may be appropriate for selected opioid-dependent patients.. To compare three pharmacologic protocols for opioid detoxification in a primary care setting.. Randomized, double-blind clinical trial with random assignment to treatment protocols.. A free-standing primary care clinic affiliated with drug treatment programs.. 162 heroin-dependent patients.. Three detoxification protocols: donidine, combined donidine and naltrexone, and buprenorphine.. Successful detoxification (that is, when study participants received a full opioid-blocking dose [50 mg] of naltrexone), treatment retention (8 days), and withdrawal symptoms.. Overall, 65% of participants (36 of 55) who received clonidine, 81% (44 of 54) who received combined clonidine and naltrexone, and 81% (43 of 53) who received buprenorphine were successfully detoxified. Retention did not differ significantly across the groups: 65% of participants (36 of 55) who received clonidine, 54% (29 of 54) who received combined clonidine and naltrexone, and 60% (32 of 53) who received buprenorphine. Participants who received buprenorphine had a significantly lower mean withdrawal symptom score than those who received clonidine or combined clonidine and naltrexone.. Participants in the combined clonidine and naltrexone group and those in the buprenorphine group were more likely to complete detoxification, although retention at 8 days did not differ among the groups. Participants who were assigned to the buprenorphine group experienced less severe withdrawal symptoms than those assigned to the other two groups.

Topics: Adolescent; Adrenergic alpha-Agonists; Adult; Buprenorphine; Clonidine; Double-Blind Method; Drug Therapy, Combination; Female; Heroin; Heroin Dependence; Humans; Inactivation, Metabolic; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Primary Health Care; Substance Withdrawal Syndrome

The effects of p.o. methadone or sublingual buprenorphine maintenance on i.v. cocaine self-administration and the response to experimenter-administered cocaine were evaluated in 12 methadone-maintained individuals. Participants lived in a clinical research center during the 4- to 5-week protocol. After stabilization on 80 mg/day methadone, half the participants were first tested during buprenorphine maintenance (8 mg/day with p.o. placebo) and half were first tested during methadone maintenance (60 mg/day with sublingual placebo). After testing on the alternate medication, all participants were returned to their entry level of methadone. Testing consisted of three daily sessions of fixed cocaine dosing (four injections; 0, 16 and 48 mg/70 kg) and three daily sessions of cocaine self-administration with a choice procedure (16, 32 and 48 mg/70 kg vs. $5). The transition from methadone to buprenorphine engendered moderate withdrawal symptoms (score of 12 on the subjective opiate withdrawal scale), which returned to base-line levels (score of 4 on the subjective opiate withdrawal scale) before testing during buprenorphine maintenance. Buprenorphine maintenance significantly reduced "I want cocaine" scores by 15% during fixed-dosing sessions. Subjective effects of fixed cocaine doses, including increased ratings of "high," "stimulated" and "good drug effect," were not affected by the maintenance medication. Heart rate was consistently 9 beats/min less, regardless of cocaine dose, during methadone maintenance. In comparison with methadone, buprenorphine maintenance decreased cocaine self-administration when 16- or 32-mg doses were available, but not when 48 mg was available. Thus, buprenorphine may have greater efficacy than methadone for controlling cocaine abuse among individuals dependent on opioids.

Topics: Adult; Buprenorphine; Cocaine; Dose-Response Relationship, Drug; Female; Humans; Infusions, Intravenous; Male; Methadone; Opioid-Related Disorders; Self Administration; Substance Withdrawal Syndrome; Surveys and Questionnaires

This article reports results for patients who completed the 16-week maintenance phase of a double-blind clinical trial comparing buprenorphine (N = 43; average dose = 9.0 mg/day sublingually) with methadone (N = 43; average dose = 54 mg/day orally) in the outpatient treatment of opioid dependence. In addition to pharmacotherapy, treatment during the clinical trial included individual counseling, weekly group therapy, and on-site medical services. Patients in both medication groups showed significant and substantial improvements over time in areas of psychosocial functioning, as assessed by the Addiction Severity Index, rates of urinalysis tests positive for opioids, and self-reports of opioid withdrawal symptoms, illicit opioid use, and cocaine use. Buprenorphine and methadone produced very similar outcomes on the wide array of outcome measures assessed, and improvements for both groups were large and occurred rapidly after treatment entry. A trend toward continued improvement in opioid-positive urines over time was noted for the buprenorphine but not the methadone group. These results provide further evidence of the efficacy of buprenorphine in the treatment of opioid dependence and provide a characterization of the time course of effects for buprenorphine and methadone. In addition, these results demonstrate the benefits of drug abuse treatment, both for drug and alcohol use and in other areas of psychosocial functioning.

Topics: Adolescent; Adult; Alcoholism; Buprenorphine; Cocaine; Double-Blind Method; Female; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Substance Abuse Detection; Substance Withdrawal Syndrome; Treatment Outcome

We assessed cognitive function following heroin and cocaine detoxification and investigated whether buprenorphine treatment improves the disruptive effects of detoxification. Three groups of male volunteers meeting DSM-III-R criteria for concurrent opiate and cocaine dependence were tested using an auditory oddball paradigm before and after detoxification, and again on the 15th day of either buprenorphine or placebo treatment. There were no significant differences in P300 amplitude, latency, or topographic distribution between drug-dependent subjects and controls on admission day. Following detoxification there was a significant decrease in P300 amplitude in the drug-dependent group at a time when self-reported signs of withdrawal were minimal. Buprenorphine treatment significantly reversed the P300 amplitude decrement following detoxification, whereas placebo-treated subjects continued to show depressed P300 amplitudes. These data demonstrate that buprenorphine treatment is effective in eliminating detoxification-induced impairments in one measure of cognitive ability.

Topics: Adult; Arousal; Attention; Brain Mapping; Buprenorphine; Cerebral Cortex; Cocaine; Event-Related Potentials, P300; Heroin Dependence; Humans; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Reaction Time; Substance Withdrawal Syndrome

Buprenorphine, a partial mu opioid agonist, is an experimental medication under development for the treatment of opioid dependence as an alternative to methadone maintenance. The present study examined the relationship between level of opioid physical dependence and response to buprenorphine administration as part of a program to develop procedures for transferring patients from methadone to buprenorphine treatment. This laboratory study characterized the agonist and antagonist effects of acute doses of buprenorphine and methadone in subjects maintained on either 30 (n = 7) or 60 (n = 6) mg/day oral methadone. Test doses of placebo [sl. and PO), methadone (15, 30, and 60 mg PO) and buprenorphine (2, 4, and 8 mg sl.) were administered to volunteers residing on a closed residential unit. Subjective, physiological, observer-rated, and cognitive/psychomotor measures were collected for 6.5 h after test doses. Test doses of methadone, but not buprenorphine, constricted pupils and produced dose-related increases on subjective report measures reflecting opioid agonist drug effects. Agonist effects of methadone were more prominent in the 30 mg than in the 60 mg methadone maintenance condition. Buprenorphine, but not methadone, precipitated opioid withdrawal signs and symptoms that were more prominent in the 60 mg than in the 30 mg methadone maintenance condition. These findings suggest that abrupt transition from methadone to buprenorphine may produce patient discomfort that is positively related to both methadone maintenance dose and buprenorphine transition dose.

Topics: Administration, Oral; Adult; Buprenorphine; Dose-Response Relationship, Drug; Humans; Male; Methadone; Middle Aged; Opioid-Related Disorders; Substance Withdrawal Syndrome; Time Factors

Buprenorphine, a mu-opioid partial agonist, has demonstrated efficacy for the treatment of opioid dependence comparable to that of methadone. The clinical utility of buprenorphine would be enhanced if it could be dosed on a less than daily basis. The current study is a parallel-group outpatient clinical trial of daily versus alternate-day dosing with 8 mg sublingual (s.l.) buprenorphine. Participants were randomly assigned to daily (n = 51) or alternate-day (n = 48) schedules of active medication administration for an 11-week double-blind trial. Patients assigned to alternate-day buprenorphine received placebo every other day. Primary outcome measures were retention in treatment and urine specimens positive for opiates. Clinic attendance, dose adequacy ratings, withdrawal symptomatology, and urine specimens positive for cocaine were secondary outcome measures. Neither endpoint analysis with the intent-to-treat sample nor time course analysis with treatment completers revealed any statistically significant differences between the dosing schedules on any outcome measure. Examination of 95% confidence intervals suggested a non-significant trend for the daily dosing schedule to have superior clinical efficacy at the dose tested. Nevertheless, these results are generally consistent with previous studies of less than daily dosing with buprenorphine and support the conclusion that an alternate-day dosing schedule can be effective in and acceptable to a substantial portion of patients.

Topics: Adult; Buprenorphine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Heroin Dependence; Humans; Male; Narcotic Antagonists; Neurologic Examination; Substance Abuse Detection; Substance Withdrawal Syndrome

Six opioid-dependent in-patients were maintained on daily sublingual doses of buprenorphine at 2, 6, and 12 mg/day for five days at each dose in a randomized, balanced sequence. Placebo buprenorphine was substituted for the next three days, and challenge doses of the mu agonist hydromorphone were administered on the three days. Planned comparisons in a 3-factor ANOVA showed dose-dependent hydromorphone effects, significant blockade of 'high' by the 12 mg buprenorphine dose, and no differences on hydromorphone-induced 'high' across 72 h of active buprenorphine. The data suggest that the blockade by buprenorphine of 'high' persists for at least 72 h after the last dose of buprenorphine.

Topics: Administration, Sublingual; Adult; Buprenorphine; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Hydromorphone; Male; Neurologic Examination; Opioid-Related Disorders; Single-Blind Method; Substance Withdrawal Syndrome; Time Factors

The effects of naltrexone-precipitated withdrawal from buprenorphine on behavior and regional cerebral blood flow (rCBF) were studied in 11 opiate-dependent patients. Patients initially received buprenorphine, 2 mg sublingually, every day for 7 days. They were then challenged sequentially with placebo and naltrexone, 25 mg orally, before single photon emission computed tomography with technetium-99m-d,l-hexamethyl-propylene amine oxime as tracer. Behavioral ratings of withdrawal severity were made before and after naltrexone/placebo administration. Naltrexone produced significantly greater signs and symptoms of opiate withdrawal than placebo. Analysis of variance revealed no significant regionally specific effect of naltrexone on rCBF ratios. Severity of withdrawal, however, showed a significant negative correlation with rCBF in the anterior cingulate cortex following naltrexone. These results are interesting as the anterior cingulate region has been implicated in the emotional component of pain and in opiate-induced analgesia.

Topics: Adult; Buprenorphine; Female; Gyrus Cinguli; Humans; Male; Naltrexone; Placebos; Regional Blood Flow; Severity of Illness Index; Substance Withdrawal Syndrome; Substance-Related Disorders; Thalamus; Tomography, Emission-Computed, Single-Photon

Eight opioid-dependent individuals were maintained on daily sublingual buprenorphine (8 mg) for 28 days and assigned randomly to one of two outpatient detoxification schedules under double-blind, double-dummy conditions. The two detoxification schedules were buprenorphine gradual (36 days; N = 3) or buprenorphine rapid (12 days; N = 5). Outcome variables were subject- and observer-ratings of opioid withdrawal, treatment retention and illicit-opioid use. Outcome measures were similar for the two groups during buprenorphine maintenance. Increases in subject-rated opioid withdrawal and illicit-opioid use, and a drop in treatment retention occurred during rapid detoxification. Stable subject-rated opioid withdrawal and treatment retention, and less illicit-opioid use occurred during gradual detoxification. These data suggest that gradual reduction in buprenorphine dose is likely to produce superior treatment outcomes than more rapid buprenorphine detoxification.

Topics: Administration, Sublingual; Adult; Buprenorphine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Neurologic Examination; Opioid-Related Disorders; Patient Compliance; Substance Withdrawal Syndrome; Treatment Outcome

In a 6-month randomized trial comparing 125 opiate-dependent patients who were assigned to four treatment groups (2 or 6 mg of buprenorphine and 35 or 65 mg of methadone), we examined the effects of cocaine use on opiate withdrawal symptoms measured on a 25-item scale on which the scores range from 0 to 75. For the methadone-maintained patients receiving the relatively low dose (35 mg), weekly withdrawal symptoms were highest when the urine toxicology for that week indicated no cocaine use. Similar associations were found for buprenorphine. Thus, when using cocaine at a low maintenance opiate dose, persistent opiate withdrawal symptoms were reduced, which is consistent with previous naloxone-precipitated withdrawal studies. Interestingly, with a higher dose of buprenorphine (6 mg), cocaine may have increased opiate withdrawal symptoms, suggesting a possible mechanism for the reduction of illicit cocaine abuse also recently observed in another study in patients treated with high dose (120 mg) methadone maintenance. This has led to a two-component model for the relationship between cocaine and opiate withdrawal-like symptoms at high versus low opiate maintenance dose. This two-component model also reconciles the contradictory findings of prior studies.

Topics: Adult; Buprenorphine; Cocaine; Comorbidity; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Methadone; Neurologic Examination; Opioid-Related Disorders; Substance Abuse Detection; Substance Withdrawal Syndrome; Substance-Related Disorders

We compared the short-term efficacy of a high-dose, 3 day regimen of buprenorphine to a standard 5-day course of clonidine in attenuating the signs and symptoms of the acute opioid abstinence syndrome during rapid detoxification from heroin in 25 men and women admitted to a closed inpatient research ward for this randomized, double-blind, parallel-group trial. Among the 18 completers, there were no significant differences between the buprenorphine and clonidine groups on five subjective and six physiological measures. However, clonidine lowered blood pressure and buprenorphine provided more effective early relief of withdrawal symptoms.

Topics: Adult; Baltimore; Buprenorphine; Clonidine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Heroin Dependence; Humans; Male; Middle Aged; Opioid-Related Disorders; Substance Abuse Treatment Centers; Substance Withdrawal Syndrome; Urban Population

Thirty-nine methadone maintenance patients were included in a 9-day, double blind, randomized, inpatient detoxification trial. Methadone was tapered to 10 mg/day and then patients were assigned to one of these 3 protocols: clonidine (0.3-0.9 mg/day), lefetamine (60-240 mg/day), buprenorphine (0.15-0.9 mg/day). Buprenorphine treatment was significantly superior to clonidine and to lefetamine (F = 3.96 df = 2, 29 P < 0.05) in controlling objective, subjective and psychological withdrawal symptomatology. Clonidine was more effective than lefetamine in suppressing withdrawal in the first 3 days of treatment (day 3: F = 4.10 df = 2, 30 P < 0.05), and this trend was apparent on the objective and psychological items. In addition to evaluations of the efficacy of the single drugs used, the study showed that tapering methadone to low doses before entering the pharmacologically assisted discontinuation phase was clinically acceptable in detoxification from long-term methadone treatment.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Clonidine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Heroin Dependence; Humans; Male; Methadone; Neurologic Examination; Opioid-Related Disorders; Patient Admission; Phenethylamines; Substance Withdrawal Syndrome

Thirteen opioid-dependent outpatients participated in a double-blind, placebo-controlled, crossover trial. Twenty-one days of daily sublingual buprenorphine administration were compared to 21-days of alternate-day buprenorphine administration where patients received twice their daily maintenance dose every other day with placebo on the interposed day. Observer- and subject-rated measures of opioid agonist and withdrawal effects, pupillary diameter, and dose identifications were collected daily. Ten subjects (77%) completed the study (n = 6, 4 mg/70 kg; n = 4, 8 mg/70 kg); 8 subjects (62%) participated in a second crossover. Sixteen of seventeen measures of opioid agonist and withdrawal effects obtained during alternate-day administration did not differ significantly from those obtained during daily dosing in the ten subjects completing the study. The only significant difference observed was in subject-rated agonist effects, which were significantly lower during alternate-day than daily administration. No differences were observed between treatments on any measure for the eight subjects completing a second crossover. These data suggest that buprenorphine can be administered safely every 48 hours by doubling the maintenance dose. This alternate-day schedule permits patients to attend the clinic less frequently without the risk of diversion associated with take-home doses, may be cost-effective for programs, and may be useful in settings in which travel to the clinic is a barrier to treatment.

Topics: Administration, Sublingual; Adult; Buprenorphine; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Opioid-Related Disorders; Patient Compliance; Substance Withdrawal Syndrome

Five inpatients dependent on both intravenous cocaine and heroin were detoxified from opiates. They were then given 5 days of double-blind treatment with active or placebo buprenorphine 2 mg/d sublingually, followed by a crossover to the converse for 5 days (buprenorphine or placebo). Intranasal cocaine challenges (2 mg/kg) were performed on Days 3 and 5 of each treatment. Buprenorphine significantly enhanced patients' ratings of cocaine-induced pleasurable effects, and augmented cocaine-induced pulse increases. The buprenorphine enhancement of subjective cocaine effects appeared to be more prominent on Day 3 than on Day 5. This reduction from Day 3 to Day 5 suggests that cocaine may interact differently with buprenorphine as treatment is more prolonged.

Topics: Adult; Affect; Arousal; Buprenorphine; Cocaine; Comorbidity; Double-Blind Method; Drug Administration Schedule; Euphoria; Female; Heroin Dependence; Humans; Male; Pilot Projects; Substance Withdrawal Syndrome; Substance-Related Disorders

The spontaneous physical dependence of buprenorphine was assessed in opioid addicts who switched from heroin to sublingual or intravenous buprenorphine. Twenty-two patients were randomly assigned to double-blind administration of methadone (n = 11) or placebo (n = 11) for 13 days after abrupt withdrawal of buprenorphine. Methadone was administered according to four pre-established dosing schedules depending on the previous amount of daily consumed buprenorphine. No methadone-treated patient required modification of the therapeutic regimen, whereas eight of eleven placebo-treated patients needed treatment with methadone. Buprenorphine withdrawal syndrome was of opioid type, began somewhat more slowly, and showed a peak until day 5. The occurrence, time-course and characteristics of buprenorphine withdrawal syndrome make it necessary to reconsider the abuse potential of this analgesic.

Topics: Adult; Buprenorphine; Double-Blind Method; Female; Heroin Dependence; Humans; Male; Methadone; Neurologic Examination; Opioid-Related Disorders; Substance Abuse Treatment Centers; Substance Withdrawal Syndrome

Data from these studies indicate that buprenorphine is efficacious in treating opioid dependence. It was possible to induct heroin addicts rapidly onto buprenorphine without precipitating an opioid withdrawal syndrome. A daily 8-mg SL dosage was sufficient to maintain individuals without producing reports of withdrawal symptoms. When buprenorphine was administered at the above dose every other day, however, mild withdrawal symptoms were reported, and responses to challenges with intravenously given hydromorphone appeared greater than when the challenges were given intramuscularly. From these results, the authors conclude that buprenorphine at this dose should be administered on a daily basis. These results are now being applied to a phase II outpatient clinical trial comparing buprenorphine with methadone.

Topics: Adult; Buprenorphine; Double-Blind Method; Female; Follow-Up Studies; Heroin Dependence; Humans; Hydromorphone; Male; Middle Aged; Naloxone; Substance Withdrawal Syndrome; Testosterone

Topics: Adult; Blood Pressure; Buprenorphine; Double-Blind Method; Female; Humans; Male; Methadone; Methoxyhydroxyphenylglycol; Naloxone; Naltrexone; Opioid-Related Disorders; Substance Withdrawal Syndrome

1. A 26-32 month follow-up of 16 heroin-dependent subjects who entered a pilot trial of treatment with buprenorphine (a mixed agonist/antagonist) suggests that positive response to treatment may identify a subgroup of untreated addicts whose levels of psychosocial functioning are intermediate between those for whom methadone (a pure agonist) or naltrexone (a pure antagonist) would be indicated. 2. Buprenorphine's pharmacologic profile provides a missing link in available modalities for opiate dependence treatment, making it acceptable for many addicts who will not accept methadone maintenance treatment, join a residential therapeutic community, or be successful on naltrexone treatment. 3. Eight of the 16 ss were abstinent from heroin while receiving 0.6-3.9 mg/day buprenorphine and counseling. Responders (mean age 34 yrs) had been heroin dependent for a mean of 9.5 years (range 6-17 yrs), all were self-supporting, 4 lived with a non-addicted spouse, 5 had no prior treatment for addiction and 3 had prior naltrexone treatment, but had discontinued it and relapsed. Non-responders (mean age 30 yrs) had been heroin dependent for a mean of 7.4 yrs (range 2-19 yrs), 7 had no regular employment, all were single and 7 had no prior treatment for addiction. 4. Levels of psychosocial functioning (work, home, leisure) and global assessments of functioning were significantly higher for buprenorphine responders than non-responders (p less than .001 and p less than .01 respectively). 5. A new formulation of buprenorphine needs to be developed for addiction treatment, ideally consisting of 0.5 mg and 2.0 mg sublingual tablets.

Topics: Adult; Buprenorphine; Female; Follow-Up Studies; Heroin Dependence; Humans; Male; Pilot Projects; Social Behavior; Substance Withdrawal Syndrome

Thirty-nine opioid-dependent outpatients were treated with the partial agonist buprenorphine at 2 to 6 mg/day for 1 month. Treatment retention was good (72%), and illicit opioid use decreased from 50% overall to 17% for those who remained in treatment. Precipitated withdrawal symptoms were mild and related to dose of buprenorphine. At the end of this month, 28 subjects were abruptly discontinued from buprenorphine and given the antagonist naltrexone. Withdrawal symptoms from buprenorphine were quite mild, and naltrexone was initiated in 20 patients (51% of total or 71% of those 28 completing 30 days on buprenorphine), but only 4 patients (10% overall) were successfully maintained on naltrexone for at least 2 weeks.

Topics: Adult; Buprenorphine; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Heroin Dependence; Humans; Male; Methadone; Naltrexone; Neurologic Examination; Substance Withdrawal Syndrome

Following one month of sublingual buprenorphine treatment, 15 patients at either 2 mg (n = 7) or 3 mg (n = 8) were hospitalized and the buprenorphine was abruptly stopped by placebo substitution. On the morning following their last dose of buprenorphine, 10 patients were given 1 mg oral naltrexone and 5 were given 0.5 mg/kg intravenous naloxone in a double blind placebo controlled challenge. The naltrexone challenges produced no increase in opioid withdrawal symptoms, plasma MHPG levels, or blood pressure compared to placebo, while naloxone produced significant symptoms and blood pressure increases compared to placebo challenges.

Topics: Administration, Sublingual; Adult; Buprenorphine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Heroin Dependence; Humans; Infusions, Intravenous; Male; Methadone; Naloxone; Naltrexone; Substance Withdrawal Syndrome

Nineteen heroin-dependent male volunteers were administered buprenorphine sublingually, in ascending daily doses of 2, 4, and 8 mg. They were maintained on 8 mg daily through study day 18. On study days 19 through 36, subjects in group 1 continued to receive burprenorphine daily; subjects in group 2 received buprenorphine or placebo on alternate days. On days 37 through 52, all subjects received placebo. Subjects receiving buprenorphine on alternate days reported significantly greater urge for an opioid, increased dysphoria scores, and pupillary dilation on placebo days. After abrupt termination of buprenorphine, no withdrawal signs were detected with the Himmelsbach scale. However, subjects reported mild-to-moderate opioid withdrawal symptoms, peaking at 3 to 5 and lasting for 8 to 10 days. Daily administration of buprenorphine provided greater control of subtle opioid withdrawal symptoms, but subjects could tolerate a between-dose interval of 48 hours.

Topics: Adult; Behavior; Buprenorphine; Drug Administration Schedule; Female; Heroin Dependence; Humans; Male; Middle Aged; Miosis; Sleep; Substance Withdrawal Syndrome

Topics: Buprenorphine; Clinical Trials as Topic; Double-Blind Method; Humans; Naloxone; Naltrexone; Opioid-Related Disorders; Placebos; Substance Withdrawal Syndrome

Subjective, physiological and behavioral effects of subcutaneously administered hydromorphone (6 mg), naloxone (0.2 mg), buprenorphine (0.2 and 0.3 mg), and two buprenorphine-naloxone combinations (buprenorphine 0.2 mg plus naloxone 0.2 mg and buprenorphine 0.3 mg plus naloxone 0.2 mg) were assessed under double-blind conditions in six opioid-dependent volunteers. Physiologic measures and subject- and observer-rated behavioral responses were measured before dosing and for 120 min after drug administration. Hydromorphone decreased pupil diameter and respiration, increased blood pressure and increased scores on subjective measures indicating opioid-like effects. Buprenorphine given alone had no significant effect on any variable measured. Naloxone given alone produced opioid abstinence-like effects which were measurable on subject- and observer-rated behavioral measures and physiological measures. Buprenorphine in combination with naloxone somewhat attenuated the naloxone-precipitated withdrawal response. Overall, the naloxone-buprenorphine combinations produced effects which were qualitatively similar to the effects of naloxone alone, suggesting a low potential for abuse of the combination product by opioid-dependent individuals.

Topics: Adult; Blood Pressure; Body Temperature; Buprenorphine; Cognition; Heart Rate; Humans; Hydromorphone; Male; Naloxone; Opioid-Related Disorders; Psychomotor Performance; Respiration; Substance Withdrawal Syndrome

Sixteen opioid dependent patients were assigned to treatment with buprenorphine for one month at three doses--2 mg (n = 10), 4 mg (n = 4), 8 mg (n = 2). Treatment retention was excellent--only one patient left due to withdrawal symptoms. Illicit opioid use was infrequent, with only 22% of the urines containing illicit opioids. Although buprenorphine dose was not associated with retention or illicit opioid use, patterns of withdrawal symptoms differed among dosage groups during the 30 day study. The 4 mg group had a substantial decline in symptoms, while the other two groups did not. Symptom levels were comparable to those during successful clonidine detoxification and much lower than those found in clonidine failures.

Topics: Adult; Buprenorphine; Clinical Trials as Topic; Female; Heroin Dependence; Humans; Male; Methadone; Substance Withdrawal Syndrome

Topics: Adult; Analysis of Variance; Buprenorphine; Clinical Trials as Topic; Heroin Dependence; Humans; Hydromorphone; Male; Methadone; Narcotic Antagonists; Substance Withdrawal Syndrome

Heroin-dependent out-patients who had been prescribed buprenorphine by general practitioners took part in a controlled study in which 2 mg or 4 mg of buprenorphine were administered by the sublingual route to assess its acceptability as a maintenance opiate and to determine the effects of its abrupt withdrawal and reintroduction a week later. Subjects who received 4 mg of buprenorphine reported being more intoxicated and having fewer symptoms of opiate withdrawal than did the subjects who received the 2-mg dose. Subjects who received the higher dose also abused opiate and benzodiazepine drugs less frequently. When buprenorphine was ceased abruptly, the subjects reported mild withdrawal discomfort for which many requested symptomatic treatment. The reintroduction of buprenorphine caused their condition to restabilize. The subjects' use of opiate drugs, as shown by urine assay, rose from a prevalence of around 15% of specimens at the beginning to about 50% of specimens at the end of the five-week study period. Sublingual buprenorphine was acceptable to opiate-addicted outpatients as a maintenance treatment. However, daily doses of greater than 4 mg will probably be required to suppress concurrent opiate abuse, and detoxification will need to be undertaken gradually.

Topics: Administration, Oral; Adult; Buprenorphine; Dose-Response Relationship, Drug; Female; Heroin Dependence; Humans; Male; Morphinans; Narcotics; Patient Dropouts; Random Allocation; Substance Withdrawal Syndrome; Surveys and Questionnaires

Buprenorphine was evaluated for its abuse potential and utility in treating narcotic addiction. The drug was morphine-like but was 25 to 50 times more potent than morphine and was longer-acting. Little if any physical dependence of clinical significance was produced by buprenorphine. The effects of morphine to 120-mg doses were blocked by buprenorphine, a blockade that persisted for 29 1/2 hours. In man, buprenorphine has less intrinsic activity than morphine, and as such, as a low abuse potential. Moreover, the drug has potential for treating narcotic addiction since it is acceptable to addicts, is long-acting, produces a low level of physical dependence such that patients may be easily detoxified, is less toxic than drugs used for maintenance therapy, and blocks the effects of narcotics.

Topics: Adult; Blood Pressure; Buprenorphine; Clinical Trials as Topic; Dose-Response Relationship, Drug; Double-Blind Method; Euphoria; Humans; Male; Methadone; Middle Aged; Morphinans; Morphine; Naloxone; Narcotics; Pulse; Pupil; Receptors, Opioid; Substance Withdrawal Syndrome; Substance-Related Disorders

To evaluate the efficacy and safety of utilizing emergency medical services units to administer high dose buprenorphine after an overdose to treat withdrawal symptoms, reduce repeat overdose, and provide a next-day substances use disorder clinic appointment to initiate long-term treatment.. This was a retrospective matched cohort study of patients who experienced an overdose and either received emergency medical services care from a buprenorphine-equipped ambulance or a nonbuprenorphine-equipped ambulance in Camden, New Jersey, an urban community with high overdose rates. There were 117 cases and 123 control patients in the final sample.. Compared with a nonbuprenorphine-equipped ambulance, exposure to a buprenorphine-equipped ambulance was associated with greater odds of engaging in opioid use disorder treatment within 30 days of an emergency medical services encounter (unadjusted odds ratio: 5.62, 95% confidence interval, 2.36 to 13.39). Buprenorphine-equipped ambulance engagement did not decrease repeat overdose compared to the comparison group. Patients who received buprenorphine experienced a decrease in withdrawal symptoms. Their clinical opiate withdrawal scale score decreased from an average of 9.27 to 3.16. buprenorphine-equipped ambulances increased on-scene time by 6.12 minutes.. Patients who encountered paramedics trained to administer buprenorphine and able to arrange prompt substance use disorder treatment after an acute opioid overdose demonstrated a decrease in opioid withdrawal symptoms, an increase in outpatient addiction follow-up care, and showed no difference in repeat overdose. Patients receiving buprenorphine in the out-of-hospital setting did not experience precipitated withdrawal. Expanded out-of-hospital treatment of opiate use disorder is a promising model for rapid access to buprenorphine after an overdose in a patient population that often has limited contact with the health care system.

Topics: Analgesics, Opioid; Buprenorphine; Cohort Studies; Drug Overdose; Emergency Medical Services; Humans; Narcotic Antagonists; Opioid-Related Disorders; Retrospective Studies; Substance Withdrawal Syndrome

Limited information exists regarding individual subgroups of recovery from opioid use disorder (OUD) following treatment and how these subgroups may relate to recovery trajectories. We used multi-dimensional criteria to identify OUD recovery subgroups and longitudinal transitions across subgroups.. In a national longitudinal observational study in the United States, individuals who previously participated in a clinical trial for subcutaneous buprenorphine injections for treatment of OUD were enrolled and followed for an average of 4.2 years after participation in the clinical trial.. We identified recovery subgroups based on psychosocial outcomes including depression, opioid withdrawal and pain. We compared opioid use, treatment utilization and quality of life among these subgroups.. Three dimensions of the recovery process were identified: depression, opioid withdrawal and pain. Using these three dimensions, participants were classified into four recovery subgroups: high-functioning (minimal depression, mild withdrawal and no/mild pain), pain/physical health (minimal depression, mild withdrawal and moderate pain), depression (moderate depression, mild withdrawal and mild/moderate pain) and low-functioning (moderate/severe withdrawal, moderate depression and moderate/severe pain). Significant differences among subgroups were observed for DSM-5 criteria (P < 0.001) and remission status (P < 0.001), as well as with opioid use (P < 0.001), treatment utilization (P < 0.001) and quality of life domains (physical health, psychological, environment and social relationships; Ps < 0.001, Cohen's fs ≥ 0.62). Recovery subgroup assignments were dynamic, with individuals transitioning across subgroups during the observational period. Moreover, the initial recovery subgroup assignment was minimally predictive of long-term outcomes.. There appear to be four distinct subgroups among individuals in recovery from OUD. Recovery subgroup assignments are dynamic and predictive of contemporaneous, but not long-term, substance use, substance use treatment utilization or quality of life outcomes.

Topics: Analgesics, Opioid; Buprenorphine; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Pain; Quality of Life; Substance Withdrawal Syndrome; United States

Medical hospitalizations for people with opioid use disorder (OUD) frequently result in patient-directed discharges (PDD), often due to untreated pain and withdrawal.. To investigate the association between early opioid withdrawal management strategies and PDD.. Retrospective cohort study using three datasets representing 362 US hospitals.. Adult patients hospitalized between 2009 and 2015 with OUD (as identified using ICD-9-CM codes or inpatient buprenorphine administration) and no PDD on the day of admission.. Opioid withdrawal management strategies were classified based on day-of-admission receipt of any of the following treatments: (1) medications for OUD (MOUD) including methadone or buprenorphine, (2) other opioid analgesics, (3) adjunctive symptomatic medications without opioids (e.g., clonidine), and (4) no withdrawal treatment.. PDD was assessed as the main outcome and hospital length of stay as a secondary outcome.. Of 6,715,286 hospitalizations, 127,158 (1.9%) patients had OUD and no PDD on the day of admission, of whom 7166 (5.6%) had a later PDD and 91,051 (71.6%) patients received some early opioid withdrawal treatment (22.3% MOUD; 43.4% opioid analgesics; 5.9% adjunctive medications). Compared to no withdrawal treatment, MOUD was associated with a lower risk of PDD (adjusted odds ratio [aOR] = 0.73, 95%CI 0.68-0.8, p < .001), adjunctive treatment alone was associated with higher risk (aOR = 1.13, 95%CI: 1.01-1.26, p = .031), and treatment with opioid analgesics alone was associated with similar risk (aOR 0.95, 95%CI: 0.89-1.02, p = .148). Among those with PDD, both MOUD (adjusted incidence rate ratio [aIRR] = 1.24, 95%CI: 1.17-1.3, p < .001) and opioid analgesic treatments (aIRR = 1.39, 95%CI: 1.34-1.45, p < .001) were associated with longer hospital stays.. MOUD was associated with decreased risk of PDD but was utilized in < 1 in 4 patients. Efforts are needed to ensure all patients with OUD have access to effective opioid withdrawal management to improve the likelihood they receive recommended hospital care.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Discharge; Retrospective Studies; Substance Withdrawal Syndrome

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

Medications for addiction treatment (MAT) are the evidence-based standard of care for treatment of opioid use disorder (OUD), but stigma continues to surround their use. We conducted an exploratory study to characterize perceptions of different types of MAT among people who use drugs.. We conducted this qualitative study in adults with a history of non-medical opioid use who presented to an emergency department for complications of OUD. A semi-structured interview that explored knowledge, perceptions, and attitudes toward MAT was administered, and applied thematic analysis conducted.. We enrolled 20 adults. All participants had prior experience with MAT. Among participants indicating a preferred treatment modality, buprenorphine was the commonly favored agent. Previous experience with prolonged withdrawal symptoms upon MAT discontinuation and the perception of "trading one drug for another" were common reasons for reluctance to engage in agonist or partial-agonist therapy. While some participants preferred treatment with naltrexone, others were unwilling to initiate antagonist therapy due to fear of precipitated withdrawal. Most participants strongly considered the aversive nature of MAT discontinuation as a barrier to initiating treatment. Participants overall viewed MAT positively, but many had strong preferences for a particular agent.. The anticipation of withdrawal symptoms during initiation and cessation of treatment affected willingness to engage in a specific therapy. Future educational materials for people who use drugs may focus on comparisons of respective benefits and drawbacks of agonists, partial agonists, and antagonists. Emergency clinicians must be prepared to answer questions about MAT discontinuation to effectively engage patients with OUD.

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

The rising prevalence of early-life opioid exposure has become a pressing public health issue in the U.S. Neonates exposed to opioids in utero are at risk of experiencing a constellation of postpartum withdrawal symptoms commonly referred to as neonatal opioid withdrawal syndrome (NOWS). Buprenorphine (BPN), a partial agonist at the mu-opioid receptor (MOR) and antagonist at the kappa-opioid receptor (KOR), is currently approved to treat opioid use disorder in adult populations. Recent research suggests that BPN may also be effective in reducing withdrawal symptoms in neonates who were exposed to opioids in utero. We sought to determine whether BPN attenuates somatic withdrawal in a mouse model of NOWS. Our findings indicate that the administration of morphine (10mg/kg, s.c.) from postnatal day (PND) 1-14 results in increased somatic symptoms upon naloxone-precipitated (1mg/kg, s.c.) withdrawal. Co-administration of BPN (0.3mg/kg, s.c.) from PND 12-14 attenuated symptoms in morphine-treated mice. On PND 15, 24h following naloxone-precipitated withdrawal, a subset of mice was examined for thermal sensitivity in the hot plate test. BPN treatment significantly increased response latency in morphine-exposed mice. Lastly, neonatal morphine exposure elevated mRNA expression of KOR, and reduced mRNA expression of corticotropin-releasing hormone (CRH) in the periaqueductal gray when measured on PND 14. Altogether, this data provides support for the therapeutic effects of acute low-dose buprenorphine treatment in a mouse model of neonatal opioid exposure and withdrawal.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Female; Mice; Morphine; Naloxone; Narcotic Antagonists; Receptors, Opioid; RNA, Messenger; Substance Withdrawal Syndrome

Buprenorphine, a partial mu-opioid receptor agonist, is a commonly prescribed medication for opioid use disorder (OUD). There is evidence that drugs may enter the male genitourinary tract by an ion-trapping process, based on the lipid solubility and degree of ionization (1). While little is known about the pharmacokinetics of drugs in seminal fluid, pH is thought to play an integral role. Limited evidence exists surrounding cervical absorption of drugs

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

Patients with opioid use disorder may have difficulty transitioning from full-agonist opioids to sublingual buprenorphine due to the risk of precipitated opioid withdrawal. Novel strategies have been developed to facilitate this transition, including the use of micro-dosing with transdermal buprenorphine. We began using a transdermal buprenorphine transition strategy at our hospital in 2019.. We performed a retrospective observational cohort study of patients treated with transdermal buprenorphine to facilitate transition from full-agonist opioids (prescribed or recreational) while hospitalized between January 2019 and December 2020. Patients were excluded if transdermal buprenorphine was given for pain, if they did not receive at least one dose of sublingual buprenorphine while hospitalized, or if their clinical course precluded analysis of their tolerance of the transition protocol. Data on the doses and timing of medications, symptoms during transition, and hospital outcomes were abstracted from the electronic medical record.. We identified 41 cases that satisfied inclusion and exclusion criteria. Thirty-five cases involved a transition from medically indicated opioids; of these, 8 cases involved a transition from methadone. Six cases involved a transition from illicit opioids used prior to hospital presentation. For patient transitioning from medically indicated opioids, the median milligram morphine equivalent (MME) on the day prior to transdermal buprenorphine application was 63.8 (range 0-900, IQR 153.8) and the median MME on the day of transdermal buprenorphine application was 34.5 (range 0-600, IQR 65.3). The median initial dose of sublingual buprenorphine administered was 8 mg (range 2-8mg, IQR 6mg), the median total first-day dose was 16mg (range 2-24mg, IQR 16mg), and the median total daily dose on the last day of follow-up was 16mg (range 2-24mg, IQR 16mg). In 38 cases, patients completed the transition to sublingual buprenorphine and were still taking buprenorphine at the time they left the hospital. The transition protocol was fairly well-tolerated, with 59% of cases tolerating it well and 32% tolerating it fairly.. Our findings suggest that the use of transdermal buprenorphine to facilitate transition to sublingual buprenorphine is generally well-tolerated, and may be helpful in hospitalized patients. We identified several areas for improvement in future practice by reviewing the clinical courses of patients who tolerated transition poorly. Limitations of the study include its retrospective chart review design, the lack of a standardized transition protocol during the study period, and the lack of standardized data in the medical record regarding patients' tolerance of the transition protocol. Future research should include prospective studies using a standardized protocol and structured, pre-planned assessments of opioid withdrawal during the transition period.. The use of transdermal buprenorphine to facilitate induction of sublingual buprenorphine therapy in hospitalized patients with OUD was generally well-tolerated in this single-center retrospective observational study. Further prospective research is needed to demonstrate efficacy and optimize treatment protocols.

Topics: Analgesics, Opioid; Buprenorphine; Hospitals; Humans; Opioid-Related Disorders; Prospective Studies; Retrospective Studies; Substance Withdrawal Syndrome

Opioid use disorder continues to have a significant impact on public health morbidity and mortality throughout the United States and elsewhere. Managing opioid withdrawal is a critical treatment goal in individuals entering treatment with an active opioid use.. What are the milestones of the changes in the expert approach to the pharmacological management of heroin withdrawal syndrome in the past century?. To determine the changes in the expert approach to the management of heroin withdrawal syndrome, as presented in a widely used textbook in the United States.. The chapters on opioid dependence in the 26 editions of Cecil Textbook of Medicine published from 1927 through 2020.. Opioid replacement taper with morphine (1927-1947), codeine (1931-1943), and methadone (1951-present) administered for 3-10 days has remained the main intervention. The anticholinergic drugs, scopolamine and atropine, were recommended from 1927 to 1943, but their use has never been backed by scientific evidence. Newer approaches relied on clonidine, an alpha-2 receptor agonist used since 1982, and buprenorphine, an opioid agonist/antagonist endorsed for the treatment of heroin withdrawal in 2000.. The pharmacological management of heroin withdrawal syndrome in the past century has progressed from the introduction of methadone to the utilization of clonidine and buprenorphine. More recent advances in treating opioid use disorder have changed the goals of opioid withdrawal management to achievement of abstinence from all opioids to facilitation of long-term treatment with medications for opioid use disorder.

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

Recently developed buprenorphine depot injections have the potential to reduce risk for diversion and misuse, and to increase adherence with fewer visits for supervised intake. However, it is unclear how patients perceive this new form of medication. The purpose of this study was to explore patients' experiences of depot injections and their reasons for continuing, discontinuing, or declining depot injection treatment.. We conducted semi-structured qualitative interviews with 32 people, 14 of whom had ongoing depot injection treatment, 11 who had discontinued depot-injections and switched to other medication and seven who had declined treatment with depot formulations. Interviews were transcribed, coded, and analysed using NVivo, based on this overall stratification into three participant groups.. The main categories relate to the effects and side effects of the depot formulation, social and practical factors, psychological benefits and disadvantages, and interactions with treatment staff. Social and practical factors were of importance for choosing depot formulations, such as increased freedom and their making it easier to combine treatment with work and family life, as well as psychological advantages including "feeling normal". Initial withdrawal symptoms that resolved themselves after a number of injections were reported by most participants. Reliable information and patient-staff relationships characterized by trust helped patients to cope with these initial problems. Those who discontinued treatment often did so near the beginning of the treatment, reporting withdrawal symptoms and insufficient effects as the main reasons. Coercion and insufficient information contributed to a negative pharmaceutical atmosphere at one of the clinics, which may have adversely influenced perceptions of depot formulations and decreased willingness to accept and continue treatment.. Buprenorphine depot injections may have social, practical, and psychological benefits compared to other formulations. However, depot injections are not perceived as an attractive option by all patients. Trust, consistent and adequate information, and awareness of the implications of the pharmaceutical atmosphere should be considered when introducing new medications.

Topics: Buprenorphine; Delayed-Action Preparations; Humans; Opioid-Related Disorders; Qualitative Research; Substance Withdrawal Syndrome

The high efficacy mu-opioid receptor (MOR) agonist methadone is an effective opioid use disorder (OUD) medication used exclusively in opioid-dependent patients. However, methadone has undesirable effects that limit its clinical efficacy. Intermediate efficacy MOR agonists may treat OUD with fewer undesirable effects. We compared the effects of methadone with the intermediate efficacy MOR agonist TRV130 (oliceridine) on fentanyl-vs.-food choice and somatic withdrawal signs in opioid-dependent and post-opioid-dependent rats. Male rats (n = 20) were trained under a fentanyl-vs.-food choice procedure. Rats were then provided extended fentanyl (3.2 µg/kg/infusion) access (6 p.m.-6 a.m.) for 10 days to produce opioid dependence/withdrawal. Rats were treated with vehicle (n = 7), TRV130 (3.2 mg/kg; n = 8), or methadone (3.2 mg/kg; n = 5) three times per day after each extended-access session (8:30 a.m., 11 a.m., 1:30 p.m.). Withdrawal sign scoring (1:55 p.m.) and choice tests (2-4 p.m.) were conducted daily. Vehicle, TRV130, and methadone effects on fentanyl choice were redetermined in post-opioid-dependent rats. Vehicle-, TRV130-, and methadone-treated rats had similar fentanyl intakes during extended access. Vehicle-treated rats exhibited increased withdrawal signs and decreased bodyweights. Both methadone and TRV130 decreased these withdrawal signs. TRV130 was less effective than methadone to decrease fentanyl choice and increase food choice in opioid-dependent rats. Neither methadone nor TRV130 decreased fentanyl choice in post-opioid-dependent rats. Results suggest that higher MOR activation is required to reduce fentanyl choice than withdrawal signs in fentanyl-dependent rats. Additionally, given that TRV130 did not precipitate withdrawal in opioid-dependent rats, intermediate efficacy MOR agonists like TRV130 may facilitate the transition of patients with OUD from methadone to lower efficacy treatments like buprenorphine.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Fentanyl; Male; Methadone; Narcotics; Opioid-Related Disorders; Rats; Receptors, Opioid; Spiro Compounds; Substance Withdrawal Syndrome; Thiophenes

In recent years, pediatric emergency departments (PED) have seen an increase in presentations related to substance use among their adolescent patient population. We aimed to examine pediatric emergency medicine (PEM) physicians' knowledge, attitudes, and beliefs on caring for adolescents with substance use.. We conducted a cross-sectional online survey of PEM physicians through the American Academy of Pediatrics Pediatric Emergency Medicine Collaborative Research Committee (PEM-CRC) listserv. The 41-item survey contained the following domains: demographics, current protocols and education for managing adolescent substance use, and attitudes about treatment of substance use. We calculated descriptive statistics for each variable within the domains.. Of 177 respondents (38.2% response rate), 55.4% were female, 45.2% aged ≥ 50 years, 78% worked in a children's hospital, and 50.8% had > 15 years clinical practice. Overall, 77.8% reported caring for adolescents with a chief complaint related to non-opioid substance use and 26.0% opioid use at least once a month. Most (80.9%) reported feeling comfortable treating major medical complications of substance use, while less than half were comfortable treating withdrawal symptoms. 73% said that they were not interested in prescribing buprenorphine.. Among this national sample of PEM physicians, 3 of 4 physicians managed substance-related visits monthly, but 52% lacked comfort in managing withdrawal symptoms and 73.1% were not interested in prescribing buprenorphine. Almost all PEM physician identified substance use-related education is important but lacked access to faculty expertise or educational content. Expanded access to education and training for PEM physicians related to substance use is needed.

Topics: Adolescent; Buprenorphine; Child; Cross-Sectional Studies; Emergency Medicine; Emergency Service, Hospital; Female; Humans; Male; Substance Withdrawal Syndrome; Substance-Related Disorders; United States

Evidence is lacking on withdrawal syndrome related to individual antidepressants and relevant risk factors for severe reactions.. To ascertain whether antidepressants are associated with an increased reporting of withdrawal syndrome as compared with other medications, and to investigate risk factors for severe reactions.. This is a case/non-case pharmacovigilance study, based on the VigiBase. There were 31,688 reports of antidepressant-related withdrawal syndrome were found. A disproportionate reporting was detected for 23 antidepressants. The estimated ROR for antidepressants altogether, compared to all other drugs, was 14.26 (95% CI 14.08-14.45), 17.01 for other antidepressants (95% CI 16.73-17.29), 13.65 for SSRIs (95% CI 13.41-13.90) and 2.8 for tricyclics (95% CI 2.59-3.02). Based on clinical priority ranking, the strongest disproportionate reporting was found for paroxetine, duloxetine, venlafaxine and desvenlafaxine, being comparable to buprenorphine. Withdrawal syndrome was reported as severe more often in males, adolescents, persons in polypharmacy, and with a longer antidepressant treatment duration (p < 0.05).. Antidepressants are associated with an increased reporting of withdrawal syndrome compared with other drug classes. When prescribing and discontinuing antidepressants, clinicians should be aware of the potentially different proclivity of withdrawal syndrome across individual antidepressants, and the liability to experience more severe withdrawal symptoms in relation to specific patient characteristics.

Topics: Adolescent; Antidepressive Agents; Bayes Theorem; Buprenorphine; Humans; Male; Pharmacovigilance; Selective Serotonin Reuptake Inhibitors; Substance Withdrawal Syndrome; World Health Organization

Buprenorphine is a partial opioid agonist that is Food and Drug Administration (FDA) approved to treat chronic pain and opioid use disorder (OUD). The national prescribing guidelines in the United States (US) recommend that patients transitioning from full opioid agonists to buprenorphine first undergo 12 or more hours of active opioid withdrawal, in order to avoid buprenorphine-precipitated opioid withdrawal. This opioid-free period imposes a significant barrier for many patients. Evidence is accumulating that using microdoses of buprenorphine to cross taper from full-agonist opioids to buprenorphine is a safe and effective way to avoid opioid withdrawal and uncontrolled pain. This microdose cross-tapering strategy is already being used across the US. The US prescribing guidelines and buprenorphine training would benefit from acknowledging this new approach. Additionally, to facilitate this strategy, the FDA should approve transdermal buprenorphine formulations for OUD and manufacturers could produce lower dose formulations of sublingual buprenorphine. The time has come for us to embrace buprenorphine microdosing cross tapers as a new standard of care.

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

Buprenorphine-naloxone has a very high affinity for the mu-receptor and can cause precipitated opioid withdrawal, typically more severe than withdrawal that occurs naturally, when administered while a full mu-opioid receptor agonist remains in a person's system. To avoid precipitated withdrawal, one needs to be in mild to moderate opioid withdrawal at the time of buprenorphine-naloxone induction. Recently, there have been reported cases of precipitated withdrawal occurring in patients taking fentanyl knowingly or unknowingly, despite them being in adequate opioid withdrawal at the time of induction. When this occurs, the current recommendation is to provide 2 mg of buprenorphine-naloxone every 1-2 hours.. Describe a case of successful management of buprenorphine-precipitated withdrawal with escalation of the dose of buprenorphine and highlight implications for future management.. We present a case of a patient with a history of opioid use disorder who was in moderate opioid withdrawal at the time of buprenorphine-naloxone induction and experienced precipitated withdrawal after buprenorphine-naloxone administration.. High-dose buprenorphine-naloxone was given to the patient and precipitated withdrawal subsided after receiving a total of 20 mg. On the next day, the patient had no symptoms of opioid withdrawal and is currently maintained on 16 mg/day.. With the rising prevalence of fentanyl-laced drugs, increased instances of precipitated withdrawal are likely to be encountered. In cases of precipitated withdrawal, giving a high dose of buprenorphine-naloxone rapidly is safe and will allow rapid reversal of withdrawal symptoms.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Fentanyl; Humans; Naloxone; Substance Withdrawal Syndrome

Topics: Adult; Buprenorphine; Female; Humans; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Retrospective Studies; Substance Withdrawal Syndrome; Treatment Outcome

The worsening opioid crisis has increased the number of infants exposed to maternal opioids. Standard treatment of newborns exposed to opioids prenatally often requires prolonged hospitalization and separation of the mother-infant dyad. These practices can potentially increase severity of withdrawal symptoms, interrupt breastfeeding, and disturb mother-infant bonding. Use of the Eat, Sleep, Console (ESC) model may ameliorate symptoms, decrease mother-infant separation, and decrease hospital length of stay.. To manage opioid exposed infants in a more holistic manner to decrease neonatal intensive care unit (NICU) admissions, reduce the need for pharmacotherapy, and evaluate response and total length of treatment after a unit protocol change from morphine to buprenorphine.. Implemented ESC model, optimized nonpharmacologic bundle, and prescribed buprenorphine therapy instead of morphine as needed for adjunctive therapy.. Admissions of opioid-exposed infants from the Mother-Baby Unit (MBU) to the NICU decreased by 22%, and the number of infants who required pharmacotherapy was reduced by 50%. The average length of pharmacotherapy fell from 14 to 6.5 days.. The successful implementation of the ESC model helped keep the mother-infant dyad together, reduced admissions to the NICU, and lessened the need for pharmacotherapy. The change to buprenorphine further reduced our average length of treatment.. Investigation of monotherapy with buprenorphine needs to be evaluated as a valid treatment option. The buprenorphine dosing and weaning chart will need to be revised and modified if indicated.

Topics: Analgesics, Opioid; Buprenorphine; Female; Humans; Infant, Newborn; Length of Stay; Mothers; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Sleep; Substance Withdrawal Syndrome

Topics: Buprenorphine; Humans; Infant, Newborn; Methadone; Opioid-Related Disorders; Substance Withdrawal Syndrome

The safety of combining buprenorphine with a benzodiazepine or barbiturate in the treatment of concurrent alcohol and opioid withdrawal has not been well established. In this study we examine a cohort of patients treated with buprenorphine and phenobarbital or benzodiazepines for co-occurring opioid and alcohol withdrawal.. This is a retrospective cohort study of ED patients treated for opioid and alcohol withdrawal from January through December 2018. The primary outcome was unexpected airway intervention, or the administration of naloxone for respiratory depression.. There were 16 patients treated for opioid and alcohol withdrawal. The mean age was 44.3 (standard deviation [SD] 13.1), 12 (75.0%) were male, and 8 (50.0%) of the patients were admitted to the hospital. For opioid withdrawal, six patients received intravenous buprenorphine, with doses between 0.3 mg to 1.8 mg; 12 patients received sublingual buprenorphine, with doses between 4 mg to 32 mg. For alcohol withdrawal, 10 patients received lorazepam with doses between 1 mg and 8 mg; 10 patients received phenobarbital with doses between 260 mg to 1040 mg. There were no unexpected airway interventions related to medications used for opioid or alcohol withdrawal. One patient with severe pneumonia was an expected intubation for respiratory failure.. We describe a cohort of patients treated for opioid and alcohol withdrawal in the ED. There were no serious adverse events related to the medications used to treat opioid or alcohol withdrawal. Further work should assess optimal use of medical therapy for opioid and alcohol withdrawal and the transition to maintenance treatment for substance use disorders.

Topics: Adult; Aged; Alcohol-Related Disorders; Buprenorphine; Emergency Service, Hospital; Female; Humans; Hypnotics and Sedatives; Lorazepam; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Phenobarbital; Retrospective Studies; Substance Withdrawal Syndrome

Buprenorphine is a partial opioid agonist commonly used to treat opioid dependence. The pharmacology of buprenorphine increases the risk of a precipitated opioid withdrawal when commencing patients on buprenorphine treatment, particularly when transferring from long acting opioids (e.g. methadone). There is little documented experience regarding the management of precipitated withdrawal. In our case, a patient developed a significant precipitated opioid withdrawal following buprenorphine administration, and was able to be successfully treated in hospital with further buprenorphine. This demonstrates that rapid increases in buprenorphine dose can be used as an effective treatment for buprenorphine-induced precipitated opioid withdrawal. The use of buprenorphine to manage withdrawal then allows the individual to continue on this highly effective treatment.

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

This case report describes a 65-year-old female with iatrogenic opioid use disorder for chronic lower back pain, who developed Takotsubo cardiomyopathy on multiple occasions following buprenorphine induction. This patient had three opioid transfers to buprenorphine, over 4 years, two of which were complicated by Takotsubo cardiomyopathy. In the transfer where she did not develop Takotsubo cardiomyopathy, she was treated with high doses of the centrally acting agonist, clonidine (three times a day, total of 600 mcg/day), up to and including the day of her transfer. This case highlights the potential consequences of a precipitated withdrawal with buprenorphine in an opioid transfer and its possible prevention with clonidine. To our knowledge, this is the first description of the recurrent Takotsubo cardiomyopathy in an opioid transfer setting. Given that buprenorphine is a partial agonist, in the presence of a full opioid agonist, it can precipitate withdrawal within minutes to hours of its administration. Opioid withdrawal can result in a sympathetic overdrive. Although complications of opioid withdrawal are extensively documented, cardiotoxicity is uncommon. As the use of buprenorphine and its new injectable formulations rise, it is important for prescribers to be aware of this life threatening complication. The prophylactic administration of clonidine can be considered to reduce the risk of cardiotoxicity, as well as manage opioid withdrawal symptoms.

Topics: Aged; Analgesics, Opioid; Buprenorphine; Cardiotoxicity; Female; Humans; Iatrogenic Disease; Opiate Substitution Treatment; Opioid-Related Disorders; Recurrence; Substance Withdrawal Syndrome; Takotsubo Cardiomyopathy

Social support and opioid replacement therapy are commonly used to treat opioid withdrawal.. The present study tested the hypothesis that social housing and buprenorphine administration can restore wheel running depressed by morphine withdrawal in rats.. Experiment 1 assessed disruptive side effects of buprenorphine and found that administration of low doses (3.2, 10, & 32 µg/kg, s.c.) had no impact on voluntary wheel running. Experiment 2 assessed the impact of social housing and acute buprenorphine administration (10 µg/kg) on morphine withdrawal. Two 75 mg morphine pellets were implanted for 3 days to induce dependence. Removal of the morphine pellets caused a decrease in body weight, increase in wet dog shakes, and depression of wheel running during the normally active dark phase of the circadian cycle. Social housing restored wheel running and reduced the number of wet dog shakes but did not affect body weight. Administration of buprenorphine restored wheel running depressed by morphine withdrawal for 2 days in individually housed rats and produced time-dependent changes in socially housed rats: Depression of wheel running in the 3 h following administration and restoration of running subsequently compared to saline-treated controls.. The impact of buprenorphine and social housing to reduce the effect of morphine withdrawal in rats is consistent with the use of opioid substitution therapy and psychotherapy/social support to treat opioid withdrawal in humans. These data provide further validation for the clinical relevance for the use of wheel running to assess spontaneous opioid withdrawal.

Topics: Animals; Buprenorphine; Housing; Morphine; Motor Activity; Narcotics; Rats; Substance Withdrawal Syndrome

Prerequisite opioid withdrawal symptoms prior to buprenorphine induction are unacceptable to many patients. We assessed whether transdermal buprenorphine minimized withdrawal while bridging to sublingual therapy among hospital inpatients.. Retrospective chart review of (n = 23) inpatients with opioid use disorder or opioid dependence due to chronic pain.. Of 23 inpatients, 65% transitioned without symptoms, while 35% experienced mild withdrawal. Ninety-six percent completed planned hospitalizations, with 83% engaged in treatment 4 weeks post-discharge.. Bridging to sublingual therapy with transdermal buprenorphine patches was feasible without withdrawal symptoms.. This strategy may facilitate buprenorphine therapy in hospital inpatients. (Am J Addict 2019;00:1-4).

Topics: Administration, Cutaneous; Administration, Sublingual; Analgesics, Opioid; Buprenorphine; Female; Humans; Inpatients; Male; Middle Aged; Opioid-Related Disorders; Retrospective Studies; Substance Withdrawal Syndrome

We assess the feasibility of using our community hospital emergency department (ED) as an immediate portal to medication-assisted treatment for patients in opioid withdrawal.. This was a prospective observational cohort study. In collaboration with an outpatient substance abuse treatment center, we alerted the public through media outlets that individuals could receive immediate buprenorphine treatment for opioid withdrawal in the ED, with rapid referral for medication-assisted treatment. If medication-assisted treatment intake was delayed, patients could return for up to 2 more days for buprenorphine administration to treat their withdrawal symptoms. We measured compliance with initial follow-up and continued treatment engagement at 30 and 90 days.. The study was conducted during 12 months. A total of 62 patients were enrolled, evaluated for buprenorphine criteria, and referred for medication-assisted treatment. Fifty subjects were compliant with their first medication-assisted treatment follow-up visit (81% [95% confidence interval 71% to 91%]), and 43 of these 50 patients were still engaged in medication-assisted treatment at 30 days (86% [95% confidence interval 76% to 96%]), with 33 of the 50 still engaged at 90 days (66% [95% confidence interval 53% to 79%]). We observed no instances of precipitated withdrawal or other adverse reactions in the ED.. A substantial number of patients responded to this program and received accelerated engagement in medication-assisted treatment. Such a program is feasible in the community hospital ED and may prevent some individuals from relapsing into high-risk illicit drug use when immediate medication-assisted treatment is not otherwise available.

Topics: Adult; Aged; Analgesics, Opioid; Buprenorphine; Emergency Service, Hospital; Female; Hospitals, Community; Humans; Male; Medication Adherence; Middle Aged; Narcotic Antagonists; New York; Opioid-Related Disorders; Prospective Studies; Substance Withdrawal Syndrome

Naloxone is a frequently utilized and effective treatment to reverse the life-threatening effects of illicit opioid intoxication. Excessive naloxone dosing in these circumstances, however, may lead to naloxone-precipitated opioid withdrawal in individuals with opioid dependence. Buprenorphine, a partial mu-opioid agonist, is increasingly utilized in the Emergency Department (ED) for the treatment of opioid withdrawal syndrome but little is known regarding its utility in cases of naloxone-precipitated opioid withdrawal. We report a case of naloxone-precipitated opioid withdrawal that was effectively treated with sublingual buprenorphine. An older male was brought into the ED with signs and symptoms of opioid toxicity that was successfully treated with pre-hospital naloxone by Emergency Medical Services. He had a clinical opioid withdrawal scale (COWS) or 10 with abdominal cramping and unintentional defecation. After a discussion of treatment options and possible adverse effects with the patient, the decision was made to administer 4 mg/1 mg of sublingual buprenorphine/naloxone film. The patient reported a rapid improvement in symptoms and at 30 min posttreatment, his COWS was 4. His COWS decreased to 3 at 1 h and this was sustained for 4 h of observation. The patient was subsequently discharged to a treatment facility for opioid use disorder. This case highlights the potential of buprenorphine as a treatment modality for acute naloxone-precipitated opioid withdrawal. Due to the risks of worsening or sustained buprenorphine-precipitated opioid withdrawal, further research is warranted to identify patients who may benefit from this therapy.

Topics: Acute Disease; Administration, Sublingual; Aged; Buprenorphine; Humans; Male; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Substance Withdrawal Syndrome

Extended-release (XR) naltrexone can prevent relapse to opioid use disorder following detoxification. However, one of the barriers to initiating XR-naltrexone is the recommendation for a 7-10-day period of abstinence from opioids prior to the first dose.. The current study evaluated the feasibility of an XR-naltrexone induction protocol that can be implemented over 1 week in the outpatient clinic.. Participants (N = 44) were seen in the clinic daily. On Day 1, after abstaining from opioids for at least 12 h, they received buprenorphine 6-8 mg. Adjunctive medications (clonidine, clonazepam, zolpidem, trazodone, and prochlorperazine) were dispensed on Days 2-5, while ascending oral doses of naltrexone were given on Days 3-5 starting with 1 mg dose. An injection of XR-naltrexone was given on Day 5, 1 h after receiving and tolerating naltrexone 24 mg.. Of the 44 participants (38 males), 35 (80%) were heroin users and 9 (20%) used prescription opioids. A total of 26 participants (59%) completed the induction and received their first injection of XR-naltrexone. XR-naltrexone was initiated in 54% (19/35) of heroin users and 78% (7/9) of prescription opioid users.. The results support the feasibility of a week-long outpatient induction onto XR-naltrexone with ascending doses of naltrexone and standing doses of adjunctive medications. By circumventing the need for a protracted period of abstinence and mitigating the severity of withdrawal symptoms experienced during naltrexone titration, this strategy has the potential to increase patient acceptability and access to relapse prevention treatment with XR-naltrexone.

Topics: Adult; Buprenorphine; Delayed-Action Preparations; Feasibility Studies; Female; Heroin Dependence; Humans; Injections, Intramuscular; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Outpatients; Recurrence; Substance Withdrawal Syndrome; Young Adult

Medically managed opioid withdrawal (detox) can increase the risk of subsequent opioid overdose. We assessed the association between mortality following detox and receipt of medications for opioid use disorder (MOUD) and residential treatment after detox.. Cohort study generated from individually linked public health data sets.. Massachusetts, USA.. A total of 30 681 opioid detox patients with 61 819 detox episodes between 2012 and 2014.. Treatment categories included no post-detox treatment, MOUD, residential treatment or both MOUD and residential treatment identified at monthly intervals. We classified treatment exposures in two ways: (a) 'on-treatment' included any month where a treatment was received and (b) 'with-discontinuation' individuals were considered exposed through the month following treatment discontinuation. We conducted multivariable Cox proportional hazards analyses and extended Kaplan-Meier estimator cumulative incidence for all-cause and opioid-related mortality for the treatment categories as monthly time-varying exposure variables.. Twelve months after detox, 41% received MOUD for a median of 3 months, 35% received residential treatment for a median of 2 months and 13% received both for a median of 5 months. In on-treatment analyses for all-cause mortality compared with no treatment, adjusted hazard ratios (AHR) were 0.34 [95% confidence interval (CI) = 0.27-0.43] for MOUD, 0.63 (95% CI = 0.47-0.84) for residential treatment and 0.11 (95% CI = 0.03-0.43) for both. In with-discontinuation analyses for all-cause mortality, compared with no treatment, AHRs were 0.52 (95% CI = 0.42-0.63) for MOUD, 0.76 (95% CI = 0.59-0.96) for residential treatment and 0.21 (95% CI = 0.08-0.55) for both. Results were similar for opioid-related overdose mortality.. Among people who have undergone medically managed opioid withdrawal, receipt of medications for opioid use disorder, residential treatment or the combination of medications for opioid use disorder and residential treatment were associated with substantially reduced mortality compared with no treatment.

Topics: Adolescent; Adult; Buprenorphine; Cohort Studies; Drug Overdose; Female; Humans; Male; Massachusetts; Methadone; Middle Aged; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Proportional Hazards Models; Residential Treatment; Retrospective Studies; Substance Withdrawal Syndrome; Young Adult

Highly potent synthetic opioids (HPSO) are increasingly responsible for opioid overdose deaths in the United States.. In an open-label, uncontrolled trial to test the feasibility of extended-release buprenorphine (BXR) injection treatment of heroin-using individuals with opioid use disorder testing positive for HPSO, participants were enrolled and began an induction with sublingual BXR (n = 5). During the induction, ancillary medications (clonidine, clonazepam, zolpidem, and prochlorperazine) were provided for breakthrough opioid withdrawal symptoms.. Two participants received the BXR injection on the second day of the induction and three participants on the third day.. All five participants were retained at least 1-month postinduction.. It may be feasible to provide BXR treatment to HPSO-positive heroin users rapidly to achieve clinical stabilization. (Am J Addict 2020;00:00-00).

Topics: Adult; Buprenorphine; Delayed-Action Preparations; Female; Heroin Dependence; Humans; Induction Chemotherapy; Injections; Male; Middle Aged; Narcotic Antagonists; Psychotropic Drugs; Substance Withdrawal Syndrome; Treatment Outcome

Identification of problematic alcohol use and substance use in the population has been a clinical challenge, especially during the heightened years of the opioid epidemic. Bringing Screening, Brief Intervention, and Referral to Treatment (SBIRT) to scale in medical settings, such as hospital emergency departments (EDs) could facilitate broad identification of substance use disorders, timely delivery of brief interventions, and successful linkages to treatment.. This large-scale data analysis pulled electronic health record (EHR) data from 23 hospitals in the state of Maryland for over 1 million patient visits between July 2014 and November 2018.. Of the 1,097,142 ED patients screened, 17.2% screened positive for problematic alcohol or any drug use in the previous 12 months. During this same period, 79,899 brief interventions were delivered, 15,961 referrals to outpatient treatment were made and 38.3% of those were successfully linked to treatment. Of the 950 patients exhibiting withdrawal symptoms, over two-thirds patients (70.1%; n = 666) were administered buprenorphine, 94.6% (n = 630) accepted a referral to buprenorphine treatment in the community, and 64.6% (n = 430) attended their first outpatient buprenorphine treatment visit. A total of 2382 patients presented to the ED with a suspected opioid overdose, over half were referred to the intervention program (53.8%) and 63.2% were successfully engaged by the PRCs in the ED.. This analysis supports the scalability of SBIRT in hospital EDs and presents an implementation model that can be replicated in EDs nationwide.

Topics: Analgesics, Opioid; Buprenorphine; Drug Overdose; Emergency Service, Hospital; Humans; Maryland; Mass Screening; Narcotic Antagonists; Opiate Substitution Treatment; Referral and Consultation; Substance Withdrawal Syndrome; Substance-Related Disorders

Fentanyl withdrawal is common, but pharmacological management has largely mirrored traditional approaches to opioid withdrawal. Observations in a large urban center suggest alternative approaches, including the need for dose modification, should be considered.

Topics: Analgesics, Opioid; Buprenorphine; Fentanyl; Humans; Narcotic Antagonists; Substance Withdrawal Syndrome

: Current data suggest that the opioid epidemic represents a worsening problem in the United States. However, prescribing rates of opioids have been steadily declining, suggesting that alternative opioids are becoming a major contributor to this crisis. One medication that has shown an increase in nonmedical use is loperamide. Loperamide is a peripheral mu-opioid agonist that is intended to be used for diarrhea. However, when taken at high doses and/or in combination with P-glycoprotein inhibitors, it acts centrally by penetrating the blood-brain-barrier. Loperamide crossing the blood-brain-barrier results in similar central nervous system depression as other opioids. Loperamide's over-the-counter availability and growing media presence has resulted in more cases of loperamide substance use disorder, predominantly to minimize opioid withdrawal symptoms and to produce a euphoric state. This case series presents 3 patients with loperamide-associated opioid use disorder who have been successfully treated with on-going buprenorphine treatment. To our knowledge, this is the first case-series to explore long-term buprenorphine treatment for loperamide use disorder. Our findings suggest that buprenorphine can be used for loperamide use disorder, most effectively when patients are in mild to moderate withdrawal. These cases also demonstrate how different waiting times were necessary before starting buprenorphine treatment in order to avoid precipitated withdrawal.

Topics: Analgesics, Opioid; Buprenorphine; Humans; Loperamide; Opioid-Related Disorders; Substance Withdrawal Syndrome; United States

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

Emergency care providers routinely treat patients with acute presentations and sequelae of opioid use disorder. An emergency physician and pharmacist implemented a protocol using buprenorphine for the treatment of patients with opioid withdrawal at an academic, Level I trauma center. We describe our experience regarding buprenorphine implementation in the emergency department (ED), characteristics of patients who received buprenorphine, and rates of outpatient follow-up.. We conducted a retrospective chart review of all patients in the ED for whom buprenorphine was administered to treat opioid withdrawal during an 18-month period from January 30, 2017-July 31, 2018. Data extraction of a priori-defined variables was recorded. We used descriptive statistics to characterize the cohort of patients.. A total of 77 patients were included for analysis. Thirty-three patients (43%) who received buprenorphine did not present with the chief complaint of opioid withdrawal. Most patients (74%) who received buprenorphine last used heroin, and presented in moderate opioid withdrawal. One case of precipitated withdrawal occurred after buprenorphine administration. Twenty-three (30%) patients received outpatient follow-up.. This study underscores the safety of ED-initiated buprenorphine and that buprenorphine administration in the ED is feasible and effective.

Topics: Adult; Buprenorphine; Emergency Medical Services; Emergency Service, Hospital; Female; Humans; Male; Narcotic Antagonists; Opioid-Related Disorders; Retrospective Studies; Substance Withdrawal Syndrome; Treatment Outcome

Patients with opioid use disorder (OUD) frequently present to the emergency department for acute treatment of overdose and withdrawal.. A 29-year-old male presented to the emergency room after intravenous heroin use followed by accidental ingestion of naltrexone. He was treated with buprenorphine with significant improvement in his Clinical Opioid Withdrawal Score, from moderately severe to mild withdrawal symptoms within a few hours.. Buprenorphine and minimal supportive care can be used to treat acute withdrawal precipitated by oral naltrexone in patients with OUD.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Humans; Male; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Substance Withdrawal Syndrome; Treatment Outcome

We assessed the efficacy of buprenorphine replacement taper therapy in a psychiatric hospital in Japan.. Based on the medical records, a retrospective analysis was performed to evaluate the outcomes of buprenorphine replacement taper therapy in 106 subjects with heroin dependence.. We found that replacement and taper therapy with buprenorphine could significantly reduce withdrawal symptoms during detoxification. In addition, the completion rate of detoxification was significantly improved and the length of hospital stay was significantly reduced relative to those who received conventional treatment without buprenorphine. However, the readmission rate increased after the introduction of detoxication therapy with buprenorphine.. The present findings suggest not only the efficacy and safety of buprenorphine replacement and taper therapy, but also the requirement for maintenance therapy for individuals with heroin dependence.

Topics: Adult; Buprenorphine; Female; Heroin Dependence; Hospitals, Psychiatric; Humans; Injections, Intramuscular; Japan; Length of Stay; Male; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Retrospective Studies; Substance Withdrawal Syndrome

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

Topics: Adult; Buprenorphine; Europe; Female; Hospitals, State; Human Rights; Humans; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Russia; Substance Withdrawal Syndrome

The opioid crisis has led to an increased number of pregnant opioid-dependent women receiving opioid-maintenance therapy (e.g. buprenorphine, BUP), but little is known about the consequences of gestational BUP exposure on pregnancy outcomes, maternal care, or offspring development.. Our translational rodent model began BUP exposure to adult female rats (N = 30) at least 7 days before conception and continued throughout the postpartum period. Both therapeutic low-dose (BUP-LD, 0.3 mg/kg, s.c.) and overexposure high-dose (BUP-HD, 1.0 mg/kg) doses of BUP were compared to saline control. Female rats were bred in house with drug-naïve adult male rats. The day after parturition, litters were culled to 5 males/5 females and assigned randomly to various behavioral tests and assessed either neonates or adolescents. Litter characteristics, maternal caregiving, Neonatal Opioid Withdrawal Syndrome (NOWS), offspring development and adolescent behaviors were evaluated.. BUP-LD decreased maternal care, delayed offspring development, decreased offspring body weight, length, temperature, and pain sensitivity (p's < .05). BUP-HD drastically reduced maternal care and offspring survival, altered litter characteristics, and increased NOWS (p's < .05).. These results demonstrate that the therapeutic BUP-LD in rats was relatively safe with subtle effects on maternal care and rodent offspring. However, overexposure BUP-HD in rats produced NOWS and compromised maternal caregiving as well as rodent offspring survival. More research is critical to validate the translational implication of these findings for human opioid-dependent mothers maintained on BUP-maintenance therapy.

Topics: Age Factors; Analgesics, Opioid; Animals; Animals, Newborn; Behavior, Animal; Buprenorphine; Dose-Response Relationship, Drug; Female; Male; Maternal Behavior; Narcotic Antagonists; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Substance Withdrawal Syndrome

Given the high rates of relapse among patients with opioid use disorder (OUD), it is crucial to identify modifiable risk factors for negative treatment outcomes. Anxiety sensitivity (AS) is 1 such risk factor that may be associated with negative OUD treatment outcomes. The present study examined the potential impact of AS on the withdrawal process, subsequent treatment engagement, and relapse among individuals with OUD. Adults undergoing inpatient detoxification (

Topics: Adult; Age Factors; Analgesics, Opioid; Anti-Anxiety Agents; Anxiety; Buprenorphine; Craving; Female; Humans; Male; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Risk Factors; Secondary Prevention; Sex Factors; Substance Withdrawal Syndrome; Treatment Failure; Young Adult

With the urgency to treat patients more effectively for opioid use disorder in the midst of the opioid epidemic, a key area for precision medicine is to improve individualized medication-assisted treatment for opioid use disorder. The expansion of medication-assisted treatment is a key to reducing illicit opioid use, preventing opioid overdose deaths, and reducing the comorbidities and societal impacts of opioid use disorder. The most common medication for opioid use disorder will soon be buprenorphine. Research to date shows the successful impact of buprenorphine treatment, including the pharmacogenomics of buprenorphine response and treatment efficacy. Buprenorphine is also a promising treatment for depression and anxiety, and neonatal opioid withdrawal syndrome (NOWS). However, the rates of success with medication-assisted treatment for opioid use disorder, particularly at the beginning of treatment, still show many individuals relapsing to illicit opioid use. With the scope of the opioid crisis, there is an urgent need for expansion of buprenorphine treatment research to provide critical information for improving outcomes of opioid use disorder. Implementing the best strategies for opioid use disorder treatment is of dire urgency and will save lives.

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

This qualitative study identifies and describes experiences and challenges to retention of individuals with opioid use disorder (OUD) who participated in a low-threshold combined buprenorphine-peer support treatment program in Baltimore.. In-depth semi-structured interviews with staff and former clients of the Project Connections Buprenorphine Program (PCBP) (9 people) and focus group discussions with current and previous clients of PCBP (7 people) were conducted. Content analysis was used to extract themes regarding barriers to enrolling and remaining in, and transitioning from the program.. Primary challenges identified by the participants included struggles with cravings and symptoms of withdrawal, comorbid mental health issues, criminal justice system involvement, medication stigma, and conflicts over level of flexibility regarding program requirements and the role of employment.. This study identified several obstacles clients face when seeking care through a combined buprenorphine-peer support model. Findings highlight potential programmatic factors that can be improved and additional resources that may support treatment retention rates and better outcomes. Despite challenges, low-threshold and community-based programs can increase access to effective maintenance treatment for OUD, especially among vulnerable populations who may not have access to formal health services.

Topics: Adult; Aged; Analgesics, Opioid; Attitude of Health Personnel; Attitude to Health; Baltimore; Buprenorphine; Community Mental Health Services; Comorbidity; Craving; Criminal Law; Employment; Female; Focus Groups; Humans; Male; Mental Disorders; Mental Health Recovery; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Peer Group; Qualitative Research; Social Stigma; Substance Withdrawal Syndrome

We present a case of elective naloxone-induced opioid withdrawal followed by buprenorphine rescue to initiate opioid use disorder treatment in the emergency department. This strategy may represent a safe alternative to prescribing buprenorphine for outpatient initiation, a method that puts the patient at risk for complications of unmonitored opioid withdrawal, including relapse. After confirmation that the naloxone-induced withdrawal was adequately treated with buprenorphine, the patient was discharged with prescribed buprenorphine to follow up in an addiction medicine clinic, where he was treated 2 days later.

Topics: Administration, Intravenous; Adult; Buprenorphine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Emergency Service, Hospital; Heroin Dependence; Humans; Male; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Substance Withdrawal Syndrome

Topics: Adult; Buprenorphine; Humans; Legislation, Medical; Male; Methadone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Prisoners; Prisons; Substance Withdrawal Syndrome; United States

Topics: Adult; Antidiarrheals; Antiemetics; Antipruritics; Buprenorphine; Clonidine; Deprescriptions; Drug Substitution; Female; Humans; Loperamide; Methadone; Methocarbamol; Muscle Relaxants, Central; Naltrexone; Narcotic Antagonists; Ondansetron; Opiate Substitution Treatment; Opioid-Related Disorders; Promethazine; Substance Withdrawal Syndrome; Sympatholytics

Despite the benefits of maintenance buprenorphine treatment for opioid use disorder (OUD), many individuals report an interest in discontinuing the medication, while also expressing worries about tapering. The purpose of this study was to develop a measure of worries about buprenorphine discontinuation ("Off Bupe") and determine the demographic and clinical characteristics associated with these worries.. Between May 2017 and May 2018, we surveyed adults in an outpatient primary care buprenorphine program (n = 138). Reliability and validity of the Off Bupe measure were examined.. Participants averaged 39 years of age, 54% were male, average duration of buprenorphine was 189 weeks and 85.5% reported eventually wanting to discontinue buprenorphine, although fewer than 10% were actively tapering. We derived two scales, withdrawal symptom worry (10 items, ɑ = 0.94) and relapse worry (7 items, ɑ = 0.88). Worry about symptoms was positively associated with current buprenorphine dose (P = 0.016), physical discomfort avoidance (P < 0.001), and inversely associated with self-efficacy to quit buprenorphine (P < 0.001) and distress tolerance (P < 0.001). Worry about opioid relapse was associated positively with age (P = 0.019), current buprenorphine dose (P = 0.004), physical discomfort avoidance (P < 0.001), and impulsivity (P = 0.002), and inversely associated with self-efficacy to quit buprenorphine (P < 0.001).. Psychometric evaluation of the "Off Bupe" scale demonstrated its content and construct validity and internal reliability.. The scale might help individuals with OUD and their providers identify concerns about discontinuing buprenorphine. (Am J Addict 2019;28:270-276).

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anxiety; Buprenorphine; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Psychiatric Status Rating Scales; Psychometrics; Recurrence; Reproducibility of Results; Self Efficacy; Substance Withdrawal Syndrome; Withholding Treatment; Young Adult

Topics: Buprenorphine; Echocardiography; Electrocardiography; Female; Humans; Middle Aged; Narcotic Antagonists; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume; Substance Withdrawal Syndrome; Takotsubo Cardiomyopathy; Troponin I

Buprenorphine is the preferred treatment of opioid use disorder during pregnancy but can cause fetal opioid dependence and neonatal opioid withdrawal syndrome (NOWS). Notably, withdrawal severity is independent of maternal buprenorphine dose, suggesting that interindividual variance in pharmacokinetics may influence risk and severity of NOWS. Using a rat model of NOWS, we tested the hypothesis that clinically relevant doses of the active metabolite norbuprenorphine (NorBUP) can induce in utero opioid dependence, manifested as naltrexone-precipitated withdrawal signs in the neonate. Pregnant Long-Evans rats were implanted with 14-day osmotic minipumps containing vehicle, morphine (positive control), or NorBUP (0.3-10 mg/kg per day) on gestation day 9. By 12 hours post-delivery, an intraperitoneal injection of the opioid antagonist naltrexone (1 or 10 mg/kg) or saline was administered to pups. Precipitated withdrawal signs were graded by raters blinded to treatment conditions. In a separate group, NorBUP concentrations in maternal and fetal blood and brain on gestation day 20 were determined by liquid chromatography-tandem mass spectrometry. Steady-state maternal blood concentrations of NorBUP in dams infused with 1 or 3 mg/kg per day were comparable to values reported in pregnant humans treated with buprenorphine (1.0 and 9.6 ng/ml, respectively), suggesting a clinically relevant dosing regimen. At these doses, NorBUP increased withdrawal severity in the neonate as shown by an evaluation of 10 withdrawal indicators. These findings support the possibility that NorBUP contributes to fetal opioid dependence and NOWS following maternal buprenorphine treatment during pregnancy.

Topics: Animals; Animals, Newborn; Buprenorphine; Female; Fetus; Opioid-Related Disorders; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Risk; Substance Withdrawal Syndrome

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

The Emergency Department (ED) frequently treats patients with drug overdoses and is an important resource for individuals with opioid use disorder who are seeking treatment. Initiating medication-assisted treatment (MAT) in the ED seems to be an effective way to link patients with opioid use disorder (OUD) to treatment programs. There is ongoing discussion on the best approach to MAT in the ED setting.. Describe a new model for managing OUD in the ED.. Information was obtained retrospectively from the electronic medical records of patients seen in a large county tertiary care center's Clinical Decision Unit (CDU) for OUD between September 1, 2017 and February 6, 2018. Data were summarized descriptively.. There were 18 different patients placed in the CDU during the study period. Ninety-five percent were induced with buprenorphine-naloxone in the CDU. The median initial Clinical Opioid Withdrawal Scale score at the time of induction was 10. The median total dose of buprenorphine-naloxone that was administered was 8/2 mg. The median amount of time spent in the CDU and ED combined was 23 h. Approximately (12/19) 63% of subjects went to their initial follow-up appointment in clinic. Nine were still active in clinic at 30 days and 4 were active at 6 months.. This retrospective chart review shows promising preliminary data for managing OUD in an ED CDU. Such strategies have the potential to increase access to care in a vulnerable patient population.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Cohort Studies; Emergency Medicine; Female; Humans; Male; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Retrospective Studies; Substance Withdrawal Syndrome

Buprenorphine, a partial μ-opioid agonist, is an effective treatment for opioid use disorder that conventionally requires symptoms of withdrawal before initiation to avoid precipitating withdrawal. Our institution implemented a microdosing approach to transition patients from full μ-opioid agonists to buprenorphine without requiring patients to undergo a period of opioid abstinence. Little has been published about this strategy in the inpatient setting in the United States, and even less has been published dealing with the transition from methadone to buprenorphine. Our objective was to demonstrate that a microdosing protocol to transition patients from methadone to buprenorphine can be feasibly implemented in a U.S. hospital setting.. Case series.. Three hospitalized adults with opioid use disorder who received a 1-week buprenorphine microdosing protocol.. In January 2019, we implemented a 1-week buprenorphine microdosing protocol for hospitalized adult patients with opioid use disorder who were initially stabilized on methadone and wished to start buprenorphine. We gave low-dose buprenorphine concurrently with each patient's full dose of methadone, and the buprenorphine dose was gradually titrated up over 7 days. On day 8, methadone was abruptly discontinued. The buprenorphine dose was further increased based on clinical judgment. All three patients were successfully transitioned from methadone 40-100 mg/day to buprenorphine 12-16 mg/day with minimal symptoms of opioid withdrawal. One patient relapsed and was lost to follow-up; two remained in treatment.. A protocol using microdosing of buprenorphine can successfully transition patients receiving full μ-opioid agonist therapy, including methadone, to buprenorphine without the need for a period of opioid abstinence.

Topics: Adult; Buprenorphine; Dose-Response Relationship, Drug; Drug Substitution; Female; Humans; Male; Methadone; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Outcome and Process Assessment, Health Care; Substance Withdrawal Syndrome

The clinical feasibility of a novel non-opioid and benzodiazepine-free protocol was assessed for the treatment of medically supervised opioid withdrawal and transition to subsequent relapse prevention strategies.. A retrospective chart review of DSM-IV diagnosed opioid-dependent patients admitted for inpatient medically supervised withdrawal examined 84 subjects (52 males, 32 females) treated with a 4-day protocol of scheduled tizanidine, hydroxyzine, and gabapentin. Subjects also received ancillary medications as needed, and routine counseling. Primary outcomes were completion of medically supervised withdrawal, and initiation of injectable extended release (ER) naltrexone treatment. Secondary outcomes included the length of hospital stay, Clinical Opiate Withdrawal Scale (COWS) scores, and facilitation to substance use disorder treatment intervention. Ancillary medication use and adverse effects were also assessed.. A total of 79 (94%) of subjects completed medically supervised withdrawal. A total of 27 (32%) subjects chose to pursue transition to ER naltrexone, and 24 of the 27 (89%) successfully received the injection prior to hospital discharge. The protocol subjects had a mean length of hospital stay of 3.6 days, and the mean COWS scores was 3.3, 3.4, 2.8, and 2.4 on Day 1, 2, 3, and 4, respectively. Furthermore, 71 (85%) engaged in an inpatient or outpatient substance use disorder (SUD) treatment program following protocol completion.. This retrospective chart review suggests the feasibility of a novel protocol for medically supervised opioid withdrawal and transition to relapse prevention strategies, including injectable ER naltrexone. This withdrawal protocol does not utilize opioid agonists or other controlled substances.‬‬‬‬.

Topics: Adult; Amines; Analgesics, Opioid; Buprenorphine; Clonidine; Counseling; Cyclohexanecarboxylic Acids; Female; Gabapentin; gamma-Aminobutyric Acid; Humans; Hydroxyzine; Male; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Retrospective Studies; Substance Withdrawal Syndrome; Treatment Outcome; Young Adult

Prevalence of cigarette smoking among opioid-dependent individuals is 6-fold that of the general U.S. adult population and their quit rates are notoriously poor. One possible reason for the modest cessation outcomes in opioid-dependent smokers may be that they experience more severe tobacco withdrawal upon quitting. In this secondary analysis, we evaluated tobacco withdrawal in opioid-dependent (OD) smokers versus smokers without co-occurring substance use disorders (SUDs). Participants were 47 methadone- or buprenorphine-maintained smokers and 25 non-SUD smokers who completed 1 of several 2-week studies involving daily visits for biochemical monitoring, delivery of financial incentives contingent on smoking abstinence, and assessment of withdrawal via the Minnesota Nicotine Withdrawal Scale (MNWS). Prior to quitting smoking, OD smokers presented with higher baseline withdrawal scores than non-SUD smokers (1.7 ± 0.2 vs. 0.7 ± 0.2, respectively;

Topics: Adult; Analgesics, Opioid; Buprenorphine; Cigarette Smoking; Comorbidity; Craving; Female; Humans; Male; Methadone; Middle Aged; Nicotiana; Nicotine; Opioid-Related Disorders; Prevalence; Substance Withdrawal Syndrome

Topics: Adult; Analgesics, Opioid; Buprenorphine; Female; Heroin Dependence; Humans; Substance Withdrawal Syndrome; Takotsubo Cardiomyopathy; Treatment Outcome

Many patients with opioid use disorder report symptoms similar to restless legs syndrome (RLS) during withdrawal. However, whether these symptoms are true RLS, their predictors and effect of treatment with pregabalin are still unknown.. A total of 19 consecutive patients with opioid use disorder who were admitted for detoxification were included in this study after obtaining informed consent. Information regarding addiction was noted, and they were screened for RLS every morning and evening. Patients were also asked to provide information regarding their sleep quality during the previous night. To control opioid withdrawal, they were prescribed buprenorphine. Pregabalin was prescribed to patients who developed RLS. For analysis, patients were divided in two groups: those with RLS and those without RLS.. The average age of the subjects included in this study was 30.2 (±10.4) years. Mean duration of substance abuse was 56.8 (±38.4) months. Ten patients developed symptoms of RLS. Groups with RLS and without RLS were comparable with reference to demographics, laboratory parameters, and dose of buprenorphine that was required to control withdrawal symptoms. On average, RLS appeared after 1.7 days of abstinence. Patients described their symptoms such as crawling, creeping sensation in the muscles or "just pain". Eight out of 10 subjects reported symptoms limited to legs; however, two described similar problems in their upper limbs as well. A change in sleep pattern was observed with delayed sleep onset at night, delayed wake time in the morning, and spending a major proportion of day asleep. Pregabalin brought significant relief to the symptoms of RLS and sleep quality.. RLS during opioid withdrawal was an independent illness seen in half of the patients. It appeared to be mediated through mu-receptors, with contributions from other factors. Pregabalin improved symptoms of RLS and quality of sleep in these patients.

Topics: Adult; Analgesics; Buprenorphine; Female; Humans; Male; Opiate Substitution Treatment; Opioid-Related Disorders; Pain; Pregabalin; Restless Legs Syndrome; Sleep; Substance Withdrawal Syndrome

Topics: Adrenergic alpha-2 Receptor Agonists; Buprenorphine; Clonidine; Humans; Methadone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Substance Withdrawal Syndrome

Topics: Adrenergic alpha-2 Receptor Agonists; Buprenorphine; Clonidine; Humans; Methadone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Substance Withdrawal Syndrome

In the current study, we examined factors predicting willingness to receive buprenorphine treatment and preferences for various buprenorphine formulations (oral, injection, implant) among persons in opioid withdrawal management.. Participants were three hundred thirty-eight persons entering brief inpatient opioid withdrawal management programs at two sites. We used t-tests and Pearson χ2 - tests of independence to compare participants willing and unwilling to be prescribed buprenorphine in the future. Among persons willing to receive buprenorphine, we used multinomial logistic regression to estimate the adjusted effects of potential correlates of type of buprenorphine formulation preferred.. Participants averaged 33.9 (±9.5) years of age, 70.4% were male, 82.8% were White, and 11.0% were Latino/a. In all, 55.6% of participants had been prescribed buprenorphine in the past, and 54.7% were willing to use prescribed buprenorphine in the future. Those reporting past month illicit buprenorphine use and prior overdose were more willing to use prescribed buprenorphine. Of these (n = 180), most preferred daily buprenorphine formulations (tablet or film) (48.6%) over a weekly or monthly injection (23.1%) or bi-annual implant (28.3%).. Past buprenorphine prescription does not predict future willingness to restart. Among those willing to use buprenorphine, newer formulations of buprenorphine appealed to more than half of the participants.

Topics: Administration, Oral; Adult; Buprenorphine; Drug Administration Schedule; Drug Implants; Female; Humans; Injections; Logistic Models; Male; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Preference; Substance Withdrawal Syndrome; Tablets; Young Adult

The treatment of pregnant women with opioid use disorder is challenging due to the myriad of physical, mental, and social complications. Factors influencing adherence to buprenorphine during pregnancy have not been identified.. Pregnant women with opioid use disorder followed in a tertiary clinic were included in a retrospective chart review from buprenorphine induction through delivery. All women who had been evaluated and treated with buprenorphine from January 1, 2014, to September 31, 2016, were included. Adherence was defined as follows: 1) adherent: attended follow up visits, negative urine toxicology screens, and phase advancement; 2) moderately adherent: attended follow up visits until delivery, had not completed six negative urine toxicology screens, or had positive urine toxicology screens (i.e., no phase advancement); 3) non-adherent: missed follow up visits and did not stay in treatment until delivery. Sociodemographic characteristics, family psychiatric history, current and lifetime psychiatric and childhood trauma along with treatment factors were compared by category of adherence.. 64 women met criteria for inclusion in this study with 41 (64%) adherent; eight (13%) moderately adherent; and 15 (23%) non-adherent. In the non-adherent group compared to the adherent group, the clinician-rated opioid withdrawal scale score was significantly higher, and the daily buprenorphine dose at last visit was significantly lower.. Women who were non-adherent to buprenorphine during pregnancy had higher severity of opioid withdrawal symptoms and lower doses of buprenorphine. These findings should be further explored with the goal of optimizing care without increasing risk for neonates.

Topics: Adult; Buprenorphine; Factor Analysis, Statistical; Female; Humans; Infant, Newborn; Medication Adherence; Methadone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Retrospective Studies; Substance Withdrawal Syndrome

Topics: Buprenorphine; Humans; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Substance Withdrawal Syndrome

Topics: Alcoholism; Antisocial Personality Disorder; Buprenorphine; Heroin Dependence; Humans; Male; Medication Errors; Middle Aged; Naltrexone; Narcotic Antagonists; Substance Withdrawal Syndrome

To determine whether maternal and infant outcomes are associated with exposure to marijuana during the third trimester in a population of opioid dependent pregnant women maintained on buprenorphine.. This retrospective cohort study of 191 maternal-infant dyads exposed to buprenorphine during pregnancy examines a variety of variables including gestational age, birthweight, method of delivery, Apgar scores at one and five minutes, duration of infant hospital stay, peak neonatal abstinence syndrome (NAS) score, duration of NAS and incidence of pharmacologic treatment of NAS in infants exposed to marijuana during the third trimester as compared to infants not exposed to marijuana during the third trimester.. Analyses failed to support any significant relationship between marijuana use in the third trimester and a variety of maternal and infant outcomes. Two important variables - the likelihood of requiring pharmacologic treatment for NAS (27.6% in marijuana exposed infants vs. 15.7% in non-marijuana exposed infants, p=0.066) and the duration of infant hospital stay (7.7days in marijuana exposed infants vs. 6.6days in non-exposed infants, p=0.053) trended toward significance.. Preliminary results indicate that marijuana exposure in the third trimester does not complicate the pregnancy or the delivery process. However, the severity of the infant withdrawal syndrome in the immediate postnatal period may be impacted by marijuana exposure. Because previous study of prenatal marijuana exposure has yielded mixed results, further analysis is needed to determine whether these findings are indeed significant.

Topics: Analgesics, Opioid; Birth Weight; Buprenorphine; Cannabis; Female; Gestational Age; Humans; Infant; Infant, Newborn; Length of Stay; Marijuana Smoking; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Third; Retrospective Studies; Substance Withdrawal Syndrome

Topics: Adult; Buprenorphine; Humans; Male; Narcotic Antagonists; Opioid-Related Disorders; Psychotic Disorders; Substance Withdrawal Syndrome

Restless legs syndrome (RLS) is a movement disorder associated with adverse health outcomes and decreased quality of life. Small case series suggest that symptoms of RLS occur during opioid withdrawal. However, the prevalence is unknown.. We conducted an observational study to determine the prevalence of RLS among inpatients patients receiving buprenorphine detoxification from opioids. To assess the specificity of RLS to opioid detoxification, we also evaluated patients receiving detoxification from alcohol as a comparison group. The diagnosis of RLS was established using a validated questionnaire.. The sample consisted of 124 adults with primary opioid use disorder and 180 with primary alcohol use disorder. In the total sample, 33.6% met a likely RLS diagnosis: 50.8% of those with opioid use disorder and 21.7% of those with alcohol use disorder (χ. Approximately half of patients undergoing inpatient opioid detoxification exhibited the symptoms characteristic of RLS. We believe that these data support the existence of a secondary form of RLS associated with opioid withdrawal.

Topics: Adult; Alcohol-Related Disorders; Analgesics, Opioid; Buprenorphine; Female; Humans; Male; Opiate Substitution Treatment; Opioid-Related Disorders; Prevalence; Restless Legs Syndrome; Substance Withdrawal Syndrome; Young Adult

Illicit use of high dosage buprenorphine has been well documented in several countries, including Tunisia.. The aim of this survey is to assess the buprenorphine withdrawal syndrome time course, and how it may be affected by the population characteristics among subjects admitted to a rehabilitation center in Tunisia.. A prospective research has permitted study of the socio-demographic characteristics and assessment of buprenorphine withdrawal syndrome among 32 subjects admitted for buprenorphine dependence by using the clinical opiate withdrawal scale. An ANOVA was conducted to examine the effect of different factors on the withdrawal scores.. 32 subjects were included. Among them 30 were males, 27 had been injecting buprenorphine, 16 were poly-drug abusers and 2 had a history of mental disorders. Buprenorphine withdrawal syndrome was of a mild intensity and had a delayed onset. Withdrawal mean scores varied between 0 and 9, and maximum values were reached at day 21. These scores varied significantly over time (p<0,001). The sex v time interaction and the mode of consumption of buprenorphine had significant effects on the withdrawal scores (p<0,001). The poly-drug consumption and the history of mental disorders did not have any significant effect on the withdrawal scores.. This study has permitted description of buprenorphine withdrawal syndrome among patients going through a detoxification treatment at a rehabilitation center. Understanding this syndrome would help elaborate effective and suitable buprenorphine dependence management plans.

Topics: Adult; Buprenorphine; Female; Humans; Male; Middle Aged; Opioid-Related Disorders; Prospective Studies; Sex Factors; Socioeconomic Factors; Substance Abuse Treatment Centers; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors; Tunisia

Topics: Adult; Alcohol Drinking; Analgesics, Opioid; Buprenorphine; Drug Interactions; Female; Humans; Middle Aged; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Substance Withdrawal Syndrome

Subsequent to initial opioid detoxification, people with opioid use disorder are typically advised to engage in follow-up treatment to prevent relapse. Medication-assisted treatments (MATs) - i.e., the opioid agonist methadone (MMT) or partial agonist/antagonist, buprenorphine/naltrexone (BUP) -- are the maintenance treatment options with the best research support for positive outcomes. A third MAT, injectable extended-release naltrexone (XR-NTX), was approved by the FDA for opioid dependence in 2010 and shows promise. However, relatively few eligible patients choose to initiate one of these MATs following initial detoxification treatment. Consistent with the health belief model, we hypothesized that beliefs about 1) efficacy of each MAT; 2) safety of each MAT; and 3) perceived consistency with being drug-free would predict stated patient preferences for a particular MAT or for no MAT. We also hypothesized that perceived structural barriers (e.g., time, transportation) would decrease the likelihood of stating a preference for a given MAT. To assess these hypotheses, we surveyed 372 people undergoing inpatient opioid detoxification treatment. Results supported hypotheses for all 3 sets of patient beliefs, with the patient group stating that they preferred a particular MAT having significantly more positive beliefs about that MAT relative to other groups (p<.001). The group that preferred "no MAT" had the most negative beliefs about all MATs. Perceived structural barriers were not related to stated preferences, except that people who preferred BUP were more likely to endorse barriers to MMT than any of the other 3 groups. Notably, a relatively high proportion (32%) of participants were most interested in XR-NTX despite a lack of prior experience with this medication. These results suggest that efforts to increase MAT enrollment following detoxification might benefit from including patient beliefs as one set of factors to assess and target for change.

Topics: Adult; Buprenorphine; Delayed-Action Preparations; Female; Humans; Interviews as Topic; Male; Methadone; Naltrexone; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Preference; Substance Withdrawal Syndrome; Young Adult

Non-medical use of opioid analgesics (OAs) has increased in the United States over the past decade. Concurrently, access to opioid agonist therapies (OATs) such as buprenorphine has expanded. However, there has been little in-depth qualitative exploration into circumstances surrounding buprenorphine diversion and non-prescribed use. This study reports on qualitative data from in-depth interviews conducted with persons in New York City reporting non-medical OA use in the past 12 months. Participants (n=42) were aged between 18 and 49 years. The majority were male (n=29) and non-Hispanic White (n=35). All participants self-reported physical opioid dependence. Motivations for non-prescribed buprenorphine use included the abatement of withdrawal symptoms or a self-initiated detoxification or treatment plan. Few participants reported buprenorphine use for euphoric effect, and no participants reported using buprenorphine as a primary drug. Buprenorphine diversion primarily occurred as a means of supporting ongoing illicit drug use, and no participants reported selling buprenorphine as a primary source of income. Participants reported misinformation around some key areas of buprenorphine induction and use, as well as stigma within peer networks and from drug treatment providers. As access to buprenorphine treatment continues to expand in the United States, enhancing patient education is a critical step toward minimizing diversion and incidental harms from non-prescribed use.

Topics: Adolescent; Adult; Analgesics, Opioid; Buprenorphine; Female; Humans; Male; Middle Aged; New York City; Opioid-Related Disorders; Prescription Drug Diversion; Prescription Drug Misuse; Qualitative Research; Social Stigma; Substance Withdrawal Syndrome; Young Adult

We describe the case of a young male patient who had consumed the morphine-like substance AH-7921 which is available via the internet. He was initially admitted to hospital because of obstipation and presented within a day of inpatient treatment for the first time with a generalized tonic-clonic epileptic seizure with subsequent urinary retention. Within a few hours, the patient then also developed bradycardia, while at the same time describing symptoms of physical opioid withdrawal which gradually deteriorated within the following hours. We initiated a treatment with buprenorphine which resulted in a considerable reduction of withdrawal symptoms, so the patient could be discharged from hospital.

Topics: Analgesics, Opioid; Benzamides; Buprenorphine; Epilepsy, Tonic-Clonic; Humans; Male; Narcotic Antagonists; Substance Withdrawal Syndrome; Urinary Retention; Young Adult

Development of a healthy gut microbiome is essential in newborns to establish immunity and protection from pathogens. Recent studies suggest that infants who develop dysbiosis may be at risk for lifelong adverse health consequences. Exposure to opioid drugs during pregnancy is a factor of potential importance for microbiome health that has not yet been investigated. Since these infants are born after an entire gestation exposed to mu opioid receptor agonists and have severe gastrointestinal and neurological symptoms, we hypothesize that these infants are at risk for dysbiosis. We speculate that opioid exposure during gestation and development of NAS at birth may lead to a dysbiotic gut microbiome, which may impair normal microbiome succession and development, and impact future health of these children.

Topics: Analgesics, Opioid; Buprenorphine; Child; Child, Preschool; Dysbiosis; Female; Gastrointestinal Tract; Humans; Infant; Infant, Newborn; Maternal Exposure; Methadone; Microbiota; Models, Theoretical; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Risk; Substance Withdrawal Syndrome

This study aimed to explore the client experience of long-term opiate substitution treatment (OST).. A qualitative grounded theory study set in a U.K. rural community drug treatment service.. Continuous OST enabled stability and a sense of "normality." Participants expressed relief at moving away from previous chaotic lifestyles and freedom from the persistent fear of opiate withdrawal. However, for some, being on a script made them feel withdrawn, lethargic, and unable to fully participate in mainstream society. Intrapersonal barriers (motivation and fear) were perceived as key barriers to abstinence.. Participants experienced long-term OST as a transition between illicit drug use and recovery. Recovery was seen as a process rather than a fixed goal, confirming that there is a need for services to negotiate individualized recovery goals, spanning harm minimization and abstinence-oriented treatment approaches.

Topics: Analgesics, Opioid; Buprenorphine; Fear; Female; Humans; Male; Methadone; Middle Aged; Motivation; Opiate Substitution Treatment; Opioid-Related Disorders; Qualitative Research; Rural Population; Substance Withdrawal Syndrome

Topics: Analgesics; Buprenorphine; Clonidine; Craving; Female; Humans; Male; Narcotic Antagonists; Opioid-Related Disorders; Substance Withdrawal Syndrome

Despite the effectiveness of agonist maintenance for opioid dependence, individuals can remain on waitlists for months, during which they are at significant risk for morbidity and mortality. Interim dosing, consisting of daily medication without counseling, can reduce these risks. In this pilot study, we examined the initial feasibility of a novel technology-assisted interim buprenorphine treatment for waitlisted opioid-dependent adults. Following buprenorphine induction during Week 1, participants (n=10) visited the clinic at Weeks 2, 4, 6, 8, 10 and 12 to ingest their medication under staff observation, provide a urine specimen and receive their remaining doses via a computerized Med-O-Wheel Secure device. They also received daily monitoring via an Interactive Voice Response (IVR) platform, as well as random call-backs for urinalysis and medication adherence checks. The primary outcome was percent of participants negative for illicit opioids at each 2-week visit, with secondary outcomes of past-month drug use, adherence and acceptability. Participants achieved high levels of illicit opioid abstinence, with 90% abstinent at the Week 2 and 4 visits and 60% at Week 12. Significant reductions were observed in self-reported past-month illicit opioid use (p<.001), opioid withdrawal (p<.001), opioid craving (p<.001) and ASI Drug composite score (p=.008). Finally, adherence with buprenorphine administration (99%), daily IVR calls (97%) and random call-backs (82%) was high. Interim buprenorphine treatment shows promise for reducing patient and societal risks during delays to conventional treatment. A larger-scale, randomized clinical trial is underway to more rigorously examine the efficacy of this treatment approach.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Drug Administration Schedule; Feasibility Studies; Female; Humans; Male; Opiate Substitution Treatment; Opioid-Related Disorders; Pilot Projects; Substance Withdrawal Syndrome; Treatment Outcome; Waiting Lists

Buprenorphine (BUP) is a psychoactive pharmaceutical drug largely used to treat opiate addiction. Short-term therapeutic monitoring is supported by toxicological analysis of blood and urine samples, whereas long-term monitoring by means of hair analysis is rarely used. Aim of this work was to develop and validate a highly sensitive ultrahigh-performance liquid chromatography tandem mass spectrometry method to detect BUP and norbuprenorphine (NBUP) in head hair.. Interindividual correlation between oral dosage of BUP and head hair concentration was investigated. Furthermore, an intra-individual study by means of segmental analysis was performed on subjects with variable maintenance dosage. Hair samples from a population of 79 patients in treatment for opiate addiction were analyzed.. The validated ultrahigh-performance liquid chromatography tandem mass spectrometry protocol allowed to obtain limits of detection and quantification at 0.6 and 2.2 pg/mg for BUP and 5.0 and 17 pg/mg for NBUP, respectively. Validation criteria were satisfied, assuring selective analyte identification, high detection capability, and precise and accurate quantification. Significant positive correlation was found between constant oral BUP dosage (1-32 mg/d) and the summed up head hair concentrations of BUP and NBUP. Nevertheless, substantial interindividual variability limits the chance to predict the oral dosage taken by each subject from the measured concentrations in head hair. In contrast, strong correlation was observed in the results of intra-individual segmental analysis, which proved reliable to detect oral dosage variations during therapy.. Remarkably, all hair samples yielded BUP concentrations higher than 10 pg/mg, even when the lowest dosage was administered. Thus, these results support the selection of 10 pg/mg as a cutoff value.

Topics: Adult; Buprenorphine; Dose-Response Relationship, Drug; Drug Monitoring; Female; Hair; Humans; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Substance Withdrawal Syndrome; Time Factors; Young Adult

The problem of lying as a feature of medication compliance has been well documented in anthropological and clinical literatures. Yet the role of the lie-its destabilizing effects on the continuity of drug treatment and therapy, as a technology of drug misuse, or as a way to understand the neuro-chemical processes of treatment (pharmacotherapy "tricking" or lying to the brain)-has been less considered, particularly in the context of opioid replacement therapy. The following paper is set against the backdrop of a three-year study of adolescents receiving a relatively new drug (buprenorphine) for the treatment of opiate dependency inside and outside of highly monitored treatment environments in the United States. Lies give order not only to the experience of addiction but also to the experience of therapy as well. In order to better understand this ordering of experience, the paper puts the widely discussed conceptual duality of the pharmakon (healing and poison) in conversation with a perilously overlooked subject in the critical study of pharmacotherapy, namely the pharmakos or the personification of sacrifice. The paper demonstrates how the patient-subject comes to represent therapeutic promise by allowing for the possibility of (and often performing) deceit.

Topics: Adolescent; Analgesics, Opioid; Behavior, Addictive; Buprenorphine; Deception; Drug Monitoring; Humans; Nervous System; Opiate Substitution Treatment; Opioid-Related Disorders; Philosophy, Medical; Substance Abuse Treatment Centers; Substance Withdrawal Syndrome

New Mexico has consistently high rates of drug-induced deaths, and opioid-related treatment admissions have been increasing over the last two decades. Youth in New Mexico are at particular risk: they report higher rates of nonmedical prescription opioid use than those over age 25, are more likely than their national counterparts to have tried heroin, and represent an increasing proportion of heroin overdoses.. Commissioned by the City of Albuquerque, semistructured interviews were conducted from April to June of 2011 with 24 substance use treatment agencies and eight key stakeholders in Albuquerque to identify recent changes in the treatment-seeking population and gaps in treatment availability. Themes were derived using template analysis and data were analyzed using NVivo 9 software.. Respondents reported a noticeable increase in youth seeking treatment for opioid use and a general increase in nonmedical prescription opioid use. Most noted difficulties with finding buprenorphine providers and a lack of youth services. Additionally, stigma, limited interagency communication and referral, barriers to prescribing buprenorphine, and a lack of funding were noted as preventing opioid users from quickly accessing effective treatment.. Recommendations for addressing these issues include developing youth-specific treatment programs, raising awareness about opioid use among youth, increasing the availability of buprenorphine through provider incentives and education, developing a resource guide for individuals seeking treatment in Albuquerque, and prioritizing interagency communication and referrals.

Topics: Adolescent; Age Factors; Analgesics, Opioid; Buprenorphine; Cause of Death; Cooperative Behavior; Cross-Sectional Studies; Health Planning Councils; Health Services Accessibility; Heroin; Heroin Dependence; Humans; Interdisciplinary Communication; Needs Assessment; New Mexico; Opioid-Related Disorders; Prescription Drugs; Referral and Consultation; Substance Withdrawal Syndrome; Young Adult

The prescribing of opioid pain medication has increased markedly in recent years, with strong opioid dispensing increasing 18-fold in Tayside, Scotland since 1995. Despite this, little data is available to quantify the problem of opioid pain medication dependence (OPD) and until recently there was little guidance on best-practice treatment. We report the case of a young mother prescribed dihydrocodeine for postoperative pain relief who became opioid dependent. When her prescription was stopped without support, she briefly used heroin to overcome her withdrawal. After re-exposure to dihydrocodeine following surgery 9 years later and treatment with methadone for dependency, she was transferred to buprenorphine/naloxone. In our clinical experience and in agreement with Department of Health and Royal College of General Practitioner guidance, buprenorphine/naloxone is the preferred opioid substitution treatment for OPD. Our patient remains within her treatment programme and has returned to work on buprenorphine 16 mg/naloxone 4 mg in conjunction with social and psychological support.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Codeine; Disease Management; Female; Heroin; Heroin Dependence; Humans; Methadone; Naloxone; Opiate Substitution Treatment; Opioid-Related Disorders; Pain, Postoperative; Substance Withdrawal Syndrome; Young Adult

Although opioid maintenance treatment (OMT) is the treatment of choice for pregnant opioid-dependent patients, some professionals argue that tapering the medication dose will reduce the severity of neonatal abstinence syndrome (NAS). This case description is based on the patient's detailed blog, and medical records from her general practitioner and the hospital. The patient is an employed, 32-year-old drug-abstinent woman in OMT. Her taper from 24 mg of buprenorphine started at 14 weeks' gestation and is slow, with withdrawal symptoms increasing gradually. In pregnancy week 31, she is off buprenorphine but she has severe withdrawal symptoms. She chose to go back on 4 mg of buprenorphine. The patient's son was born in pregnancy week 38+3, weighs 2950 g and does not require pharmacological treatment for NAS. The fetus most probably did experience fetal stress during the patient's tapering. It was the right decision by the patient to go back on buprenorphine.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Female; Fetus; Gestational Age; Humans; Infant, Newborn; Male; Narcotics; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Parturition; Pregnancy; Pregnancy Complications; Substance Withdrawal Syndrome

This study explores strategies that Suboxone misusers utilize while in drug treatment. Ethnographic interviews were conducted with 14 patients who had cycled in and out of Suboxone treatment. The objective of the study is to identify strategies implemented by patients who intermittently use opiates/opioids while in Suboxone treatment. Findings indicate that some patients serially stop and start treatment in a Harm Reduction setting in New York City. Many patients suggest that they manage their opiate/opioid dependency through a sequential use of Suboxone and heroin to avoid withdrawal and to continue their misuse of opiates/opioids. Results are discussed in conjunction with the difficulties inherent to substance abuse treatment and suggestions for improvement are offered.

Topics: Adult; Behavior, Addictive; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Drug Combinations; Drug Users; Female; Harm Reduction; Heroin Dependence; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; New York City; Opiate Substitution Treatment; Patient Acceptance of Health Care; Prescription Drug Misuse; Qualitative Research; Recurrence; Social Environment; Substance Abuse Treatment Centers; Substance Withdrawal Syndrome

There are few systematic assessments of street-obtained buprenorphine use from community-based samples in the United States. The objective of this study was to characterize the prevalence, correlates, and reasons for street-obtained buprenorphine use among current and former injection drug users (IDUs) in Baltimore, Maryland.. In 2008, participants of the ALIVE (AIDS Linked to the IntraVenous Experience) study, a community-based cohort of IDUs, were administered a survey on buprenorphine. Street-obtained buprenorphine represented self-reported use of buprenorphine obtained from the street or a friend in the prior three months.. Six hundred and two respondents were predominantly male (65%), African-American (91%), and 30% were HIV-positive. Overall, nine percent reported recent street-obtained buprenorphine use, and only 2% reported using to get high. Among active opiate users, 23% reported recent use of street-obtained buprenorphine. Use of buprenorphine prescribed by a physician, injection and non-injection drug use, use of street-obtained methadone and prescription opiates, homelessness, and opioid withdrawal symptoms were positively associated, while methadone treatment, health insurance, outpatient care, and HIV-infection were negatively associated with recent street-obtained buprenorphine use in univariate analysis. After adjustment, active injection and heroin use were positively associated with street-obtained buprenorphine use. Ninety-one percent reported using street-obtained buprenorphine to manage withdrawal symptoms.. While 9% reported recent street-obtained buprenorphine use, only a small minority reported using buprenorphine to get high, with the majority reporting use to manage withdrawal symptoms. There is limited evidence of diversion of buprenorphine in this sample and efforts to expand buprenorphine treatment should continue with further monitoring.

Topics: Baltimore; Buprenorphine; Epidemiologic Methods; Female; Health Knowledge, Attitudes, Practice; Humans; Ill-Housed Persons; Illicit Drugs; Male; Middle Aged; Narcotics; Opioid-Related Disorders; Substance Abuse, Intravenous; Substance Withdrawal Syndrome

Topics: Buprenorphine; Female; Humans; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications; Randomized Controlled Trials as Topic; Research Design; Substance Withdrawal Syndrome

Pre-clinical research indicates that opioids reduce extracellular glutamate in acute opioid treatment, whereas during withdrawal, glutamatergic neurotransmission is increased and withdrawal symptoms can be blocked by glutamate receptor antagonists. The glutamate hypothesis of addiction suggests that withdrawal-associated hyperglutamatergic states destabilize the glutamatergic system chronically and contribute to relapse. magnetic resonance spectroscopy at three tesla optimized for glutamate assessment (TE 80 ms) was performed in the anterior cingulate gyrus (ACC) and frontal white matter (fWM) of 17 opiate-dependent patients during opiate maintenance therapy and 20 healthy controls. Controlling for age and gray matter content, glutamate in the ACC was positively associated with the number of previous withdrawals. For glutamate + glutamine (Glx), a significant group-age interaction was found. Whereas Glx declines with age in healthy controls, Glx increases with age in opiate-dependent patients. The number of previous withdrawals did not correlate with age. In fWM spectra, increased Cho concentrations were observed in opiate-dependent patients. Both new findings, the positive correlation of glutamate and previous withdrawals and increasing Glx with age in contrast to an age-dependent Glx decrease in controls indicate a destabilization of the glutamate system in opiate-dependent patients and support the glutamate hypothesis of addiction. Increased Cho concentrations in fWM corroborate findings of WM abnormalities in opioid-dependent subjects.

Topics: Adult; Analysis of Variance; Buprenorphine; Case-Control Studies; Female; Glutamic Acid; Gyrus Cinguli; Heroin Dependence; Humans; Magnetic Resonance Spectroscopy; Male; Methadone; Middle Aged; Narcotics; Substance Withdrawal Syndrome

Because the outcome of methadone and buprenorphine substitution treatment in adolescents is unclear, we completed a retrospective cohort study of 100 consecutive heroin-dependent adolescents who sought these treatments over an 8-year recruitment period. The participants' average age was 16.6 years, and 54 were female. Half of the patient group remained in treatment for over 1 year. Among those still in treatment at 12 months, 39% demonstrated abstinence from heroin. The final route of departure from the treatment program was via planned detox for 22%, dropout for 32%, and imprisonment for 8%. The remaining 39% were transferred elsewhere for ongoing opiate substitution treatment after a median period of 23 months of treatment. Males were more likely to exit via imprisonment (p < .05), but other outcomes were not predicted by gender. There were no deaths during treatment among these 100 patients who had a cumulative period of 129 person years at risk. Our findings suggest that this treatment delivers reductions in heroin use and that one fifth of patients will exit treatment following detox completion within a 1- to 2-year time frame.

Topics: Adolescent; Buprenorphine; Cohort Studies; Female; Heroin Dependence; Humans; Male; Methadone; Narcotics; Opiate Substitution Treatment; Prisoners; Retrospective Studies; Sex Factors; Substance Withdrawal Syndrome; Time Factors; Treatment Outcome

Thenorphine is a new potent long-acting partial opioid agonist. In present study, the effect of thienorphine on noradrenalin (NA) in the locus coeruleus (LC) and dopamine (DA) and its metabolites in the nucleus acumbens (NAc) and the striatum were examined in freely moving rats during acute and chronic thienorphine treatment followed by naloxone-precipitated withdrawal using the in vivo microdialysis technique. Acute thienorphine (1.0mg/kg, s.c.) treatment had no effect on the level of NA in the LC and the level of DA in the NAc and the striatum. Chronic thienorphine (1.0mg/kg, s.c.) third per day for continued 5 days treatment followed by naloxone-precipitated (5.0mg/kg, i.p.) had not alter the extracellular NA level in the LC and the extracellular level of DA in the NAc and the striatum, but significantly increased the level of DOPAC in the striatum. These changes are thought to reflect a direct effect of thienorphine on release of NA and DA. Thus thienorphine deserves further study as a new treatment for opioid dependence.

Topics: 3,4-Dihydroxyphenylacetic Acid; Analgesics, Opioid; Animals; Buprenorphine; Corpus Striatum; Dopamine; Locus Coeruleus; Male; Microdialysis; Naloxone; Norepinephrine; Nucleus Accumbens; Rats; Rats, Wistar; Substance Withdrawal Syndrome

Buprenorphine/naloxone is used for the treatment of opioid dependence. In the following case, a potential use for the medication combination is explored in the arena of transplant surgery. Psychiatry was consulted for a 29-year-old woman with iatrogenic opioid dependence after bilateral ventricular assist device placement for congenital cardiomyopathy. Her ejection fraction was less than 15% and she was considered a poor candidate for transplant due to drug-seeking behaviors. We transitioned her onto buprenorphine/naloxone to prevent abuse and control symptoms, qualifying her for cardiac transplant. After transplant, we coordinated care with cardiothoracic surgeons to restart buprenorphine/naloxone, and the patient has been stable for 8 months.

Topics: Adult; Buprenorphine; Cardiomyopathies; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Heart Transplantation; Heart-Assist Devices; Humans; Iatrogenic Disease; Naloxone; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Pain, Postoperative; Substance Withdrawal Syndrome

The dosing of opioid receptor agonist medications adequately and on an individual basis is crucial in the pharmacotherapy of opioid dependence. Clinical tools that are able to measure dose appropriateness are sorely needed. The recently developed and validated Opiate Dosage Adequacy Scale (ODAS) comprehensively evaluates the main outcomes relevant for methadone dose optimization, namely relapse, cross-tolerance, objective and subjective withdrawal symptoms, craving and overdose. Based on the ODAS, we developed a new assessment tool (BUprenorphine-naloxone Dosage Adequacy eVAluation [BUDAVA]) for evaluating dosage adequacy in patients in treatment with buprenorphine-naloxone.. The main goal of this observational study was to explore whether the BUDAVA questionnaire could be used to assess buprenorphine-based, long-term substitution therapy for heroin addiction.. The study included heroin-dependent patients who had been in treatment with buprenorphine-naloxone for at least 3 months. Patients (n = 196) were recruited from 11 drug abuse treatment centres in Italy. Dosage adequacy was assessed with the BUDAVA questionnaire. Patients classified as inadequately treated had their dosage modified. After 1 week, they were again administered the questionnaire to assess the adequacy of the new dosage.. The buprenorphine-naloxone dosage was found to be inadequate in 61 of the 196 patients. In 13 patients, the treatment scored as inadequate only in the subjective withdrawal symptoms item of the questionnaire and therefore no dosage adjustment was made in the 2 weeks that have characterized this work. The remaining 48 inadequately treated patients had their dosage modified (42 dose increases and six dose decreases). After 1 week on the modified dosage, in 24 of these patients the new regimen was found by the assessment with the questionnaire to be adequate.. These preliminary results suggest that the BUDAVA questionnaire may be useful for guiding buprenorphine-naloxone maintenance dose adjustments in heroin-dependent patients.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Chi-Square Distribution; Drug Dosage Calculations; Drug Monitoring; Heroin Dependence; Humans; Italy; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Predictive Value of Tests; Receptors, Opioid; Secondary Prevention; Substance Withdrawal Syndrome; Surveys and Questionnaires; Time Factors; Treatment Outcome

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

Opioid dependence in the setting of pregnancy provides a distinct set of challenges for providers. Treatment plans must take into consideration psychiatric and medical comorbidities while balancing risks and benefits for the maternal-fetal dyad. Treatment is best offered through a comprehensive treatment program designed to effectively deliver opioid agonist maintenance treatment along with psychosocial and obstetric care. As misuse of prescription analgesics increases in the United States, identification of the problem in pregnancy will become more important because this misuse is expected to lead to an increased prevalence of opioid dependence in pregnancy. Buprenorphine as maintenance treatment of opioid dependence during pregnancy has promise and may offer some benefits, but more research is needed, especially regarding induction of actively addicted women during pregnancy. For the present, methadone maintenance remains the standard of care for agonist treatment of opioid dependence in pregnancy against which other treatments must be compared.

Topics: Adolescent; Alcohol-Related Disorders; Analgesics, Opioid; Buprenorphine; Child; Comorbidity; Delivery, Obstetric; Female; Humans; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pain Management; Pregnancy; Pregnancy Complications; Prenatal Care; Prenatal Exposure Delayed Effects; Prescription Drugs; Self Medication; Substance Withdrawal Syndrome; United States

Topics: Adult; Buprenorphine; Drug Administration Schedule; Humans; Male; Psychoses, Substance-Induced; Psychotic Disorders; Substance Withdrawal Syndrome

Topics: Acidosis, Lactic; Anorexia; Asthenia; Buprenorphine; Cachexia; Humans; Male; Methadone; Middle Aged; Neuralgia, Postherpetic; Opioid-Related Disorders; Substance Withdrawal Syndrome; Thiamine; Thiamine Deficiency

Buprenorphine, a synthetic opioid that acts at both μ and κ opioid receptors, can decrease cocaine use in individuals with opioid addiction. However, the potent agonist action of buprenorphine at μ opioid receptors raises its potential for creating opioid dependence in non-opioid-dependent cocaine abusers. Here, we tested the hypothesis that a combination of buprenorphine and naltrexone (a potent μ opioid antagonist with weaker δ and κ antagonist properties) could block compulsive cocaine self-administration without producing opioid dependence. The effects of buprenorphine and various doses of naltrexone on cocaine self-administration were assessed in rats that self-administered cocaine under conditions of either short access (noncompulsive cocaine seeking) or extended access (compulsive cocaine seeking). Buprenorphine alone reproducibly decreased cocaine self-administration. Although this buprenorphine-alone effect was blocked in a dose-dependent manner by naltrexone in both the short-access and the extended-access groups, the combination of the lowest dose of naltrexone with buprenorphine blocked cocaine self-administration in the extended-access group but not in the short-access group. Rats given this low dose of naltrexone with buprenorphine did not exhibit the physical opioid withdrawal syndrome seen in rats treated with buprenorphine alone, and naltrexone at this dose did not block κ agonist-induced analgesia. The results suggest that the combination of buprenorphine and naltrexone at an appropriate dosage decreases compulsive cocaine self-administration with minimal liability to produce opioid dependence and may be useful as a treatment for cocaine addiction.

Topics: Animals; Buprenorphine; Cocaine; Cocaine-Related Disorders; Male; Naloxone; Naltrexone; Rats; Rats, Wistar; Substance Withdrawal Syndrome

Topics: Buprenorphine; Clonidine; Evidence-Based Medicine; Humans; Inactivation, Metabolic; Methadone; Naloxone; Naltrexone; Narcotic Antagonists; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Prognosis; Risk Factors; Substance Withdrawal Syndrome; Time Factors

To characterize the range of symptoms experienced by pregnant methadone-maintained (MM) and buprenorphine-maintained (BM) women to determine whether these differ from those experienced by a control group of nonopioid exposed pregnant women. Opioid-maintained (OM) patients report high rates of symptoms related to direct opioid effects and withdrawal. Pregnancy is associated with a range of symptoms, some overlapping with opioid effects and withdrawal.. Prospective, nonrandomized, open-label comparison study undertaken in a large teaching maternity hospital in South Australia. Pregnant BM (n = 25), MM (n = 25) and nonopioid exposed controls (n = 25) were recruited and matched for age, parity, gravidity, alcohol consumption, and smoking status. Symptom report patterns, maternal withdrawal, and additional substance use were assessed.. MM women reported 10 and BM women reported 2 symptoms throughout pregnancy at rates greater than controls. Methadone-maintained women reported significantly (P < 0.05) more symptoms than BM women compared to controls throughout pregnancy. Methadone-maintained women reported 8 and BM women reported 3 symptoms in the third trimester at rates greater than controls. Methadone-maintained women reported greater opioid withdrawal than controls; this did not occur in BM women. Additional substance use was comparable between BM and MM women but greater than controls.. Patterns of symptom reports may have clinical implications for maternal and fetal health during pregnancy for OM women including optimization of opioid dosing regimens, education regarding maternal nutritional intake and preventing postnatal depression, thereby ensuring maternal health and fetal development during pregnancy and enhancing mother-infant bonding and healthy child development postnatally.

Topics: Adult; Buprenorphine; Case-Control Studies; Female; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Self Report; Substance Withdrawal Syndrome

Buprenorphine (Subutex) was piloted in two Scottish prisons between 2004 and 2006 and consequently used within other penal establishments in Scotland. This 2007 qualitative study aimed to explore the use of Subutex and its associated effects on 14 participants on detoxification programmes.. All participants were male, aged from 21 to 44 years with prison sentences ranging from a few months to life imprisonment. Buprenorphine was unavailable to female prisoners at the time of this study. Participants were recruited from seven Scottish prisons. All 14 participants were on detoxification programmes, each was prescribed Subutex, and each was selected from a larger investigation that included both those undergoing detoxification and maintenance (n=21). All participants had previously also used methadone on previous detoxification programmes.. It can be concluded that the majority of detoxification participants within this study indicated that Subutex was a more effective treatment than methadone as it helped reduce craving, eased the process of withdrawal and improved sleeping patterns. In addition, the majority of participants noted higher levels of motivation and the ability to set goals towards obtaining an improved quality of life.. This study provides an alternative perspective to the use of Subutex within prison settings, when compared with results from previous quantitative studies reported. The study also highlights inconsistencies drawn from studies in this area, which may be an artefact of study design. It is recommended that further qualitative studies be conducted to explore further this alternative perspective. Finally, the issue of methodological approach taken should be addressed within the context of a related, but independent, research forum.

Topics: Adult; Buprenorphine; Humans; Male; Narcotic Antagonists; Opiate Substitution Treatment; Patient Satisfaction; Prisoners; Qualitative Research; Scotland; Substance Withdrawal Syndrome; Substance-Related Disorders; Young Adult

This study aimed to investigate patient perspectives regarding coming off maintenance opioid substitution treatment (OST). The study explored previous experiences, current interest and concerns about stopping treatment, and perceptions of how and when coming off treatment should be supported.. A cross-sectional survey was used. Participants were 145 patients receiving OST at public opioid treatment clinics in Sydney, Australia.. Sixty-two percent reported high interest in coming off treatment in the next 6 months. High interest was associated with having discussed coming off treatment with a greater number of categories of people (OR=1.72), not citing concern about heroin relapse (OR=3.18), and shorter duration of current treatment episode (OR=0.99). Seventy-one percent reported previous withdrawal attempts and 23% had achieved opioid abstinence for ≥3 months following a previous withdrawal attempt. Attempts most commonly involved jumping off (59%), and doctor-controlled (52%) or self-controlled (48%) gradual reduction. For future attempts respondents were most interested in doctor-controlled (68%) or self-controlled (41%) gradual reduction. Concerns regarding coming off treatment included withdrawal discomfort (68%), increased pain (50%), and relapse to heroin use (48%).. While some patients may require lifetime maintenance, the issue of coming off treatment is important to many patients and should be discussed regularly throughout treatment and where appropriate supported by a menu of clinical options.

Topics: Analgesics, Opioid; Buprenorphine; Consumer Health Information; Cross-Sectional Studies; Female; Humans; Male; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Self-Help Groups; Substance Withdrawal Syndrome

The dual antagonist effects of the mixed-action μ-opioid partial agonist/κ-opioid antagonist buprenorphine have not been previously compared in behavioral studies, and it is unknown whether they are comparably modified by chronic exposure. To address this question, the dose-related effects of levorphanol, trans-(-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl] benzeneacetamide (U50,488), heroin, and naltrexone on food-maintained behavior in rhesus monkeys were studied after acute and chronic treatment with buprenorphine (0.3 mg/kg/day). In acute studies, the effects of levorphanol and U50,488 were determined at differing times after buprenorphine (0.003-10.0 mg/kg i.m.). Results show that buprenorphine produced similar, dose-dependent rightward shifts of the levorphanol and U50,488 dose-response curves that persisted for ≥ 24 h after doses larger than 0.1 mg/kg buprenorphine. During chronic treatment with buprenorphine, the effects of levorphanol, U50,488, heroin, and naltrexone were similarly determined at differing times (10 min to 48 h) after intramuscular injection. Overall, results show that buprenorphine produced comparable 3- to 10-fold rightward shifts in the U50,488 dose-response curve under both acute and chronic conditions, but that chronic buprenorphine produced larger (10- to ≥ 30-fold) rightward shifts in the heroin dose-effect function than observed acutely. Naltrexone decreased operant responding in buprenorphine-treated monkeys, and the position of the naltrexone dose-effect curve shifted increasingly to the left as the time after daily buprenorphine treatment increased from 10 min to 48 h. These results suggest that the μ-antagonist, but not the κ-antagonist, effects of buprenorphine are augmented during chronic treatment. In addition, the leftward shift of the naltrexone dose-effect function suggests that daily administration of 0.3 mg/kg buprenorphine is adequate to produce opioid dependence.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Animals; Buprenorphine; Dose-Response Relationship, Drug; Drug Tolerance; Female; Levorphanol; Macaca mulatta; Male; Naltrexone; Narcotic Antagonists; Substance Withdrawal Syndrome

To develop evidence-based practice guidelines for the pharmacological treatment of opioid abuse and dependence.. An international task force of the World Federation of Societies of Biological Psychiatry (WFSBP) developed these practice guidelines after a systematic review of the available evidence pertaining to the treatment of opioid dependence. On the basis of the evidence, the Task Force reached a consensus on practice recommendations, which are intended to be clinically and scientifically meaningful for physicians who treat adults with opioid dependence. The data used to develop these guidelines were extracted primarily from national treatment guidelines for opioid use disorders, as well as from meta-analyses, reviews, and publications of randomized clinical trials on the efficacy of pharmacological and other biological treatments for these disorders. Publications were identified by searching the MEDLINE database and the Cochrane Library. The literature was evaluated with respect to the strength of evidence for efficacy, which was categorized into one of six levels (A-F).. There is an excellent evidence base supporting the efficacy of methadone and buprenorphine or the combination of buprenorphine and naloxone for the treatment of opioid withdrawal, with clonidine and lofexidine as secondary or adjunctive medications. Opioid maintenance with methadone and buprenorphine is the best-studied and most effective treatment for opioid dependence, with heroin and naltrexone as second-line medications.. There is enough high quality data to formulate evidence-based guidelines for the treatment of opioid abuse and dependence. This task force report provides evidence for the efficacy of a number of medications to treat opioid abuse and dependence, particularly the opioid agonists methadone or buprenorphine. These medications have great relevance for clinical practice.

Topics: Adult; Aryl Hydrocarbon Hydroxylases; Buprenorphine; Cytochrome P-450 CYP2B6; Cytochrome P-450 CYP2D6; Drug Therapy, Combination; Evidence-Based Medicine; Genetic Variation; Humans; Methadone; Narcotic Antagonists; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Oxidoreductases, N-Demethylating; Psychotherapy; Receptors, Opioid; Social Support; Standard of Care; Substance Withdrawal Syndrome

This series of studies examines the pharmacokinetic/pharmacodynamic interactions between buprenorphine, an opioid partial agonist increasingly used in treatment of opioid dependence, and rifampin, a medication used as a first line treatment for tuberculosis; or rifabutin, an alternative antituberculosis medication.. Opioid-dependent individuals on stable doses of buprenorphine/naloxone underwent two, 24-h blood sampling studies: (1) for buprenorphine pharmacokinetics and (2) following 15 days of rifampin 600 mg daily or rifabutin 300 mg daily for buprenorphine and rifampin or rifabutin pharmacokinetics.. Rifampin administration produced significant reduction in plasma buprenorphine concentrations (70% reduction in mean area under the curve (AUC); p=<0.001) and onset of opiate withdrawal symptoms in 50% of participants (p=0.02). While rifabutin administration to buprenorphine-maintained subjects resulted in a significant decrease in buprenorphine plasma concentrations (35% decrease in AUC; p<0.001) no opiate withdrawal was seen. Compared with historical control data, buprenorphine had no significant effect on rifampin pharmacokinetics, but was associated with 22% lower rifabutin mean AUC (p=0.009), although rifabutin and its active metabolite concentrations remained in the therapeutic range.. Rifampin is a more potent inducer of buprenorphine metabolism than rifabutin with pharmacokinetic and pharmacodynamic adverse consequences. Those patients requiring rifampin treatment for tuberculosis and receiving buprenorphine therapy are likely to require an increase in buprenorphine dose to prevent withdrawal symptoms. Rifabutin administration was associated with decreases in buprenorphine plasma concentrations, but no clinically significant adverse events were observed.

Topics: Adult; Antitubercular Agents; Buprenorphine; Drug Interactions; Female; Humans; Male; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Rifabutin; Rifampin; Substance Withdrawal Syndrome

We examined the use, procurement, and motivations for the use of diverted buprenorphine/naloxone among injecting and noninjecting opioid users in an urban area.. A survey was self-administered among 51 injecting opioid users and 49 noninjecting opioid users in Providence, RI. Participants were recruited from a fixed-site syringe exchange program and a community outreach site between August and November 2009.. A majority (76%) of participants reported having obtained buprenorphine/naloxone illicitly, with 41% having done so in the previous month. More injection drug users (IDUs) than non-IDUs reported the use of diverted buprenorphine/naloxone (86% vs 65%, P = 0.01). The majority of participants who had used buprenorphine/naloxone reported doing so to treat opioid withdrawal symptoms (74%) or to stop using other opioids (66%) or because they could not afford drug treatment (64%). More IDUs than non-IDUs reported using diverted buprenorphine/naloxone for these reasons. Significantly more non-IDUs than IDUs reported ever using buprenorphine/naloxone to "get high" (69% vs 32%, P < 0.01). The majority of respondents, both IDUs and non-IDUs, were interested in receiving treatment for opioid dependence, with greater reported interest in buprenorphine/naloxone than in methadone. Common reasons given for not being currently enrolled in a buprenorphine/naloxone program included cost and unavailability of prescribing physicians.. The use of diverted buprenorphine/naloxone was common in our sample. However, many opioid users, particularly IDUs, were using diverted buprenorphine/naloxone for reasons consistent with its therapeutic purpose, such as alleviating opioid withdrawal symptoms and reducing the use of other opioids. These findings highlight the need to explore the full impact of buprenorphine/naloxone diversion and improve the accessibility of buprenorphine/naloxone through licensed treatment providers.

Topics: Adolescent; Adult; Aged; Attitude to Health; Buprenorphine; Comorbidity; Female; Humans; Illicit Drugs; Male; Middle Aged; Motivation; Naloxone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Rhode Island; Substance Abuse, Intravenous; Substance Withdrawal Syndrome; Urban Population; Young Adult

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

Buprenorphine/naloxone was approved by the FDA for office-based opioid maintenance therapy (OMT), with little long-term follow-up data from actual office-based practice. 18-Month outcome data on the office-based use of buprenorphine/naloxone (bup/nx) and the impact of socioeconomic status and other patient characteristics on the duration and clinical effects of bup/nx are reported.. This retrospective chart review and cross-sectional telephone interview provide treatment retention of opioid-dependent patients receiving bup/nx-OMT in an office-based setting. 176 opioid-dependent patients from two different socioeconomic groups (high and low SES) were begun on bup/nx, started intensive outpatient treatment, and followed-up after a minimum of 18 months (18-42 months) by telephone interview to assess treatment outcome.. 110 subjects (67%) completed the interview, 77% remained on bup/nx with no difference in retention between high and low SES groups. Those on bup/nx at follow-up were more likely to report abstinence, to be affiliated with 12-step recovery, to be employed and to have improved functional status.. Bup/nx-OMT is a viable treatment option and when coupled with a required abstinence oriented addiction counseling program is effective in promoting abstinence, self-help group attendance, occupational stability, and improved psychosocial outcomes in both low SES and high SES patient populations over an 18-42-month period.

Topics: Adult; Aged; Buprenorphine; Cross-Sectional Studies; Employment; Female; Follow-Up Studies; Humans; Long-Term Care; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Patient Compliance; Retrospective Studies; Socioeconomic Factors; Substance Withdrawal Syndrome; Treatment Outcome; Young Adult

Several lines of evidence support a role for the endogenous opioid system in mediating behaviors associated with drug dependence. Specifically, recent findings suggest that the kappa-opioid receptor (KOR) may play a role in aspects of nicotine dependence, which contribute to relapse and continued tobacco smoking.. The objective of this study is to determine the involvement of the KOR in the initial behavioral responses of nicotine, nicotine reward, and nicotine withdrawal using the highly selective KOR antagonist JDTic. JDTic doses of 1, 4, 8, or 16 mg/kg were administered subcutaneously (s.c.) 18 h prior to nicotine treatment.. JDTic dose-dependently blocked acute nicotine-induced antinociception in the tail-flick but not the hot-plate test and did not significantly attenuate morphine's antinociceptive effect in either the tail-flick or hot-plate test. Furthermore, JDTic (8 and 16 mg/kg, s.c.) failed to block the expression of nicotine reward as measured by the conditioned place preference model. In contrast, JDTic and the KOR antagonist norBNI attenuated the expression of both the physical (somatic signs and hyperalgesia) and affective (anxiety-related behavior and conditioned place aversion) nicotine withdrawal signs.. Our findings clearly show that the KOR is involved in mediating the withdrawal aspects of nicotine dependence. The results from this study suggest that blockade of the KOR by selective KOR antagonists may be useful smoking cessation pharmacotherapies.

Topics: Analgesics; Animals; Anxiety; Buprenorphine; Dose-Response Relationship, Drug; Hyperalgesia; Hypothermia; Male; Mice; Morphine; Nicotine; Piperidines; Receptors, Opioid, kappa; Reward; Substance Withdrawal Syndrome; Tetrahydroisoquinolines

Physicians are as likely to experience drug and alcohol addiction as anyone in the general population. They are more likely than others, however, to abuse prescription medications. Dealing with an impaired colleague is a difficult, emotionally charged job for physician leaders and hospital administrators, who've often had little training on how to handle such a situation. In addition to describing a case of an addicted physician, this article reviews data about the incidence of addiction among physicians and the challenges associated with confronting such a problem. It also describes the legal reporting requirements and resources such as the Minnesota Health Professionals Services Program and Physicians Serving Physicians that can help physicians get into treatment programs designed specifically for health care professionals. Physicians who go through such treatment programs and subsequent monitoring have been found to have remarkable recovery rates.

Topics: Adult; Buprenorphine; Combined Modality Therapy; Denial, Psychological; Fentanyl; Humans; Male; Mandatory Reporting; Minnesota; Narcotic Antagonists; Peer Group; Physician Impairment; Psychotherapy, Group; Substance Abuse Treatment Centers; Substance Abuse, Intravenous; Substance Withdrawal Syndrome; Substance-Related Disorders

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

Sublingual buprenorphine [Subutex(R)] is used to treat opioid dependence. However, illicit intravenous (IV) injection of buprenorphine is a widespread problem. This survey investigated the IV misuse of buprenorphine among patients receiving drug replacement therapy at the Drug Addiction Centre in Udine, Italy. All patients who were receiving treatment with buprenorphine or methadone at the Drug Addiction Centre were invited to fill in a voluntary and anonymous questionnaire consisting of five questions. The questions asked if the patient had ever misused buprenorphine intravenously, when the misuse had occurred, the patient's reasons for misusing buprenorphine, the patient's perception of their experience, and the patient's perception of how widespread IV misuse of buprenorphine is. 307 patients completed the questionnaire, 93 and 214 of whom, respectively, were receiving buprenorphine and methadone. In total, 23.12% of patients admitted an IV misuse of buprenorphine, with a significantly greater prevalence among patients currently receiving buprenorphine (35.48%) than those receiving methadone (17.75%; p < 0.001). Younger patients were also more likely to have misused buprenorphine, and tended to have done so before coming to the Drug Addiction Centre. The most frequent motivation for IV misuse was treatment of heroin addiction or withdrawal symptoms (50.71%), while only 12.67% of patients reported that their motivation was to experience pleasure or euphoria. The majority of patients who had misused buprenorphine intravenously (53.52%) had a negative experience, and methadone recipients were significantly more likely to find the experience negative than buprenorphine recipients (68.42% vs 36.36%; p = 0.007). Almost half of the patients (45.93%) thought that at least 50% of patients had taken buprenorphine by IV injection. The results of our study confirm the widespread IV misuse of buprenorphine. Misuse was most common among patients currently receiving buprenorphine treatment and younger patients. For the majority of patients, the reason for IV misuse was to treat their dependence. We believe that the prevalence of buprenorphine misuse could be reduced by adopting appropriate clinical practices and treating patients with the buprenorphine/naloxone combination rather than buprenorphine alone.

Topics: Administration, Sublingual; Adolescent; Adult; Age Factors; Analgesics, Opioid; Behavior, Addictive; Buprenorphine; Female; Health Care Surveys; Humans; Injections, Intravenous; Italy; Male; Methadone; Middle Aged; Motivation; Opioid-Related Disorders; Perception; Prevalence; Risk Factors; Substance Abuse Treatment Centers; Substance Abuse, Intravenous; Substance Withdrawal Syndrome; Surveys and Questionnaires; Young Adult

Pharmacological therapy has an important place in the management of opioid dependence. Methadone has been the mainstay of therapy but has a number of limitations. Buprenorphine monotherapy is another option, but misuse and diversion can have negative consequences. The opioid receptor antagonist, naloxone, has been added to buprenorphine to create a combination product with a reduced potential for misuse and diversion. This study evaluated the use of buprenorphine/naloxone for 24 weeks as a pharmacological management of opioid-dependent patients after therapeutic switch from buprenorphine alone. Patients (n = 43) received sublingual tablets of buprenorphine/naloxone. The buprenorphine dose was 2-24 mg (mean 16). Patients saw a physician, including an interview using a structured data sheet, and had counselling each week. Assessments were performed at week 2 (period 1), week 6 (period 2), week 16 (period 3) and week 24 (period 4). Laboratory immunoenzymatic testing was performed weekly to detect drugs in the urine. The management of withdrawal symptoms was rated as 'satisfactory' by 67% of patients during period 1 and 91% during period 4. The majority of patients was highly satisfied with therapy and considered that buprenorphine/naloxone provided good control of cravings. Two patients dropped out of therapy, but all others continued to receive buprenorphine throughout the study. Approximately 50% of patients stated that they disliked the sensory properties (taste, colour, odour and feel) of buprenorphine/naloxone. Adverse effects were as would be expected on the basis of the mechanism of action of buprenorphine (i.e. opioid-induced constipation) and for patients undergoing drug withdrawal. Only 2% of patients attempted the intravenous misuse of buprenorphine/naloxone, none of whom experienced any gratifying effects. Opioid-dependent patients maintained on buprenorphine monotherapy can be safely switched to a sublingual buprenorphine/naloxone tablet without any loss of treatment effectiveness. Buprenorphine/naloxone can be administered in an outpatient or primary care setting, and effectively controls cravings and withdrawal symptoms. Patient satisfaction was high, making retention in treatment more likely.

Topics: Administration, Sublingual; Adult; Analgesics, Opioid; Behavior, Addictive; Buprenorphine; Counseling; Drug Combinations; Female; Humans; Italy; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Patient Satisfaction; Substance Abuse Detection; Substance Abuse Treatment Centers; Substance Abuse, Intravenous; Substance Withdrawal Syndrome; Taste; Time Factors; Treatment Outcome; Young Adult

Opioid dependence is a growing problem. Methadone is an established agent for the treatment of opioid dependence, but there is a risk of this agent being abused, a potential for interaction with antiretroviral agents and a risk of cardiac toxicity. Another option is the partial mu-opioid receptor opioid agonist buprenorphine, which has been used successfully to manage opioid dependence. While the risk of abuse is lower than that for methadone, there is still a risk. The sublingual combination formulation of buprenorphine and the opioid receptor antagonist naloxone (buprenorphine/naxolone) is a newer agent with reduced abuse potential, and has been shown to have promising efficacy for opioid dependence. We describe the results of an observational study investigating the safety and efficacy of buprenorphine/naloxone in opioid-dependent patients. A total of 77 patients were included and were switched from buprenorphine to sublingual tables of buprenorphine/naloxone; the buprenorphine dosage was titrated to achieve good control of withdrawal symptoms. The prevalence of withdrawal symptoms, craving, constipation, cramps, insomnia, sexual activity, depression, sweating, distress, bone/joint pain and drowsiness were compared over the first 30 days of treatment (period 1) and the total 120-day study duration (period 2). The average buprenorphine/naloxone dose in period 1 was 7.3 mg/day and 12.7 mg/day in period 2. Most patients did not experience any withdrawal symptoms in either period 1 or period 2. Fewer than 20% of patients experienced any cravings over the 120-day study period. Importantly, the adverse effects observed were usually mild, with very few patients experiencing significant adverse effects. This study shows that buprenorphine/naloxone is an effective and well tolerated treatment for opioid withdrawal when the dosage is titrated to achieve good control of withdrawal symptoms. Switching from buprenorphine alone to buprenorphine/naloxone was possible with very little discomfort for the patient and effective retained patients in treatment.

Topics: Administration, Sublingual; Adult; Analgesics, Opioid; Behavior, Addictive; Buprenorphine; Drug Combinations; Female; Humans; Injections, Intravenous; Italy; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Substance Abuse Detection; Substance Abuse Treatment Centers; Substance Abuse, Intravenous; Substance Withdrawal Syndrome; Time Factors; Treatment Outcome; Young Adult

Abuse and misuse of pharmacological therapies represent major challenges in the healthcare system, particularly in patients receiving long-acting opioid drugs for the treatment of heroin or opioid addiction. The partial mu-opioid receptor agonist buprenorphine is used to treat opioid dependence, but diversion and misuse may occur. The sublingual combination formulation of buprenorphine and the opioid receptor antagonist naloxone (buprenorphine/naxolone) is associated with a reduced abuse potential, and has been shown to have promising efficacy for the treatment of opioid dependence. This observational study assessed the safety and efficacy of sublingual buprenorphine/naloxone combination therapy in patients with opioid dependence after therapeutic switch from buprenorphine monotherapy. A total of 94 patients being treated with buprenorphine monotherapy (average dose 8 mg/day; mean duration of therapy 840 days) were switched to buprenorphine/naloxone combination therapy. Patients were asked to rate their level of satisfaction with buprenorphine/naloxone combination treatment with respect to the management of withdrawal symptoms, and urinary toxicology tests were carried out before and 14 days after switching to combination therapy. Within 3 months, 75/94 patients (80%) previously treated with buprenorphine monotherapy had switched to sublingual buprenorphine/naloxone combination treatment (average dose buprenorphine 8 mg). Among patients receiving combination treatment for >3 months, 83% were receiving medication either weekly or fortnightly, based on the results of toxicological testing. A reduction in positive urinary toxicology tests was observed in patients within two weeks after being switched to combination treatment (before switch: 28, 9 and 2 positive tests for heroin, cocaine and heroin + cocaine, respectively vs 11, 3 and 1 after switch) and a total of 64 patients of the 75 who switched to combination therapy (85%) were satisfied with the management of withdrawal symptoms during buprenorphine/naloxone treatment. Few adverse events were reported and no patients dropped out of treatment. This study shows that switching from buprenorphine monotherapy to sublingual buprenorphine/naloxone combination therapy is effective and well tolerated, and associated with good control of withdrawal symptoms in the majority of patients. In addition, combination therapy reduced illicit drug use (based on negative urinary toxicology texts) and allowed the time betwe

Topics: Administration, Sublingual; Analgesics, Opioid; Behavior, Addictive; Buprenorphine; Drug Combinations; Female; Humans; Injections, Intravenous; Italy; Male; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Patient Satisfaction; Substance Abuse Detection; Substance Abuse Treatment Centers; Substance Abuse, Intravenous; Substance Withdrawal Syndrome; Time Factors; Treatment Outcome

Buprenorphine/naloxone is a new option for the management of opioid dependence. It has a reduced potential for abuse or misuse compared with methadone and buprenorphine alone, and has a long half-life allowing less frequent dosing. Buprenorphine/naloxone appears to be well suited for the management of opioid dependence in an office-based setting. The aim of this study was to evaluate the efficacy and safety of a buprenorphine/naloxone combination treatment in an office-based setting. Therefore, we evaluated the effect on misuse/diversion, quality of care, quality of life and service delivery. Seventy-eight patients were switched to buprenorphine/naloxone from either methadone or buprenorphine alone; the median duration of previous buprenorphine or methadone treatment was 10 years. Patients received buprenorphine/naloxone and were evaluated throughout a 1-year follow-up period. Treatment was self-administered by the patients every 2 weeks and the mean buprenorphine dosage at 1 year was 8 mg/day. Comparisons were made before and after the switch for patients who switched from buprenorphine alone to buprenorphine/naloxone. Switching to buprenorphine/naloxone was not associated with clinically relevant problems in 50% of patients studied. Buprenorphine/naloxone provided satisfactory coverage of withdrawal symptoms in 78.1% of patients, and 50% of patients were satisfied with buprenorphine/naloxone therapy. Seventy-eight per cent of patients reported improved psychosocial functioning. The majority of patients (approximately 85%) were negative for opioids during toxicological testing. A significantly higher proportion of treatment recipients were highly satisfied during buprenorphine/naloxone administration (p < 0.001 compared with buprenorphine given before the switch). Other outcomes were similar during buprenorphine and buprenorphine/naloxone administration. Fortnightly self-administration of buprenorphine/naloxone appeared to be cost saving for the clinic. Buprenorphine/naloxone is an effective and safe treatment option for the outpatient management of opioid dependence.

Topics: Administration, Sublingual; Analgesics, Opioid; Behavior, Addictive; Buprenorphine; Cost-Benefit Analysis; Counseling; Delivery of Health Care; Drug Administration Schedule; Drug Combinations; Drug Costs; Female; Humans; Injections, Intravenous; Italy; Male; Naloxone; Narcotic Antagonists; Office Visits; Opioid-Related Disorders; Patient Satisfaction; Quality of Health Care; Substance Abuse Detection; Substance Abuse, Intravenous; Substance Withdrawal Syndrome; Time Factors; Treatment Outcome

Some studies report differences in opioid withdrawal between racial/ethnic groups. However, it is not known if these differences are reflected in differential treatment response. Data from National Institute on Drug Abuse (NIDA) Clinical Trials Network-003 were used to examine racial/ethnic differences before and during stabilization with buprenorphine. At induction, non-Hispanic Caucasians had higher objective and subjective withdrawal scores and greater opioid craving than minority participants. No significant between-group differences were observed on these scales following buprenorphine. Non-Hispanic Caucasians and Hispanics reported more adverse events than African Americans. Although ethnic and racial differences were observed prior to buprenorphine treatment, scores following buprenorphine treatment were similar between groups.

Topics: Adult; Black or African American; Buprenorphine; Female; Hispanic or Latino; Humans; Male; Middle Aged; Narcotic Antagonists; National Institute on Drug Abuse (U.S.); Opioid-Related Disorders; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome; United States; White People; Young Adult

Topics: Buprenorphine; Drug Combinations; Drug Overdose; Humans; Methadone; Motivation; Naloxone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Recurrence; South Africa; Substance Withdrawal Syndrome

Despite data supporting its efficacy, barriers to implementation of buprenorphine for office-based treatment are present. Complications can occur during buprenorphine inductions, yet few published studies have examined this phase of treatment. To examine factors associated with complications during buprenorphine induction, we conducted a retrospective chart review of the first 107 patients receiving buprenorphine treatment in an urban community health center. The primary outcome, defined as complicated induction (precipitated or protracted withdrawal), was observed in 18 (16.8%) patients. Complicated inductions were associated with poorer treatment retention (than routine inductions) and decreased over time. Factors independently associated with complicated inductions included recent use of prescribed methadone, recent benzodiazepine use, no prior experience with buprenorphine, and a low initial dose of buprenorphine/naloxone. Findings from this study and further investigation of patient characteristics and treatment characteristics associated with complicated inductions can help guide buprenorphine treatment strategies.

Topics: Adult; Benzodiazepines; Buprenorphine; Community Health Centers; Dose-Response Relationship, Drug; Female; Humans; Male; Methadone; Middle Aged; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Retrospective Studies; Substance Withdrawal Syndrome; Time Factors; Treatment Outcome; Urban Health Services

The aim of the study was to investigate the relationship between methadone and buprenorphine treatment and self-reported symptoms in HIV-infected opioid dependent individuals receiving antiretroviral therapy (ART).. Longitudinal study.. The French MANIF2000 cohort was used to compare self-reported symptoms in buprenorphine and methadone patients also receiving ART.. We selected individuals receiving ART and OAT (342 visits among 106 patients).. Symptoms were self-reported using a list of 14 symptoms (e.g. nausea, fatigue, fever) perceived during the previous 4 weeks, including three painful symptoms (abdominal or muscular pain, headaches). A two-step Heckman approach enabled us to account for the non-random assignment of OAT: a probit model identified predictors of starting either buprenorphine or methadone. A Poisson regression based on generalized estimating equations (GEE) was then used to identify predictors of the number of symptoms while adjusting for the non-random assignment of OAT.. The median (interquartile range) number of symptoms was 4 (1-6) and 2 (1-6) among buprenorphine and methadone patients, respectively. After adjustment for non-random assignment of OAT type, depressive and opioid withdrawal symptoms, anxiolytics consumption and daily cannabis use, methadone patients were more likely to report a lower number of symptoms than those receiving buprenorphine.. Methadone patients on ART report fewer symptoms than buprenorphine patients on ART under current treatment conditions in France. Further experimental research is still needed to identify an OAT-ART strategy which would minimize the burden of self-reported symptoms and potential interactions, while assuring sustainability and response to both treatments.

Topics: Anti-Retroviral Agents; Attitude to Health; Buprenorphine; Cohort Studies; Depression; Female; France; Health Services Accessibility; HIV Infections; Humans; Longitudinal Studies; Male; Medication Adherence; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pain; Self Report; Substance Abuse, Intravenous; Substance Withdrawal Syndrome; Treatment Outcome

Methadone and buprenorphine are both efficacious treatments for opioid dependency, but they also have different pharmacological properties and clinical delivery methods that can affect their acceptability to patients. This study was intended to increase our knowledge of heroin-dependent individuals' perceptions of methadone vs. buprenorphine maintenance based on actual experiences with each. The study sample consists of heroin-dependent men at the Rikers Island jail in New York City who were voluntarily randomly assigned to methadone or buprenorphine maintenance in jail. Methadone patients were more likely to report feeling uncomfortable the first few days, having side/withdrawal effects during treatment, and being concerned about continued dependency on medication after release. In contrast, buprenorphine patients' main issue was the bitter taste. All of the buprenorphine patients stated that they would recommend the medication to others, with almost all preferring it to methadone. Ninety-three percent of buprenorphine vs. 44% of methadone patients intended to enroll in those respective treatments after release, with an added one-quarter of the methadone patients intending to enroll in buprenorphine instead. These results reinforce the importance of increasing access to buprenorphine treatment in the community for indigent heroin-dependent offenders.

Topics: Adult; Buprenorphine; Heroin Dependence; Humans; Male; Methadone; Narcotics; New York City; Opiate Substitution Treatment; Patient Preference; Prisoners; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome; Taste

Topics: Adult; Analgesics, Opioid; Aorta; Blood Pressure; Buprenorphine; Female; Hemodynamics; Heroin; Heroin Dependence; Humans; Substance Withdrawal Syndrome

Topics: Buprenorphine; Humans; Methadone; Narcotics; Opioid-Related Disorders; Social Support; Substance Withdrawal Syndrome

Despite evidence supporting the efficacy of buprenorphine relative to established detoxification agents such as clonidine, little research has examined: 1) how best to implement buprenorphine detoxification in outpatient settings; and 2) whether extending the length of buprenorphine detoxification improves treatment engagement and outcomes.. The current study examined the impact on 1) successful detoxification completion; 2) transition to longer-term treatment; and 3) treatment engagement of two different length opioid detoxifications using buprenorphine.. The study compared data obtained from two consecutive studies of early treatment engagement strategies. In one study (n = 364), opioid-addicted participants entered treatment through a Brief (5-day) buprenorphine detoxification. In the other study (n = 146), participants entered treatment through an Extended (i.e., 30-day) buprenorphine detoxification.. Results indicated a greater likelihood of successful completion and of transition among participants who received the Extended as compared to the Brief detoxification. Extended detoxification participants attended more counseling sessions and submitted fewer drug-positive urine specimens during the first 30 days of treatment, inclusive of detoxification, than did Brief detoxification participants.. Results demonstrate that longer periods of detoxification improve participant engagement in treatment and early treatment outcomes.. Current findings demonstrate the feasibility of implementing an extended buprenorphine detoxification within a community-based treatment clinic.

Topics: Adult; Buprenorphine; Clinical Trials as Topic; Counseling; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Substance Abuse Detection; Substance Abuse Treatment Centers; Substance Withdrawal Syndrome; Time Factors; Treatment Outcome

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

Topics: Analgesics, Opioid; Buprenorphine; Child, Preschool; Critical Care; Emergency Medicine; Female; Humans; Methadone; Substance Abuse Detection; Substance Withdrawal Syndrome

In the Netherlands, the policy on care for prisoners who are addicted to opiates is still heterogeneous. The recent guidelines entitled 'Medicinal care for drug addicts in penal institutions' should contribute towards unambiguous and more evidence-based treatment for this group. In addition, it should improve and bring the care pathways within judicial institutions and mainstream healthcare more into line with one another. Each rational course of medicinal treatment will initially be continued in the penal institution. In penal institutions the help on offer is mainly focused on abstinence from illegal drugs while at the same time limiting the damage caused to the health of the individual user. Methadone is regarded at the first choice for maintenance therapy. For patient safety, this is best given in liquid form in sealed cups of 5 mg/ml once daily in the morning. Recently a combination preparation containing buprenorphine and naloxone - a complete opiate antagonist - has become available. On discontinuation of opiate maintenance treatment intensive follow-up care is necessary. During this period there is considerable risk of a potentially lethal overdose. Detoxification should be coupled with psychosocial or medicinal intervention aimed at preventing relapse. Naltrexone is currently the only available opiate antagonist for preventing relapse. In those addicted to opiates, who also take benzodiazepines without any indication, it is strongly recommended that these be reduced and discontinued. This can be achieved by converting the regular dosage into the equivalent in diazepam and then reducing this dosage by a maximum of 25% a week.

Topics: Analgesics, Opioid; Buprenorphine; Dose-Response Relationship, Drug; Humans; Methadone; Naloxone; Netherlands; Practice Patterns, Physicians'; Prisoners; Substance Withdrawal Syndrome; Substance-Related Disorders

Maternal drug addiction can cause problems for the fetus and the newborn, and hamper long-term development. The prevalence of drug addiction during pregnancy varies from 1 % to more than 10 % depending on the country and the maternity unit. Management of these mothers can be further complicated by medical, social and psychological problems. Compared to methadone, heroin replacement therapy with buprenorphine provides better stabilization of the mother and causes fewer withdrawal symptoms in the newborn. Despite numerous publications on the effects of this partly preventive medication, data on buprenorphine pharmacology at birth are scarce. In this study, 20 newborns of mothers using oral buprenorphine were observed until the end of the withdrawal syndrome, when present. Buprenorphine plasma levels were determined with HPLC and mass spectrometry in the mother at delivery and in the newborn at birth (cord blood), 24 and 48 hours. Fifteen newborns were born at term (mean +/- SD birth weight 3029 +/- 273 g), and the other five between 32 and 36 weeks. All Apgar scores were > or =7. Withdrawal symptoms were observed in 8 of the 15 infants born to mothers taking buprenorphine alone, and lasted between 5 and 35 days. The newborns were classified in three groups. Groups I (N8) and II (N7) comprised newborns with and without withdrawal symptoms, respectively. In group III (N5), the mothers were polyintoxicated (as shown by urinary drug or neurotropic substance screening) and the newborns were symptomatic for 1 to 69 days. Buprenorphine plasma levels in the mothers ranged from 0 to 2.9 microg/L, suggesting large differences in adherence. At birth there was no significant difference in the mean plasma buprenorphine level between newborns with and without withdrawal symptoms; the respective values were 0.7 (0.4-1.3) and 0.5 (0-0.6) microg/L. In asymptomatic newborns (group II), buprenorphine was no longer detectable at 48 h, whereas in symptomatic newborns (group I), the mean level rose from 0.7 microg/l at birth to 1.5 microg/L at 48 h (+114 %). In the absence of breastfeeding, this increase appears to be related to tissue release of this strongly lipophilic compound. The difference in plasma buprenorphine kinetics between groups I and II might be explained by genetic polymorphism of drug-metabolizing enzymes. The paradoxically high plasma buprenorphine levels at 48 hours in infants with withdrawal symptoms are intriguing. One possibility is that the mothers missed

Topics: Buprenorphine; Female; Heroin Dependence; Humans; Infant, Newborn; Male; Narcotics; Pregnancy; Pregnancy Complications; Substance Withdrawal Syndrome; Young Adult

The use of heroin, cocaine, and other drugs is well researched in New York City, but prescription opioids (POs) have been overlooked. This study documents patterns of PO use, misuse, and diversion among street drug users, and begins to indicate how drug culture practices interact with the legitimate therapeutic goals of PO prescriptions (e.g. pain management).. Staff completed interviews inquiring about the reasons for use of POs and illicit drugs with 586 street drug users. Ethnographers wrote extensive field notes about subjects' complex patterns of PO use.. Methadone was used (71.9%) and sold (64.7%) at a higher level than OxyContin, Vicodin, and Percocet, used by between 34% and 38% of the users and sold by between 28% and 41% of the sellers. Recent PO use is associated with the recency of using heroin and cocaine (p<.001). Half of the heroin/cocaine sellers sold POs, and one quarter of the PO sellers only sold POs. Subjects were classified into four groups by whether they diverted POs or used POs to relieve pain or withdrawal rather than for euphoria. This classification was associated with frequency of PO use, whether POs were obtained from doctors/pharmacies or from drug dealers and family members, and those mostly likely to use POs for pain and withdrawal.. POs are an important component of street drug users' drug-taking regimes, especially those who are Physically Ill Chemical Abusers (PICA). Future research is needed to model PO use, misuse, and diversion among this population.

Topics: Administration, Intranasal; Adult; Aged; Analgesics, Opioid; Buprenorphine; Cocaine-Related Disorders; Drug Prescriptions; Ethnicity; Female; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Narcotic Antagonists; Narcotics; New York City; Pain; Patient Selection; Socioeconomic Factors; Substance Abuse, Intravenous; Substance Withdrawal Syndrome; Substance-Related Disorders

Opioid dependence is a complex medical condition affecting neurocognitive and physical functioning. Forced or abrupt opioid withdrawal may cause profound physical and psychological suffering, including nausea, vomiting, diarrhoea, extreme agitation and/or anxiety. Opioid-dependent individuals are especially vulnerable at the time of arrest or initial detention, when they may, as a result of their chemical dependency, be coerced into providing incriminating testimony, or be driven to engage in risky behaviour (such as sharing needles in detention) in order to avoid painful withdrawal symptoms. Upon incarceration, many opioid-dependent prisoners are forced to undergo abrupt opioid withdrawal (both from legally prescribed agonist therapy such as methadone as well as illicit opioids). Physical and psychological symptoms attendant to withdrawal may impair capacity to make informed legal decisions, and cause prisoners to risk HIV and other blood-borne diseases by sharing injection equipment. Although prisons must provide at least the standard of care to prisoners that is available in the general population, medication-assisted treatment, endorsed by international health and drug agencies as an integral part of HIV prevention and care strategies for opioid-dependent drug users, is unavailable to most prisoners. Medication-assisted treatment is a well-studied and validated pharmacological therapy for the medical condition known as opioid dependence. The failure to ensure prisoner access to this medical therapy threatens fundamental human rights protections against cruel, inhuman or degrading treatment and rights to health and to life. It also poses serious ethical problems for health care providers, violating basic principles of beneficence and non-maleficence (i.e., do good/do no harm). Governments must take immediate action to ensure access to opioid substitution to prisoners to ensure fulfilment of ethical and human rights obligations.

Topics: Buprenorphine; Health Services Accessibility; Human Rights; Humans; Methadone; Narcotics; Opioid-Related Disorders; Prisoners; Prisons; Substance Withdrawal Syndrome

Topics: Adult; Analgesics, Opioid; Buprenorphine; Humans; Male; Opioid-Related Disorders; Psychoses, Substance-Induced; Psychotic Disorders; Substance Withdrawal Syndrome

Morphine and buprenorphine have analgesic and anxiolytic-like properties. While their analgesic effects have been well characterized, their anxiolytic-like properties have not.. Effects of acute morphine and buprenorphine on the expression of acoustic fear-potentiated startle (FPS) and naloxone pretreatment were assessed. Effects of chronic morphine and buprenorphine on tolerance, cross-tolerance, and withdrawal were also examined.. Fear-conditioned rats were given subcutaneous drug treatment immediately before testing for FPS. Experiment 1, rats were administered morphine (0.03, 0.25, 0.63, 2.5, or 10 mg/kg) or buprenorphine (0.004, 0.0075, 0.015, 0.03, or 0.25 mg/kg). Experiment 2, rats were given saline or naloxone (0.5 mg/kg) and 5 min later given saline, morphine (2.5 mg/kg), or buprenorphine (0.03 mg/kg). Experiment 3, rats received once-daily injections of saline, morphine (10 mg/kg), or buprenorphine (0.25 mg/kg) for 7 days. Immediately before testing, saline-treated rats were given saline, morphine (2.5 mg/kg), or buprenorphine (0.03 mg/kg), morphine-treated rats were given morphine (2.5 mg/kg) or buprenorphine (0.03 mg/kg), and buprenorphine-treated rats were given buprenorphine (0.03 mg/kg) or morphine (2.5 mg/kg). Tolerance and cross-tolerance in analgesia were assessed via the tail-flick test, as were naloxone-precipitated withdrawal.. Morphine and buprenorphine had parallel dose-response curves in blocking FPS, with buprenorphine 40 times more potent than morphine. Naloxone reversed these effects. Morphine and buprenorphine showed tolerance and cross-tolerance in their anxiolytic-like and analgesic effects. Chronic buprenorphine produced less withdrawal than chronic morphine.. Cross-tolerance between morphine and buprenorphine suggests a common receptor mediating their anxiolytic-like and analgesic effects.

Topics: Animals; Anti-Anxiety Agents; Buprenorphine; Conditioning, Operant; Dose-Response Relationship, Drug; Drug Tolerance; Fear; Male; Morphine; Naloxone; Narcotic Antagonists; Narcotics; Pain Measurement; Rats; Rats, Sprague-Dawley; Reflex, Startle; Substance Withdrawal Syndrome

Managed withdrawal (i.e., detoxification) from opioid dependence is a widespread clinical procedure that is a necessary step for those pursuing abstinence. Buprenorphine is one effective detoxification treatment, however, consensus regarding effective detoxification procedures is lacking.. This study evaluated the efficacy of a buprenorphine transdermal formulation (i.e., patch) in suppressing opioid withdrawal, its safety and tolerability, and its biodelivery when applied for 7 days.. Physically dependent opioid (heroin) users (n = 12) completed a 10-day opioid detoxification in a residential research unit. Each received a single patch application that remained in place for 7 days. Blood samples were drawn prior to patch application and once daily thereafter. Assessments, four times daily, included: the amount of rescue medications ordered to treat withdrawal discomfort; self-report and observer ratings of opioid withdrawal and agonist effects; and vital sign measures.. Overall, the patch appeared safe and well-tolerated. Buprenorphine plasma levels peaked 48 h after patch application at 0.59 ng/ml. Indices of withdrawal (self-reports, observer ratings, rescue medication) were significantly reduced within 24 h of patch application, continued to decline thereafter, and did not reappear following patch removal.. This study confirms that transdermal buprenorphine is safe and clinically effective, and suggests that a 7-day application may provide an effective and comfortable means of detoxification. This patch formulation would appear to be a useful opioid detoxification treatment by reducing compliance concerns, and administering buprenorphine in a formulation less likely to be diverted to illicit use.

Topics: Administration, Cutaneous; Adult; Area Under Curve; Buprenorphine; Chemistry, Pharmaceutical; Female; Humans; Hydromorphone; Male; Middle Aged; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Substance Withdrawal Syndrome

Despite the widespread medical use of glucocorticoids, reports of factitious administration of these hormones have been uncommon. We herein report an outbreak of Cushing's syndrome in Tehran among the addicts using Tamgesic (a brand of Buprenorphine) to help them through the narcotic withdrawal stage, without knowledge of the glucocorticoid content of the black-market drug.. Case histories of 19 patients with a final diagnosis of iatrogenic Cushing's syndrome were reviewed. Liquid chromatography/mass spectrometry (LC-Mass) method was used to evaluate glucocorticoid existence in the brand. High performance liquid chromatography was used to determine plasma dexamethasone level.. No buprenorphine was present in the vials. Each Tamgesic vial contained 0.4 mg of Dexamethasone disodium phosphate; Heroin was also found in them. The duration of injection abuse and the total dexamethasone intake was 4.5 (1-18) months and 2.6 (0.8-8) mg/day, respectively. Median plasma dexamethasone concentration was 5.8 nmol/l, with a range of 5-8.7. Physical findings of the cases were not different from those of the classic endogenous Cushing's syndrome but their serum cortisol and urinary free cortisol were suppressed. Severe life-threatening complications were demonstrated in five cases.. Surreptitious use of steroids resulting in Cushing's syndrome may be more common in opium addicts; a high degree of suspicion is needed to uncover this disorder. Whenever facing a cushingoid appearance in addicts, the possibility of using black market drugs with corticosteroid contents should be kept in mind.

Topics: Adult; Buprenorphine; Cushing Syndrome; Dexamethasone; Drug Contamination; Humans; Hydrocortisone; Iatrogenic Disease; Male; Middle Aged; Opioid-Related Disorders; Opium; Substance Withdrawal Syndrome

To examine the use of buprenorphine for the treatment of opioid withdrawal (OW) in an emergency department (ED) setting.. The medical records of all adult patients who presented to the study ED during a 10 week period for OW were abstracted. Subjects were categorized as receiving buprenorphine, symptomatic treatment or no pharmacologic treatment for their OW. The three groups were compared by patient and service characteristics, withdrawal symptoms and outcomes.. Of the 11,019 patients who presented to the ED during the 10 week study period, 158 (1.4%) were eligible. Subjects were more likely to receive buprenorphine (56%) compared to symptomatic treatment only (26%) or no pharmacologic treatment (18%). Subjects who received buprenorphine were more likely to have a history of suicide ideation (34% versus 12% p<0.05) compared to subjects who received symptomatic treatment(s) and were less likely to present with a gastrointestinal complaint (9% versus 25% p<0.05). Subjects who received buprenorphine were less likely to return to the same ED within 30 days for a drug-related visit (8%) compared to those who received symptomatic treatment (17%) (p<0.05).. Buprenorphine was a common treatment for OW in this ED without any documented adverse outcomes. Given that it did not result in an increase in drug-related return ED visits and its proven efficacy in other settings, a prospective evaluation of its potential value to ED patients who present with OW is warranted.

Topics: Academic Medical Centers; Baltimore; Buprenorphine; Emergency Service, Hospital; Humans; Narcotic Antagonists; Opioid-Related Disorders; Substance Withdrawal Syndrome; Urban Population

Fentanyl is a potent mu-opioid receptor agonist that is widely used for the treatment of severe chronic pain. Discontinuation of fentanyl administration has been shown to induce a negative emotional state.. The aim of the present studies was to investigate the effects of the partial mu-opioid receptor agonist buprenorphine on the negative emotional state associated with precipitated and spontaneous fentanyl withdrawal in rats.. Fentanyl and saline were chronically administered via osmotic minipumps. A discrete-trial intracranial self-stimulation procedure was used to provide a measure of brain reward function. Somatic signs were recorded from a checklist of opioid abstinence signs.. Naloxone induced a deficit in brain reward function in rats chronically treated with fentanyl. Buprenorphine dose-dependently prevented the naloxone-induced deficit in brain reward function. Discontinuation of fentanyl administration was also associated with a deficit in brain reward function. After explantation of the minipumps, the administration of buprenorphine induced a potentiation of brain reward function in the fentanyl-withdrawing rats, but did not affect brain reward function of saline-treated control rats. Buprenorphine prevented the somatic withdrawal signs associated with spontaneous fentanyl withdrawal and attenuated the somatic signs associated with precipitated fentanyl withdrawal.. Buprenorphine prevents affective and somatic fentanyl withdrawal signs. Moreover, buprenorphine is rewarding in rats previously exposed to fentanyl, but not in opioid-naïve rats. This pattern of results suggests that buprenorphine may be an effective treatment for the anhedonic-state associated with fentanyl withdrawal, but further study of buprenorphine's abuse potential is warranted.

Topics: Analgesics, Opioid; Animals; Behavior, Animal; Buprenorphine; Disease Models, Animal; Dose-Response Relationship, Drug; Emotions; Fentanyl; Male; Naloxone; Narcotic Antagonists; Narcotics; Rats; Rats, Wistar; Receptors, Opioid, mu; Reward; Substance Withdrawal Syndrome; Time Factors

For opioid-dependent patients, the need for detoxification has been a barrier to entry into long-term residential treatment. This report describes a retrospective observational cohort study with the first 38 opioid-dependent patients entering First Step, a 14-day buprenorphine-naloxone (Suboxone) detoxification regimen integrated into a long-term residential therapeutic community (TC) program. Eighty-nine percent (34 of 38) of First Step patients completed a 14-day buprenorphine taper protocol, 50% (19 of 38) completed an initial 3- to 4-week stay, and 39% (15 of 38) completed at least 3 months of residential treatment at the TC. Retention did not differ significantly in a demographically matched concurrently admitted control group without impending opioid withdrawal, in which 65% (24 of 37) completed an initial 3- to 4-week stay (p = .20) and 57% (21 of 37) completed at least 3 months of treatment (p = .14). Withdrawal symptoms were mild, and there were no instances of precipitated withdrawal. The findings suggest the potential for buprenorphine to serve as a bridge, improving the viability of long-term residential treatment for managing opioid dependence.

Topics: Adult; Alcoholism; Buprenorphine; Clinical Trials as Topic; Cocaine-Related Disorders; Female; Heroin Dependence; Humans; Long-Term Care; Male; Middle Aged; Naloxone; Narcotic Antagonists; Narcotics; Neurologic Examination; New York City; Opioid-Related Disorders; Patient Dropouts; Residential Treatment; Retrospective Studies; Substance Withdrawal Syndrome; Therapeutic Community

Buprenorphine has been approved for heroin detoxification, but little is known about its impact on everyday practice. Concerns about buprenorphine include expense, limited knowledge about its use, patient limits, and social and clinical attitudes regarding opioid treatment for heroin dependence. On the other hand, randomized clinical trials suggest that buprenorphine is superior to clonidine with regard to withdrawal symptom relief. In June 2004, a community-based residential medical detoxification center switched from clonidine to buprenorphine treatment for all new and returning heroin clients. This study is a retrospective chart review of subject outcomes with clonidine (n = 100) versus buprenorphine (n = 100). Bivariate analysis suggested few cohort differences in pretreatment demographics and client characteristics. In contrast, buprenorphine was significantly associated with increased length of stay and treatment completion. The positive associations between buprenorphine and both treatment completion and length of stay persisted and were slightly enhanced after regression analysis adjusted for potential confounders. Additionally, clinical staff reported better subject engagement in treatment and psychosocial group sessions. This single-site study is an example of successful integration of an evidence-based treatment into community-based practice.

Topics: Acute Disease; Adult; Buprenorphine; Clonidine; Diffusion of Innovation; Female; Heroin; Heroin Dependence; Humans; Length of Stay; Male; Middle Aged; Narcotics; Oregon; Patient Acceptance of Health Care; Retrospective Studies; Substance Withdrawal Syndrome; Treatment Outcome

Attitudes, perceived social norms, and intentions were assessed for 376 counselors and 1,083 clients from outpatient, methadone, and residential drug treatment programs regarding four medications used to treat opiate dependence: methadone, buprenorphine, clonidine, and ibogaine. Attitudes, social norms, and intentions to use varied by treatment modality. Methadone clients and counselors had more positive attitudes toward the use of methadone, whereas their counterparts in residential and outpatient settings had neutral or negative assessments. Across modalities, attitudes, perceived social norms, and intentions toward the use of buprenorphine were relatively neutral. Assessments of clonidine and ibogaine were negative for clients and counselors in all settings. Social normative influences were dominant across settings and medications in determining counselor and client intentions to use medications, suggesting that perceptions about beliefs of peers may play a critical role in use of medications to treat opiate dependence.

Topics: Adult; Ambulatory Care; Attitude of Health Personnel; Buprenorphine; Clonidine; Counseling; Culture; Female; Focus Groups; Heroin Dependence; Humans; Ibogaine; Male; Methadone; Middle Aged; Narcotics; Opioid-Related Disorders; Patient Admission; Patient Satisfaction; Peer Group; Psychotropic Drugs; Substance Withdrawal Syndrome; Treatment Outcome

Topics: Buprenorphine; Drug Prescriptions; Humans; Inactivation, Metabolic; Methadone; Naloxone; Narcotic Antagonists; Narcotics; Practice Guidelines as Topic; Prisons; Substance Withdrawal Syndrome

The U.S. Federal Food and Drug Administration approved buprenorphine for drug abuse treatment in 2002, and it became available for clinical use in early 2003. Maryhaven, a community treatment program, participated in a National Institute on Drug Abuse Clinical Trials Network trial evaluating buprenorphine-naloxone (BNX; Suboxone) short-term taper for medically managed opioid withdrawal and later adopted this treatment. In a retrospective review, the first 64 patients treated with a BNX taper were compared with two groups of patients treated with clonidine before and after the implementation of the BNX program. Significantly more patients (about 80%) receiving BNX continued in further treatment compared to about 30% of those receiving clonidine. Patient outcomes are discussed in the context of the critical need for treatment continuation following detoxification. Common questions of potential adopters of the BNX taper are presented and addressed. Overall, BNX was readily integrated into the existing treatment service.

Topics: Adult; Analgesics; Analgesics, Opioid; Analysis of Variance; Buprenorphine; Clonidine; Drug Administration Schedule; Female; Humans; Male; Ohio; Opioid-Related Disorders; Patient Acceptance of Health Care; Patient Dropouts; Retrospective Studies; Substance Withdrawal Syndrome

Buprenorphine and methadone are both effective for the control of the acute signs and symptoms of opiate withdrawal, but it is not known if there are differences between these two medications for other important clinical outcomes. This observational, non-randomized study evaluated completion rates of patients over a 13-month period when buprenorphine replaced methadone as the medication used for short-term inpatient opiate detoxification. Of the 644 patients in the study, the 303 treated with buprenorphine were more likely to complete detoxification than the 341 treated with methadone (89% vs. 78%; P < .001). Improvement in completion rates coincided with the introduction of buprenorphine. We conclude that as compared to methadone, buprenorphine is associated with greater rates of completion of inpatient detoxification.

Topics: Adolescent; Adult; Buprenorphine; Female; Follow-Up Studies; Hospitals, Teaching; Humans; Length of Stay; Male; Methadone; Middle Aged; Narcotics; New York; Opioid-Related Disorders; Patient Dropouts; Substance Abuse Treatment Centers; Substance Withdrawal Syndrome

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

Buprenorphine misuse by injecting drug users was assessed in a survey of 350 needle exchangers, either amphetamine (57%) or heroin users (42%). 89% of heroin users and 24% of amphetamine users reported using buprenorphine at some time during the previous year. Most users reported illicit acquisition. Among illicit users, 87% of heroin users reported intake for withdrawal treatment or self-detoxification, and 11% for euphoria. Euphoria seeking was more common among amphetamine users (62%, p < 0.001). Intravenous misuse was reported by 43% of illicit users, and snorting by 29%. Sole sublingual intake was more common among heroin users than among amphetamine users (46 vs. 20%, p < 0.05), and less common among patients reporting euphoria seeking (20 vs. 46%, p < 0.05).

Topics: Administration, Inhalation; Administration, Sublingual; Adult; Amphetamine-Related Disorders; Buprenorphine; Comorbidity; Cross-Sectional Studies; Euphoria; Female; Health Surveys; Heroin Dependence; Humans; Illicit Drugs; Male; Motivation; Needle-Exchange Programs; Opioid-Related Disorders; Substance Abuse, Intravenous; Substance Withdrawal Syndrome; Sweden

Risk-sensitive foraging theory refers to a group of different models that predict the occurrence of risk-prone behavior; therefore, these models may help to characterize the risky behavior that is a hallmark of opioid dependence. The daily energy budget (DEB) rule, one model of risk-sensitivity, suggests that foragers will prefer highly variable food sources over less variable ones when all current options provide means that are insufficient to meet metabolic requirements. The tenets of the DEB rule were tested in the context of opioid dependence, the primary hypothesis being that opioid withdrawal may foster risky choice. Intravenous and intranasal-using opioid-dependent patients enrolled in a buprenorphine treatment program read scripts simulating opioid-agonist and -antagonist symptoms, and then made a series of decisions between two different opioid dealers. One dealer provided a constant source of heroin, and the other, a variable source. Separate measures were utilized to expose participants to either variability in delay of opioids or quantity of opioids. Participants were also required to complete a money questionnaire in which two hypothetical slot machines differed in respect to payoff amounts and probabilities. Results demonstrate that preference for the risky option was mediated by hypothetical drug deprivation in all circumstances, but this effect was more considerable in opioid-dependent participants who used intravenously. The current findings suggest that intravenous delivery places greater metabolic constraints on the user and therefore engenders greater risk-taking during withdrawal. The DEB rule is applicable to opioid dependence and provides a useful framework from which to examine the behaviors associated with opioid withdrawal.

Topics: Administration, Intranasal; Adult; Buprenorphine; Choice Behavior; Female; Humans; Male; Narcotic Antagonists; Narcotics; Risk Factors; Substance Abuse, Intravenous; Substance Withdrawal Syndrome; Surveys and Questionnaires

The goal of the present study was to develop and validate an animal model of unlimited access to intravenous heroin self-administration combined with responding for food and water to characterize the transition to drug dependence. Male Wistar rats were allowed to lever press for heroin (60 microg/kg/0.1 ml infusion/s; fixed ratio 1; 20-s time out) and nosepoke for food and water in consecutive, daily 23-h sessions. Daily heroin intake increased over days, reaching significance by Day 14. Drug-taking increased across the circadian cycle, reflected as increases in both the nocturnal peak and diurnal nadir of heroin intake. Changes in the circadian pattern of food intake and meal patterning preceded and paralleled the changes in heroin intake. By Day 7, the circadian amplitude of feeding was blunted. Nocturnal intake decreased because rats consumed smaller and briefer meals. Diurnal intake increased due to increased meal frequency, whereas total daily food intake decreased. To control for time or experience in the self-administration boxes as a possible confound, rats with saline (no drug) tethers were tested and did not display significant changes in food intake pattern. Body weight gain slowed slightly in heroin rats relative to saline controls. Separate groups of rats revealed that significant physical dependence as measured by physical signs of opiate withdrawal following a naloxone injection (1.0 mg/kg, subcutaneous (s.c.)) was reached by Day 14. Significant increases in heroin intake could be produced using low doses of naloxone (0.003-0.03 mg/kg, s.c.) on days 28-31 of heroin access. After 6 weeks of heroin self-administration, rats injected with buprenorphine (0, 0.01, 0.04, and 0.2 mg/kg, s.c.) showed a dose-dependent reduction in heroin intake. Changes in the pattern of drug and food intake in the present unlimited heroin access model may serve as independent motivational markers for the transition to a drug-dependent state.

Topics: Analgesics, Opioid; Animals; Biomarkers; Body Weight; Brain; Buprenorphine; Circadian Rhythm; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Interactions; Eating; Feeding Behavior; Heroin; Injections, Intravenous; Male; Motivation; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Rats; Rats, Wistar; Self Administration; Substance Withdrawal Syndrome

Several medications are approved for treatment of opiate abuse, but determinants of their clinical effectiveness are not completely understood. States of opiate dependence or withdrawal may constitute one important set of determinants. To test this hypothesis, the effects of naloxone, buprenorphine, and methadone were assessed on choice between heroin and food in nondependent rhesus monkeys and in heroin-dependent monkeys undergoing withdrawal. A choice procedure was used to permit dissociation of medication effects on the relative reinforcing properties of heroin from nonselective effects on response rates. In nondependent monkeys, increasing unit doses of heroin (0-0.1 mg/kg/injection) maintained dose-dependent increases in heroin choice. Chronic 5-day treatment with naloxone (0.01-0.32 mg/kg/h) or buprenorphine (0.01-0.1 mg/kg/day) produced dose-dependent rightward shifts in heroin choice dose-effect curves, whereas chronic methadone (0.1-0.56 mg/kg/h) had little effect on heroin choice up to doses that suppressed responding. In heroin-dependent monkeys, opiate withdrawal produced overt abstinence signs as well as increases in heroin choice, manifested as leftward shifts in heroin choice dose-effect curves. The withdrawal-associated increases in heroin choice suggest that opiate withdrawal increased the relative reinforcing efficacy of heroin in comparison with food, an effect that may be related to relapse in humans. Methadone prevented withdrawal-associated increases in heroin choice, whereas buprenorphine was less effective. These findings suggest that agonist medications such as methadone may derive their clinical utility from their ability to attenuate withdrawal-associated increases in opiate reinforcement. Moreover, this procedure may be useful for exploring mechanisms underlying withdrawal-associated increases in opiate reinforcement and for testing candidate medications.

Topics: Animals; Buprenorphine; Disease Models, Animal; Feeding Behavior; Heroin; Heroin Dependence; Macaca mulatta; Male; Methadone; Naloxone; Self Administration; Substance Withdrawal Syndrome

Longitudinal studies have indicated that most opioid agonist-using patients are not able to successfully complete tapering attempts. Little is known, however, about tapering within a treatment environment that is supportive of indefinite agonist treatment and medication tapering. In this study, all records of patients beginning a slow methadone taper were reviewed (N = 30). No patient successfully completed methadone tapering. Four patients (13.3%) successfully switched to buprenorphine/naloxone, one of whom tapered off buprenorphine/naloxone. Three patients (10%) were continuing their taper at the study's end. One patient transferred to another program, one was administratively discharged, and one had his taper stopped for mishandling doses. The remaining patients (n = 20, 66.7%) stopped their tapers for the following reasons: feeling unstable/withdrawal symptoms (n = 4, 13.3%), drug use/positive urinalysis results (n = 12, 40%), psychiatric instability (n = 3, 10%), and pain management (n = 1, 3.3%). Only one patient prematurely left treatment secondary to a failed taper attempt. Patients attempting tapers should be informed about the difficulty involved and be monitored closely for signs of instability. For a few patients, a taper to a lower methadone dose and a switch to buprenorphine/naloxone are obtainable. Program policies that support both tapering attempts and indefinite maintenance are described in this article.

Topics: Adult; Buprenorphine; Drug Administration Schedule; Female; Heroin Dependence; Humans; Male; Mental Health Services; Methadone; Middle Aged; Naloxone; Narcotic Antagonists; Program Development; Substance Withdrawal Syndrome

Topics: Anesthesia, General; Buprenorphine; Clonidine; Drug Therapy, Combination; Heroin Dependence; Humans; Naltrexone; Narcotic Antagonists; Substance Withdrawal Syndrome

Topics: Anesthesia, General; Buprenorphine; Clonidine; Drug Therapy, Combination; Heroin Dependence; Humans; Naltrexone; Narcotic Antagonists; Substance Withdrawal Syndrome

Topics: Anesthesia, General; Buprenorphine; Clonidine; Humans; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Substance Withdrawal Syndrome

Topics: Anesthesia, General; Buprenorphine; Clonidine; Drug Therapy, Combination; Humans; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Substance Withdrawal Syndrome

A 2-year-old Japanese girl had transient left ventricular apical ballooning on echocardiography and ST-segment elevation and T-wave inversion on electrocardiogram after withdrawal of bupirenorphine and midazolam. The findings improved within 2 weeks. There are many case reports of adults with takotsubo cardiomyopathy but none in children. Takotsubo cardiomyopathy is not well known by pediatric cardiologists, so pediatric cases may have been overlooked. Awareness of a phenomenon similar to takotsubo cardiomyopathy, even in young children, may be important.

Topics: Age Factors; Analgesics, Opioid; Buprenorphine; Cardiomyopathies; Child, Preschool; Echocardiography; Electrocardiography; Female; Humans; Hypertrophy, Left Ventricular; Midazolam; Respiratory Insufficiency; Substance Withdrawal Syndrome; Ventricular Function, Left

The TaqI A polymorphism (A(1)) of the dopamine D(2) receptor gene (DRD2), although not a specific predictor of opioid dependence, has been strongly associated with high levels of prior heroin use and poor treatment outcomes among methadone maintenance patients. The aims of this study were to confirm these findings via a retrospective analysis of A(1) allele frequency in methadone (n = 46) and buprenorphine (n = 25) patients, and non-opioid-dependent controls (n = 95). Subjects were genotyped at the DRD2 TaqI A locus using PCR amplification followed by TaqI restriction enzyme digestion and gel electrophoresis. For methadone and buprenorphine subjects, heroin use (prior to treatment), treatment outcomes, and withdrawal occurrence were determined from comprehensive case notes. No significant differences in A(1) allele frequency (%) were observed between: methadone (19.6%), buprenorphine (18.0%), and control (17.9%) groups (P > 0.7); successful and poor treatment outcome groups, methadone: 20.0% and 19.2%, respectively (P = 1.0); buprenorphine: 18.4% and 20.0%, respectively (P = 1.0). Also, there were no significant relationships between TaqI A genotype and prior heroin use (P = 0.47). However, among the successful methadone subjects, significantly fewer A(1) allele carriers experienced withdrawal than non-A(1) carriers (P = 0.04). In conclusion, the DRD2 genotype effects did not affect opioid maintenance treatment outcomes. This suggests the need for a further prospective investigation into the role of the DRD2 A(1) allele in heroin use and response to maintenance pharmacotherapies for opioid dependence.

Topics: Adult; Alleles; Analgesics, Opioid; Buprenorphine; Deoxyribonucleases, Type II Site-Specific; Female; Gene Frequency; Genotype; Heroin Dependence; Humans; Male; Methadone; Receptors, Dopamine D2; Retrospective Studies; Substance Withdrawal Syndrome; Time Factors; Treatment Outcome

The approval in 2003 for the use of buprenorphine in opiate addiction treatment has provided physicians with a new pharmacological tool to combat opiate addiction. We surveyed a sample of 100 inpatients who completed short-term opiate detoxification treatment utilizing a combination of buprenorphine and clonidine to assess patient perspectives regarding the usefulness and tolerability of this medication regimen and to compare it to their past opiate detox experiences, if any. Patients identified pain (63%), sleep problems (57%), and anxiety (56%) as the symptoms they perceived to be most helped with buprenorphine. Over 90% of patients with past detoxification treatments rated buprenorphine treatment to be as good as or better than their past treatments. Reports of a euphoric effect were minimal (7%) and no patients reported any generalized worsening of their opiate withdrawal symptoms. We conclude that based upon patient perspectives that combining buprenorphine with clonidine is a useful and well-tolerated medication regimen for the treatment of opiate withdrawal.

Topics: Buprenorphine; Clonidine; Drug Combinations; Female; Humans; Inactivation, Metabolic; Male; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Patients; Substance Withdrawal Syndrome; Surveys and Questionnaires

The purpose of this study was the evaluation of clinical heroin symptoms and buprenorphine drug addiction in the withdrawal period with the purpose of their comparison, study of parameters of bone metabolism in the both groups. In the study group were included 40 patients with heroin and 27 with buprenorphine addiction in the period of abstinence. Our investigations have shown, that in the both groups, among clinical symptoms ossalgias, arthralgias and mialgias attributes to the expressed dysfunction of vegetative system, were most prominent. Decrease of sexual functions was found in half of inspected patients. Biochemical investigations have shown intensive clearance of calcium with the urine that indicates intensifying resorbtion processes in the bone tissue. Symptoms of hypogonadism were accompanied by the decrease of the level of testosterone in the blood. Parameters of mineral consistency of the bone tissue was decreased both in patients with heroin and buprenorphine addiction.

Topics: Behavioral Symptoms; Biomarkers; Bone and Bones; Bone Density; Buprenorphine; Female; Heroin; Heroin Dependence; Humans; Male; Morphine Dependence; Pain; Radiography; Substance Withdrawal Syndrome

Research indicates that persons addicted to opiates are likely to relapse following treatment or are at risk of terminating treatment early. The withdrawal experience may be one factor underlying early treatment discharge and several medications, including buprenorphine-naloxone, have been used to reduce withdrawal symptoms during detoxification. This retrospective study sought to determine whether patients who received buprenorphine-naloxone were retained in treatment longer than those who did not receive the medication. Data were collected on 170 patients admitted to the detoxification unit who either received (n = 85) or did not receive (n = 85) the medication. Differences in lengths of stay were found between the groups, thus warranting future research on the usefulness of buprenorphine-naloxone during detoxification and subsequent treatment. The importance of detoxification as an initial phase of treatment in relation to patient retention is discussed.

Topics: Adolescent; Adult; Analgesics, Opioid; Buprenorphine; Drug Administration Schedule; Female; Humans; Inactivation, Metabolic; Male; Mental Health Services; Middle Aged; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Patient Compliance; Substance Withdrawal Syndrome; Treatment Outcome

Previous studies indicate that buprenorphine has efficacy in medically supervised opioid withdrawal, but the optimal dosing for maximum tolerability and ease of administration remains undetermined. Five heroin-dependent individuals entered this open-label study of inpatient detoxification with a single 24 mg dose of buprenorphine. The mean Clinical Opiate Withdrawal Scale (COWS) score prior to buprenorphine administration was 17.6 (SD = 3.36). COWS scores declined significantly thereafter. There was one episode of precipitated withdrawal that resolved within four hours. Use of ancillary medications was minimal. This study suggests that a single high dose of buprenorphine can be used safely and effectively for inpatient detoxification.

Topics: Adult; Buprenorphine; Female; Heroin Dependence; Humans; Male; Pilot Projects; Substance Withdrawal Syndrome

Conditioned place aversion in rats has face validity as a measure of the aversive stimulus effects of opiate withdrawal that reflects an important motivational component of opiate dependence. The purpose of the present study was to validate conditioned place aversion as sensitive to medications that will alleviate the aversive stimulus effects of opiate withdrawal in humans, and to extend this model to the exploration of the neuropharmacological basis of the motivational effects of opiate withdrawal. Male Sprague-Dawley rats were implanted with two subcutaneous morphine pellets and 5 days later began place conditioning training following subcutaneous administration of a low dose of naloxone. Animals were subjected to three pairings of a low dose of naloxone (15 microg/kg, s.c.) to one arm of a three-chambered place conditioning apparatus. Buprenorphine administered prior to each pairing dose-dependently blocked the place aversion produced by precipitated opiate withdrawal. A corticotropin-releasing factor-1 (CRF1) receptor antagonist (antalarmin) also reversed the place aversion produced by precipitated opiate withdrawal. Antalarmin did not produce a place preference or place aversion by itself in morphine-dependent rats. No effect was observed with pretreatment of the dopamine partial agonist terguride or the selective serotonin reuptake inhibitor fluoxetine. Also, chronic pretreatment with acamprosate (a glutamate receptor modulator used to prevent relapse in alcohol dependence) did not alter naloxone-induced place aversion. Buprenorphine by itself in dependent rats produced a mild place preference at low doses and a mild place aversion at higher doses. These results suggest that buprenorphine blocks the aversive stimulus effects of precipitated opiate withdrawal in rats and provides some validity for the use of place conditioning as a measure that is sensitive to potential opiate-dependence medications. In addition, these results suggest that CRF1 antagonists can block the aversive stimulus effects of opiate withdrawal and may be potential therapeutic targets for opiate dependence.

Topics: Acamprosate; Analgesics, Opioid; Animals; Antidepressive Agents, Second-Generation; Avoidance Learning; Buprenorphine; Conditioning, Operant; Dose-Response Relationship, Drug; Drug Implants; Fluoxetine; Lisuride; Male; Morphine; Naloxone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Pyrimidines; Pyrroles; Rats; Rats, Sprague-Dawley; Receptors, Corticotropin-Releasing Hormone; Substance Withdrawal Syndrome; Taurine

In France, since 1996, any general practitioner (GP) can prescribe high-dosage buprenorphine maintenance treatment (BMT) for opioid-dependent patients. The health authorities initially provided mandatory specific training, but since 1998, such training is only delivered by specialized networks and the pharmaceutical industry. Among a random sample of GPs from southeastern France (N=345), we found that many untrained GPs, as well as a significant minority of trained GPs, were likely to prescribe an ineffective dosage of buprenorphine or a potentially dangerous treatment (BMT+a short half-life benzodiazepine). These results highlight the necessity to edit clear guidelines, especially concerning situations of polyaddiction and psychiatric comorbidity, and to extend and improve BMT training in France with a renewed involvement of health authorities for quality control of such training. They even suggest that GPs' participation to specialized training sessions should become a mandatory prerequisite for prescribing BMT.

Topics: Adult; Attitude of Health Personnel; Buprenorphine; Drug Prescriptions; Education, Medical, Continuing; Family Practice; Female; France; Health Care Surveys; Humans; Male; Middle Aged; Opioid-Related Disorders; Physicians, Family; Practice Guidelines as Topic; Receptors, Opioid, mu; Substance Withdrawal Syndrome; Surveys and Questionnaires

To describe the social and medical profiles of incarcerated (in detention or after sentencing) opiate addicts, whether or not they had already begun substitution treatment at arrival, and assess the impact of high-dose buprenorphine substitution therapy on the health of prisoners and the course of their incarceration.. A prospective survey was conducted on opiate addicts on admission to prison and after 2 months of incarceration, from December 2001 to February 2003, in 6 prison centres in the South East of France.. During incarceration, no significant difference (other than in medical follow-up) appeared between the prisoners receiving substitution treatment and those who went through withdrawal on arrival. The first group differed from the second in several respects: their occupational history before incarceration was less stable, their history of drug addiction and incarceration was more serious (injection, psychotropic use, number of prior incarcerations, early age at first incarceration). The buprenorphine patients also differed in their more intense use of medical follow-up before incarceration.. The impact of buprenorphine substitution therapy during incarceration could not be demonstrated, but prisoners receiving this treatment had a substantially different profile than those who were not receiving treatment when they arrived in prison.

Topics: Adult; Age Factors; Buprenorphine; Dose-Response Relationship, Drug; Female; France; Health Care Surveys; Humans; Male; Opioid-Related Disorders; Prisoners; Prospective Studies; Substance Withdrawal Syndrome; Treatment Outcome

Topics: Anesthesia, General; Buprenorphine; Clonidine; Female; Heroin Dependence; Humans; Male; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Substance Withdrawal Syndrome; Treatment Failure

Opioid withdrawal, stress or cues associated with opioid consumption can induce opioid craving. If opioids are not available, opioid-dependent patients usually search for alternative drugs. Because several non-opioid drugs stimulate the endogenous opioidergic system, this concept may explain their frequent use by opioid-dependent patients. We hypothesized that non-opioid drugs alleviate opioid withdrawal symptoms and are therefore consumed by opioid addicts. We asked 89 opioid-dependent patients participating in an out-patient opioid maintenance program to estimate the potential of several non-opioid drugs in being able to alleviate opioid withdrawal. We applied a five-point Lickert scale (1 = very good reduction of opioid withdrawal; 5 = no reduction of opioid withdrawal). Patients could also indicate a worsening of opioid withdrawal. Values (mean +/- SD) were: for benzodiazepines, 3.2 +/- 1.1; tricyclic antidepressants, 3.6 +/- 1.1; cannabis, 3.6 +/- 1.0; alcohol, 4.1 +/- 1.1; cocaine, 4.2 +/- 1.1; amphetamine, 4.4 +/- 0.9; nicotine, 4.7 +/- 0.7; and caffeine, 4.9 +/- 0.5. A worsening of opioid withdrawal was reported by 62% of the patients for cocaine, 62% for amphetamine, 50% for caffeine, 37.5% for cannabis, 27% for nicotine, 26% for alcohol, 8% for tricyclic antidepressants and 3% for benzodiazepines. Our study shows a low efficacy of non-opioid drugs in alleviating opioid withdrawal symptoms. The data basis of this study was good and the sample was suitable to be asked for estimations of drug-drug interactions. Of the patients, 26 - 62% even reported a worsening of opioid withdrawal for cannabis, alcohol, cocaine and amphetamine. Only benzodiazepines and tricyclic antidepressants were reported to have a moderate positive effect on opioid withdrawal.

Topics: Adult; Buprenorphine; Drug Administration Schedule; Female; Humans; Inactivation, Metabolic; Male; Methadone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Substance Withdrawal Syndrome; Surveys and Questionnaires

Topics: Adolescent; Adolescent Behavior; Behavior Therapy; Buprenorphine; Humans; Hydrocodone; Naltrexone; Opioid-Related Disorders; Patient Compliance; Substance Withdrawal Syndrome; Treatment Outcome; United States

Topics: Alcohol-Induced Disorders; Buprenorphine; Humans; Infusions, Parenteral; Narcotic Antagonists; Narcotics; Substance Withdrawal Syndrome; Thiamine; Vitamin B Complex

In October 2002, the U.S. Food and Drug Administration approved buprenorphine-naloxone (Suboxone) sublingual tablets as an opioid dependence treatment available for use outside traditionally licensed opioid treatment programs. The NIDA Center for Clinical Trials Network (CTN) sponsored two clinical trials assessing buprenorphine-naloxone for short-term opioid detoxification. These trials provided an unprecedented field test of its use in twelve diverse community-based treatment programs. Opioid-dependent men and women were randomized to a thirteen-day buprenorphine-naloxone taper regimen for short-term opioid detoxification. The 234 buprenorphine-naloxone patients averaged 37 years old and used mostly intravenous heroin. Direct and rapid induction onto buprenorphine-naloxone was safe and well tolerated. Most patients (83%) received 8 mg buprenorphine-2 mg naloxone on the first day and 90% successfully completed induction and reached a target dose of 16 mg buprenorphine-4 mg naloxone in three days. Medication compliance and treatment engagement was high. An average of 81% of available doses was ingested, and 68% of patients completed the detoxification. Most (80.3%) patients received some ancillary medications with an average of 2.3 withdrawal symptoms treated. The safety profile of buprenorphine-naloxone was excellent. Of eighteen serious adverse events reported, only one was possibly related to buprenorphine-naloxone. All providers successfully integrated buprenorphine-naloxone into their existing treatment milieus. Overall, data from the CTN field experience suggest that buprenorphine-naloxone is practical and safe for use in diverse community treatment settings, including those with minimal experience providing opioid-based pharmacotherapy and/or medical detoxification for opioid dependence.

Topics: Administration, Sublingual; Adult; Buprenorphine; Community Health Services; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Approval; Drug Therapy, Combination; Humans; Male; Middle Aged; Multicenter Studies as Topic; Naloxone; Narcotic Antagonists; Narcotics; National Institutes of Health (U.S.); Opioid-Related Disorders; Randomized Controlled Trials as Topic; Rehabilitation Centers; Substance Withdrawal Syndrome; Time Factors; United States

Two formulations of buprenorphine were approved in the United States for treatment of opioid dependence in 2002. This newly available treatment offers a safe and effective alternative to addicted individuals who are not currently in treatment. This article focuses on the steps that physicians and patients may take, as of this writing, if they should wish to participate in this new treatment. The content is clinically oriented and intelligible to an audience that is not medically trained. In the article, buprenorphine is placed in context of the standard opioid pharmacotherapy of methadone maintenance, and the expansion of opioid pharmacotherapy into the office setting is described.

Topics: Buprenorphine; Drug Approval; Humans; Narcotic Antagonists; Opioid-Related Disorders; Substance Withdrawal Syndrome; United States

Infants placed on extracorporeal membrane oxygenation (ECMO) or mechanical ventilation often need continuous morphine infusions for pain relief and sedation. The resulting physical dependence requires an additional 2-3-week hospital stay to taper the morphine to avoid withdrawal. Buprenorphine effectively blocks abstinence in dependent adults, and in infants it could accelerate or eliminate the tapering schedule, thereby enabling earlier hospital dismissals.. Morphine-dependent infant rats were used in this study to determine the effectiveness of buprenorphine in blocking abstinence. Postnatal day-14 (P14) rats were implanted with osmotic minipumps that delivered saline (1 microl x h(-1)) or morphine (2 mg x kg(-1) h(-1)) for 72 h. The minipumps were then removed to allow the rats to undergo spontaneous morphine withdrawal.. The withdrawal period lasted approximately 72 h out of a 96-h observation period. The following signs were significant during these hours: wet-dog shakes, 1-72 h; abdominal stretches, 1-72 h; forepaw tremors, 1-24 h; splayed hind-limbs, 1-72 h; ptosis, 4-72 h; and evoked vocalization, 4 and 8 h. A single 1 mg x kg(-1) buprenorphine dose significantly decreased wet-dog shakes from 1 to 72 h, abdominal stretches from 1 to 48 h, forepaw tremors and splayed hind-limbs 1-8 h, and ptosis and evoked vocalization at 4 and 8 h. Repeated administration of 1 mg x kg(-1) buprenorphine before pump removal and at 24, 48 and 72 h resulted in a greater magnitude of blockade of abstinence throughout the 96-h observation period.. Buprenorphine may prove to be a suitable drug for treating opioid withdrawal in human infants.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Male; Morphine; Morphine Dependence; Rats; Rats, Sprague-Dawley; Sodium Chloride; Substance Withdrawal Syndrome; Time Factors; Treatment Outcome

A large number of patients with heroin dependency fail to enter a treatment program because of dropping out during or immediately after detoxification. This article presents an open study of symptom relief of 10 patients withdrawing from heroin with a high-dose rapid tapering buprenorphine detoxification protocol. It also presents a pseudo-experimental comparison between 208 patients treated with a clonidine/dextropropoxiphene detoxification protocol and 246 patients treated with the high-dose rapid tapering buprenorphine detoxification protocol to evaluate differences in patients' ability to continue in treatment of addiction immediately after detoxification. The results indicate that 24 mg of sublingually administered buprenorphine beginning when the patient judges himself to be in a withdrawal state followed by another three days of daily administered and rapidly decreased doses resulted in a significant reduction of withdrawal symptoms. Also, when the clonidine/dextropropoxiphene protocol was replaced with this buprenorphine protocol the number of patients continuing in treatment immediately after discharge from the detoxification ward increased from 41.3% to 58.1%. Buprenorphine given in high doses with rapid tapering when withdrawal symptoms occur seems to offer an effective symptom-alleviating treatment, probably also decreasing the number of drop-outs after detoxification.

Topics: Adult; Buprenorphine; Chi-Square Distribution; Female; Heroin Dependence; Humans; Male; Middle Aged; Substance Withdrawal Syndrome

Topics: Buprenorphine; Federal Government; Humans; Narcotic Antagonists; Opioid-Related Disorders; Public Policy; Societies, Medical; Substance Withdrawal Syndrome; United States

Topics: Buprenorphine; Drug Combinations; Humans; Methadone; Naloxone; Narcotics; Opioid-Related Disorders; Substance Withdrawal Syndrome

New methods of ultra-rapid opiate detoxification (URD) under intravenous sedation have been criticized because of limited data on safety and long-term follow-up. Premedication with buprenorphine has been advocated to improve safety by decreasing vomiting. Prior research has not explored URD in socially impaired patients.. Sixteen patients were detoxified with URD and prospectively evaluated over at least 30 months. Data of this procedure were compared with those of our previous study without buprenorphine preparation (Drug Alcohol Depend. 52(3) (1998) 243). The 16 patients were followed up by a general practitioner (GP) before and after URD. The GPs also supervised the 7-day course of buprenorphine treatment prescribed for the 16 patients prior to URD.. During the procedure, only one episode of vomiting occurred instead of 13 out of 20 in our previous study. Post-procedure, only two patients experienced moderate withdrawal symptoms, such as persistent nausea, abdominal cramps and vomiting lasting from 24 to 48 h, in comparison with most patients in the previous study without buprenorphine. After a period of at least 30 months (36.0+/-6.38), the 16 patients were still alive and were regularly monitored by their GP. Only two of the 16 never relapsed after URD and reported total opiate abstinence. Fourteen patients relapsed; 12 of these were prescribed a licensed methadone substitution program and two were still using heroin.. In this small sample, the data indicated that URD with buprenorphine preparation was safe and that it markedly decreased post-procedure morbidity. No patient died over a minimum 30-month follow-up period. Furthermore, the procedure was employed with socially impaired patients. In the long term, a few patients were still free of opiates, while the majority opted for a methadone maintenance program, showing that URD can serve as one possible step in a long-term treatment program.

Topics: Adult; Buprenorphine; Conscious Sedation; Family Practice; Female; Follow-Up Studies; Heroin Dependence; Humans; Male; Naltrexone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Outcome and Process Assessment, Health Care; Premedication; Recurrence; Substance Withdrawal Syndrome; Time Factors; Vomiting

To survey and assess the drug dependence and abuse potential liability of buprenorphine among opiate abusers.. Subjects of opiate dependence with history of buprenorphine use for 3 d at least were surveyed by interview. Physical dependence of buprenorphine was assessed using 30 items opiate withdrawal scale (OWS), which composed of 30 symptoms/signs. A 4-point scale was used to rate each symptoms/signs: zero (0), mild (1), moderate (2), and severe (3). Subjects were asked to rate their symptoms according to severity of previous experienced buprenorphine withdrawal. The estimate of the degree of subjective euphoria for buprenorphine was assessed using visual analogue scale (VAS).. Subjects 1235 who met the research criteria cases completed this survey in multi-detoxification treatment centers. The main initial purposes of buprenorphine use were detoxification (77.4 %) and protracted abstinence treated (26.6 %) respectively. The scores of OWS of buprenorphine were between 0.2 to 1.3; The mean scores of OWS in 3 different categories of frequency of buprenorphine use on "continuous use", "un-continuous use", and "sometimes continuous, sometimes un-continuous" were 0.9+/-0.9, 0.4+/-0.5, and 0.7+/-0.4, respectively (F=70.846, P<0.05). The degree of subjective euphoria for buprenorphine was slight to sub-moderate (mean score of VAS was 27 mm+/-24 mm). The mean scores of VAS in different routes of buprenorphine administration of sublingual and injection were (24+/-23) mm and (27+/-24) mm, respectively. No significant difference was found between sublingual and injection use of buprenorphine (u=1.516, P>0.05).. Both physical and psychic dependence of buprenorphine were low.

Topics: Adolescent; Adult; Buprenorphine; Drug Evaluation; Female; Humans; Male; Narcotic Antagonists; Opioid-Related Disorders; Substance Withdrawal Syndrome

This interim final rule amends the Federal opioid treatment program regulations by adding buprenorphine and buprenorphine combination products to the list of approved opioid treatment medications that may be used in federally certified and registered opioid treatment programs. The Food and Drug Administration (FDA) recently approved Subutex[reg] (buprenorphine) and Suboxone[reg] (buprenorphine in fixed combination with naloxone) for the treatment of opiate dependence. These two products will join methadone and ORLAAM[reg] as medications that may be used in opioid treatment programs for the maintenance and detoxification treatment of opioid dependence. Opioid treatment programs that choose to use these new products in the treatment of opioid dependence will adhere to the same Federal treatment standards established for methadone and ORLAAM[reg]. The Secretary invites public comments on this action.

Topics: Buprenorphine; Drug Approval; Drug Therapy, Combination; Humans; Naloxone; Opioid-Related Disorders; Substance Withdrawal Syndrome; United States

Topics: Buprenorphine; Drug and Narcotic Control; Drug Prescriptions; Humans; Narcotics; Opioid-Related Disorders; Public Policy; Substance Withdrawal Syndrome; United States

Six opiate-dependent drug users presented to the local emergency department within a 10-day period with symptoms of severe opioid withdrawal immediately following intravenous use of recently acquired street 'heroin'. The withdrawal picture was similar to that described in patients undergoing rapid opioid detoxification, suggesting that the substance injected was contaminated with an opiate antagonist. A number of potential compounds are discussed, including naltrexone and buprenorphine, and recommendations for the medical management of severe opiate withdrawal within an emergency setting are outlined. [Lubman DI, Koutsogiannis Z, Kronborg I. Emergency management of inadvertent accelerated opiate withdrawal in dependent opiate users.

Topics: Adult; Buprenorphine; Emergency Medical Services; Female; Humans; Inactivation, Metabolic; Male; Naltrexone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Severity of Illness Index; Substance Abuse, Intravenous; Substance Withdrawal Syndrome

Topics: Analgesics, Opioid; Buprenorphine; Clinical Trials as Topic; Clonidine; Heroin Dependence; Humans; Methadone; Narcotic Antagonists; Opioid-Related Disorders; Retrospective Studies; Substance Withdrawal Syndrome; Tramadol

This study aimed to establish a buprenorphine regime suitable for the short-term management of out-patient heroin withdrawal using an open-label, single-group case series. Eighteen dependent injecting heroin users underwent an 8-day withdrawal episode with supervised dosing of sublingual Subutex tablets. Buprenorphine doses were titrated daily over a 5-day period. Fifteen subjects (83%) completed the 5-day regime, and 14 (78%) completed the 8-day withdrawal episode. The mean doses ((SD) were 6.1 (1.2) mg on day 1; 9.6 (1.7) mg on day 2; 10.1 (1.9) mg on day 3; 8.9 (2.0) mg on day 4; 4.1 (1.5) mg on day 5; and a total regime dose of 38.9 (5.8) mg. Withdrawal severity was mild, with minimal rebound upon the cessation of dosing. Five subjects reported no heroin use, and five subjects reported using on only one occasion during the 8 days. An out-patient buprenorphine regime is recommended.

Topics: Adult; Ambulatory Care; Buprenorphine; Drug Administration Schedule; Female; Heroin Dependence; Humans; Male; Patient Satisfaction; Severity of Illness Index; Substance Withdrawal Syndrome

By diverting his dispensed medication, our patient collected 11 buprenorphine tablets (8 mg each), which he took in one day. The result was not respiratory depression, but instead severe opiate withdrawal lasting four days--this scenario has not previously been reported. This case highlights features of the unique pharmacology of buprenorphine and some key issues for its use in the management of heroin dependence.

Topics: Adult; Buprenorphine; Drug Overdose; Heroin Dependence; Humans; Male; Narcotic Antagonists; Patient Compliance; Receptors, Opioid; Self Medication; Substance Withdrawal Syndrome

The occurrence of an opioid addiction within an opioid treatment of pain or diarrhoea in inflammatory bowel disease is rarely reported. We report on a 36-year-old male with a 14 years lasting left sided chronic ulcerative colitis who developed after the initiation of a therapy with tincture of opium because of abdominal pain and diarrhoea an opioid addiction with the consumption of opium and later buprenorphin. Additionally to the diagnostics and therapy of the ulcerative colitis a detoxication was carried out. The diarrhoea slightly increased during the buprenorphin withdrawal. Diarrhoea refractory to other treatment should be treated by loperamid because of its lacking effects on the central nervous system. In chronic abdominal or musculoskeletal pain in inflammatory bowel disease opioids can be used if no surgical or other medical pain relief is possible. A consequent control of the therapeutic and side effects of the opioid therapy is necessary, especially of an abuse of opioid medication. The published case reports of a therapeutic induction of opioid addiction demonstrate that psychiatric comorbidity is an essential or even necessary risk factor. A checklist with seven criteria of opioid addiction during opioid therapy is presented.

Topics: Abdominal Pain; Adult; Buprenorphine; Colitis, Ulcerative; Combined Modality Therapy; Diarrhea; Dose-Response Relationship, Drug; Humans; Male; Opioid-Related Disorders; Opium; Self Medication; Substance Withdrawal Syndrome

Iatrogenic physical dependence has been documented in human infants infused i.v. with fentanyl or morphine to maintain continuous analgesia and sedation during extracorporeal membrane oxygenation and mechanical ventilation. Many infants are slowly weaned from the opioid. However, this approach requires extended hospital stays. Little is known about the potential benefits of substitution therapy to prevent abstinence. Therefore, the hypothesis was tested that s.c. and p.o. buprenorphine substitution would ameliorate spontaneous withdrawal in fentanyl-dependent rat pups. Analgesia in the tail-flick test was used to indicate behaviorally active doses of buprenorphine in opioid-naïve postnatal day 17 rats. Other postnatal day 14 rat pups were surgically implanted with osmotic minipumps that infused saline (1 microL/h) or fentanyl (60 microg/kg/h) for 72 h. Vehicle or buprenorphine was administered s.c. or p.o. before the initiation of spontaneous withdrawal brought about the removal of the osmotic minipumps. The major withdrawal signs of wet-dog shakes, jumping, wall climbing, forepaw tremor, and mastication were counted during a 3-h period of withdrawal. The major scored sign, scream on touch, was assessed every 15 min for 3 h. Injection of naloxone after the 3-h observation did not reveal any residual dependence. Subcutaneous buprenorphine administration significantly ameliorated all signs of withdrawal. Surprisingly, p.o. buprenorphine was nearly as efficacious as the s.c. route of administration. These results indicate that buprenorphine substitution therapy may be effective in fentanyl-dependent human infants.

Topics: Administration, Oral; Animals; Buprenorphine; Female; Fentanyl; Injections, Subcutaneous; Narcotic Antagonists; Rats; Rats, Sprague-Dawley; Substance Withdrawal Syndrome

This paper describes the time course of withdrawal and relapse in opioid-dependent volunteers (n = 8) who completed a gradual outpatient buprenorphine dose taper (28 days). Compliance with treatment was very high, as evidenced by clinic attendance (96-100%). Urinalysis showed that 6 of the 8 volunteers had relapsed to opiates by the end of the dose taper, even though reports of withdrawal were generally low. Relapse may have been triggered by a desire to re-experience the drug's positive subjective effects, craving, or low motivation to remain drug-free. A longer taper combined with an expanded range of treatments may improve prognosis.

Topics: Adult; Buprenorphine; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Motivation; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Recurrence; Substance Withdrawal Syndrome; Surveys and Questionnaires

The developmental effects of exposure to various doses of buprenorphine, methadone, or water during the perinatal period were studied in the rat. Rats were exposed to buprenorphine (0.3, 1.0, or 3.0 mg/kg/day), methadone (9 mg/kg/day), and/or water prenatally, postnatally, or both pre- and postnatally, via maternally implanted osmotic minipumps. Fetal and maternal mortality and morbidity were assessed, as well as the acquisition of several developmental milestones, pup weight gain, precipitated withdrawal, and the antinociceptive effect of morphine. Although perinatal exposure to buprenorphine failed to produce severe maternal and fetal or neonatal mortality, it was associated with a significant amount of perinatal mortality and perturbations of pup development. Pups developed physical dependence to both drugs, as evidenced by the ability of naloxone challenge to precipitate withdrawal. Both drugs induced tolerance to the antinociceptive effects of morphine in the tail-flick test. The effects of buprenorphine varied with the dose used, and the highest dose did not always produce the greatest effect. There were some similarities between the effects of perinatal buprenorphine and perinatal methadone; however, differences were also observed between the effects of the two drugs, which may be related to the different affinities and efficacies of the drugs at different opioid receptor subtypes.

Topics: Animals; Animals, Newborn; Buprenorphine; Drinking; Eating; Female; Growth; Litter Size; Methadone; Narcotics; Pain Measurement; Rats; Rats, Sprague-Dawley; Substance Withdrawal Syndrome; Weight Gain

A pilot study was carried out in Bangladesh during August and September, 1995, using a "snowball" technique with 30 male multiple drug users in order to investigate buprenorphine use, characteristics of the users, their reasons for its use and the drug's effects.

Topics: Adult; Bangladesh; Buprenorphine; Female; Heroin Dependence; Humans; Illicit Drugs; Male; Narcotic Antagonists; Substance Withdrawal Syndrome; Substance-Related Disorders

There is currently no consensus on the best approach to the management of opiate detoxification. In the current open-label study, 69 opiate-dependent individuals requesting outpatient detoxification were allocated to two different medication regimes: lofexidine and buprenorphine. Allocation was dependent on the timing of their presentation. Lofexifidine is a structural analogue of clonidine, and used widely in the UK. Buprenorphine is a partial opiate agonist with unusual pharmacological properties. Outcomes were better for the buprenorphine-receiving group (n=38). Clients receiving buprenorphine had a less severe withdrawal syndrome, and were more likely to complete their detoxification. In addition, for the buprenorphine-receiving group it was found that the withdrawal syndrome was least in those prescribed an initial dose of 4 mg. The findings and their implications are discussed. The design of the study precludes definitive conclusions regarding relative efficacy.

Topics: Adult; Buprenorphine; Chi-Square Distribution; Clonidine; Community Health Services; Female; Humans; Logistic Models; Male; Narcotic Antagonists; Opioid-Related Disorders; Outcome Assessment, Health Care; Prospective Studies; Statistics, Nonparametric; Substance Withdrawal Syndrome

A descriptive study conducted at the Louis-Harris Institute enrolled 600 patients taking methadone or buprenorphine (Subutex((R))) substitution therapy who were followed by general practitioners or specialists working in specialized clinics. The objective was to look for factors correlated with persistent injecting practices. Several factors were found to be statistically correlated with persistent injecting practices: impulsiveness, depressive state, and relative under-dosing (first daily or globally) in patients on Subutex((R)). Considering these factors, a better psychosocial impact could be achieved by providing sufficient attention to anxious or depressive states aggravating the effects of impulsiveness (co-usage of certain substances, psychotonics, search for certain psychopathological states) and paying special attention to the more impulsive subjects. Optimal coverage with earlier orientation to appropriate psychiatric care requires a team effort including educators, social workers and healthcare professionals. Such measures must be conducted within the framework of good clinical practices to establish a coherent multidisciplinary healthcare scheme which should help eliminate this source of more or less overt somatic complications. Such good clinical practice could also facilitate safe extinction of the conditioning inferred by addicted behavior (persistent injecting practices) which could persist only a few months after the end of the stimulus (cessation of emotional pain).

Topics: Adult; Analgesics, Opioid; Buprenorphine; Female; Humans; Male; Methadone; Opioid-Related Disorders; Substance Abuse, Intravenous; Substance Withdrawal Syndrome

Buprenorphine might be an alternative drug to be used in opiate detoxification. Its main advantage is that it carries a low risk for respiratory depression, it gives less euphoria and limited withdrawal effects. In a pilot detoxification project ten heroin addicts were given buprenorphine; seven completed the course. Before detoxification seven patients showed five or more signs on the Himmelsbach scale [6]. After the second day four patients showed no signs, four patients displayed one sign, two patients two signs. Buprenorphine may be a valuable alternative to clonidine, dextropropoxiphene and methadone in the detoxification of opiate addicts.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Female; Heroin Dependence; Humans; Inactivation, Metabolic; Male; Narcotic Antagonists; Pilot Projects; Substance Abuse, Intravenous; Substance Withdrawal Syndrome

Topics: Animals; Buprenorphine; Humans; Methadone; Naloxone; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Substance Withdrawal Syndrome

Maintenance therapy of drug-addict mothers with medical and psychosocial support may reduce complications (prematurity, growth retardation, fetal distress and fetal death). Methadone has been widely used during pregnancy with beneficial effects. Buprenorphine (BUP) is used more and more and shows the same beneficial effects.. Twenty-four pregnant women received BUP and their infants were enrolled in the study. Thirteen retrospective (GI) and 11 prospective (GII) cases were studied. In the GII, the women were treated and followed up in an interdisciplinary manner.. Complications in GII were less frequent than in GI: 9 vs 30% of prematurity, 9 vs 46% of fetal growth retardation and 0 vs 23% of acute fetal distress. However, the frequency of withdrawal syndrome was the same in both groups, 63 vs 69%, though improvements came more rapidly in GII.. This study shows that the use of BUP during pregnancy, combined with medical and psychosocial support, may reduce addiction complications. This support has to be maintained after the birth.

Topics: Adult; Buprenorphine; Female; Humans; Infant, Newborn; Infant, Premature; Narcotics; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prospective Studies; Social Support; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Adult; Buprenorphine; Female; Humans; Narcotic Antagonists; Opioid-Related Disorders; Substance Withdrawal Syndrome

Topics: Ambulatory Care; Buprenorphine; Hospitalization; Humans; Methadone; Narcotics; Opioid-Related Disorders; Recurrence; Risk Factors; Substance Withdrawal Syndrome

Topics: Analgesics, Opioid; Antidiarrheals; Buprenorphine; Dehydration; Female; Humans; Infant, Newborn; Male; Maternal-Fetal Exchange; Opium; Pregnancy; Substance Withdrawal Syndrome

To evaluate the clinical efficacy of buprenorphine (Bup) in treatment of acute heroin withdrawal.. Bup was given sublingually daily to 60 cases of heroin addicts in 3 groups: low, medium, and high doses. Withdrawal signs and symptoms of heroin were rated by Clinical Institute Narcotic Assessment. Craving for heroin during detoxification was assessed by Visual Analogue Scale. The side effects of Bup was assessed by Treatment Emergent Symptom Scale.. The mean daily consumption of Bup in low, medium, and high group was 2.0, 2.9, and 3.6 mg, respectively. Bup not only suppressed objective signs and withdrawal symptoms for heroin withdrawal, but also reduced the duration for heroin detoxification over 7-8 d.. Bup is an effective and rapid detoxification agent with fewer side effects for treatment of acute heroin withdrawal.

Topics: Adult; Buprenorphine; Female; Heroin Dependence; Humans; Male; Narcotic Antagonists; Substance Withdrawal Syndrome

Buprenorphine is a partial mu opioid agonist with demonstrated efficacy in the treatment of opioid dependence. One potential advantage of buprenorphine over full mu opioid agonists is its reported low physical dependence profile. This study systematically examined physical dependence produced by maintenance with a clinically relevant dose of buprenorphine using antagonist challenge procedures. In this residential laboratory study, eight opioid-dependent volunteers maintained on 8 mg/day of sublingual buprenorphine were each challenged on independent occasions with placebo, i.m. naloxone (0.3, 1.0, 3.0 and 10.0 mg/70 kg) and p.o. naltrexone (0.3, 1.0 and 3.0 mg/70 kg) 14 hr after their daily buprenorphine dose using a repeated measures, cross-over design. Both naloxone and naltrexone precipitated time- and dose-dependent withdrawal, as evidenced by changes in subject-rated, observer-rated and physiological measures. Significant precipitated withdrawal occurred at 3.0 and 10 mg/70 kg i.m. of naloxone and 3.0 mg/70 kg p.o. of naltrexone. These results indicate that buprenorphine maintenance produces physical dependence and that i.m. naloxone and p.o. naltrexone produce equivalent effects in withdrawal precipitation under these conditions. Findings have implications for selection of antagonist doses for use in formulating combination agonist/antagonist medications and for use in transition of drug abusers from buprenorphine to antagonist maintenance therapies.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Naloxone; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Substance Withdrawal Syndrome

One purpose of this study was to characterize the acute effects of the partial mu-opioid agonist buprenorphine administered to human subjects undergoing maintenance treatment with ascending doses of morphine. A second purpose was to examine the development of tolerance, cross-tolerance and physical dependence under the same morphine maintenance conditions. Six opioid-dependent volunteers were treated chronically with ascending morphine doses of 15, 30, 60 and 120 mg/day. Each morphine dosing level was maintained for 2 weeks, with test drugs administered during the second week of maintenance of each morphine dose. Both morphine (30 mg i.m.) and buprenorphine (6 mg i.m.) constricted pupils and produced reports of opioid-like subjective effects. The magnitude of these effects was inversely related to the morphine maintenance dose, with no effects being detected at higher maintenance levels. Naloxone (0.3 mg) produced little effect at lower morphine maintenance doses but precipitated withdrawal at higher maintenance doses. Buprenorphine failed to precipitate withdrawal even when subjects were treated with 120 mg/day morphine. These findings indicate that dose-dependent tolerance to morphine, cross-tolerance to buprenorphine and physical dependence develop during morphine maintenance. The finding that buprenorphine does not act as an antagonist under these dosing conditions further supports the clinical observation that there are conditions under which patients dependent on short-acting opioids can be comfortably transferred directly to buprenorphine maintenance treatment.

Topics: Adult; Buprenorphine; Dose-Response Relationship, Drug; Humans; Male; Middle Aged; Morphine; Naloxone; Substance Withdrawal Syndrome

Adequate dosage of sublingual buprenorphine is now recommended for substitution treatment of severe opioid dependance. We report two cases of acute discomfort, probably linked to withdrawal syndrome, after an IV injection of high doses of buprenorphine in opiate dependant patients. Data on the pharmacokinetics and neurobiochemical aspects of buprenorphine are compared with those of other opiates. A major issue of this work is a guideline for inducing substitution treatment with this "unique" partial agonist/antagonist of endorphinic receptors.

Topics: Acute Disease; Adult; Buprenorphine; Female; Humans; Injections, Intravenous; Male; Narcotics; Opioid-Related Disorders; Substance Withdrawal Syndrome

Buprenorphine is an opioid partial agonist being developed for possible use in the treatment of opioid dependence. In a previous study up to 8 mg of buprenorphine administered 20 hr after a daily dose of methadone in methadone-maintained volunteers produced neither agonist-like nor antagonist-like effects. The purpose of this study was to examine the effects of buprenorphine challenges given 2 hr after a daily methadone dose in maintained volunteers. Seven male volunteers maintained on 30 mg of methadone daily underwent pharmacologic challenges two to three times per week. Medication challenges consisted of double-blind i.m. injections of buprenorphine (0.5-8.0 mg), the opioid antagonist naloxone (0.1 and 0.2 mg), the prototypic opioid mu agonist hydromorphone (5 and 10 mg) or saline. Assessments of physiologic measures, volunteers' self-reports and observer ratings of drug effects were collected in a laboratory session for 2 hr after drug administration, and then for 8 additional hr postsession. Results from the laboratory session showed that on subject and observer ratings naloxone produced typical antagonist-like effects, hydromorphone produced mild agonist-like effects and buprenorphine produced antagonist-like effects. Interestingly, buprenorphine's antagonist activity was not directly dose-related; its most prominent antagonist effects occurred at the 1- and 2-mg doses. These results are consistent with buprenorphine's action as a partial mu opioid agonist and demonstrate that antagonist-like effects can occur under some conditions suggesting buprenorphine should have a low abuse liability in methadone-maintained patients.

Topics: Adult; Buprenorphine; Humans; Male; Methadone; Middle Aged; Naloxone; Opioid-Related Disorders; Psychomotor Performance; Pupil; Substance Withdrawal Syndrome

This study was conducted to characterize the opiate dependence potential of a number of opiate and non-opiate psychoactive drugs in morphine-dependent cynomolgus monkeys (Macaca fascicularis). In addition, the agonist/antagonist profiles of buprenorphine and butorphanol were directly compared. Six male cynomolgus monkeys were maintained on morphine (3.0 mg/kg, q.i.d.) for 6 months. On evaluation days, monkeys were scored for opiate withdrawal signs 18 h after the last dose of morphine. Single dose suppression studies were conducted by giving subcutaneous injections of morphine (3 or 6 mg/kg), naloxone (0.01, 0.05 or 0.1 mg/kg), buprenorphine (1, 3, 10, 30 or 100 micrograms/kg), butorphanol (0.01, 0.1, 1.0 or 3.2 mg/kg), haloperidol (0.01, 0.05 or 0.1 mg/kg), imipramine (2, 5 or 10 mg/kg) or saline and measuring the number and frequency of withdrawal signs that appeared over a 2-h period. In a separate precipitation experiment either saline or 0.01 or 0.1 mg/kg butorphanol was administered 2 h after the last maintenance dose of morphine. In the single dose suppression test, morphine completely suppressed most withdrawal signs while naloxone increased the severity of withdrawal. All doses of buprenorphine increased many withdrawal signs such as backward gait, rearing, chafing face, chain biting, vomiting, masturbation, and vocalizations after intimidation. Only a few signs were reduced, but the overall withdrawal scores were not significantly increased. Low doses of butorphanol suppressed some signs while the highest dose almost completely eliminated all withdrawal signs. Butorphanol also failed to precipitate opiate withdrawal, and actually reversed the signs present in the saline-treated monkeys. Imipramine and haloperidol had little effect on the morphine withdrawal syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Behavior, Animal; Buprenorphine; Butorphanol; Haloperidol; Imipramine; Macaca fascicularis; Male; Morphine; Morphine Dependence; Naloxone; Psychotropic Drugs; Substance Withdrawal Syndrome

Topics: Buprenorphine; Clinical Trials as Topic; Heroin; Heroin Dependence; Humans; Methadone; Narcotics; Quality of Life; Social Support; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors

The effects of dizocilpine and buprenorphine pretreatment on behavior reinforced by orally delivered phencyclidine (PCP) and saccharin, and on PCP withdrawal-induced disruptions in food-maintained responding were examined. Sixteen male rhesus monkeys were used in six different experimental protocols. Two groups of monkeys (N = 4-5) self-administered PCP (0.25 mg/ml) and water under concurrent FR 16 schedules, and were pretreated with IM injections of saline, and dizocilpine (0.001-0.1 mg/kg), or buprenorphine (0.003-0.8 mg/kg) 30 min before the 3-h sessions for 5 days. Two other groups (N = 5) were treated similarly except they had access to saccharin (0.03% or 0.3% w/v) and water under concurrent FR 16 schedules. In two other groups (N = 3), the effects of saline, dizocilpine (0.005-0.1 mg/kg), or buprenorphine (0.2 and 0.8 mg/kg) pretreatment were studied on PCP (0.25 mg/ml) withdrawal-induced disruptions in food-maintained responding. Dizocilpine and buprenorphine reduced both PCP (0.25 mg/ml) and saccharin (0.03% or 0.3% w/v) self-administration, especially at the 0.1-mg/kg dizocilpine dose and 0.2-mg/kg buprenorphine dose. Dizocilpine attenuated the PCP withdrawal effect, but buprenorphine had no effect on behavioral disruptions induced by PCP withdrawal. When dizocilpine was administered 2 days after PCP withdrawal began, the withdrawal effects were almost completely reversed. These results suggest that although drugs from the same and different pharmacological classes can suppress self-administration of drug and nondrug reinforcers, the same doses may produce an opposite effect or no effect on food-maintained behavior during PCP withdrawal.

Topics: Animals; Buprenorphine; Dizocilpine Maleate; Macaca mulatta; Male; Phencyclidine; Saccharin; Self Administration; Substance Withdrawal Syndrome

Naloxone-induced withdrawal was studied in seven patients currently dependent only on injecting buprenorphine, within 3 to 6 hours of their last dose. Withdrawal severity began to rise from 5 minutes and reached a peak at 60 minutes after 1.2 mg naloxone given intravenously. The mean withdrawal severity score was significantly higher at 30, 60 and 90 minutes compared to the baseline. The most frequent withdrawal signs and symptoms were mydriasis, systolic hypertension, tachypnoea, muscle pains, yawning, anxiety, restlessness and craving.

Topics: Adolescent; Adult; Buprenorphine; Humans; Male; Naloxone; Neurologic Examination; Opioid-Related Disorders; Prospective Studies; Substance Abuse Detection; Substance Abuse, Intravenous; Substance Withdrawal Syndrome

Buprenorphine was introduced as a potent analgesic with low abuse potential. Reports of buprenorphine abuse by opiate abusers have accumulated over the years, highlighting its use as a cheap alternative to heroin. The lower potency compared with heroin is being compensated by using a cocktail of buprenorphine with benzodiazepines or cyclizine. This study of 18 cases seen over 3 years broadly confirms these findings. Four cases reported haematemesis during acute withdrawal, a symptom not reported in earlier studies.

Topics: Adult; Attitude to Health; Behavior, Addictive; Buprenorphine; Humans; Inactivation, Metabolic; India; Injections, Intravenous; Male; Substance Withdrawal Syndrome; Substance-Related Disorders

Beta endorphin (BE) is a polypeptide agonist for the brain's endogenous opioid system. Levels of BE are elevated by opioid antagonists such as naloxone and depressed by short-acting agonists such as heroin and morphine; they become normalized during steady-state methadone. Buprenorphine (BUP) is a partial opioid agonist whose effects on BE levels were examined in six former heroin addicts and 14 methadone-maintained patients before and after being switched to sublingual BUP 2 mg daily for 1 month. In six former methadone-treated subjects BE levels also were measured after stopping BUP and after naloxone challenge. Levels of BE were not significantly lower in subjects started on BUP after stopping heroin (n = 6) (8.0 versus 8.1 ng/ml) or in subjects started on BUP after stopping methadone (n = 14) (11.6 vs 15.6 ng/ml). However, BE levels were lower on BUP than after naloxone challenge (n = 6) (7.0 versus 34.9 ng/ml). Levels of BE did not significantly change between the first 2 weeks ("early") and "later," although BE levels on methadone significantly correlated with BE levels on BUP in the "early" but not the "later" phase. The BE levels on BUP also did not differ from BE levels of unmedicated normals.

Topics: Adult; beta-Endorphin; Buprenorphine; Female; Heroin; Humans; Male; Methadone; Middle Aged; Naloxone; Radioimmunoassay; Substance Withdrawal Syndrome; Substance-Related Disorders

Buprenorphine is a mixed opioid agonist/antagonist which appears to produce less physical dependence and respiratory depression than typical mu-agonist opioids. These effects suggest its use for analgesia for drug abusers. However, buprenorphine may precipitate withdrawal from other opioids. The present case illustrates the utility of buprenorphine and describes a method to transfer a patient from a mu-agonist to buprenorphine without precipitating withdrawal or interrupting analgesia.

Topics: Adult; Buprenorphine; Crohn Disease; Drug Administration Schedule; Humans; Male; Morphine; Morphine Dependence; Naloxone; Neurologic Examination; Pain; Pain Measurement; Single-Blind Method; Substance Withdrawal Syndrome

1. Doses of buprenorphine (0.01, 0.1, 0.5, 1, 5, 10 and 50 mg/kg) were administered to determine buprenorphine's ability to precipitate abstinence symptoms in morphine-dependent mice. 2. When buprenorphine was administered in the fourth day of morphine addiction, the results demonstrate that the administration of the partial agonist opioid produce a bell-shaped dose-response curve. 3. The highest dose (50 mg/kg) was partially inactive while lower doses causing similar percentage than group treated with naloxone with respect to the appearance of the most of the symptoms of abstinence studied (diarrhoea, tremor, shaking-"wet dog shakes"-, jumping and weight loss). 4. Our findings demonstrate the bell-shaped response curve of the antagonist effects of buprenorphine.

Topics: Animals; Behavior, Animal; Buprenorphine; Diarrhea; Dose-Response Relationship, Drug; Male; Mice; Mice, Inbred Strains; Morphine Dependence; Naloxone; Substance Withdrawal Syndrome; Tremor

Topics: Buprenorphine; Double-Blind Method; Humans; Methadone; Opioid-Related Disorders; Substance Withdrawal Syndrome

Topics: Adult; Buprenorphine; Double-Blind Method; Female; Humans; Male; Methadone; Middle Aged; Naloxone; Opioid-Related Disorders; Outpatients; Substance Withdrawal Syndrome

Topics: Buprenorphine; Combined Modality Therapy; Electronarcosis; Humans; Naloxone; Opioid-Related Disorders; Substance Withdrawal Syndrome

Topics: Buprenorphine; Drug Industry; Humans; Substance Withdrawal Syndrome

Withdrawal contractures following brief exposure of guinea-pig ileum to enkephalin analogues, dynorphin A-(1-13) and beta-endorphin and the opiate drugs morphine, ketocyclazocine, buprenorphine and MR2034 were investigated. Following 2 min contact with the ileum a withdrawal contracture was induced by washout of (Met5)- and (Leu5)-enkephalin and by several enkephalin analogues but not by washout of (D-Ala2,D-Leu5)-enkephalinamide or any of the other drugs tested. Addition of naloxone precipitated withdrawal to all opioids tested except the kappa receptor preferential drugs ketocyclazocine and MR2034 and the mu receptor partial agonist, buprenorphine. The heights of the withdrawal contractures to enkephalin analogues were found to be dependent on the concentration of agonist and of naloxone, and on the duration of the contact period of opioid with the ileum. The naloxone-precipitated withdrawal responses to morphine, dynorphin A-(1-13) and the washout withdrawal response to (Met5)-enkephalin were inhibited by substance P antagonists thus supporting the previous proposal that substance P mediates the opiate withdrawal response. This study has shown that mu receptor agonists produced dependence in the guinea-pig ileum revealed by a withdrawal contracture on addition of naloxone, whereas dependence on kappa receptor agonists could not be revealed with naloxone. Since the guinea-pig ileum preparation has millimicron and kappa receptors it was concluded that the endogenous opioid peptides, enkephalins, beta-endorphin and dynorphin A-(1-13), all induced dependence by acting on mu receptors in this preparation.

Topics: Animals; Benzomorphans; Buprenorphine; Cyclazocine; Endorphins; Ethylketocyclazocine; Female; Guinea Pigs; Ileum; In Vitro Techniques; Male; Muscle, Smooth; Naloxone; Narcotics; Substance P; Substance Withdrawal Syndrome

The mixed agonist-antagonist analgesics buprenorphine, butorphanol, nalbuphine, pentazocine and picenadol were compared to the prototype mu and kappa agonists morphine and Mr 2033, respectively, in the following tests in rhesus monkeys: overt behavioral effects upon acute administration in drug-naive animals; discriminative stimulus properties in monkeys trained to respond to either etorphine or ethylketazocine; self-administration of the test agent relative to codeine; single dose suppression and precipitation in withdrawn and non-withdrawn morphine-dependent monkeys, respectively; and primary addiction studies in drug-naive animals. Whereas both buprenorphine and nalbuphine precipitate withdrawal in morphine-dependent monkeys, withdrawal following chronic administration of buprenorphine resulted in no observable signs of abstinence, while nalbuphine withdrawal was similar to that seen in morphine-dependent monkeys. Butorphanol, pentazocine and picenadol all produced mild dependence of the kappa-type; that is, natural withdrawal behavior similar to that seen following chronic Mr 2033 administration.

Topics: Animals; Behavior, Animal; Benzomorphans; Buprenorphine; Butorphanol; Codeine; Discrimination, Psychological; Humans; Macaca mulatta; Morphinans; Morphine; Morphine Dependence; Nalbuphine; Narcotic Antagonists; Pentazocine; Piperidines; Substance Withdrawal Syndrome

In non-withdrawn maximally-dependent rhesus monkeys, both naloxone (NOX) and nalorphine (NAL) precipitated withdrawal when given 2 h after morphine (M). When these drugs were given 15 h after M, at which time the animals were in severe withdrawal and M blood levels were much lower, they promptly exacerbated withdrawal. Thus, mu antagonists may act competitively in non-withdrawn addicts and noncompetitively in withdrawn subjects. Buprenorphine (BRN), the partial mu agonist, precipitated withdrawal in stable addicts and partly suppressed withdrawal signs in abstinent addicts. Finally, ethyl-ketocyclazocine (EKC), the purported kappa agonist, did not precipitate but partly suppressed withdrawal at doses producing severe side effects. Perhaps this suppression is associated with kappa activity.

Topics: Animals; Buprenorphine; Cyclazocine; Ethylketocyclazocine; Humans; Macaca mulatta; Morphine Dependence; Naloxone; Narcotic Antagonists; Narcotics; Receptors, Opioid; Receptors, Opioid, mu; Substance Withdrawal Syndrome

The capacity of morphine to suppress natural and precipitated withdrawal was compared in morphine-dependent rhesus monkeys. A similar severity of withdrawal was induced by 14-hr deprivation or precipitated by naloxone, naltrexone, cyclazocine, Win 44,441 or MR 2266. Regardless of the procedure used to induce withdrawal, behavioral signs were completely suppressed by a cumulative dose of 17.5 mg/kg morphine. Thus, an equivalent level of withdrawal induced by reversible antagonists is as sensitive to subsequent morphine administration as is deprivation-induced abstinence. This is in accordance with the theory that vacancy of opiate receptors normally occupied by morphine is related to the level of abstinence observed. In contrast to Win 44,441, however, an equivalent level of withdrawal precipitated by buprenorphine required 175 mg/kg morphine for complete suppression. This is more informative than comparing duration of action; when given as 24-h pretreatments, a high dose of Win 44,441 (10 mg/kg) was only slightly less effective than buprenorphine (3.2 mg/kg) in antagonizing morphine-induced stupor in normal monkeys. Comparison of the ability of morphine to suppress precipitated withdrawal provides evidence of the relative reversibility of antagonists in vivo and demonstrates the extraordinarily stable nature by which buprenorphine acts at opiate receptors.

Topics: Animals; Behavior, Animal; Buprenorphine; Humans; Macaca mulatta; Morphine; Morphine Dependence; Narcotic Antagonists; Receptors, Opioid; Substance Withdrawal Syndrome

Topics: Anti-Anxiety Agents; Buprenorphine; Double-Blind Method; Dronabinol; Drug Synergism; Heroin Dependence; Humans; Marijuana Abuse; Methadone; Opioid-Related Disorders; Pentazocine; Smoking Prevention; Substance Withdrawal Syndrome; Substance-Related Disorders; Tripelennamine

Topics: Buprenorphine; Humans; Morphinans; Substance Withdrawal Syndrome; Substance-Related Disorders

Buprenorphine is a powerful new analgesic agent with agonist and antagonist opiate receptor activity. Its withdrawal symptoms have been reported as being mild; however, its potential for abuse is not known. A case of buprenorphine abuse is reported, in which the patient's history and his response to naloxone suggest that important underlying factors were physical tolerance and dependence.

Topics: Adult; Buprenorphine; Humans; Male; Morphinans; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Analgesics; Buprenorphine; Chlordiazepoxide; Clonidine; Diazepam; Humans; Morphine; National Institutes of Health (U.S.); Substance Withdrawal Syndrome; Substance-Related Disorders; Tobacco Use Disorder; Tolmetin; United States

This study was designed to assess the dependence-producing capacity of the opiate partial agonist, buprenorphine. Rats chronically treated with buprenorphine for 4 days showed only very weak signs of withdrawal upon cessation of buprenorphine treatment or upon challenge with naloxone, although complete tolerance had developed to the drug at this time. However, more intense withdrawal could be induced when buprenorphine treatment was followed by substitution treatment with morphine. Even one injection of morphine given 12 h after the last buprenorphine treatment enabled the precipitation of withdrawal with naloxone. Naloxone could not precipitate signs of withdrawal in naive rats treated with this dose of morphine. Thus, contrary to some claims in the literature, buprenorphine, like other opiate agonists and partial agonists, induces dependence. The fact that only few signs of withdrawal are seen in direct dependence tests, probably reflects the slow dissociation of the drug from the receptor - which probably limits the intensity of withdrawal by preventing the rapid uncovery of the receptor upon discontinuance of treatment with the drug or upon injection of an antagonist. In addition, the maximum degree of dependence induced by buprenorphine - in comparison to pure agonists is limited, like that of other partial agonists.

Topics: Animals; Buprenorphine; Drug Tolerance; Humans; Male; Methadone; Morphinans; Morphine; Naloxone; Rats; Receptors, Opioid; Substance Withdrawal Syndrome; Substance-Related Disorders

Intravenous injections of buprenorphine, a partial opiate agonist and antagonist, maintained operant responding under second order schedule control (FR 3 VR 16:S) across a dose range of 0.005 to 0.10 mg/kg/inj. A drug naive monkey and four monkeys with a history of morphine self-administration all self-administered buprenorphine at all doses studied. Four monkeys showed dose-related increases in the total amount of buprenorphine (mg/kg) self-administered each day as the available dose increased from 0.01 to 0.10 mg/kg/inj. Injections per day remained equivalent to the number of injections at the lowest dose studied or increased significantly (p less than 0.05, 0.01), as the dose per injection increased in three monkeys. Even at high buprenorphine doses, there was no evidence of sedation. Monkeys consistently self-administered significantly more buprenorphine than saline in control studies (p less than 0.01). Buprenorphine's agonistic effects appear to persist for 24 to 48 hours. When saline and buprenorphine were available on alternate days, monkeys did not distinguish between them, but when 3 days of saline were alternated with 1 day of buprenorphine (0.03 mg/kg/inj), monkeys took significantly more buprenorphine than saline (p less than 0.02--0.001). Abrupt discontinuation of buprenorphine (0.10 mg/kg/inj) did not result in discernible withdrawal signs. The effects of buprenorphine on food intake were inconsistent, but there were no significant changes in body weight as a function of chronic buprenorphine self-administration or withdrawal. These data indicate that buprenorphine is a positive reinforcer in rhesus monkeys and maintains behavior leading to its administration on second order schedules over a wide dose range. Despite its opiate agonist properties, there was no evidence of physical dependence.

Topics: Animals; Buprenorphine; Drug Interactions; Food; Humans; Macaca mulatta; Morphinans; Reinforcement Schedule; Reinforcement, Psychology; Self Administration; Substance Withdrawal Syndrome; Substance-Related Disorders

Heroin-dependent men were given buprenorphine (a partial opiate agonist-antagonist) or a placebo under duoble-blind conditions on a clinical research ward where they could acquire heroin (21 to 40.5 milligrams per day, intravenously). Buprenorphine significantly (P less than .001) suppressed the self-administration of heroin over 10 days. Control subjects took between 93 and 100 percent of the available heroin. The effects of buprenorphine were dose-dependent; a dose of 8 milligrams per day reduced heroin use by 69 to 98 percent; a dose of 4 milligrams per day reduced heroin use by 45 percent. Termination of buprenorphie maintenance did not result in opiate withdrawal signs or symptoms. The subjects liked buprenorphine and indicated that it was preferable to methadone or naltrexone. Buprenorphine should be a safe and effective new pharmacotherapy for heroin dependence.

Topics: Adult; Buprenorphine; Double-Blind Method; Heroin Dependence; Humans; Informed Consent; Morphinans; Substance Withdrawal Syndrome; Substance-Related Disorders