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CNS Drugs Jun 2019Opioid use disorder affects over 26 million individuals worldwide. There are currently three World Health Organization-recommended and US Food and Drug... (Review)
Review
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
PubMed: 31062259
DOI: 10.1007/s40263-019-00637-z -
Pain Medicine (Malden, Mass.) Apr 2020An expert panel convened to reach a consensus on common misconceptions surrounding buprenorphine, a Schedule III partial µ-opioid receptor agonist indicated for chronic... (Review)
Review
OBJECTIVE
An expert panel convened to reach a consensus on common misconceptions surrounding buprenorphine, a Schedule III partial µ-opioid receptor agonist indicated for chronic pain. The panel also provided clinical recommendations on the appropriate use of buprenorphine and conversion strategies for switching to buprenorphine from a full µ-opioid receptor agonist for chronic pain management.
METHODS
The consensus panel met on March 25, 2019, to discuss relevant literature and provide recommendations on interpreting buprenorphine as a partial µ-opioid receptor agonist, prescribing buprenorphine before some Schedule II, III, or IV options, perioperative/trauma management of patients taking buprenorphine, and converting patients from a full µ-opioid receptor agonist to buprenorphine.
RESULTS
The panel recommended that buprenorphine's classification as a partial µ-opioid receptor agonist not be clinically translated to mean partial analgesic efficacy. The panel also recommended that buprenorphine be considered before some Schedule II, III, or IV opioids in patients with a favorable risk/benefit profile on the basis of metabolic factors, abuse potential, and tolerability and that buprenorphine be continued during the perioperative/trauma period. In addition, switching patients from a full µ-opioid receptor agonist to buprenorphine should be considered with no weaning period at starting doses that are based on the previous opioid dose.
CONCLUSIONS
These recommendations provide a framework for clinicians to address most clinical scenarios regarding buprenorphine use. The overall consensus of the panel was that buprenorphine is a unique Schedule III opioid with favorable pharmacologic properties and a safety profile that may be desirable for chronic pain management.
Topics: Analgesics, Opioid; Buprenorphine; Chronic Pain; Drug Substitution; Humans; Practice Guidelines as Topic; Receptors, Opioid, mu
PubMed: 31917418
DOI: 10.1093/pm/pnz356 -
Journal of Addiction Medicine 2019: Buprenorphine is an effective treatment for opioid use disorder. As a high-affinity, partial agonist for the mu-opioid receptor, buprenorphine suppresses opioid... (Review)
Review
: Buprenorphine is an effective treatment for opioid use disorder. As a high-affinity, partial agonist for the mu-opioid receptor, buprenorphine suppresses opioid withdrawal and craving, reduces illicit opioid use, and blocks exogenous opioid effects including respiratory depression. Other pharmacologic benefits of buprenorphine are its superior safety profile compared with full opioid agonists and its long half-life that allows daily or less-than-daily dosing. New and innovative buprenorphine formulations, with pharmacokinetic profiles that differ from the original tablet formulation, continue to be developed. These include higher bioavailability transmucosal tablets and films and also 6-month implantable and monthly injectable products. This growing array of available formulations allows more choices for patients and increased opportunity for clinicians to individualize treatment; thus, it is important for buprenorphine prescribers to understand these differences.
Topics: Analgesics, Opioid; Biological Availability; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Drug Implants; Drug Interactions; Humans; Injections; Opioid-Related Disorders; Substance Withdrawal Syndrome; Tablets
PubMed: 30531584
DOI: 10.1097/ADM.0000000000000457 -
JAMA Internal Medicine Jun 2018Buprenorphine treatment for opioid use disorder may be improved by sustained-release formulations. (Comparative Study)
Comparative Study Randomized Controlled Trial
Weekly and Monthly Subcutaneous Buprenorphine Depot Formulations vs Daily Sublingual Buprenorphine With Naloxone for Treatment of Opioid Use Disorder: A Randomized Clinical Trial.
IMPORTANCE
Buprenorphine treatment for opioid use disorder may be improved by sustained-release formulations.
OBJECTIVE
To determine whether treatment involving novel weekly and monthly subcutaneous (SC) buprenorphine depot formulations is noninferior to a daily sublingual (SL) combination of buprenorphine hydrochloride and naloxone hydrochloride in the treatment of opioid use disorder.
DESIGN, SETTING, AND PARTICIPANTS
This outpatient, double-blind, double-dummy randomized clinical trial was conducted at 35 sites in the United States from December 29, 2015, through October 19, 2016. Participants were treatment-seeking adults with moderate-to-severe opioid use disorder.
INTERVENTIONS
Randomization to daily SL placebo and weekly (first 12 weeks; phase 1) and monthly (last 12 weeks; phase 2) SC buprenorphine (SC-BPN group) or to daily SL buprenorphine with naloxone (24 weeks) with matched weekly and monthly SC placebo injections (SL-BPN/NX group).
MAIN OUTCOMES AND MEASURES
Primary end points tested for noninferiority were response rate (10% margin) and the mean proportion of opioid-negative urine samples for 24 weeks (11% margin). Responder status was defined as having no evidence of illicit opioid use for at least 8 of 10 prespecified points during weeks 9 to 24, with 2 of these at week 12 and during month 6 (weeks 21-24). The mean proportion of samples with no evidence of illicit opioid use (weeks 4-24) evaluated by a cumulative distribution function (CDF) was an a priori secondary outcome with planned superiority testing if the response rate demonstrated noninferiority.
RESULTS
A total of 428 participants (263 men [61.4%] and 165 women [38.6%]; mean [SD] age, 38.4 [11.0] years) were randomized to the SL-BPN/NX group (n = 215) or the SC-BPN group (n = 213). The response rates were 31 of 215 (14.4%) for the SL-BPN/NX group and 37 of 213 (17.4%) for the SC-BPN group, a 3.0% difference (95% CI, -4.0% to 9.9%; P < .001). The proportion of opioid-negative urine samples was 1099 of 3870 (28.4%) for the SL-BPN/NX group and 1347 of 3834 (35.1%) for the SC-BPN group, a 6.7% difference (95% CI, -0.1% to 13.6%; P < .001). The CDF for the SC-BPN group (26.7%) was statistically superior to the CDF for the SL-BPN/NX group (0; P = .004). Injection site adverse events (none severe) occurred in 48 participants (22.3%) in the SL-BPN/NX group and 40 (18.8%) in the SC-BPN group.
CONCLUSIONS AND RELEVANCE
Compared with SL buprenorphine, depot buprenorphine did not result in an inferior likelihood of being a responder or having urine test results negative for opioids and produced superior results on the CDF of no illicit opioid use. These data suggest that depot buprenorphine is efficacious and may have advantages.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02651584.
Topics: Administration, Sublingual; Adult; Buprenorphine; Double-Blind Method; Female; Humans; Injections, Subcutaneous; Male; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Treatment Outcome
PubMed: 29799968
DOI: 10.1001/jamainternmed.2018.1052 -
Pharmacologic Treatment of Opioid Use Disorder: a Review of Pharmacotherapy, Adjuncts, and Toxicity.Journal of Medical Toxicology :... Dec 2018Opioid use disorder continues to be a significant source of morbidity and mortality in the USA and the world. Pharmacologic treatment with methadone and buprenorphine... (Review)
Review
Opioid use disorder continues to be a significant source of morbidity and mortality in the USA and the world. Pharmacologic treatment with methadone and buprenorphine has been shown to be effective at retaining people in treatment programs, decreasing illicit opioid use, decreasing rates of hepatitis B, and reducing all cause and overdose mortality. Unfortunately, barriers exist in accessing these lifesaving medications: users wishing to start buprenorphine therapy require a waivered provider to prescribe the medication, while some states have no methadone clinics. As such, users looking to wean themselves from opioids or treat their opioid dependence will turn to alternative agents. These agents include using prescription medications, like clonidine or gabapentin, off-label, or over the counter drugs, like loperamide, in supratherapeutic doses. This review provides information on the pharmacology and the toxic effects of pharmacologic agents that are used to treat opioid use disorder. The xenobiotics reviewed in depth include buprenorphine, clonidine, kratom, loperamide, and methadone, with additional information provided on lofexidine, akuamma seeds, kava, and gabapentin.
Topics: Buprenorphine; Humans; Methadone; Narcotic Antagonists; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders
PubMed: 30377951
DOI: 10.1007/s13181-018-0685-1 -
BMJ (Clinical Research Ed.) Apr 2017To compare the risk for all cause and overdose mortality in people with opioid dependence during and after substitution treatment with methadone or buprenorphine and... (Meta-Analysis)
Meta-Analysis Review
To compare the risk for all cause and overdose mortality in people with opioid dependence during and after substitution treatment with methadone or buprenorphine and to characterise trends in risk of mortality after initiation and cessation of treatment. Systematic review and meta-analysis. Medline, Embase, PsycINFO, and LILACS to September 2016. Prospective or retrospective cohort studies in people with opioid dependence that reported deaths from all causes or overdose during follow-up periods in and out of opioid substitution treatment with methadone or buprenorphine. Two independent reviewers performed data extraction and assessed study quality. Mortality rates in and out of treatment were jointly combined across methadone or buprenorphine cohorts by using multivariate random effects meta-analysis. There were 19 eligible cohorts, following 122 885 people treated with methadone over 1.3-13.9 years and 15 831 people treated with buprenorphine over 1.1-4.5 years. Pooled all cause mortality rates were 11.3 and 36.1 per 1000 person years in and out of methadone treatment (unadjusted out-to-in rate ratio 3.20, 95% confidence interval 2.65 to 3.86) and reduced to 4.3 and 9.5 in and out of buprenorphine treatment (2.20, 1.34 to 3.61). In pooled trend analysis, all cause mortality dropped sharply over the first four weeks of methadone treatment and decreased gradually two weeks after leaving treatment. All cause mortality remained stable during induction and remaining time on buprenorphine treatment. Overdose mortality evolved similarly, with pooled overdose mortality rates of 2.6 and 12.7 per 1000 person years in and out of methadone treatment (unadjusted out-to-in rate ratio 4.80, 2.90 to 7.96) and 1.4 and 4.6 in and out of buprenorphine treatment. Retention in methadone and buprenorphine treatment is associated with substantial reductions in the risk for all cause and overdose mortality in people dependent on opioids. The induction phase onto methadone treatment and the time immediately after leaving treatment with both drugs are periods of particularly increased mortality risk, which should be dealt with by both public health and clinical strategies to mitigate such risk. These findings are potentially important, but further research must be conducted to properly account for potential confounding and selection bias in comparisons of mortality risk between opioid substitution treatments, as well as throughout periods in and out of each treatment.
Topics: Buprenorphine; Drug Overdose; Humans; Methadone; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Risk
PubMed: 28446428
DOI: 10.1136/bmj.j1550 -
Drugs Aug 2018The buprenorphine receptor binding profile is unique in that it binds to all three major opioid receptors (mu, kappa, delta), and also binds to the orphan-like receptor,... (Review)
Review
The buprenorphine receptor binding profile is unique in that it binds to all three major opioid receptors (mu, kappa, delta), and also binds to the orphan-like receptor, the receptor for orphanin FQ/nociceptin, with lower affinity. Within the mu receptor group, buprenorphine analgesia in rodents is dependent on the recently discovered arylepoxamide receptor target in brain, which involves a truncated 6-transmembrane mu receptor gene protein, distinguishing itself from morphine and most other mu opioids. Although originally designed as an analgesic, buprenorphine has mainly been used for opioid maintenance therapy and only now is increasingly recognized as an effective analgesic with an improved therapeutic index relative to certain potent opioids. Albeit a second-, third-, or fourth-line analgesic, buprenorphine is a reasonable choice in certain clinical situations. Transdermal patches and buccal film formulations are now commercially available as analgesics. This review discusses buprenorphine pharmacodynamics and pharmacokinetics, use in certain populations, and provides a synopsis of systematic reviews and randomized analgesic trials. We briefly discuss postoperative management in patients receiving buprenorphine maintenance therapy, opioid equivalence to buprenorphine, rotations to buprenorphine from other opioids, and clinical relevance of buprenorphine-related QTc interval changes.
Topics: Administration, Sublingual; Analgesics, Opioid; Animals; Buprenorphine; Chemistry, Pharmaceutical; Chronic Pain; Dose-Response Relationship, Drug; Drug Therapy, Combination; Drug Tolerance; Humans; Narcotic Antagonists; Observational Studies as Topic; Randomized Controlled Trials as Topic; Receptors, Opioid; Substance-Related Disorders; Systematic Reviews as Topic; Transdermal Patch
PubMed: 30051169
DOI: 10.1007/s40265-018-0953-z -
Biomolecules May 2021Chronic pain, including neuropathic pain, represents an untreated disease with important repercussions on the quality of life and huge costs on the national health... (Review)
Review
Chronic pain, including neuropathic pain, represents an untreated disease with important repercussions on the quality of life and huge costs on the national health system. It is well known that opioids are the most powerful analgesic drugs, but they represent the second or third line in neuropathic pain, that remain difficult to manage. Moreover, these drugs show several side effects that limit their use. In addition, opioids possess addictive properties that are associated with misuse and drug abuse. Among available opioids compounds, buprenorphine has been suggested advantageous for a series of clinical reasons, including the effectiveness in neuropathic pain. Some properties are partly explained by its unique pharmacological characteristics. However, questions on the dynamic profile remain to be answered. Pharmacokinetics optimization strategies, and additional potentialities, are still to be explored. In this paper, we attempt to conceptualize the potential undiscovered dynamic profile of buprenorphine.
Topics: Analgesics; Buprenorphine; Chronic Pain; Humans; Neuralgia; Quality of Life
PubMed: 34072706
DOI: 10.3390/biom11060816 -
American Family Physician Mar 2018Opioid misuse, including the use of heroin and the overprescribing, misuse, and diversion of opioid pain medications, has reached epidemic proportions in the United... (Review)
Review
Opioid misuse, including the use of heroin and the overprescribing, misuse, and diversion of opioid pain medications, has reached epidemic proportions in the United States. As a result, there has been a dramatic increase in opioid use disorder and associated overdoses and deaths. Addiction is a chronic brain disease with a genetic component that affects motivation, inhibition, and cognition. Patient characteristics associated with successful buprenorphine maintenance treatment include stable or controlled medical or psychiatric comorbidities and a safe, substance-free environment. As a partial opioid agonist, buprenorphine has a ceiling effect that limits respiratory depression and adds to its safety in accidental or intentional overdose. Buprenorphine and combinations of buprenorphine and naloxone are generally well tolerated; adverse effects include anxiety, constipation, dizziness, drowsiness, headache, nausea, and sedation. Family physicians who meet specific requirements can obtain a Drug Addiction Treatment Act of 2000 waiver by notifying the Substance Abuse and Mental Health Services Administration of their intent to begin dispensing and/or prescribing buprenorphine. Medication-assisted treatment with buprenorphine is as effective as methadone in terms of treatment retention and decreased opioid use when prescribed at fixed dosages of at least 7 mg per day; dosages of 16 mg per day are clearly superior to placebo. Sporadic opioid use is not uncommon in the first few months of medication-assisted treatment and should be addressed by increased visit frequency and more intensive engagement with behavioral therapies. Follow-up visits should include documentation of any relapses, reemergence of cravings or withdrawal, random urine drug testing, pill or wrapper counts, and checks of state prescription drug database records.
Topics: Buprenorphine; Drug Prescriptions; Humans; Narcotic Antagonists; Opioid-Related Disorders; Treatment Outcome
PubMed: 29671504
DOI: No ID Found -
CMAJ : Canadian Medical Association... Mar 2023
Topics: Humans; Delayed-Action Preparations; Buprenorphine
PubMed: 36972908
DOI: 10.1503/cmaj.220730-f