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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 -
The American Journal on Addictions Jul 2021Buprenorphine's high-binding affinity as a partial µ-opioid agonist displaces preexisting full agonists causing precipitated withdrawal, which requires most individuals... (Review)
Review
BACKGROUND AND OBJECTIVES
Buprenorphine's high-binding affinity as a partial µ-opioid agonist displaces preexisting full agonists causing precipitated withdrawal, which requires most individuals starting buprenorphine to endure moderate withdrawal prior to induction to avoid precipitated withdrawal. A novel approach called microinduction has emerged to remove this prerequisite. Our aim is to review the literature on these alternative approaches.
METHODS
Using keywords including buprenorphine, buprenorphine/naloxone, transdermal buprenorphine, suboxone, microinduction, microdosing, rapid induction, buprenorphine-dosing protocol, the authors searched PubMed/Medline, EMBASE, PsycINFO, PsychARTICLES, and Scopus databases from the date of inception through April 30, 2020, which yielded 1726 results, which, in turn, after manual exclusion for irrelevant content and publication in languages other than English, generated a total of 18 papers.
RESULTS
On the basis of 18 papers included in this review, 63 patients were successfully transitioned to buprenorphine using different microdosing techniques, primarily in the inpatient setting. From the available data, patients were transitioned from a variety of opioids over a range of dosing without significant withdrawal, and initial doses ranged most frequently from 0.2 to 0.5 mg. While the timeframe for the various schedules ranged from 3 to 112 days, most transitioned over a period of 4 to 8 days, and most participants completed the cross titration at 8 to 16 mg.
DISCUSSION AND CONCLUSIONS
The growing literature demonstrates some initial promise for alternative induction models, specifically targeting patients averse to withdrawal, patients prescribed opioids for chronic pain, patients on high-dose methadone, and patients using illicit or pharmaceutical fentanyl.
SCIENTIFIC SIGNIFICANCE
This manuscript provides a review of the existing literature to help clinicians better understand the approaches to microdosing of buprenorphine in various clinical settings and populations. (Am J Addict 2020;00:00-00).
Topics: Buprenorphine; Drug Administration Schedule; Humans; Naloxone
PubMed: 33378137
DOI: 10.1111/ajad.13135 -
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 -
Clinical Pharmacokinetics 2005Buprenorphine is a semi-synthetic opioid derived from thebaine, a naturally occurring alkaloid of the opium poppy, Papaver somniferum. The pharmacology of buprenorphine... (Meta-Analysis)
Meta-Analysis Review
Buprenorphine is a semi-synthetic opioid derived from thebaine, a naturally occurring alkaloid of the opium poppy, Papaver somniferum. The pharmacology of buprenorphine is unique in that it is a partial agonist at the opioid mu receptor. Buprenorphine undergoes extensive first-pass metabolism and therefore has very low oral bioavailability; however, its bioavailability sublingually is extensive enough to make this a feasible route of administration for the treatment of opioid dependence. The mean time to maximum plasma concentration following sublingual administration is variable, ranging from 40 minutes to 3.5 hours. Buprenorphine has a large volume of distribution and is highly protein bound (96%). It is extensively metabolised by N-dealkylation to norbuprenorphine primarily through cytochrome P450 (CYP) 3A4. The terminal elimination half-life of buprenorphine is long and there is considerable variation in reported values (mean values ranging from 3 to 44 hours). Most of a dose of buprenorphine is eliminated in the faeces, with approximately 10-30% excreted in urine. Naloxone has been added to a sublingual formulation of buprenorphine to reduce the abuse liability of the product. The presence of naloxone does not appear to influence the pharmacokinetics of buprenorphine. Buprenorphine crosses the placenta during pregnancy and also crosses into breast milk. Buprenorphine dosage does not need to be significantly adjusted in patients with renal impairment; however, since CYP3A activity may be decreased in patients with severe chronic liver disease, it is possible that the metabolism of buprenorphine will be altered in these patients. Although there is limited evidence in the literature to date, drugs that are known to inhibit or induce CYP3A4 have the potential to diminish or enhance buprenorphine N-dealkylation. It appears that the interaction between buprenorphine and benzodiazepines is more likely to be a pharmacodynamic (additive or synergistic) than a pharmacokinetic interaction. The relationship between buprenorphine plasma concentration and response in the treatment of opioid dependence has not been well studied. The pharmacokinetic and pharmacodynamic properties of buprenorphine allow it to be a feasible option for substitution therapy in the treatment of opioid dependence.
Topics: Biological Availability; Buprenorphine; Humans; Metabolic Clearance Rate; Opioid-Related Disorders
PubMed: 15966752
DOI: 10.2165/00003088-200544070-00001 -
Journal of Addiction MedicineAs overdose deaths from fentanyl continue to increase, optimizing use of medications for opioid use disorder has become increasingly important. Buprenorphine is a highly... (Review)
Review
OBJECTIVES
As overdose deaths from fentanyl continue to increase, optimizing use of medications for opioid use disorder has become increasingly important. Buprenorphine is a highly effective medication for reducing the risk of overdose death, but only if a patient remains in treatment. Shared decision making between prescribers and patients is important to establish a dose that meets each patient's treatment needs. However, patients frequently face a dose limit of 16 or 24 mg/d based on dosing guidelines on the Food and Drug Administration's package label.
METHODS
This review discusses patient-centered goals and clinical criteria for determining dose adequacy, reviews the history of buprenorphine dose regulation in the United States, examines pharmacological and clinical research results with buprenorphine doses up to 32 mg/d, and evaluates whether diversion concerns justify maintaining a low buprenorphine dose limit.
RESULTS
Pharmacological and clinical research results consistently demonstrate buprenorphine's dose-dependent benefits up to at least 32 mg/d, including reductions in withdrawal symptoms, craving, opioid reward, and illicit use while improving retention in care. Diverted buprenorphine is most often used to treat withdrawal symptoms and reduce illicit opioid use when legal access to it is limited.
CONCLUSIONS
In light of established research and profound harms from fentanyl, the Food and Drug Administration's current recommendations on target dose and dose limit are outdated and causing harm. An update to the buprenorphine package label with recommended dosing up to 32 mg/d and elimination of the 16 mg/d target dose would improve treatment effectiveness and save lives.
Topics: Humans; Buprenorphine; Analgesics, Opioid; Narcotic Antagonists; Opioid-Related Disorders; Fentanyl; Drug Overdose; Substance Withdrawal Syndrome
PubMed: 37788601
DOI: 10.1097/ADM.0000000000001189 -
Anesthesiology Clinics Sep 2018As part of a national effort to combat the current US opioid epidemic, use of currently Food and Drug Administration-approved drugs for the treatment of opioid use... (Review)
Review
As part of a national effort to combat the current US opioid epidemic, use of currently Food and Drug Administration-approved drugs for the treatment of opioid use disorder/opioid addiction (buprenorphine, methadone, and naltrexone) is on the rise. To provide optimal pain control and minimize the risk of relapse and overdose, providers need to have an in-depth understanding of how to manage these medications in the perioperative setting. This article reviews key principles and discusses perioperative considerations for patients with opioid use disorder on buprenorphine, methadone, or naltrexone.
Topics: Buprenorphine; Humans; Methadone; Naltrexone; Opioid-Related Disorders; Pain Management; Perioperative Care
PubMed: 30092933
DOI: 10.1016/j.anclin.2018.04.002 -
Drug and Alcohol Dependence Feb 1985Buprenorphine is a mixed agonist-antagonist with high affinity at both mu and kappa opiate receptors. Its pharmacological profile is determined primarily by partial... (Review)
Review
Buprenorphine is a mixed agonist-antagonist with high affinity at both mu and kappa opiate receptors. Its pharmacological profile is determined primarily by partial agonism at mu-receptors and unusually slow kinetics at these receptors. Its intrinsic activity is such that in nearly all clinical situations it is as effective an analgesic as morphine with considerably longer duration and much more favourable acute safety. In long-term dosing studies in rodents and primates buprenorphine did not produce the manifestations of physical dependence when treatment was stopped. In self-administration studies in the same species only limited levels of reinforcing efficacy were demonstrated when compared with the opiates. In human former opiate addicts the limited potential of buprenorphine to produce psychological dependence was confirmed as was the favourable physical dependence profile. Some misuse of buprenorphine has been reported in 3 of the 29 countries in which buprenorphine is marketed despite its wide clinical acceptance, particularly as the sublingual formulation.
Topics: Animals; Buprenorphine; Chemical Phenomena; Chemistry; Depression, Chemical; Discrimination, Psychological; Dose-Response Relationship, Drug; Humans; Macaca mulatta; Morphinans; Morphine; Rats; Receptors, Opioid; Receptors, Opioid, kappa; Receptors, Opioid, mu; Reinforcement, Psychology; Respiration; Self Administration; Substance-Related Disorders
PubMed: 2986930
DOI: 10.1016/0376-8716(85)90067-5 -
Psychological Medicine Apr 2020Depression and post-traumatic stress disorder (PTSD) are leading causes of disability and loss of life by suicide. Currently, there are less than satisfactory medical... (Review)
Review
BACKGROUND
Depression and post-traumatic stress disorder (PTSD) are leading causes of disability and loss of life by suicide. Currently, there are less than satisfactory medical solutions to treat these mental disorders. Here, we explore recent preclinical and clinical studies demonstrating the potential of using buprenorphine to treat major depressive disorder, treatment-resistant depression, and PTSD.
METHOD
Bibliographic databases were searched to include preclinical and clinical studies demonstrating the therapeutic potential of buprenorphine and the involvement of the kappa opioid receptor (KOR) in mediating these effects.
RESULTS
Original clinical studies examining the effectiveness of buprenorphine to treat depression were mixed. The majority of participants in the PTSD studies were males and suffer from chronic pain and/or substance use disorders. Nonetheless, these recent studies and analyses established proof of concept warranting farther investigations. Additionally, KOR likely mediates the antidepressant and some of the anxiolytic effects of buprenorphine. Still, it appears that the full spectrum of buprenorphine's beneficial effects might be due to activity at other opioid receptors as well.
CONCLUSIONS
Pharmaceuticals' abilities to treat medical conditions directly relates to their ability to act upon the endogenous biological systems related to the conditions. Thus, these recent findings are likely a reflection of the central role that the endogenous opioid system has in these mental illnesses. Further studies are necessary to study the involvement of endogenous opioid systems, and specifically KOR, in mediating buprenorphine's beneficial effects and the ability to treat these medical conditions while minimizing risks for misuse and diversion.
Topics: Adolescent; Adult; Aged; Analgesics, Opioid; Antidepressive Agents; Buprenorphine; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Drug Combinations; Female; Humans; Male; Middle Aged; Naltrexone; Prospective Studies; Stress Disorders, Post-Traumatic; Young Adult
PubMed: 32204739
DOI: 10.1017/S0033291720000525 -
Best Practice & Research. Clinical... Sep 2020Reclassification of chronic pain as a disease may be helpful because patients with chronic pain require significant treatment and rehabilitation with a clear diagnosis.... (Review)
Review
Reclassification of chronic pain as a disease may be helpful because patients with chronic pain require significant treatment and rehabilitation with a clear diagnosis. This can help address critical factors including suffering, quality of life, participation, and with family and social life, which continue to become more important in evaluating the quality of the health care we give our patients today. During the past decade of the opioid epidemic, methadone was the primary treatment for opioid addiction until buprenorphine was approved. Buprenorphine's high-affinity partial agonist properties make it a good alternative to methadone due to lower abuse potential and safer adverse effect profile while maintaining significant efficacy. Expanded out-patient prescribing options have allowed physician and physician extenders such as physician assistants and nurse practitioners to treat these patients that otherwise would have been required to utilize methadone. With unique pharmacological properties, buprenorphine is a safe and effective analgesic for chronic pain. The literature for buprenorphine shows great potential for its utilization in the treatment of chronic pain.
Topics: Analgesics, Opioid; Buprenorphine; Chronic Pain; Drug Partial Agonism; Drug Therapy, Combination; Drug Utilization; Humans
PubMed: 33004153
DOI: 10.1016/j.bpa.2020.06.005 -
Journal of General Internal Medicine Jun 2023
Topics: Humans; Buprenorphine; Narcotic Antagonists; Opiate Substitution Treatment
PubMed: 36988866
DOI: 10.1007/s11606-023-08038-1