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Drug and Alcohol Dependence May 2023Methadone maintenance therapy is a leading treatment strategy for stabilizing and rehabilitating patients with opioid dependence; however, findings related to the risk... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Methadone maintenance therapy is a leading treatment strategy for stabilizing and rehabilitating patients with opioid dependence; however, findings related to the risk of motor vehicle collisions after methadone use have been conflicting. In the present study, we compiled the available evidence on the risk of motor vehicle collisions after methadone use.
METHODS
We completed a systematic review and meta-analysis of studies identified on six databases. Two reviewers independently screened the identified epidemiological studies, extracted data, and used the Newcastle-Ottawa Scale to assess the quality of the studies. Risk ratios were retrieved for analysis, conducted using random-effects model. Sensitivity analyses, subgroup analyses, and tests for publication bias were conducted.
RESULTS
Among 1446 identified relevant studies, a total of 7 epidemiological studies enrolling 33226142 participants met the inclusion criteria. Overall, study participants with methadone use had a higher risk of motor vehicle collisions than did those without methadone use (pooled relative risk 1.92, 95% CI 1.25-2.95; number needed to harm 11.3, 95% CI 5.3-41.6); the I statistic was 95.1%, indicating substantial heterogeneity. Subgroup analyses revealed that database type explained 95.36% of the between-study variance (p = 0.008). Egger's (p = 0.376) and Begg's (p = 0.293) tests revealed no evidence of publication bias. Sensitivity analyses indicated that the pooled results were robust.
CONCLUSION
The present review revealed that methadone use is significantly associated with a nearly doubled risk of motor vehicle collisions. Therefore, clinicians should exercise caution in implementing methadone maintenance therapy for drivers.
Topics: Humans; Methadone; Opioid-Related Disorders; Opiate Substitution Treatment; Accidents, Traffic; Motor Vehicles
PubMed: 36933540
DOI: 10.1016/j.drugalcdep.2023.109832 -
Pathophysiology : the Official Journal... Feb 2023The prevalence of opioid use among pregnant people has been increasing over the past few decades, with a parallel increase in the rate of neonatal abstinence syndrome.... (Review)
Review
The prevalence of opioid use among pregnant people has been increasing over the past few decades, with a parallel increase in the rate of neonatal abstinence syndrome. Opioid agonist treatment (OAT) including methadone and buprenorphine is the recommended management method for opioid use disorders during pregnancy. Methadone has been extensively studied during pregnancy; however, buprenorphine was introduced in the early 2000s with limited data on the use of different preparations during pregnancy. Buprenorphine-naloxone has been incorporated into routine practice; however, only a few studies have investigated the use of this medication during pregnancy. To determine the safety and efficacy of this medication, we conducted a systematic review of maternal and neonatal outcomes among buprenorphine-naloxone-exposed pregnancies. The primary outcomes of interest were birth parameters, congenital anomalies, and severity of neonatal abstinence syndrome. Secondary maternal outcomes included the OAT dose and substance use at delivery. Seven studies met the inclusion criteria. Buprenorphine-naloxone doses ranged between 8 and 20 mg, and there was an associated reduction of opioid use during pregnancy. There were no significant differences in gestational age at delivery, birth parameters, or prevalence of congenital anomalies between buprenorphine-naloxone-exposed neonates and those exposed to methadone, buprenorphine monotherapy, illicit opioids, or no opioids. In studies comparing buprenorphine-naloxone to methadone, there were reduced rates of neonatal abstinence syndrome requiring pharmacotherapy. These studies demonstrate that buprenorphine-naloxone is a safe and effective opioid agonist treatment for pregnant people with OUD. Further large-scale, prospective data collection is required to confirm these findings. Patients and clinicians may be reassured about the use of buprenorphine-naloxone during pregnancy.
PubMed: 36810423
DOI: 10.3390/pathophysiology30010004 -
Addiction (Abingdon, England) Jun 2023To estimate the efficacy of multiple psychosocial interventions for opioid-dependent people receiving methadone maintenance treatment (MMT). (Meta-Analysis)
Meta-Analysis
AIMS
To estimate the efficacy of multiple psychosocial interventions for opioid-dependent people receiving methadone maintenance treatment (MMT).
METHODS
Systematic review and network meta-analysis of randomized controlled trials (RCTs) reporting the effect of psychosocial intervention for opioid-dependent people receiving MMT in outpatient clinics. We searched multiple data sources (Medline, Embase, Web of Science, PsycINFO and Cochrane Library) from inception to January 2022, finding 21 RCTs evaluating a total of 2862 people with opioid dependence receiving MMT. The primary outcome was the opioid-positive rate (assessed by urinalysis) and the secondary outcome was treatment discontinuation (the number of patients who terminated the study for any reason). We performed random-effects Bayesian meta-analysis. We used relative ranking using surface under the cumulative ranking method and certainty of evidence using grading of recommendations, assessment, development and evaluations.
RESULTS
Cognitive-behavioral therapy (CBT) [odds ratio (OR) = 0.66, 95% credible interval (CI) = 0.66-0.96; low certainty] and educational and behavioral counseling (EBC) (OR = 0.28, 95% CI = 0.12-0.25; high certainty) were more effective than treatment as usual (TAU) in efficacy. In terms of treatment discontinuation, at the end of the follow-up period there was no statistical significance among psychosocial interventions. According to the ranking probabilities, EBC might be the most effective treatment and behavioral couples' therapy (BCT) might be the best discontinuation treatment.
CONCLUSIONS
Educational and behavioral counseling and cognitive-behavioral therapy appear to be the most effective psychosocial interventions for opioid-dependent people receiving methadone maintenance treatment.
Topics: Humans; Analgesics, Opioid; Cognitive Behavioral Therapy; Methadone; Network Meta-Analysis; Psychosocial Intervention
PubMed: 36787637
DOI: 10.1111/add.16167 -
Addictive Behaviors Apr 2023Craving is a distressing symptom of opioid use disorder (OUD) that can be alleviated with medications for OUD (MOUD). Buprenorphine is an effective MOUD that may... (Review)
Review
BACKGROUND
Craving is a distressing symptom of opioid use disorder (OUD) that can be alleviated with medications for OUD (MOUD). Buprenorphine is an effective MOUD that may suppress craving; however, treatment discontinuation and resumed opioid use is common during the early phases of treatment. More information on the craving response through the high-risk period of initiating buprenorphine may provide meaningful information on how to better target craving, which in turn may enhance outcomes. This systematic review investigated buprenorphine doses and formulations on craving during the induction and maintenance phases of treatment, and for context also compared the craving response to other MOUD (i.e., methadone, extended-release naltrexone [XR-NTX]).
METHODS
PubMed, PsycInfo, Embase, and Cochrane Central databases were searched for randomized trials of buprenorphine versus placebo, various buprenorphine formulations/doses, or other MOUD that included a measure of opioid craving.
RESULTS
A total of 10 studies were selected for inclusion. Buprenorphine and buprenorphine/naloxone (BUP/NAL) were each associated with lower craving than placebo over time. Craving was greater among those prescribed lower versus higher buprenorphine doses. In comparison to other MOUD, buprenorphine or BUP/NAL was linked to greater craving than methadone in 3 of the 6 studies. BUP/NAL was associated with greater reported craving than XR-NTX.
DISCUSSION
Craving is reduced over time with buprenorphine and BUP/NAL, although other MOUD may provide greater reductions in craving. Although there is currently considerable variability in the measurement of craving, it may be a valuable concept to address with individuals receiving MOUD, especially early in treatment.
Topics: Humans; Buprenorphine; Analgesics, Opioid; Narcotic Antagonists; Craving; Delayed-Action Preparations; Randomized Controlled Trials as Topic; Opioid-Related Disorders; Naltrexone; Buprenorphine, Naloxone Drug Combination; Methadone
PubMed: 36565531
DOI: 10.1016/j.addbeh.2022.107589 -
Addiction & Health Apr 2022Medicinal plants have revealed much attention as an alternative or complementary treatment for opioid withdrawal syndrome. The current review collects all available...
BACKGROUND
Medicinal plants have revealed much attention as an alternative or complementary treatment for opioid withdrawal syndrome. The current review collects all available literature to verify the efficiency of herbal remedies in the management of symptoms associated with opioid withdrawal.
METHODS
A systematic literature search was conducted from January 1990 to May 2021 on four bibliographic databases (Scopus, PubMed, Embase, and Web of Science) using the search terms "medicinal plant", "withdrawal syndrome", "opioid", and all their equivalents. All randomized controlled trials (RCTs), published in the English language were included for data synthesis. The search was performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA). The Cochrane risk of bias tool was used to verify the quality of the included clinical trials.
FINDINGS
A total of 12 RCTs were collected and used for data synthesis. The results of these studies indicated that herbal medicines were effective in treating opioid withdrawal syndrome and could alleviate the withdrawal symptoms, such as abdominal constrictions, diarrhea, bone pain, perspiration, and insomnia, when compared to conventional medications such as buprenorphine, clonidine, and methadone. However, more than 30% of RCTs were found to be at high risk of bias in the areas of selection, performance, detection, attrition, and reporting.
CONCLUSION
Although several RCTs have proven that herbal remedies are effective in reducing opioid withdrawal symptoms, the findings need to be viewed more carefully. Further RCTs with more participants, longer duration, and less risk of bias are needed in the claimed cases.
PubMed: 36544511
DOI: 10.22122/AHJ.2022.195961.1247 -
Drug and Alcohol Dependence Dec 2022While six U.S. states have already officially authorized cannabinoids to substitute opioids and treat opioid use disorder, the therapeutic benefits of cannabinoids... (Review)
Review
BACKGROUND
While six U.S. states have already officially authorized cannabinoids to substitute opioids and treat opioid use disorder, the therapeutic benefits of cannabinoids remain unclear, especially when weighted against their adverse effects.
METHODS
We conducted a systematic review of studies examining the association between opioid withdrawal and cannabis use or delta-9-tetrahydrocannabinol (THC) administration. We searched multiple databases from inception to July 30, 2022, and assessed study quality.
RESULTS
Eleven studies were identified, with a total of 5330 participants, of whom 64 % were male. Nine observational studies examined the association between cannabis use and opioid withdrawal. Two randomized, placebo-controlled clinical trials (RCTs) investigated the withdrawal-alleviating effects of dronabinol, a synthetic form of THC. Four observational studies found an association between cannabis use and the alleviation of opioid withdrawal; one reported exacerbation of opioid withdrawal symptoms; and four reported no association. RCTs reported that THC alleviated opioid withdrawal, albeit with dose-dependent increases in measures of abuse liability, dysphoria, and tachycardia. There was high heterogeneity in measurements of opioid withdrawal and the type and dose of opioid at baseline.
CONCLUSIONS
Although there is preliminary evidence that cannabis and its main psychoactive constituent, THC, may alleviate opioid withdrawal, these effects are likely to have a narrow therapeutic window. Further, the potential of cannabinoids to alleviate opioid withdrawal is determined by complex interactions between patient characteristics and pharmacological factors. Collectively, these findings have clinical, methodological, and mechanistic implications for treating opioid withdrawal during cannabinoid use, and for efforts to alleviate opioid withdrawal using non-opioid therapeutics.
Topics: Humans; Male; Female; Cannabis; Dronabinol; Cannabinoids; Cannabinoid Receptor Agonists; Hallucinogens; Substance Withdrawal Syndrome; Narcotics; Analgesics, Opioid
PubMed: 36434879
DOI: 10.1016/j.drugalcdep.2022.109702 -
Drug and Alcohol Dependence Dec 2022Evidence maps are emerging data visualization of a systematic review. There are no published evidence maps summarizing opioid use disorder (OUD) interventions.
BACKGROUND
Evidence maps are emerging data visualization of a systematic review. There are no published evidence maps summarizing opioid use disorder (OUD) interventions.
AIM
Our aim was to publish an interactive summary of all peer-reviewed interventional and observational trials assessing the treatment of OUD and common clinical outcomes.
METHODS
PubMed, Embase, PsycInfo, Cochrane Central Register of Clinical Trials, and Web of Science were queried using multiple OUD-related MESH terms, without date limitations, for English-language publications. Inclusions were human subjects, treatment of OUD, OUD patient or community-level outcomes, and systematic reviews of OUD interventions. Exclusions were laboratory studies, reviews, and case reports. Two reviewers independently scanned abstracts for inclusion before coding eligible full-text articles by pre-specified filters: research design, study population, study setting, intervention, outcomes, sample size, study duration, geographical region, and funding sources.
RESULTS
The OUD Evidence Map (https://med.nyu.edu/research/lee-lab/research/opioid-use-disorder-treatment-evidence-map) identified and assessed 12,933 relevant abstracts through 2020. We excluded 9455 abstracts and full text reviewed 2839 manuscripts; 888 were excluded, 1591 were included in the final evidence map. The most studied OUD interventions were methadone (n = 754 studies), buprenorphine (n = 499), and naltrexone (n = 134). The most common outcomes were heroin/opioid use (n = 708), treatment retention (n = 557), and non-opioid drug use (n = 368). Clear gaps included a wider array of opioid agonists for treatment, digital behavioral interventions, studies of OUD treatments in criminal justice settings, and overdose as a clinical outcome.
CONCLUSION
This OUD Evidence Map highlights the importance of pharmacologic interventions for OUD and reductions in opioid use. Future iterations will update results annually and scan policy-level interventions.
Topics: Humans; Opiate Substitution Treatment; Analgesics, Opioid; Opioid-Related Disorders; Buprenorphine; Methadone; Naltrexone
PubMed: 36332588
DOI: 10.1016/j.drugalcdep.2022.109657 -
The Journal of Pain Feb 2023To assess studies examining the prevalence of chronic pain (CP) in patients treated with Opioid Substitution Treatment (OST - buprenorphine or methadone) for Opioid Used... (Meta-Analysis)
Meta-Analysis Review
To assess studies examining the prevalence of chronic pain (CP) in patients treated with Opioid Substitution Treatment (OST - buprenorphine or methadone) for Opioid Used Disorder (OUD), we conducted a systematic review and meta-analysis of the literature between the years 2000 and 2020. We searched EMBASE, PsycINFO, Cochrane, and MEDLINE databases and included studies assessing the prevalence of CP in OUD adults treated with OST. The studies were assessed for risk of bias and overall quality and the results were pooled using a random-effects model. Subgroup analyses and meta-regressions were used to identify possible factors associated with CP. Twenty-three studies reported data on the prevalence of CP in patients treated with OST were evaluated. The prevalence obtained was 45.3% (CI95% [38.7; 52.1]). Overall, 78.3% of the studies had a low risk of bias. Subgroup analysis estimates did not vary according to gender, OST, and CP duration. However, it appeared that the clinical settings was associated with a lower CP prevalence when assessed in primary care sites. Our study provided an estimate regarding the prevalence of CP among OST patients. These patients deserve specific attention from health professionals and health authorities. Thus, the real challenge in OST patients is the implementation of a multidisciplinary approach to manage CP. PERSPECTIVE: Our meta-analysis provided an estimate of CP prevalence, reaching almost 50% of OUD patients with OST. Thus, the urgent challenge in OST patients is to pay systematic attention to chronic pain diagnosis, along with the implementation of a multidisciplinary patient-focused approach for an appropriate management of CP. REGISTRATION: PROSPERO (CRD42021284790).
Topics: Adult; Humans; Opiate Substitution Treatment; Chronic Pain; Prevalence; Opioid-Related Disorders; Methadone; Buprenorphine; Analgesics, Opioid
PubMed: 36220483
DOI: 10.1016/j.jpain.2022.08.008 -
Addiction Science & Clinical Practice Oct 2022Novel buprenorphine dosing strategies have emerged with an aim to transition patients from opioid agonists to buprenorphine without prerequisite opioid withdrawal. We...
BACKGROUND
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?
METHODS
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.
RESULT
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.
CONCLUSION
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
PubMed: 36195895
DOI: 10.1186/s13722-022-00336-z -
The Cochrane Database of Systematic... Sep 2022There are ongoing concerns regarding pharmaceutical opioid-related harms, including overdose and dependence, with an associated increase in treatment demand. People... (Review)
Review
BACKGROUND
There are ongoing concerns regarding pharmaceutical opioid-related harms, including overdose and dependence, with an associated increase in treatment demand. People dependent on pharmaceutical opioids appear to differ in important ways from people who use heroin, yet most opioid agonist treatment research has been conducted in people who use heroin. OBJECTIVES: To assess the effects of maintenance opioid agonist pharmacotherapy for the treatment of pharmaceutical opioid dependence.
SEARCH METHODS
We updated our searches of the following databases to January 2022: the Cochrane Drugs and Alcohol Group Specialised Register, CENTRAL, MEDLINE, four other databases, and two trial registers. We checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs).
SELECTION CRITERIA
We included RCTs with adults and adolescents examining maintenance opioid agonist treatments that made the following two comparisons. 1. Full opioid agonists (methadone, morphine, oxycodone, levo-alpha-acetylmethadol (LAAM), or codeine) versus different full opioid agonists or partial opioid agonists (buprenorphine) for maintenance treatment. 2. Full or partial opioid agonist maintenance versus non-opioid agonist treatments (detoxification, opioid antagonist, or psychological treatment without opioid agonist treatment).
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods.
MAIN RESULTS
We identified eight RCTs that met inclusion criteria (709 participants). We found four studies that compared methadone and buprenorphine maintenance treatment, and four studies that compared buprenorphine maintenance to either buprenorphine taper (in addition to psychological treatment) or a non-opioid maintenance treatment comparison. We found low-certainty evidence from three studies of a difference between methadone and buprenorphine in favour of methadone on self-reported opioid use at end of treatment (risk ratio (RR) 0.49, 95% confidence interval (CI) 0.28 to 0.86; 165 participants), and low-certainty evidence from four studies finding a difference in favour of methadone for retention in treatment (RR 1.21, 95% CI 1.02 to 1.43; 379 participants). We found low-certainty evidence from three studies showing no difference between methadone and buprenorphine on substance use measured with urine drug screens at end of treatment (RR 0.81, 95% CI 0.57 to 1.17; 206 participants), and moderate-certainty evidence from one study of no difference in days of self-reported opioid use (mean difference 1.41 days, 95% CI 3.37 lower to 0.55 days higher; 129 participants). There was low-certainty evidence from three studies of no difference between methadone and buprenorphine on adverse events (RR 1.13, 95% CI 0.66 to 1.93; 206 participants). We found low-certainty evidence from four studies favouring maintenance buprenorphine treatment over non-opioid treatments in terms of fewer opioid positive urine drug tests at end of treatment (RR 0.66, 95% CI 0.52 to 0.84; 270 participants), and very low-certainty evidence from four studies finding no difference on self-reported opioid use in the past 30 days at end of treatment (RR 0.63, 95% CI 0.39 to 1.01; 276 participants). There was low-certainty evidence from three studies of no difference in the number of days of unsanctioned opioid use (standardised mean difference (SMD) -0.19, 95% CI -0.47 to 0.09; 205 participants). There was moderate-certainty evidence from four studies favouring buprenorphine maintenance over non-opioid treatments on retention in treatment (RR 3.02, 95% CI 1.73 to 5.27; 333 participants). There was moderate-certainty evidence from three studies of no difference in adverse effects between buprenorphine maintenance and non-opioid treatments (RR 0.50, 95% CI 0.07 to 3.48; 252 participants). The main weaknesses in the quality of the data was the use of open-label study designs, and difference in follow-up rates between treatment arms.
AUTHORS' CONCLUSIONS
There is very low- to moderate-certainty evidence supporting the use of maintenance agonist pharmacotherapy for pharmaceutical opioid dependence. Methadone or buprenorphine did not differ on some outcomes, although on the outcomes of retention and self-reported substance use some results favoured methadone. Maintenance treatment with buprenorphine appears more effective than non-opioid treatments. Due to the overall very low- to moderate-certainty evidence and small sample sizes, there is the possibility that the further research may change these findings.
Topics: Adolescent; Analgesics, Opioid; Buprenorphine; Heroin; Humans; Methadone; Opioid-Related Disorders; Pharmaceutical Preparations
PubMed: 36063082
DOI: 10.1002/14651858.CD011117.pub3