-
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 -
Social Psychiatry and Psychiatric... Apr 2022This systematic review summarizes and presents the current state of research quantifying the relationship between mental disorder and overdose for people who use opioids. (Review)
Review
PURPOSE
This systematic review summarizes and presents the current state of research quantifying the relationship between mental disorder and overdose for people who use opioids.
METHODS
The protocol was published in Open Science Framework. We used the PECOS framework to frame the review question. Studies published between January 1, 2000, and January 4, 2021, from North America, Europe, the United Kingdom, Australia, and New Zealand were systematically identified and screened through searching electronic databases, citations, and by contacting experts. Risk of bias assessments were performed. Data were synthesized using the lumping technique.
RESULTS
Overall, 6512 records were screened and 38 were selected for inclusion. 37 of the 38 studies included in this review show a connection between at least one aspect of mental disorder and opioid overdose. The largest body of evidence exists for internalizing disorders generally and mood disorders specifically, followed by anxiety disorders, although there is also moderate evidence to support the relationship between thought disorders (e.g., schizophrenia, bipolar disorder) and opioid overdose. Moderate evidence also was found for the association between any disorder and overdose.
CONCLUSION
Nearly all reviewed studies found a connection between mental disorder and overdose, and the evidence suggests that having mental disorder is associated with experiencing fatal and non-fatal opioid overdose, but causal direction remains unclear.
Topics: Analgesics, Opioid; Drug Overdose; Europe; Humans; Opiate Overdose; Psychotic Disorders
PubMed: 34796369
DOI: 10.1007/s00127-021-02199-2 -
CMAJ : Canadian Medical Association... Oct 2023Higher doses of opioids, mental health comorbidities, co-prescription of sedatives, lower socioeconomic status and a history of opioid overdose have been reported as... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Higher doses of opioids, mental health comorbidities, co-prescription of sedatives, lower socioeconomic status and a history of opioid overdose have been reported as risk factors for opioid overdose; however, the magnitude of these associations and their credibility are unclear. We sought to identify predictors of fatal and nonfatal overdose from prescription opioids.
METHODS
We systematically searched MEDLINE, Embase, CINAHL, PsycINFO and Web of Science up to Oct. 30, 2022, for observational studies that explored predictors of opioid overdose after their prescription for chronic pain. We performed random-effects meta-analyses for all predictors reported by 2 or more studies using odds ratios (ORs) and 95% confidence intervals (CIs).
RESULTS
Twenty-eight studies (23 963 716 patients) reported the association of 103 predictors with fatal or nonfatal opioid overdose. Moderate- to high-certainty evidence supported large relative associations with history of overdose (OR 5.85, 95% CI 3.78-9.04), higher opioid dose (OR 2.57, 95% CI 2.08-3.18 per 90-mg increment), 3 or more prescribers (OR 4.68, 95% CI 3.57-6.12), 4 or more dispensing pharmacies (OR 4.92, 95% CI 4.35-5.57), prescription of fentanyl (OR 2.80, 95% CI 2.30-3.41), current substance use disorder (OR 2.62, 95% CI 2.09-3.27), any mental health diagnosis (OR 2.12, 95% CI 1.73-2.61), depression (OR 2.22, 95% CI 1.57-3.14), bipolar disorder (OR 2.07, 95% CI 1.77-2.41) or pancreatitis (OR 2.00, 95% CI 1.52-2.64), with absolute risks among patients with the predictor ranging from 2-6 per 1000 for fatal overdose and 4-12 per 1000 for nonfatal overdose.
INTERPRETATION
We identified 10 predictors that were strongly associated with opioid overdose. Awareness of these predictors may facilitate shared decision-making regarding prescribing opioids for chronic pain and inform harm-reduction strategies SYSTEMATIC REVIEW REGISTRATION: Open Science Framework (https://osf.io/vznxj/).
Topics: Humans; Analgesics, Opioid; Chronic Pain; Drug Overdose; Opiate Overdose; Prescriptions; Observational Studies as Topic
PubMed: 37871953
DOI: 10.1503/cmaj.230459 -
Drug and Alcohol Dependence Sep 2020Socioeconomic marginalization (SEM) is an important but under-explored determinant of opioid overdose with important implications for health equity and associated public...
BACKGROUND
Socioeconomic marginalization (SEM) is an important but under-explored determinant of opioid overdose with important implications for health equity and associated public policy initiatives. This systematic review synthesizes evidence on the role of SEM in both fatal and non-fatal overdose among people who use opioids.
METHODS
Studies published between January 1, 2000 and March 31, 2018 were identified through searching electronic databases, citations, and by contacting experts. The titles, abstracts, citation information, and descriptor terms of citations were screened by two team members. Data were synthesized using the lumping technique.
RESULTS
A total of 37 studies met inclusion criteria and were included in the review, with 34 of 37 finding a significant association between at least one socioeconomic factor and overdose. The included studies contained variables related to eight socioeconomic factors: criminal justice system involvement, income, employment, social support, health insurance, housing/homelessness, education, and composite measures of socio-economic status. Most studies found associations in the hypothesized direction, whereby increased SEM was associated with a higher rate or increased likelihood of the overdose outcome measured. The review revealed an underdeveloped evidence base.
CONCLUSIONS
Nearly all reviewed studies found a connection between a socioeconomic variable and overdose, but more research is needed with an explicit focus on SEM, using robust and nuanced measures that capture multiple dimensions of disadvantage, and collect data over time to better inform decision making around opioid overdose.
Topics: Analgesics, Opioid; Drug Overdose; Educational Status; Humans; Income; Opiate Overdose; Social Problems; Socioeconomic Factors
PubMed: 32650191
DOI: 10.1016/j.drugalcdep.2020.108127 -
Presse Medicale (Paris, France : 1983) 2017Heroin use can be responsible for many respiratory complications including asthma. (Review)
Review
INTRODUCTION
Heroin use can be responsible for many respiratory complications including asthma.
OBJECTIVES
Systematic literature review of data on asthma in heroin users.
DOCUMENTARY SOURCES
Medline, on the period 1980-2017 with the following keywords: keywords: "asthma" or "bronchospasm" and "heroin" or "opiate" or "opiates", limits "title/abstract"; the selected languages were English or French. Among 97 articles, 67 abstracts have given use to a dual reading to select 23 studies.
RESULTS
The seven case reports included 21 patients (mean age: 28 years [19-46 years]; sex-ratio: 2.5 [males: 71.5%]). Heroin was inhaled (71.4%), sniffed (19%) or injected by intravenous route (9.5%). Associated addictive substances were tobacco (81%), cannabis (38%), alcohol (4.7%) and cocaine (4.7%). Outcome was fatal in 3 subjects (14.3%). Other studies included one cross-sectional study, 3 case-control studies and 12 longitudinal studies (11 retrospective studies and one prospective study). The proportion of heroin users was higher in asthmatic subjects and the prevalence of asthma and bronchial hyperreactivity was higher in heroin users. Heroin use can be responsible for asthma onset, with a temporal relationship between the onset of heroin use and asthma onset in 28 to 31% of subjects. A positive association between inhaled heroin use and acute asthma exacerbation was observed. Asthma treatment observance was lower in heroin users. In case of asthma exacerbation, heroin users were more likely to seek care in the emergency department, to be admitted in intensive care units and to require intubation and invasive ventilation. Asthma deaths related to heroin use mainly occurred following an intravenous injection (especially in the case of overdose), but also following heroin use by nasal (sniff) or pulmonary route.
CONCLUSION
Heroin use may be responsible for asthma onset, acute asthma exacerbations (which may require intubation and invasive ventilation) or deaths related to asthma. Heroin use must be sought in case of asthma exacerbation in young persons and practitioners must help heroin users to stop their consumption.
Topics: Administration, Intranasal; Asthma; Bronchial Hyperreactivity; Heroin Dependence; Humans
PubMed: 28734637
DOI: 10.1016/j.lpm.2017.06.002 -
The International Journal on Drug Policy Mar 2022Opioid agonist therapy (OAT) has been severely disrupted by the COVID-19 pandemic. The risks of opioid withdrawal, overdose, and diversion have increased, so there is an... (Review)
Review
BACKGROUND
Opioid agonist therapy (OAT) has been severely disrupted by the COVID-19 pandemic. The risks of opioid withdrawal, overdose, and diversion have increased, so there is an urgent need to adapt OAT to best support people who use drugs (PWUD). This review examines the views and experiences of PWUD, health care providers, and health system administrators on OAT during major disruptions to medical care to inform appropriate health system responses during the current pandemic and beyond.
METHODS
We conducted a systematic review and qualitative evidence synthesis. We searched three comprehensive datasets for qualitative and mixed-methods studies that examined OAT in the context of major disruptions such as natural disasters, and analyzed included studies using thematic analysis and the constant comparative method. We used conceptual frameworks of health systems resilience and adaptive systems to interpret our findings.
RESULTS
We included 10 studies published between 2002 and 2020 that examined OAT in the context of hurricanes, earthquakes, and terrorist attacks. We organized our results into three themes: uncertainty, inconsistency, and vulnerability; regulatory inflexibility; and lack of coordination. The highly regulated but poorly coordinated systems of OAT provision lacked flexibility to adapt to major disruptions, thereby manufacturing vulnerability for both PWUD and health workers.
CONCLUSIONS
OAT programs must be resilient and adaptable to face major disruptions while maintaining quality care. Our findings provide guidance to develop and implement innovative strategies that increase the adaptive potential of OAT programs while focusing on the needs of PWUD.
Topics: Analgesics, Opioid; COVID-19; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Pandemics; SARS-CoV-2
PubMed: 34902805
DOI: 10.1016/j.drugpo.2021.103556 -
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 -
Value in Health : the Journal of the... Feb 2021The rapid increase in opioid overdose and opioid use disorder (OUD) over the past 20 years is a complex problem associated with significant economic costs for healthcare...
OBJECTIVES
The rapid increase in opioid overdose and opioid use disorder (OUD) over the past 20 years is a complex problem associated with significant economic costs for healthcare systems and society. Simulation models have been developed to capture and identify ways to manage this complexity and to evaluate the potential costs of different strategies to reduce overdoses and OUD. A review of simulation-based economic evaluations is warranted to fully characterize this set of literature.
METHODS
A systematic review of simulation-based economic evaluation (SBEE) studies in opioid research was initiated by searches in PubMed, EMBASE, and EbscoHOST. Extraction of a predefined set of items and a quality assessment were performed for each study.
RESULTS
The screening process resulted in 23 SBEE studies ranging by year of publication from 1999 to 2019. Methodological quality of the cost analyses was moderately high. The most frequently evaluated strategies were methadone and buprenorphine maintenance treatments; the only harm reduction strategy explored was naloxone distribution. These strategies were consistently found to be cost-effective, especially naloxone distribution and methadone maintenance. Prevention strategies were limited to abuse-deterrent opioid formulations. Less than half (39%) of analyses adopted a societal perspective in their estimation of costs and effects from an opioid-related intervention. Prevention strategies and studies' accounting for patient and physician preference, changing costs, or result stratification were largely ignored in these SBEEs.
CONCLUSION
The review shows consistently favorable cost analysis findings for naloxone distribution strategies and opioid agonist treatments and identifies major gaps for future research.
Topics: Analgesics, Opioid; Costs and Cost Analysis; Humans; Methadone; Models, Economic; Naloxone; Narcotic Antagonists; Opiate Overdose; Opiate Substitution Treatment; Opioid Epidemic; Opioid-Related Disorders
PubMed: 33518022
DOI: 10.1016/j.jval.2020.07.013 -
The Cochrane Database of Systematic... May 2016There are increasing concerns regarding pharmaceutical opioid harms including overdose and dependence, with an associated increase in treatment demand. People dependent... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There are increasing concerns regarding pharmaceutical opioid 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 agonist pharmacotherapy for the treatment of pharmaceutical opioid dependence.
SEARCH METHODS
The search included the Cochrane Drugs and Alcohol Group's Specialised Register of Trials; the Cochrane Central Register of Controlled Trials (CENTRAL, 2015, Issue 5); PubMed (January 1966 to May 2015); EMBASE (Ovid) (January 1974 to May 2015); CINAHL (EBSCOhost) (1982 to May 2015); ISI Web of Science (to May 2014); and PsycINFO (Ovid) (1806 to May 2014).
SELECTION CRITERIA
We included randomised controlled trials 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 and2. full or partial opioid agonist maintenance versus placebo, detoxification only, or psychological treatment (without opioid agonist treatment).
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodological procedures.
MAIN RESULTS
We identified six randomised controlled trials that met inclusion criteria (607 participants).We found moderate quality evidence from two studies of no difference between methadone and buprenorphine in self reported opioid use (risk ratio (RR) 0.37, 95% confidence interval (CI) 0.08 to 1.63) or opioid positive urine drug tests (RR 0.81, 95% CI 0.56 to 1.18). There was low quality evidence from three studies of no difference in retention between buprenorphine and methadone maintenance treatment (RR 0.69, 95% CI 0.39 to 1.22). There was moderate quality evidence from two studies of no difference between methadone and buprenorphine on adverse events (RR 1.10, 95% CI 0.64 to 1.91).We found low quality evidence from three studies favouring maintenance buprenorphine treatment over detoxification or psychological treatment in terms of fewer opioid positive urine drug tests (RR 0.63, 95% CI 0.43 to 0.91) and self reported opioid use in the past 30 days (RR 0.54, 95% CI 0.31 to 0.93). There was no difference on days of unsanctioned opioid use (standardised mean difference (SMD) -0.31, 95% CI -0.66 to 0.04). There was moderate quality evidence favouring buprenorphine maintenance over detoxification or psychological treatment on retention in treatment (RR 0.33, 95% CI 0.23 to 0.47). There was moderate quality evidence favouring buprenorphine maintenance over detoxification or psychological treatment on adverse events (RR 0.19, 95% CI 0.06 to 0.57).The main weaknesses in the quality of the data was the use of open-label study designs.
AUTHORS' CONCLUSIONS
There was low to moderate quality evidence supporting the use of maintenance agonist pharmacotherapy for pharmaceutical opioid dependence. Methadone or buprenorphine appeared equally effective. Maintenance treatment with buprenorphine appeared more effective than detoxification or psychological treatments.Due to the overall low to moderate quality of the evidence and small sample sizes, there is the possibility that the further research may change these findings.
Topics: Analgesics, Opioid; Buprenorphine; Humans; Methadone; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Prescription Drug Misuse; Randomized Controlled Trials as Topic
PubMed: 27157143
DOI: 10.1002/14651858.CD011117.pub2 -
Drug and Alcohol Dependence Sep 2021Non-fatal opioid-related overdoses have increased significantly over the past two decades and there have been increasing reports of brain injuries and/or neurocognitive... (Review)
Review
BACKGROUND
Non-fatal opioid-related overdoses have increased significantly over the past two decades and there have been increasing reports of brain injuries and/or neurocognitive impairments following overdose events. Limited preclinical research suggests that opioid overdoses may cause brain injury; however, little is known about such injuries in humans. The purpose this systematic review is to summarize existing studies on neurocognitive impairments and/or brain abnormalities associated with an opioid-related overdose in humans.
METHODS
PubMed, Web of Science, Ovid MEDLINE and PsyINFO were searched, without year restrictions, and identified 3099 articles. An additional 24 articles were identified by reviewing references. Articles were included if they were published in English, reported study findings in humans, included individuals 18 years of age or older, and reported an objective measure of neurocognitive impairments and/or brain abnormalities resulting from an opioid-related overdose. Six domains of bias (selection, performance, attrition, detection (two dimensions) and reporting were evaluated and themes were summarized.
RESULTS
Seventy-nine journal articles, published between 1973-2020, were included in the review. More than half of the articles were case reports (n = 44) and there were 11 cohort studies, 18 case series, and 6 case-control studies. All of the studies were categorized as at-risk of bias, few controlled for confounding factors, and methodological differences made direct comparisons difficult. Less than half of the studies reported toxicology results confirming an opioid-related overdose; 64.6 % reported brain MRI results and 27.8 % reported results of neuropsychological testing. Only two studies had within subject comparative data to document changes in the brain possibly associated with an overdose. Despite these limitations, existing publications suggest that brain injuries and neurocognitive impairments are associated with opioid overdose. Additional research is needed to establish the incidence of overdose-related brain injuries and the potential impact on functioning, as well as engagement in treatment of substance use disorders.
CONCLUSIONS
Respiratory depression is a defining characteristic of opioid overdose and prolonged cerebral hypoxia may cause brain injuries and/or neurocognitive impairments. The onset, characteristics, and duration of such injuries is variable and additional research is needed to understand their clinical implications.
Topics: Adolescent; Adult; Analgesics, Opioid; Brain; Drug Overdose; Humans; Opiate Overdose; Substance-Related Disorders
PubMed: 34271512
DOI: 10.1016/j.drugalcdep.2021.108838