Mortality among regular or dependent users of heroin and other opioids: a systematic review and meta-analysis of cohort studies
TL;DR: Mortality among opioid-dependent users varies across countries and populations; treatment is clearly protective against mortality even in non-randomized observational studies; study characteristics predict mortality levels.
Abstract: Aims To review the literature on mortality among dependent or regular users of opioids across regions, according to specific causes, and related to a number of demographic and clinical variables. Methods Multiple search strategies included searches of Medline, EMBASE and PsycINFO, consistent with the methodology recommended by the Meta‐analysis of Observational Studies in Epidemiology (MOOSE) group; grey literature searches; and contact of experts for any additional unpublished data from studies meeting inclusion criteria. Random‐effects meta‐analyses were conducted for crude mortality rates (CMRs) and standardized mortality ratios (SMRs), with stratified analyses where possible. Meta‐regressions examined potentially important sources of heterogeneity across studies. Results Fifty‐eight prospective studies reported mortality rates from opioid‐dependent samples. Very high heterogeneity across studies was observed; pooled all‐cause CMR was 2.09 per 100 person‐years (PY; 95% CI; 1.93, 2.26), and the pooled SMR was 14.66 (95% CI: 12.82, 16.50). Males had higher CMRs and lower SMRs than females. Out‐of‐treatment periods had higher mortality risk than in‐treatment periods (pooled RR 2.38 (CI: 1.79, 3.17)). Causes of death varied across studies, but overdose was the most common cause. Multivariable regressions found the following predictors of mortality rates: country of origin; the proportion of sample injecting; the extent to which populations were recruited from an entire country (versus subnational); and year of publication. Conclusions Mortality among opioid‐dependent users varies across countries and populations. Treatment is clearly protective against mortality even in non‐randomized observational studies. Study characteristics predict mortality levels; these should be taken into account in future studies.
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TL;DR: Buprenorphine maintenance compared to placebo and to methadone maintenance in the management of opioid dependence, including its ability to retain people in treatment, suppress illicit drug use, reduce criminal activity, and mortality is evaluated.
Abstract: Methadone is widely used as a replacement for illicit opioid use such as heroin in medically-supported opioid substitution maintenance programmes. Two other drugs have been used to help reduce illicit opioid use, specifically buprenorphine and LAAM (levo-alpha-acetylmethadol). LAAM is not used in current clinical practice. Buprenorphine is currently used and can reduce illicit opioid use compared with placebo, although it is less effective than methadone. Buprenorphine is an opioid drug that is not as potent as heroin and methadone, although the effects of buprenorphine may last longer. Buprenorphine can be taken once every two days. The trials include different formulations of buprenorphine: sublingual solution, sublingual tablets, combined buprenorphine/naloxone sublingual tablet and an implant. Key results The review of trials found that buprenorphine at high doses (16 mg) can reduce illicit opioid use effectively compared with placebo, and buprenorphine at any dose studied retains people in treatment better than placebo. Buprenorphine appears to be less effective than methadone in retaining people in treatment, if prescribed in a flexible dose regimen or at a fixed and low dose (2 - 6 mg per day). Buprenorphine prescribed at fixed doses (above 7 mg per day) was not different from methadone prescribed at fixed doses (40 mg or more per day) in retaining people in treatment or in suppression of illicit opioid use.
1,599 citations
TL;DR: The excess risks of mortality and suicide in all mental disorders justify a higher priority for the research, prevention, and treatment of the determinants of premature death in psychiatric patients.
1,300 citations
Cites background from "Mortality among regular or dependen..."
...Another recent review (6) provided an SMR for opioid use of 14....
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...After exclusions, a final sample of 20 systematic reviews and meta-analyses (1,6,14-31) were included (Figure 1, Table 1)....
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TL;DR: 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.
Abstract: Objective 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.
Design Systematic review and meta-analysis.
Data sources Medline, Embase, PsycINFO, and LILACS to September 2016.
Study selection 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.
Data extraction and synthesis 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.
Results 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.
Conclusions 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.
1,114 citations
TL;DR: The regional and global distribution of use and estimated health burden from illicit drugs is outlined, and the health-related harms of cannabis use differ from those of amphetamine, cocaine, and opioid use, in that cannabis contributes little to mortality.
1,083 citations
TL;DR: The burden of disease attributable to alcohol and drug use varied substantially across geographical locations, and much of this burden was due to the effect of substance use on other health outcomes.
756 citations
References
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TL;DR: This paper examines eight published reviews each reporting results from several related trials in order to evaluate the efficacy of a certain treatment for a specified medical condition and suggests a simple noniterative procedure for characterizing the distribution of treatment effects in a series of studies.
33,234 citations
"Mortality among regular or dependen..." refers methods in this paper
...Random-effects meta-analyses of these pooled estimates and risk ratios and were performed using the ‘metan’ package of STATA version 10 [20], which uses inversevariance weighting to calculate: fixed- and randomeffects pooled summary estimates; confidence limits; a test for differences between study effects; and an estimate of between-study variance [21,22]....
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TL;DR: A checklist contains specifications for reporting of meta-analyses of observational studies in epidemiology, including background, search strategy, methods, results, discussion, and conclusion should improve the usefulness ofMeta-an analyses for authors, reviewers, editors, readers, and decision makers.
Abstract: ObjectiveBecause of the pressure for timely, informed decisions in public health
and clinical practice and the explosion of information in the scientific literature,
research results must be synthesized. Meta-analyses are increasingly used
to address this problem, and they often evaluate observational studies. A
workshop was held in Atlanta, Ga, in April 1997, to examine the reporting
of meta-analyses of observational studies and to make recommendations to aid
authors, reviewers, editors, and readers.ParticipantsTwenty-seven participants were selected by a steering committee, based
on expertise in clinical practice, trials, statistics, epidemiology, social
sciences, and biomedical editing. Deliberations of the workshop were open
to other interested scientists. Funding for this activity was provided by
the Centers for Disease Control and Prevention.EvidenceWe conducted a systematic review of the published literature on the
conduct and reporting of meta-analyses in observational studies using MEDLINE,
Educational Research Information Center (ERIC), PsycLIT, and the Current Index
to Statistics. We also examined reference lists of the 32 studies retrieved
and contacted experts in the field. Participants were assigned to small-group
discussions on the subjects of bias, searching and abstracting, heterogeneity,
study categorization, and statistical methods.Consensus ProcessFrom the material presented at the workshop, the authors developed a
checklist summarizing recommendations for reporting meta-analyses of observational
studies. The checklist and supporting evidence were circulated to all conference
attendees and additional experts. All suggestions for revisions were addressed.ConclusionsThe proposed checklist contains specifications for reporting of meta-analyses
of observational studies in epidemiology, including background, search strategy,
methods, results, discussion, and conclusion. Use of the checklist should
improve the usefulness of meta-analyses for authors, reviewers, editors, readers,
and decision makers. An evaluation plan is suggested and research areas are
explored.
17,663 citations
"Mortality among regular or dependen..." refers methods in this paper
...First, searches of the peerreviewed literature (Medline, EMBASE and PsycINFO) were conducted, consistent with the methodology recommended by the Meta-analysis of Observational Studies in Epidemiology (MOOSE) group [15]....
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TL;DR: The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) initiative developed recommendations on what should be included in an accurate and complete report of an observational study, resulting in a checklist of 22 items (the STROBE statement) that relate to the title, abstract, introduction, methods, results, and discussion sections of articles.
Abstract: Much biomedical research is observational. The reporting of such research is often inadequate, which hampers the assessment of its strengths and weaknesses and of a study's generalisability. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Initiative developed recommendations on what should be included in an accurate and complete report of an observational study. We defined the scope of the recommendations to cover three main study designs: cohort, case-control, and cross-sectional studies. We convened a 2-day workshop in September 2004, with methodologists, researchers, and journal editors to draft a checklist of items. This list was subsequently revised during several meetings of the coordinating group and in e-mail discussions with the larger group of STROBE contributors, taking into account empirical evidence and methodological considerations. The workshop and the subsequent iterative process of consultation and revision resulted in a checklist of 22 items (the STROBE Statement) that relate to the title, abstract, introduction, methods, results, and discussion sections of articles. 18 items are common to all three study designs and four are specific for cohort, case-control, or cross-sectional studies. A detailed Explanation and Elaboration document is published separately and is freely available on the Web sites of PLoS Medicine, Annals of Internal Medicine, and Epidemiology. We hope that the STROBE Statement will contribute to improving the quality of reporting of observational studies.
15,454 citations
"Mortality among regular or dependen..." refers methods in this paper
...In the data extraction stage we obtained information about study design and participants as recommended by the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines [17,18], parallel to the CONSORT guidelines for reporting of randomized trials [19]....
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TL;DR: The revised CONSORT statement is intended to improve the reporting of an RCT, enabling readers to understand a trial's conduct and to assess the validity of its results.
4,977 citations