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Meta-Analysis
. 2020 May 1;77(5):493-502.
doi: 10.1001/jamapsychiatry.2019.4170.

All-Cause and Cause-Specific Mortality Among People Using Extramedical Opioids: A Systematic Review and Meta-analysis

Sarah Larney  1   2 , Lucy Thi Tran  1 , Janni Leung  3   4 , Thomas Santo Jr  1 , Damian Santomauro  4   5   6 , Matt Hickman  7 , Amy Peacock  1 , Emily Stockings  1 , Louisa Degenhardt  1
Affiliations
Meta-Analysis

All-Cause and Cause-Specific Mortality Among People Using Extramedical Opioids: A Systematic Review and Meta-analysis

Sarah Larney et al. JAMA Psychiatry. .

Abstract

Importance: Extramedical opioid use has escalated in recent years. A better understanding of cause-specific mortality in this population is needed to inform comprehensive responses.

Objective: To estimate all-cause and cause-specific crude mortality rates (CMRs) and standardized mortality ratios (SMRs) among people using extramedical opioids, including age- and sex-specific estimates when possible.

Data sources: For this systematic review and meta-analysis, MEDLINE, PsycINFO, and Embase were searched for studies published from January 1, 2009, to October 3, 2019, and an earlier systematic review on this topic published in 2011.

Study selection: Cohort studies of people using extramedical opioids and reporting mortality outcomes were screened for inclusion independently by 2 team members.

Data extraction and synthesis: Data were extracted by a team member and checked by another team member. Study quality was assessed using a custom set of items that examined risk of bias and quality of reporting. Data were pooled using random-effects meta-analysis models. Heterogeneity was assessed using stratified meta-analyses and meta-regression.

Main outcomes and measures: Outcome measures were all-cause and cause-specific CMRs and SMRs among people using extramedical opioids compared with the general population of the same age and sex.

Results: Of 8683 identified studies, 124 were included in this analysis (100 primary studies and 24 studies providing additional data for primary studies). The pooled all-cause CMR, based on 99 cohorts of 1 262 592 people, was 1.6 per 100 person-years (95% CI, 1.4-1.8 per 100 person-years), with substantial heterogeneity (I2 = 99.7%). Heterogeneity was associated with the proportion of the study sample that injected opioids or was living with HIV infection or hepatitis C. The pooled all-cause SMR, based on 43 cohorts, was 10.0 (95% CI, 7.6-13.2). Excess mortality was observed across a range of causes, including overdose, injuries, and infectious and noncommunicable diseases.

Conclusions and relevance: The findings suggest that people using extramedical opioids experience significant excess mortality, much of which is preventable. The range of causes for which excess mortality was observed highlights the multiplicity of risk exposures experienced by this population and the need for comprehensive responses to address these. Better data on cause-specific mortality in this population in several world regions appear to be needed.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Larney reported receiving grants from the National Health and Medical Research Council and the National Institutes of Health during the conduct of the study and grants from Indivior outside the submitted work. Dr Leung reported receiving support from a development fellowship from the University of Queensland. Dr Stockings reported receiving grants from the Australian National Health and Medical Research Council. Dr Santomauro reported being employed by the Queensland Centre for Mental Health Research, which receives core funding from the Department of Health, Queensland Government, and reported receiving personal fees from Queensland Health outside the submitted work. Dr Hickman reported receiving financial support from the National Institute for Health Research Health Protection Research Unit in Evaluation of Interventions at University of Bristol; receiving personal fees from MSD, Gilead, and AbbVie outside the submitted work; and serving as a National Institute for Health Research senior investigator. Dr Peacock reported receiving grants from the Australian Government Department of Health and the Australian National Health and Medical Research Council during the conduct of the study and financial support from Seqirus and Mundipharma outside the submitted work. Dr Degenhardt reported receiving grants from the National Health and Medical Research Council and the National Institutes of Health during the conduct of the study and from Indivior and Seqirus outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. PRISMA Flow Diagram of Studies of Mortality Among People Using Extramedical Opioids
Figure 2.
Figure 2.. Distribution of Causes of Death in 19 Cohorts of People Using Extramedical Opioids
ID indicates infectious diseases; NCD, noncommunicable diseases.
See this image and copyright information in PMC

References

    1. Larance B, Degenhardt L, Lintzeris N, Winstock A, Mattick R. Definitions related to the use of pharmaceutical opioids: extramedical use, diversion, non-adherence and aberrant medication-related behaviours. Drug Alcohol Rev. 2011;30(3):236-245. doi:10.1111/j.1465-3362.2010.00283.x - DOI - PubMed
    1. Degenhardt L, Charlson F, Ferrari A, et al. ; GBD 2016 Alcohol and Drug Use Collaborators . The global burden of disease attributable to alcohol and drug use in 195 countries and territories, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Psychiatry. 2018;5(12):987-1012. doi:10.1016/S2215-0366(18)30337-7 - DOI - PMC - PubMed
    1. OECD Addressing Problematic Opioid Use in OECD Countries. Paris: OECD Health Policy Studies; 2019.
    1. Zibbell JE, Iqbal K, Patel RC, et al. ; Centers for Disease Control and Prevention (CDC) . Increases in hepatitis C virus infection related to injection drug use among persons aged ≤30 years—Kentucky, Tennessee, Virginia, and West Virginia, 2006-2012. MMWR Morb Mortal Wkly Rep. 2015;64(17):453-458. - PMC - PubMed
    1. Peters PJ, Pontones P, Hoover KW, et al. ; Indiana HIV Outbreak Investigation Team . HIV infection linked to injection use of oxymorphone in Indiana, 2014-2015. N Engl J Med. 2016;375(3):229-239. doi:10.1056/NEJMoa1515195 - DOI - PubMed

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