Journal
JAMA PSYCHIATRY
Volume 78, Issue 9, Pages 979-993Publisher
AMER MEDICAL ASSOC
DOI: 10.1001/jamapsychiatry.2021.0976
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Funding
- Australian National Drug and Alcohol Research Centre scholarship
- University of New SouthWales Sydney
- Australian Government Department of Health
- National Health and Medical Research Council Senior Principal Research Fellowship [APP1135991]
- National Institutes of Health National Institute on Drug Abuse grant [R01DA1104470]
- National Institutes of Health NIAID [RFA-AI-18-026]
- Advancing the Health of People Who Use Drugs: Hepatitis C and Drug Dependence Program [APP1150078]
- National Institutes of Health Project Health Protection Research Unit in Behavioural Science and Evaluation at University of Bristol
- National Drug and Alcohol Research Centre
- University of New SouthWales Scientia PhD Scholarships
- National Health and Medical Research Council Emerging Leadership grant
- National Health and Medical Research Council Investigator Award
- Kirby Institute
- Accion Estrategica en Salud del Gobierno de Espana [AES PI19/00982]
- Michael Smith Foundation for Health Research
- Health Canada Substance Use and Addictions Program
- National Health and Medical Research Council Early Career Fellowship [1119992]
- Health Research Board, Ireland [HRAPHR-2015-1088]
- Medical Research Council Addiction Research Clinical Training Programme [MR/N00616X/1]
- Ministry of Science and Innovation, Institute of Health Carlos III, Spain [RD17/0017/0003, PI20/0883]
- National Health and Medical Research Council [1176131]
- National Health and Medical Research Council of Australia [1176131] Funding Source: NHMRC
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This systematic review and meta-analysis found that OAT was associated with lower rates of mortality. However, access to OAT remains limited, and insurance coverage remains low. Work to improve access globally may have important population-level benefits.
IMPORTANCE Mortality among people with opioid dependence is higher than that of the general population. Opioid agonist treatment (OAT) is an effective treatment for opioid dependence; however, there has not yet been a systematic review on the relationship between OAT and specific causes of mortality. OBJECTIVE To estimate the association of time receiving OAT with mortality. DATA SOURCES The Embase, MEDLINE, and PsycINFO databases were searched through February 18, 2020, including clinical trial registries and previous Cochrane reviews. STUDY SELECTION All observational studies that collected data on all-cause or cause-specific mortality among people with opioid dependence while receiving and not receiving OAT were included. Randomized clinical trials (RCTs) were also included. DATA EXTRACTION AND SYNTHESIS This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Data on study, participant, and treatment characteristics were extracted; person-years, all-cause mortality, and cause-specific mortality were calculated. Crude mortality rates and rate ratios (RRs) were pooled using random-effects meta-analyses. MAIN OUTCOMES AND MEASURES Overall all-cause and cause-specific mortality both by setting and by participant characteristics. Methadone and buprenorphine OAT were evaluated specifically. RESULTS Fifteen RCTs including 3852 participants and 36 primary cohort studies including 749 634 participants were analyzed. Among the cohort studies, the rate of all-cause mortality during OAT was more than half of the rate seen during time out of OAT (RR, 0.47; 95% CI, 0.42-0.53). This association was consistent regardless of patient sex, age, geographic location, HIV status, and hepatitis C virus status and whether drugs were taken through injection. Associations were not different for methadone (RR, 0.47; 95% CI, 0.41-0.54) vs buprenorphine (RR, 0.34; 95% CI, 0.26-0.45). There was lower risk of suicide (RR, 0.48; 95% CI, 0.37-0.61), cancer (RR, 0.72; 95% CI, 0.52-0.98), drug-related (RR, 0.41; 95% CI, 0.33-0.52), alcohol-related (RR, 0.59; 95% CI, 0.49-0.72), and cardiovascular-related (RR, 0.69; 95% CI, 0.60-0.79) mortality during OAT. In the first 4 weeks of methadone treatment, rates of all-cause mortality and drug-related poisoning were almost double the rates during the remainder of OAT (RR, 2.01; 95% CI, 1.55-5.09) but not for buprenorphine (RR, 0.58; 95% CI, 0.18-1.85). All-cause mortality was 6 times higher in the 4 weeks after OAT cessation (RR, 6.01; 95% CI, 4.32-8.36), remaining double the rate for the remainder of time not receiving OAT (RR, 1.81; 95% CI, 1.50-2.18). Opioid agonist treatment was associated with a lower risk of mortality during incarceration (RR, 0.06; 95% CI, 0.01-0.46) and after release from incarceration (RR, 0.09; 95% CI, 0.02-0.56). CONCLUSIONS AND RELEVANCE This systematic review and meta-analysis found that OAT was associated with lower rates of mortality. However, access to OAT remains limited, and insurance coverage remains low. Work to improve access globally may have important population-level benefits.
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