Publication Highlights

Opioid use disorder (OUD) is associated with a high risk of premature death. Medication-assisted treatment (MAT) is the primary treatment for opioid dependence. We comprehensively assessed the effects of different MAT-related characteristics on mortality among those with OUD by a systematic review and meta-analysis. The all-cause and overdose crude mortality rates (CMRs) and relative risks (RRs) by treatment status, different type, period, and dose of medication, and retention time were pooled using random effects, subgroup analysis, and meta-regression. Thirty cohort studies involving 370,611 participants (1,378,815 person-years) were eligible in the meta-analysis. From 21 studies, the pooled all-cause CMRs were 0.92 per 100 person-years (95% CI: 0.79–1.04) while receiving MAT, 1.69 (1.47–1.91) after cessation, and 4.89 (3.54–6.23) for untreated period. Based on 16 studies, the pooled overdose CMRs were 0.24 (0.20–0.28) while receiving MAT, 0.68 (0.55–0.80) after cessation of MAT, and 2.43 (1.72–3.15) for untreated period. Compared with patients receiving MAT, untreated participants had higher risk of all-cause mortality (RR 2.56 [95% CI: 1.72–3.80]) and overdose mortality (8.10 [4.48–14.66]), and discharged participants had higher risk of all-cause death (2.33 [2.02–2.67]) and overdose death (3.09 [2.37–4.01]). The all-cause CMRs during and after opioid substitution treatment with methadone or buprenorphine were 0.93 (0.76–1.10) and 1.79 (1.47–2.10), and corresponding estimate for antagonist naltrexone treatment were 0.26 (0–0.59) and 1.97 (0–5.18), respectively. Retention in MAT of over 1-year was associated with a lower mortality rate than that with retention ≤1 year (1.62, 1.31–1.93 vs. 5.31, −0.09–10.71). Improved coverage and adherence to MAT and post-treatment follow-up are crucial to reduce the mortality. Long-acting naltrexone showed positive advantage on prevention of premature death among persons with OUD.

Implications

This study provided strong quantitative evidence that links mortality rate and mortality risk to different characteristics of MAT, further highlighting the importance of MAT in the prevention of premature death among individuals with OUDs. Opioids-related deaths remain a large burden to public health [4]. Increased efforts and interventions should be focused on lengthening retention time and target patients in their early stage of medication treatment initiation and cessation, and post-treatment follow-up should be emphasized after medication treatment cessation. Despite the protective effect of MAT on mortality, barriers still exist in the access to and utilization of MAT [7]. Facing the situation of limited coverage of OST and other harm reduction interventions in worldwide [72], increased coverage and expanding access to MAT are crucial components of the effort to reduce opioids-related deaths and alleviate disease burden. Naltrexone represents an alternative option to deliver medication treatment for those with OUDs, especially in the form of implants or extended-release, given that it was associated with a lower mortality rate than methadone and buprenorphine treatment. More research is still needed regarding to the effects of long-acting naltrexone treatment on mortality and other aspects among individuals with OUDs.