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Effects of medication-assisted treatment on mortality among opioids users: a systematic review and meta-analysis


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.

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This work was supported by the Thirteenth Five-Year Program of the Chinese Ministry of Science and Technology (No. 2016YFC0800907), PUHSC-UMHS Joint Institute (No. BMU2017JI003) and the State Scholarship Fund of China (No. 201706015001).

Author contributions

YB, JS and LL were responsible for study design. JM and YB were responsible for the literature search and study selection. JM, MS, RW, and ML were responsible for data extraction and quality assessment. JM was responsible for statistical analysis and manuscript drafting. JS, LL, RW, MS, ML, JL, LD, MF, FB, MI, and YB were responsible for critical revision of the manuscript.

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Conflict of interest

In the past three years, LD and MF have received investigator-initiated untied educational grants for studies of opioid medications in Australia from Indivior, Mundipharma and Seqirus.The other authors declare that they have no conflict of interest.

Correspondence to Yan-Ping Bao or Jie Shi or Lin Lu.

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