Effects of opiate substitution treatment on mortality for opioids users: a systematic review and meta-analysis

Abstract Background Opioid dependence is associated with high risk of premature death. Opiate-substitution treatment (OST) is the major treatment in community for opioid dependence worldwide. We aimed to estimate crude mortality rates (CMRs) and the effects of OST on mortality risk by meta-analysis. Methods We searched PubMed and Embase databases for articles that were published until Sept 30, 2016 with a combination of terms including opiate treatment, substitution or maintenance, or buprenorphine, mortality, and or cohort studies. We restricted the search to articles written in English. We assessed the CMRs and relative risks (RR) for different OST status. We did subgroup analysis and meta-regression to determine the effect of treatment period, drug type, and drug dose on mortality. Findings 29 longitudinal cohort studies involving 395 055 participants (1 611 377·8 person-years) were eligible for inclusion in the meta-analysis. From 22 studies, the pooled all-cause CMRs of opioids users were 0·90 per 100 person-years (95% CI 0·77–1·02) while receiving OST, 1·63 (1·41–1·84) after cessation of OST, and 4·91 (3·52–6·30) for an untreated period. On the basis of ten studies, the pooled overdose CMRs were 0·18 (0·16–0·20) while receiving OST, 0·76 (0·52–1·00) after cessation of OST, and 2·02 (1·30–2·74) for an untreated period. Compared with patients receiving OST, untreated participants had higher risk of all-cause mortality (RR 2·48; 95% CI 1·73–3·54) and overdose mortality (6·60; 4·73–9·21), and participants discharged from OST had a higher risk for all-cause mortality (2·27; 1·99–2·59) and a higher risk of fatal overdose (3·76; 2·24–6·30). The risk of death was greatest in the first 2 weeks after discharge from OST (all-cause CMR 4·71; 95% CI 1·69–7·73). We found evidence that buprenorphine was associated with a lower mortality risk than methadone after terminating OST (0·81; 0·70–0·93). We found no difference of mortality risk to be associated with different types and dosages of medication. Interpretation OST could decrease mortality risk in opioids users, especially death from drug overdose. The findings highlight the importance of OST in the prevention of premature death among opioids users. Prevention of discharge from OST and post-treatment follow-up should be encouraged to reduce mortality. Funding Thirteenth Five-Year Programme of the Chinese Ministry of Science and Technology (2016YFC0800907).