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    Slow release oral morphine versus methadone for the treatment of opioid use disorder
    Objective: To assess the efficacy of Slow release oral morphine (SROM) as a treatment for opioid use disorder. Design: Systematic review and meta-analysis of randomized controlled trials (RCT). Data sources: Three electronic databases were searched through May 1st, 2018: the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE. We also searched the following electronic registers for ongoing trials:, World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), Current Controlled Trials, and the EU Clinical Trials Register. Eligibility criteria for selecting studies: We included RCTs of any duration, assessing the effect of SROM on measures of treatment retention, heroin use and craving in adults who met the diagnostic criteria for opioid use disorder. Data extraction and synthesis: Two independent reviewers extracted data and assessed risk of bias. Data were pooled using the random-effects model and expressed as Risk Ratios (RR) or mean differences (MDs) with 95% CIs. Heterogeneity was assessed (chi-squared statistic) and quantified (I2 statistic) and a sensitivity analysis was undertaken to assess the impact of particular high-risk trials. Results: Among 1315 records screened and four studies reviewed, four unique randomized trials met inclusion criteria (n = 471), and compared SROM with methadone. In the meta-analysis, we observed no significant differences between SROM and methadone in improving treatment retention (risk ratio [RR] = 0.98; 95% Confidence Interval [CI]: 0.94 - 1.02, p = 0.34), and heroin use (RR = 0.96; 95% CI: 0.61- 1.52, p = 0.86). Craving data was not amenable to meta-analysis. Available data implied no differences in adverse events, heroin, cocaine, or benzodiazepine use. Conclusions: Meta-analysis of existing randomized trials suggests SROM may be generally equal to methadone in retaining patients in treatment and reducing heroin use as methadone while potentially resulting in less craving. The methodological quality of the included RCTs was low-to-moderate.
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