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Slow release oral morphine versus methadone for the treatment of opioid use disorder
  1. Jan Klimas1,2,
  2. Lauren Gorfinkel3,
  3. Salvatore M Giacomuzzi4,
  4. Christian Ruckes5,
  5. M Eugenia Socías1,
  6. Nadia Fairbairn1,2,
  7. Evan Wood1,2
  1. 1BC Centre on Substance Use, Vancouver, Canada
  2. 2Department of Medicine, University of British Columbia, Vancouver, Canada
  3. 3Columbia University, New York, USA
  4. 4Universitätsklinik Innsbruck-Ambulanz für Abhängigkeitserkrankungen, Innsbruck, Austria
  5. 5University Medical Center Mainz, Interdisciplinary Center Clinical Trials, Mainz, Germany
  1. Correspondence to Dr Jan Klimas; jan.klimas{at}


Objective To assess the efficacy of slow release oral morphine (SROM) as a treatment for opioid use disorder (OUD).

Design Systematic review and meta-analysis of randomised controlled trials (RCTs).

Data sources Three electronic databases were searched through 1 May 2018: the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE. We also searched the following electronic registers for ongoing trials:, WHO International Clinical Trials Registry Platform, Current Controlled Trials and the EU Clinical Trials Register.

Eligibility criteria for selecting studies We included RCTs of all durations, assessing the effect of SROM on measures of treatment retention, heroin use and craving in adults who met the diagnostic criteria for OUD.

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 (RRs) or mean differences with 95% CIs. Heterogeneity was assessed (χ2 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 randomised trials met the 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 (RR=0.98; 95%CI: 0.94 to 1.02, p=0.34) and heroin use (RR=0.96; 95% CI: 0.61 to 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 randomised trials suggests SROM may be generally equal to methadone in retaining patients in treatment and reducing heroin use while potentially resulting in less craving. The methodological quality of the included RCTs was low-to-moderate.

  • opioid use disorder
  • substance misuse
  • substance use treatment
  • oral morphine
  • meta-analysis

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  • Contributors JK and EW conceived the idea for and designed the study. JK and LG conducted the research and wrote the first draft of the manuscript. SMG, CR, MES, NF contributed to the study design, interpretation of the findings and preparation of the manuscript. All authors reviewed and approved the final version of the manuscript. Ahmed Adam screened the titles, fulltexts and assessed risk of bias in the included studies.

  • Funding The study was supported by the US National Institutes of Health (R25DA037756). This research was undertaken, in part, thanks to funding from the Canada Research Chairs program through a Tier 1 Canada Research Chair in Inner City Medicine that supports Dr. Evan Wood. A European Commission grant (701698) supported Dr. Jan Klimas. The study was also supported by the Canadian Institutes of Health Research through the Canadian Research Initiative on Substance Misuse (SMN–139148) - and a Foundation Grant to Dr. Evan Wood. We thank Ahmed Adam for help with searching and screening. Dr. M. Eugenia Socías is supported by Michael Smith Foundation for Health Research (MSFHR) and Canadian Institutes of Health Research (CIHR) fellowship awards. Dr. Nadia Fairbairn is supported by a Michael Smith Foundation for Health Research/St. Paul’s Foundation Scholar Award.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement The data are extracted from published papers that are available via the individual journal websites.

  • Patient consent for publication Not required.

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