Slow release oral morphine versus methadone for the treatment of opioid use disorder

Abstract

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: ClinicalTrials.gov, 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.

Keywords: meta-analysis; opioid use disorder; oral morphine; substance misuse; substance use treatment.

Figure 1

Flowchart of studies. Slow release oral morphine (SROM) as therapy for opioid use disorder (OUD) Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram.

Figure 2

(A) Forest plot of the effects of slow release oral morphine (SROM) on heroin use as measured by urine drug tests among persons with opioid use disorders (OUD) in randomised controlled trials (RCTs); Intention to Treat (ITT) population. (B) Forest plot of the effects of SROM on retention in treatment among persons with OUD in RCTs; ITT population. RR, risk ratio.