Abstract
OBJECTIVE: To synthesize and determine the relative effectiveness of diverse opioid agonist treatment (OAT) medications, including injectables, for opioid use disorder (OUD). METHODS: We searched EMBASE, PubMed, and CENTRAL for Randomised Controlled Trials (RCTs) (CRD42018109469) and previously published systematic reviews of head-to-head trials of OAT medications. The primary outcome was treatment retention, and secondary outcomes included days of opioid use, days of cocaine use, and proportion of participants involved in criminalized activities. We calculated odds ratios (ORs) and mean differences (MDs) and corresponding 95% credible intervals (CrI) using Bayesian network meta-analyses (NMAs) to indirectly compare treatments at varying lengths of follow-up (3 to 12 months). Sensitivity analyses examined influence of follow-up duration and other trial factors. RESULTS: Twenty-four RCTs were included. Diacetylmorphine plus oral methadone and injectable hydromorphone plus oral methadone had similar retention compared to one another (OR: 1.05; 95%CrI: 0.27, 4.10). Diacetylmorphine plus oral methadone had similar or statistically favourable retention versus low, medium, and high doses of conventional OATs: buprenorphine (OR: 13.55; 95%CrI: 4.51, 42.52; OR: 5.07; 95%CrI: 2.03, 12.47; OR: 2.21; 95%CrI: 0.18, 21.54) and methadone (OR: 5.88; 95%CrI: 2.34, 16.33; OR: 3.66; 95%CrI: 1.57, 8.82; OR: 3.67; 95%CrI: 1.83, 8.35). Similarly, injectable hydromorphone plus oral methadone also showed favourable or similar retention relative to conventional OATs. Limiting analyses to trials that included only OAT-experienced patients, that offered no extra participation incentive, and/or with 6 months (± 0.5) of follow-up generally did not change the direction of the findings. Injectable hydromorphone plus oral methadone was also statistically favoured in terms of reduced days of opioid use relative to methadone, but mean differences in days of cocaine use were similar. Diacetylmorphine plus oral methadone was associated with a smaller proportion of participation in criminalized activities relative to methadone alone. CONCLUSION: Both diacetylmorphine and injectable hydromorphone supplemented with methadone showed favourable retention compared to methadone and buprenorphine, depending on the strength of the OAT being co-prescribed or being compared to. These results provide further support for alternatives to conventional OATs such as diacetylmorphine or injectable hydromorphone for treatment retention.