Retention in opioid agonist treatment: a rapid review and meta-analysis comparing observational studies and randomized controlled trials

Background: Although oral opioid agonist therapies (OATs), buprenorphine and methadone, are effective first-line treatments, OAT remains largely underutilized due to low retention rates and wide variation across programs. This rapid review therefore sought to summarize the retention rates reported by randomized controlled trials (RCTs) and controlled observational study designs that compared methadone to buprenorphine (or buprenorphine-naloxone). Methods: We searched four electronic databases (EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials, CINAHL, up to April 2018) for RCTs and controlled observational studies that compared oral fixed-dose methadone to buprenorphine versus methadone (or buprenorphine-naloxone). Data were extracted separately for two different definitions of retention in treatment: (1) length of time retained in the study and (2) presence on the final day of a study. Separate random effects meta-analyses were performed for RCTs and controlled observational studies. Data from controlled observational studies where retention was measured as the length of time retained in the study were not amenable to meta-analysis. Results: Among 7603 studies reviewed, 10 RCTs and 3 observational studies met inclusion criteria (n = 5065) and compared fixed-dose oral buprenorphine with methadone. Across studies, the average retention rate was highly variable (RCTs: buprenorphine 20.0-82.5% and methadone 30.7-83.8%; observational studies: buprenorphine 20.2-78.3% and methadone 48.3-74.8%). For time period retained in the study, we observed no significant difference in treatment retention for buprenorphine versus methadone in RCTs (standardized mean difference [SMD] = - 0.07; 95% CI - 0.35-0.21, p = 0.63; quality of evidence: low). For presence on the final study day, we observed no significant difference between buprenorphine and methadone treatment retention in RCTs (risk ratio [RR] = 0.89; 95% CI 0.73-1.08, p = 0.24; quality of evidence: low) and controlled observational studies (RR = 0.75; 95% CI 0.36-1.58, p = 0.45). Conclusion: Meta-analysis of existing RCTs suggests retention in oral fixed-dose opioid agonist therapy with methadone appears to be generally equal to buprenorphine (or buprenorphine-naloxone), with wide variation across studies. Similarly, a meta-analysis of three controlled observational studies indicated no difference in treatment retention although there was significant heterogeneity among the included studies. The length of follow-up did not appear to affect the retention rate.