Abstract
BackgroundAlthough 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).MethodsWe 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.ResultsAmong 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).ConclusionMeta-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.Systematic review registrationPROSPERO CRD42018104452.
Highlights
Oral opioid agonist therapies (OATs), buprenorphine and methadone, are effective first-line treatments, opioid agonist treatment (OAT) remains largely underutilized due to low retention rates and wide variation across programs
In some of the most affected jurisdictions, over 70% of men and nearly 50% of women who have died of a prescription opioid overdose death did not have an active prescription in the 60 days prior to their death, suggesting the presence of significant diversion of prescription opioid medications [2]
Fentanyl contamination in the illicit drug market continues to contribute to an increase in opioid-related overdose deaths [5, 6], and a substantial proportion of opioid use disorder (OUD) starts with prescription opioids [7]
Summary
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. In some of the most affected jurisdictions, over 70% of men and nearly 50% of women who have died of a prescription opioid overdose death did not have an active prescription in the 60 days prior to their death, suggesting the presence of significant diversion of prescription opioid medications [2] When these analgesics first became available via unsafe prescribing practices in pain treatment, large numbers of opioid naïve persons developed prescription opioid use disorder (OUD) [3]. Fentanyl contamination in the illicit drug market continues to contribute to an increase in opioid-related overdose deaths [5, 6], and a substantial proportion of OUD starts with prescription opioids [7]. Only a fraction of people with OUD ever access treatment [1], and those who do are often poorly retained [10]
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