Associations of methadone and buprenorphine‐naloxone doses with unregulated opioid use, treatment retention, and adverse events in prescription‐type opioid use disorders: Exploratory analyses of the OPTIMA study

Background and Objectives Buprenorphine/naloxone (BUP‐NX) and methadone are used to treat opioid use disorder (OUD), yet there is insufficient evidence on the impact of doses on interventions' effectiveness and safety when treating OUD attributable to other opioids than heroin. Methods We explored associations between methadone and BUP‐NX doses and treatment outcomes using data from OPTIMA, a 24‐week, pragmatic, open‐label, multicenter, pan‐Canadian, randomized controlled, two‐arm parallel trial with participants (N = 272) with OUD who primarily use opioids other than heroin. Participants were randomized to receive flexible take‐home BUP‐NX (n = 138) or standard supervised methadone treatment (n = 134). We examined associations between highest BUP‐NX and methadone doses, and (1) percentage of opioid‐positive urine drug screens (UDS); (2) retention in the assigned treatment; and (3) adverse events (AEs). Results The mean (SD) highest BUP‐NX and methadone dose were 17.31 mg/day (8.59) and 67.70 mg/day (34.70). BUP‐NX and methadone doses were not associated with opioid‐positive UDS percentages or AEs. Methadone dose was associated with higher retention in treatment (odds ratio [OR]: 1.025; 95% confidence interval [CI]: 1.010; 1.041), while BUP‐NX dose was not (OR: 1.055; 95% CI: 0.990; 1.124). Higher methadone doses (70–110 mg/day) offered higher odds of treatment retention. Discussion and Conclusion Methadone dose was associated with higher retention, which may be related to its full µ‐opioid receptor agonism. Future research should notably ascertain the effect of pace of titration on a wide range of outcomes. Scientific Significance Our results extend previous findings of high doses of methadone increasing retention to be applied in our population using opioids other than heroin, including highly potent opioids.