Sex-based effectiveness in buprenorphine/naloxone and methadone treatment for opioid use disorder: Findings from the OPTIMA trial.

Abstract

Opioid use disorder (OUD) is a public health challenge globally. Few studies examine sex differences in opioid agonist therapy outcomes, especially in contexts of high potency opioid consumption. Clarifying these could inform personalized treatment strategies. We conducted exploratory sex-stratified analyses using data from a 24-week, multicentric, pragmatic, open-label randomized controlled trial. Participants with OUD (n male=179, n female=93) were randomized to flexible take-home dosing of buprenorphine/naloxone (n male=95, n female=43) or standard methadone (n male=84, n female=50) models of care. Retention was defined as having both an active prescription and a positive urine drug screen for the assigned treatment at week 24. Opioid use was assessed as the proportion of opioid-positive urine samples. Craving was measured using the Brief Substance Craving Scale and withdrawal using the Clinical Opiate Withdrawal Scale. Substance-use-related problems were evaluated via the Addiction Severity Index (ASI). In sex-stratified analyses, retention appeared overall lower for females (buprenorphine/naloxone=11.6%, methadone=26.0%) than males (buprenorphine/naloxone =28.4%, methadone=38.1%). Females showed higher opioid use overall; there was no treatment group effect on opioid use in either sex (p > 0.05). Both sexes improved in drug and psychiatric ASI domains (p < 0.05), while family-related problems improved only in males (p = 0.036). Craving decreased in both sexes, with females reporting lower craving on buprenorphine/naloxone than on methadone (p < 0.001). Withdrawal scores were higher with buprenorphine/naloxone versus methadone in males only (p = 0.026). We found potential sex differences in treatment outcomes, suggesting that these may benefit from sex-based adaptations. Future research into this possibility is warranted.