Sex differences in outcomes of methadone maintenance treatment for opioid use disorder: a systematic review and meta-analysis

BACKGROUND: Opioid use disorder is a serious international concern with limited treatment success. Men and women differ in their susceptibility to opioid use disorder and response to methadone treatment and can therefore benefit from sex-specific treatment. We performed a systematic review of the literature on outcomes of methadone maintenance treatment for opioid use disorder in men and women related to drug use, health status and social functioning. METHODS: We searched PubMed, Embase, PsycINFO and CINAHL for observational or randomized controlled studies involving adults 18 years of age or older undergoing methadone treatment for opioid use disorder. Studies were included if they investigated sex differences in methadone treatment outcomes. Two authors independently reviewed and extracted data. Meta-analyses were performed when possible; risk of bias and quality of evidence were also assessed. RESULTS: Twenty studies with 9732 participants were included, of which 18 were observational and 2 were randomized controlled trials. Men and women differed significantly in alcohol use (odds ratio [OR] 0.52, 95% confidence interval [CI] 0.31 to 0.86), amphetamine use (OR 1.47, 95% CI 1.12 to 1.94), legal involvement (OR 0.63, 95% CI 0.47 to 0.84) and employment during treatment (OR 0.39, 95% CI 0.21 to 0.73). Opioid use patterns were similar among men and women. Risk of bias was moderate, and quality of evidence was generally low. INTERPRETATION: Sex differences were evident in polysubstance use, legal involvement and employment status among men and women receiving methadone treatment for opioid use disorders. Although the quality of evidence was low, our review highlights the need for improved implementation of sex-specific treatment strategies.