Pharmacological Treatments for Alcohol Use Disorder: Considering the Role of Sex and Gender

Purpose of Review This qualitative literature review examined sex and gender differences in alcohol use disorder (AUD) pharmacotherapy treatment response. Specifically, we reviewed the clinical and preclinical literature evaluating sex and gender differences in responses to US Food and Drug Administration (FDA) and European Medicine Agency (EMA) approved medications, and repurposed, or off-label, medications for the treatment of AUD. Recent Findings Despite important sex and gender differences in AUD, the effect of sex and gender in the pharmacological treatment of AUD has been understudied. Relatively low representation of women in clinical studies has limited well powered investigations of gender effects on treatment response. Additionally, most preclinical support for AUD medications comes from studies in males. More recent AUD pharmacotherapy research has identified potential sex and gender differences in the efficacy of several pharmacological treatments for AUD. Although findings are mixed, clinical data suggest naltrexone may be more effective at reducing alcohol use in men, while baclofen may be more effective at reducing alcohol use in women. Preclinical studies have indicated sex-differences in the efficacy of topiramate and mifepristone, with putative higher efficacy of topiramate in males and mifepristone in females. Summary Historically, sex and gender differences have not been adequately considered in AUD medication development research. In order to improve translation of preclinical findings and clinical utility, sex and gender must be considered at each stage of drug development research.