Sex-based Differences in the Efficacy and Tolerability of Selective Serotonin Reuptake Inhibitors in Adults with Major Depressive Disorder: A Systematic Review and Meta-analysis

Purpose of the Review: Sex-based differences in antidepressant outcomes may influence treatment decisions in major depressive disorder (MDD). This systematic review and meta-analysis evaluated sex-based differences in the efficacy and tolerability of selective serotonin reuptake inhibitors (SSRIs) in adults with MDD. Collection and Analysis of Data: PubMed, Cochrane Library, and Scopus were searched electronically, supplemented by citation searching. Two reviewers independently screened records and assessed full-text articles for eligibility. Of 3,523 records identified, 100 duplicates were removed, and 237 full-text articles were assessed, resulting in 10 included studies published between 2005 and 2025. Eligible studies included at least one SSRI arm with extractable sex-stratified outcome data specific to SSRIs. Risk of bias was assessed using RoB 2, the Newcastle–Ottawa Scale, and design-appropriate appraisal tools. Certainty of evidence was evaluated using GRADE. Pooled estimates were generated using random-effects meta-analysis.