Antidepressant-Induced Sexual Dysfunction in Adults: A Targeted Scoping Review and Clinical Update.

Abstract

To conduct a scoping review of the prevalence, risk factors, neurobiological mechanisms, and clinical management of antidepressant-induced sexual dysfunction (AISD) in adults, including emerging evidence on post-SSRI sexual dysfunction (PSSD) and potential strategies for mitigation. A targeted scoping review with narrative synthesis was conducted using PubMed to identify English-language studies published from 2000 to 2025. A total of 65 studies were reviewed. Outcomes assessed included the frequency and severity of AISD, associated patient-related and drug-related predictors, and the reported effectiveness of pharmacologic and behavioral interventions. AISD appears to be a common and potentially under-recognized adverse effect of antidepressants, particularly with SSRIs and serotonin-norepinephrine reuptake inhibitors (SNRIs). Reported risk factors have been associated with higher antidepressant dose, male sex, older age, pre-existing sexual dysfunction, and greater depressive severity. Mechanistic contributors have been proposed and include serotonergic overactivation (notably 5-HT₂A/₂C receptors), dopaminergic and nitric oxide suppression, prolactin elevation, and possible epigenetic modulation, especially in cases of persistent dysfunction such as PSSD. Bupropion, mirtazapine, and agomelatine have been associated in several studies with more favorable sexual side effect profiles. Management strategies with supporting evidence have included dose reduction, switching to lower-risk agents, and augmentation with PDE5 inhibitors or bupropion. Nonpharmacologic interventions, such as exercise, psychotherapy, and mindfulness-based strategies, have shown preliminary benefit in selected studies and may serve as adjunctive options. AISD is a multifactorial adverse effect of antidepressant therapy that may persist in some individuals and can adversely affect quality of life and treatment adherence. Systematic assessment and individualized intervention may help mitigate impact, though optimal strategies remain incompletely defined. Increased recognition of PSSD highlights the need for further methodologically rigorous research into its pathophysiology, prevalence, and treatment.