Authors
Mingfeng Xie, Pei Huang, Shihuai Wang, Jingyi Ma, Yan Zeng, Jie Sun
Published in
The International journal of risk & safety in medicine. Pages 9246479261468499. Jul 10, 2026. Epub Jul 10, 2026.
Abstract
BackgroundSelective serotonin reuptake inhibitors (SSRIs) are first-line treatments for depression but are associated with significant sexual side effects. Post-SSRI Sexual Dysfunction (PSSD) describes a persistent syndrome of sexual dysfunction, including genital anesthesia and anhedonia, that continues or emerges after drug cessation. Despite recent warnings from regulatory bodies like the EMA, PSSD remains under-recognized.MethodsA systematic review was conducted using PubMed, Web of Science, and Scopus databases up to April 2024. Studies focusing on PSSD pathophysiology, diagnostic criteria, and therapeutic interventions were analyzed.ResultsPrevalence estimates suggest persistent symptoms in up to 74% of affected cohorts beyond 6 months. The pathophysiology is multifactorial, involving 5-HT1A receptor desensitization, neurosteroid (allopregnanolone) depletion via 5α-reductase inhibition, and epigenetic silencing of dopaminergic reward circuits. Diagnosis is clinical, based on 2022 standardized criteria, distinguishing PSSD from depressive relapse by specific somatic symptoms like genital numbness. No FDA-approved treatments exist, though off-label use of dopamine agonists and low-power laser therapy shows preliminary promise.ConclusionPSSD is a severe iatrogenic condition requiring heightened pharmacovigilance. Future research must prioritize biomarker identification and prospective trials for targeted neurosteroid therapies.
PMID:
42430418
Bibliographic data and abstract were imported from PubMed on 11 Jul 2026.
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