Post-marketing safety evaluation of paroxetine: a real-world pharmacovigilance analysis based on the FDA adverse event reporting system

Objective Paroxetine, a selective serotonin reuptake inhibitor widely used in the management of major depressive disorders and other psychiatric disorders, remains insufficiently characterized regarding its adverse event spectrum. Thus, this study wanted to conduct a comprehensive evaluation of its post-marketing safety profile by analyzing reports from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). Methods Adverse event data related to paroxetine were extracted from the FAERS spanning the period from the first quarter of 2004 through the second quarter of 2025. Demographic distributions and reporter characteristics were analyzed to describe the exposed population. Signal detection was performed using four established disproportionality algorithms, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). Results A total of 39,404 adverse event reports associated with paroxetine were included in the analysis. Female patients accounted for the majority of cases (57.41%), followed by males (32.84%). The most frequently reported preferred term (PT) was “drug withdrawal syndrome,” categorized under systemic diseases and administration site conditions, with 6,601 cases. This event demonstrated strong positive signals across all disproportionality metrics (ROR = 27.27, PRR = 26.31, χ 2 = 148,641, IC = 4.61, EBGM = 23.47). The highest signal strengths were observed within the SOC of congenital, familial, and genetic disorders. Notably, the PT “carcinogenic effect on offspring,” although reported only three times, exhibited markedly elevated values (ROR = 952.54, PRR = 952.52, χ 2 = 712.89, IC = 7.90, EBGM = 238.88), indicating an extremely disproportionate reporting frequency compared with baseline levels. Most adverse events (12.49%) appeared within the first 30 days of paroxetine therapy prescription. Conclusion The pharmacovigilance assessment of paroxetine systematically identified significant safety signals. These findings provide important post-marketing evidence to strengthen drug safety surveillance and facilitate more informed, patient-centered therapeutic decisions in clinical settings.