Background Perinatal depression (PND) is a prevalent and serious mental health concern affecting women during pregnancy and the postpartum period. Although several drugs have been implicated in PND etiology in previous studies, large-scale systematic evaluations of drug-associated PND using real-world pharmacovigilance data remain scarce. Methods We conducted a retrospective pharmacovigilance study utilizing the FDA Adverse Event Reporting System data spanning from Q1 2004 to Q2 2025. Disproportionality analysis, logistic regression, LASSO regression, and time-to-onset analysis were employed to examine drug-PND associations from multiple analytical perspectives. Results Disproportionality analyses identified 28 drugs with positive signals as potentially associated with PND. Multi-factor analysis identified age under 26 years, weight exceeding 74 kg, and use of sodium oxybate, levonorgestrel, ethinylestradiol/etonogestrel, or lurasidone as independent risk factors for drug-related PND. The model achieved a ROC-AUC of 0.907, indicating excellent discriminatory performance. Conclusion This study identified specific drugs and demographic factors associated with PND risk, offering valuable insights for pharmacovigilance and clinical medication management.
Chen et al. (Fri,) studied this question.