Real-world safety profile of zuranolone for postpartum depression: A FAERS analysis

Zuranolone, the first oral medication specifically designed to treat postpartum depression (PPD), was approved by the FDA in August 2023. However, reports on post-marketing adverse drug reactions (ADRs) related to it remain relatively limited. Therefore, this study aims to identify disproportional ADRs signals associated with zuranolone.

We extracted FAERS data from Q3 2023 to Q1 2025 and performed signal detection for zuranolone using both the reporting odds ratio (ROR) method and Bayesian confidence propagation neural network (BCPNN) method. Clinical prioritization of safety signals was performed on Preferred Terms (PTs) not listed in the product labeling. Conduct sensitivity analyses on subgroups of perinatal depression.

We identified 477 unique cases using zuranolone. Statistical disproportionality analysis detected positive signals for zuranolone predominantly in Nervous system disorders and Psychiatric disorders. Among adverse reactions (AEs) not listed in zuranolone's prescribing information, feeling drunk demonstrated the strongest positive signal, followed by bradyphrenia, intrusive thoughts, tachyphrenia, and hangover. It is worth noting that one death case due to suicide was reported in this analysis, which was submitted by a physician. Sensitivity analyses confirmed most positive signals aligned with initial findings (top 30 PTs).

Our pharmacovigilance study identified a high reporting frequency of psychiatric and neurological ADRs associated with zuranolone use. Given the inherent limitations in establishing causality through FAERS data, we emphasize the need for future clinical monitoring and research to further substantiate the potential causal relationship between zuranolone and these reported AEs.