Safety evaluation of zuranolone in the management of postpartum depression: A real-world pharmacovigilance study using the FDA adverse event reporting system (FAERS)

ObjectiveAs the first oral treatment FDA-approved for postpartum depression, the long-term adverse effects of zuranolone have not been fully investigated. This study aims to characterize the real-world safety profile of zuranolone.MethodsFAERS data from the third quarter of 2023 to the second quarter of 2025 were retrieved, covering adverse event (AEs) reports related to zuranolone. Signal detection was performed using ROR, PRR, BCPNN, and MGPS algorithms.FindingsOur study identified a total of 299 Preferred Terms with zuranolone as the primary suspect drug, involving 648 patients. Among the 24 identified System Organ Classes, nervous system disorders and psychiatric disorders were the most frequently reported AEs associated with zuranolone. Beyond the AEs already listed in the drug label, intrusive thoughts and feeling drunk exhibited strong signal intensity, though these findings require cautious interpretation. Our study identified unexpected safety concerns, including panic attack, tachyphrenia, suicidal ideation, dissociation, brain fog, and dysphemia, suggesting potential risks of depression switching to mania, suicide, addiction, and cognitive or speech-related impairments. The signal of exposure via breast milk highlights a unique population concern. Sleep-related AEs, such as somnolence, hypersomnia, and initial insomnia, highlight the central nervous system effects of zuranolone. Additionally, rare movement symptom-related AEs were observed, including tremor, muscle twitching, and motor dysfunction.ConclusionOur findings suggest that safety concerns associated with traditional GABAkines may persist in zuranolone. Given the specific patient population for zuranolone, clinicians should be particularly vigilant about its potential risks in certain clinical contexts, particularly breast milk exposure and the potential risk of sedation. Prospective clinical studies are warranted for continued monitoring of rare or long-term AEs. Further safety evaluations and clinical management strategies are essential.