Fluoxetine-associated adverse event signals with a focus on seizure: A study based on the FAERS database, network...

To evaluate fluoxetine-associated adverse event reporting signals in the FDA Adverse Event Reporting System (FAERS), focusing on seizure, and to explore potential biological plausibility using network pharmacology and molecular docking.

FAERS reports with fluoxetine as the suspected drug were extracted. Clinical characteristics, adverse event profiles, seriousness, outcomes, and time-to-onset were analyzed. Disproportionality analysis was performed using reporting odds ratio (ROR). Overlapping targets between fluoxetine and seizure were identified, followed by GO/KEGG enrichment, PPI analysis, and molecular docking.

Females accounted for 58.11% of fluoxetine-associated reports, and serious adverse events accounted for 86.45%. Psychiatric disorders and nervous system disorders were the main SOC categories, with RORs of 4.24 and 1.71, respectively. Seizure was reported in 496 cases (0.48%). Most adverse events occurred within 0-30 days, with a median onset of 11 days, while 14.34% occurred after 360 days. Mechanistic analysis identified 37 overlapping targets, mainly enriched in ion transport, neurotransmitter receptor activity, serotonergic and dopaminergic synapses, and inflammatory pathways. MAOA, BDNF, IL1B, CRH, IL6, and NTRK2 were identified as core targets. Docking suggested stable binding of fluoxetine with MAOA and NTRK2.

Fluoxetine-associated adverse events showed prominent psychiatric and neurological features. Seizure, although infrequent, warrants pharmacovigilance attention. MAOA and NTRK2 may be key candidate targets involved in fluoxetine-associated seizure.