Pharmacovigilance of SSRIs in Children and Adolescents with Depression: Disproportionality Analysis of Serotonin Adverse Events Using the FAERS Database.

INTRODUCTION

Depression in minors is a growing global health concern with limited pharmacological options. This study evaluated the safety profiles of four selective serotonin reuptake inhibitors (SSRIs)-fluoxetine, sertraline, escitalopram, and fluvoxamine- in children and adolescents, focusing on serious adverse events (SAEs).

METHODS

Pediatric adverse event reports from the FAERS database (Q1 2004-Q1 2025) were analyzed. Only reports listing the study drugs as Primary Suspect were included; duplicates were removed. Events were coded using MedDRA 26.1 and analyzed at system organ class (SOC) and preferred term (PT) levels. Disproportionality analyses used reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma-Poisson shrinker (MGPS), with Bayesian shrinkage (EBGM05) applied to low-frequency signals.

RESULTS

Psychiatric events, including suicidal ideation, suicide attempts, and self-injury, showed the most consistent signals. Fluoxetine and sertraline had broad profiles; escitalopram showed higher disproportionality for psychiatric, cardiac, and perinatal events; fluvoxamine showed elevated signals for impulsive behaviors and rare systemic events. Neurological events, such as serotonin syndrome and tremor, were consistently reported; congenital and perinatal signals had limited statistical stability.

DISCUSSION: SSRIs share common psychiatric AE signals in minors, but differences in strength and distribution likely reflect real-world exposure, metabolic pathways, and structural properties rather than causal differences.

CONCLUSION

FAERS-based pharmacovigilance provides a comparative overview of SSRI safety, with multi-algorithm assessment and Bayesian shrinkage enhancing low-frequency signal reliability, informing safer SSRI use and guiding future studies integrating pharmacokinetics and pharmacogenomics.