Association of aggression and anti-seizure medications in pediatric patients: Disproportionality analysis using the FDA adverse event reporting system.

BACKGROUND

Aggression is one of the most common adverse events that negatively impacts quality of life and leads to anti-seizure medications (ASMs) discontinuation in patients with epilepsy. Pediatric patients may be more susceptible to aggression with ASMs. However, very few studies have systemically evaluated aggression associated with ASMs in a large sample of pediatric patients with epilepsy.

OBJECTIVE

The present study aimed to investigate the association of aggression with ASM use in pediatric patients by data mining of the self-reporting US Food and Drug Administration Adverse Event Report System (FAERS) database.

METHODS

FAERS data from January 2004 to June 2025 were analyzed with R software (version 4.5.1). Disproportionality analysis was performed using four methods, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Multi-Item Gamma Poisson Shrinker (MGPS), and Bayesian Confidence Propagation Neural Network (BCPNN), in order to evaluate the association between ASMs and aggression in pediatric population.

RESULTS

A total of 940 reports of ASMs-related aggression in pediatric population from FAERS database were analyzed. Potential positive signals for aggression, defined as detected by four algorithms, were identified for brivaracetam, clonazepam, levetiracetam and perampanel in school children (6-12 years old, excluding 12 years old); and for brivaracetam, levetiracetam, perampanel, pregabalin, and valproic acid in teenagers (12-18 years old, excluding 18 years old).

CONCLUSIONS

Signals of aggression related to different ASMs were identified. Significantly strong signals were observed for perampanel, levetiracetam and brivaracetam. Compared to infants and preschooler, ASM-associated aggression is more common in school children and teenagers.