Principal component analysis of antiseizure medication-induced hostility/aggression and factor analysis of levetiracetam using the food and drug administration adverse event reporting system.

BACKGROUND: Epilepsy affects approximately 50 million people worldwide. Antiseizure medications (ASMs) are essential for seizure control. However, adverse psychiatric effects, particularly hostility and aggression, affect treatment adherence and the quality of life. The risk factors and mechanisms underlying these adverse effects remain unclear.

OBJECTIVE: This study aimed to classify ASM-induced hostility/aggression using the Food and Drug Administration Adverse Event Reporting System (FAERS), a global pharmacovigilance database, focusing on the risk factors and onset patterns of levetiracetam-induced hostility/aggression.

METHODS: The FAERS database (2004 Q1-2022 Q1) was analyzed to calculate the reporting odds ratios for ASM-induced hostility/aggression, which were classified using a principal component analysis. Levetiracetam-induced adverse effects and the associated independent risk factors were examined. Weibull distribution analysis was used to assess the time-to-onset patterns RESULTS: Principal component analysis identified eight ASM-induced adverse effects, including "aggression," "anger," "homicidal ideation," and "hostility." In those taking levetiracetam aged ≥ 12 years, male sex, younger age, and specific concomitant medications were independent risk factors for levetiracetam-induced adverse effects. Levetiracetam-induced adverse effects exhibited an early failure pattern, with a median onset of 4.5 days in patients aged ≥ 12 years and 1.5 days in those < 12 years.

CONCLUSION: In this study, we classified ASM-induced hostility/aggression and estimated the risk factors for levetiracetam-induced adverse effects. In particular, we identified early-onset patterns and high-risk patient profiles. These findings are consistent with clinical observations and provide insight into the mechanisms underlying these adverse effects, which will contribute to proactive risk management and personalized treatment strategies.