Newer Antiseizure Medications and Suicidality: Analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS) Database

Abstract

Background: The association between antiseizure medications (ASMs) and suicidality remains controversial. Analyses of additional datasets are needed to further elucidate the complex relationship between antiseizure medications and suicidality.

Objective: The aim of this study was to compare the safety profile of newer ASMs with older ASMs through an analysis of the US Food and Drug Administration Adverse Event Reporting System (FAERS) database, with a focus on suicidality.

Methods: We queried over 17 million reports in the FAERS database from 2012 to 2021 and identified cases involving ASMs. After removing incomplete and duplicate reports, the study cohort consisted of lacosamide (n = 7593), perampanel (n = 1813), clobazam (n = 3827), brivaracetam (n = 1166), and vigabatrin (n = 5293) compared with a control group of older ASMs (topiramate, lamotrigine, valproic acid, carbamazepine, levetiracetam; n = 71,535). Cases of suicidality (completed suicide, suicidal ideation, attempted suicide, suicidal behavior, suicidal depression) were identified in each group. Adjusted (age and sex) odds ratios (aOR) and associated 95% confidence intervals (CI) were calculated using logistic regression analysis for each new drug when compared with the control group of older ASM drugs.

Results: A total of 6309 cases of suicidality were identified among reports with ASMs. Most reports were sourced from healthcare professionals (5516, 87.4%). The proportion of reports involving suicidality were 210/7593 (2.8%) for lacosamide, 185/1813 (10.2%) for perampanel, 108/3827 (2.8%) for clobazam, 57/1166 (4.9%) for brivaracetam, 14/5293 (0.3%) for vigabatrin, and 5735/71,535 (8.0%) for older ASMs. Compared with older ASMs, the aOR for suicidality was 0.33 (95% CI 0.28-0.38) for lacosamide, 1.34 (95% CI 1.15-1.56) for perampanel, 0.35 (95% CI 0.29-0.43) for clobazam, 0.60 (95% CI 0.45-0.77) for brivaracetam, and 0.03 (95% CI 0.02-0.05) for vigabatrin.

Conclusion: When compared with older ASMs, four newer ASMs (lacosamide, clobazam, brivaracetam, and vigabatrin) were found to have significantly lower odds of suicidality, while perampanel was found to significantly increase the odds of suicidality. Pronounced variability (greater than 30 fold) in the proportion of FAERS reports associated with suicidality among the drugs studied was identified. The results of this case control study of FDA adverse event reports spanning 10 years and 6309 cases of suicidality expand our understanding of the safety profile of newer ASMs.