An analysis of suicidal and self-injurious behavior reports with antiseizure medications in the FDA adverse event database

Mokshal H Porwal; Abrahim N Razzak; Vinay Kumar; Ahmed Z Obeidat; Umesh Sharma

doi:10.1016/j.eplepsyres.2024.107382

An analysis of suicidal and self-injurious behavior reports with antiseizure medications in the FDA adverse event database

Epilepsy Res. 2024 May 17:203:107382. doi: 10.1016/j.eplepsyres.2024.107382. Online ahead of print.

Authors

Mokshal H Porwal¹, Abrahim N Razzak², Vinay Kumar³, Ahmed Z Obeidat⁴, Umesh Sharma⁵

Affiliations

¹ Department of Neurosurgery, Allegheny General Hospital, 320 E North Ave, Pittsburgh, PA 15212, USA; Department of Neurology, Medical College of Wisconsin, 8701 W Watertown Plank Rd, Milwaukee, WI 53226, USA.
² Department of Neurology, Medical College of Wisconsin, 8701 W Watertown Plank Rd, Milwaukee, WI 53226, USA. Electronic address: arazzak@mcw.edu.
³ Department of Neurology, Temple University, 1801 N Broad St., Philadelphia, PA 19122, USA.
⁴ Department of Neurology, Medical College of Wisconsin, 8701 W Watertown Plank Rd, Milwaukee, WI 53226, USA.
⁵ Department of Neurology, University of Central Florida, 4000 Central Florida Blvd, Orlando, FL 32816, USA.

PMID: 38761467
DOI: 10.1016/j.eplepsyres.2024.107382

Abstract

Background: Pharmacovigilance systems such as the FDA Adverse Event Reporting System (FAERS), are established models for adverse event surveillance that may have been missed during clinical trials. We aimed to analyze twenty-five anti-seizure medications (ASMs) in FAERS to assess for increased reporting of suicidal and self-injurious behavior.

Methods: Twenty-five ASMs were analyzed: brivaracetam, cannabidiol, carbamazepine, clobazam, clonazepam, diazepam, eslicarbazepine, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, phenobarbital, phenytoin, pregabalin, primidone, rufinamide, stiripentol, tiagabine, topiramate, valproate, vigabatrin, zonisamide. Reports of "suicidal and self-injurious behavior" were collected from January 1, 2004, to December 31, 2020, using OpenVigil 2.1 tool with indication as "Epilepsy". Relative reporting ratio, proportional reporting ratio, and reporting odds ratio were calculated utilizing all other drug reports for epilepsy patients as a control.

Results: Significant relative operating ratio, ROR (greater than 1, p<0.05) were observed for diazepam (2.909), pregabalin (2.739), brivaracetam (2.462), gabapentin (2.185), clonazepam (1.649), zonisamide (1.462), lacosamide (1.333), and levetiracetam (1.286).

Conclusions: Of the 25 ASMs that were analyzed in this study, 4 (16%) were identified to have been linked with a likely true adverse event. These drugs included diazepam, brivaracetam, gabapenetin, and pregabalin. Although several limitations are present with the FAERS database, it is imperative to closely monitor patient comorbidities for increased risk of suicidality with the use of several ASMs.

Keywords: Anti-seizure medications; black box warning; food and drug administration; pharmacovigilance surveillance; suicidal and self-injurious behavior.