A pharmacovigilance approach for assessing the occurrence of suicide-related events induced by antiepileptic drugs using the Japanese adverse drug event report database

Takenao Koseki; Mikako Horie; Satomi Kumazawa; Tetsuo Nakabayashi; Shigeki Yamada

doi:10.3389/fpsyt.2022.1091386

A pharmacovigilance approach for assessing the occurrence of suicide-related events induced by antiepileptic drugs using the Japanese adverse drug event report database

Front Psychiatry. 2023 Jan 9:13:1091386. doi: 10.3389/fpsyt.2022.1091386. eCollection 2022.

Authors

Takenao Koseki¹, Mikako Horie¹, Satomi Kumazawa¹, Tetsuo Nakabayashi², Shigeki Yamada¹

Affiliations

¹ Department of Clinical Pharmacy, Fujita Health University School of Medicine, Toyoake, Japan.
² Center for Regulatory Science, Pharmaceuticals and Medical Devices Agency, Tokyo, Japan.

Abstract

Increased suicidality after antiepileptic drug (AED) treatment remains controversial. This study aimed to investigate the occurrence of suicide-related events (SREs) in Japan. SREs signals with AEDs used orally were evaluated by calculating reporting odds ratios (RORs) and information components (ICs) using the Japanese Adverse Drug Event Report (JADER) database from April 2004 to December 2021. Additionally, factors affecting the occurrence of SREs and time-to-onset from the initial AED treatment were analyzed. Of 22 AEDs, 12 (perampanel hydrate, nitrazepam, levetiracetam, clonazepam, clobazam, sodium valproate, phenobarbital, lamotrigine, lacosamide, gabapentin, zonisamide, and carbamazepine) showed signals of SREs. Patients in their 20 and 30 s, female sex, and concomitant use of multiple AEDs affected the occurrence of SREs. In six AEDs, the median time-to-onset of SREs in patients taking all AEDs was <100 days. The pharmacovigilance approach revealed that several AEDs displayed suicidality signals. Female patients, those in their 20 and 30 s, undergoing combination therapy with ≥2 AEDs, and patients early (<100 days from the initial treatment) in the course of AED therapy should be cautioned about SREs.

Keywords: Japanese adverse drug event report; antiepileptic drugs; perampanel hydrate; pharmacovigilance; suicidality.

Grants and funding

This study received funding from the Teijin Pharma Limited through a scholarship donation. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication.