Koseki Takenao, Horie Mikako, Kumazawa Satomi, Nakabayashi Tetsuo, Yamada Shigeki
Department of Clinical Pharmacy, Fujita Health University School of Medicine, Toyoake, Japan.
Center for Regulatory Science, Pharmaceuticals and Medical Devices Agency, Tokyo, Japan.
Front Psychiatry. 2023 Jan 9;13:1091386. doi: 10.3389/fpsyt.2022.1091386. eCollection 2022.
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.
抗癫痫药物（AED）治疗后自杀倾向增加仍存在争议。本研究旨在调查日本自杀相关事件（SREs）的发生情况。通过使用2004年4月至2021年12月的日本药品不良事件报告（JADER）数据库计算报告比值比（RORs）和信息成分（ICs），评估口服使用的AEDs的SREs信号。此外，分析了影响SREs发生的因素以及从初始AED治疗到发病的时间。在22种AEDs中，有12种（水合吡仑帕奈、硝西泮、左乙拉西坦、氯硝西泮、氯巴占、丙戊酸钠、苯巴比妥、拉莫三嗪、拉科酰胺、加巴喷丁、唑尼沙胺和卡马西平）显示出SREs信号。20多岁和30多岁的患者、女性以及同时使用多种AEDs会影响SREs的发生。在6种AEDs中，服用所有AEDs的患者发生SREs的中位发病时间<100天。药物警戒方法显示，几种AEDs显示出自杀倾向信号。对于女性患者、20多岁和30多岁的患者、接受≥2种AEDs联合治疗的患者以及AED治疗过程中早期（初始治疗后<100天）的患者，应警惕SREs。
