Importance Most antiseizure medications (ASMs) carry a US Food and Drug Administration-mandated class label warning of increased suicidality risk, based on a meta-analysis comparing suicidality between individuals treated with medications vs placebo in randomized clinical trials done before 2008. ASMs approved since then carry this warning although they were not similarly studied. Objective To review all placebo-controlled phase 2 and 3 studies of 10 ASMs approved since 2008 to evaluate the risk of suicidality of these drugs compared with placebo. Data Sources Primary publications and secondary safety analyses in PubMed of all phase 2 and 3 randomized placebo-controlled epilepsy trials of ASMs approved since 2008, using keywords epilepsy, antiepileptic drugs, seizures, suicidality, suicidal ideation, and the names of individual drugs. Study Selection All phase 2 and 3 randomized clinical trials of adjunctive treatment of drug-resistant epilepsy and their secondary safety analyses. Data Extraction and Synthesis Articles were reviewed for frequency of suicidality (ideation, attempts, and completed suicides). Mode of suicidality ascertainment included treatment-emergent adverse event reports, Standardized Medical Dictionary for Regulatory Activities queries for events in prespecified categories including suicidal ideation and behavior, prospective collection of suicidality data as a prespecified safety outcome using the Columbia-Suicide Severity Rating Scale, and retrospective evaluation by blinded review using the Columbia-Classification Algorithm of Suicide Assessment. A meta-analysis compared risk for drugs vs placebo of each outcome for all drugs overall and by individual drugs and trials. Main Outcomes and Measures Suicidality (total and by ideation), attempts, and completed suicides. Results Excluding studies that did not evaluate suicidality (everolimus and fenfluramine) or did not evaluate it prospectively (lacosamide, ezogabine, and clobazam), 5 drugs were analyzed: eslicarbazepine, perampanel, brivaracetam, cannabidiol, and cenobamate. Suicidality was evaluated in 17 randomized clinical trials of these drugs, involving 5996 patients, of whom 4000 patients were treated with ASMs and 1996 with placebo. There was no evidence of increased risk of suicidal ideation (drugs vs placebo overall risk ratio, 0.75; 95% CI, 0.35-1.60) or attempt (risk ratio, 0.75; 95% CI, 0.30-1.87) overall or for any individual drug. Suicidal ideation occurred in 12 of 4000 patients treated with ASMs (0.30%) vs 7 of 1996 patients treated with placebo (0.35%) (P = .74). Three patients treated with ASMs and no patients treated with placebo attempted suicide (P = .22). There were no completed suicides. Conclusions and Relevance There is no current evidence that the 5 ASMs evaluated in this study increase suicidality in epilepsy and merit a suicidality class warning.

中文翻译：

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新型抗癫痫药物的自杀风险：荟萃分析。

重要性 大多数抗癫痫药物 (ASM) 都带有美国食品和药物管理局规定的类别标签，警告自杀风险增加，这是基于一项荟萃分析，比较了 2008 年之前进行的随机临床试验中接受药物治疗的个体与安慰剂治疗的个体之间的自杀倾向。自 2008 年以来批准的 ASM然后进行此警告，尽管它们没有经过类似的研究。目的回顾自 2008 年以来批准的 10 种 ASM 的所有安慰剂对照 2 期和 3 期研究，以评估这些药物与安慰剂相比的自杀风险。数据来源 PubMed 自 2008 年以来批准的所有 ASM 的 2 期和 3 期随机安慰剂对照癫痫试验的主要出版物和次要安全性分析，使用关键字癫痫、抗癫痫药物、癫痫发作、自杀、自杀意念和单个药物的名称。研究选择 耐药性癫痫辅助治疗的所有 2 期和 3 期随机临床试验及其二级安全性分析。数据提取和综合文章审查了自杀的频率（想法、企图和完成的自杀）。自杀确定模式包括治疗出现的不良事件报告、监管活动标准化医学词典查询预先指定类别中的事件，包括自杀意念和行为、使用哥伦比亚自杀严重程度评定量表前瞻性收集自杀数据作为预先指定的安全结果，以及使用哥伦比亚分类自杀评估算法通过盲法进行回顾性评估。一项荟萃分析比较了所有药物总体以及单个药物和试验的每种结果的药物风险与安慰剂风险。主要结果和措施 自杀（全部和按意念）、企图和完成的自杀。结果 排除未评估自杀性的研究（依维莫司和芬氟拉明）或未进行前瞻性评估的研究（拉考沙胺、依佐加滨和氯巴占），分析了 5 种药物：艾司利卡西平、吡仑帕奈、布立西坦、大麻二酚和辛诺巴酯。在这些药物的 17 项随机临床试验中评估了自杀性，涉及 5996 名患者，其中 4000 名患者接受了 ASM 治疗，1996 名患者接受了安慰剂治疗。没有证据表明自杀意念（药物与安慰剂的总体风险比，0.75；95% CI，0.35-1.60）或企图（风险比，0.75；95% CI，0.30-1. 87) 整体或任何单独的药物。接受 ASM 治疗的 4000 名患者中有 12 名（0.30%）出现自杀意念，而接受安慰剂治疗的 1996 名患者中有 7 名（0.35%）（P = .74）。3 名接受 ASM 治疗的患者和没有接受安慰剂治疗的患者企图自杀 (P = .22)。没有完成的自杀事件。结论和相关性 目前没有证据表明本研究中评估的 5 种 ASM 会增加癫痫患者的自杀率并应获得自杀级别警告。