Anticonvulsant Medications and the Risk of Suicide, Attempted Suicide, or Violent Death
Anticonvulsant Medications and the Risk of Suicide, Attempted Suicide, or Violent Death
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DOI：
10.1001/jama.2010.410
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发表时间：
2010-04-14
影响因子：
120.7
通讯作者：
Schneeweiss, Sebastian
中科院分区：
文献类型：
--
作者：
Patorno, Elisabetta;Bohn, Rhonda L.;Schneeweiss, Sebastian
背景 2008 年，美国食品和药物管理局强制要求抗惊厥药物必须贴上警告标签，以说明自杀念头和行为的风险增加。该决定基于一项荟萃分析，规模不足以调查个别药物。目的评估与个别抗惊厥药相关的自杀行为和联合自杀行为或暴力死亡的风险。设计一项队列研究，研究开始使用抗惊厥药物的患者与开始使用参考抗惊厥药物的患者相比，自杀行为和联合自杀行为或暴力死亡的风险。设置和患者来自 HealthCore 综合研究数据库 (HIRD) 的 15 岁及以上开始使用抗惊厥药物的患者。 2001 年 7 月至 2006 年 12 月期间服用抗惊厥药。 主要结果指标 使用 Cox 比例风险模型和倾向评分匹配分析来评估个体抗惊厥药与托吡酯和卡马西平相比，尝试或完成自杀以及联合自杀行为或暴力死亡的风险，控制精神合并症和其他危险因素。结果 该研究确定了 26 例完成自杀，801 例自杀在 297 620 次新的抗惊厥药物治疗中，有 41 例自杀未遂事件和 41 例暴力死亡事件（总体中位随访时间为 60 天）。在至少 100 次治疗中使用的抗惊厥药物的自杀完成、自杀未遂和暴力死亡的复合结局发生率范围为扑米酮每 1000 人年 6.2 例，奥卡西平每 1000 人年 34.3 例。加巴喷丁（风险比[HR]，1.42；95%置信区间[CI]，1.11-1.80）、拉莫三嗪（HR，1.84；95% CI，1.43-2.37）、奥卡西平（HR，2.07；95% CI，1.522.80）、与托吡酯相比，噻加宾（HR，2.41；95% CI，1.65-3.52）和丙戊酸钠（HR，1.65；95% CI，1.25-2.19）。包括暴力死亡在内的分析得出了类似的结果。与卡马西平相比，年轻和老年患者、情绪障碍患者以及癫痫或癫痫发作患者亚组中，加巴喷丁使用者的风险增加。 结论 这项探索性分析表明，与使用托吡酯相比，使用加巴喷丁、拉莫三嗪、奥卡西平和噻加宾可能会增加自杀行为或暴力死亡的风险。贾马。 2010； 303(14)：1401-1409
Context In 2008, the US Food and Drug Administration mandated warning labeling for anticonvulsant medications regarding the increased risk of suicidal thoughts and behaviors. The decision was based on a meta-analysis not sufficiently large to investigate individual drugs.Objective To evaluate the risk of suicidal acts and combined suicidal acts or violent death associated with individual anticonvulsants.Design A cohort study of the risk of suicidal acts and combined suicidal acts or violent death in patients beginning use of anticonvulsant medications compared with patients initiating a reference anticonvulsant drug.Setting and Patients Patients 15 years and older from the HealthCore Integrated Research Database (HIRD) who began taking an anticonvulsant between July 2001 and December 2006.Main Outcome Measures Cox proportional hazards models and propensity score-matched analyses were used to evaluate risk of attempted or completed suicide and combined suicidal acts or violent death, controlling for psychiatric comorbidities and other risk factors, among individual anticonvulsants compared with topiramate and secondarily carbamazepine.Results The study identified 26 completed suicides, 801 attempted suicides, and 41 violent deaths in 297 620 new episodes of treatment with an anticonvulsant (overall median follow-up, 60 days). The incidence of the composite outcomes of completed suicides, attempted suicides, and violent deaths for anticonvulsants used in at least 100 treatment episodes ranged from 6.2 per 1000 person-years for primidone to 34.3 per 1000 person-years for oxcarbazepine. The risk of suicidal acts was increased for gabapentin (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.11-1.80), lamotrigine (HR, 1.84; 95% CI, 1.43-2.37), oxcarbazepine (HR, 2.07; 95% CI, 1.522.80), tiagabine (HR, 2.41; 95% CI, 1.65-3.52), and valproate (HR, 1.65; 95% CI, 1.25-2.19), compared with topiramate. The analyses including violent death produced similar results. Gabapentin users had increased risk in subgroups of younger and older patients, patients with mood disorders, and patients with epilepsy or seizure when compared with carbamazepine.Conclusion This exploratory analysis suggests that the use of gabapentin, lamotrigine, oxcarbazepine, and tiagabine, compared with the use of topiramate, may be associated with an increased risk of suicidal acts or violent deaths. JAMA. 2010; 303(14): 1401-1409