Perampanel with concomitant levetiracetam and topiramate: Post hoc analysis of adverse events related to hostility and aggression
Perampanel with concomitant levetiracetam and topiramate: Post hoc analysis of adverse events related to hostility and aggression
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DOI：
10.1016/j.yebeh.2017.06.038
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发表时间：
2017-10-01
影响因子：
2.6
通讯作者：
Laurenza, Antonio
中科院分区：
文献类型：
--
作者：
Chung, Steve;Williams, Betsy;Laurenza, Antonio
在4项III期注册试验中（3项针对部分性癫痫发作患者，N = 1480； 1项针对PGTCS患者，N = 163）， perampanel给药于已经同时服用1-3种抗癫痫药物（AEDS）的患者，在减少癫痫发作频率方面显示出统计学上优于安慰剂的疗效。然而，在这些研究中使用perampanel与精神和行为不良反应的风险相关，包括攻击性、敌意、易怒、愤怒、杀人念头和威胁。本研究是对这4项试验的汇总数据进行事后分析，以确定左乙拉西坦和/或托吡酯联合治疗是否会增加敌意和攻击相关不良事件的风险。治疗突发事件（teae）是通过基于医学词典规范活动（MedDRA）标准MedDRA查询（SMQ）敌意和攻击相关事件的“狭义和广义”搜索来确定的。在peramplate治疗的患者中观察到敌意和攻击相关teae的发生率相似：a)接受左乙拉西坦（N = 340）与未接受左乙拉西坦的患者（N = 779）相比；b)接受托吡酯治疗的患者（N = 223）与未接受托吡酯治疗的患者（N = 896）相比；c)同时服用左乙拉西坦和托吡酯（N = 47），与未服用左乙拉西坦和托吡酯的患者（N = 1072）相比。与敌意和攻击性相关的严重和严重teae非常罕见，无论是否同时使用左乙拉西坦和/或托吡酯治疗，其发生率相似。综上所述，这些结果表明，在接受perampanel治疗的患者中，左乙拉西坦和/或托吡酯联合治疗对敌意或攻击相关teae的发生没有明显的影响。(C) 2017年作者。Elsevier Inc.出版。
In 4 Phase III registration trials (3 in patients with partial seizures, N = 1480; 1 in patients with PGTCS, N = 163), perampanel administered to patients already receiving 1-3 concomitant antiepileptic drugs (AEDS) demonstrated statistically superior efficacy compared to placebo in reducing seizure frequency. However, use of perampanel in these studies was associated with a risk of psychiatric and behavioral adverse reactions, including aggression, hostility, irritability, anger, and homicidal ideation and threats. The present study is a post hoc analysis of pooled data from these 4 trials to determine if concomitant treatment with levetiracetam and/or topiramate increased the risk of hostility- and aggression-related AEs. Treatment-emergent AEs (TEAEs) were determined using a "Narrow & Broad" search based on the Medical Dictionary for Regulatory Activities (MedDRA) standard MedDRA query (SMQ) for hostility- and aggression-related events. The rate of hostility- and aggression-related TEAEs was observed to be similar among perampanel-treated patients: a) receiving levetiracetam (N = 340) compared to those not receiving levetiracetam (N = 779); b) receiving topiramate (N = 223) compared to those not receiving topiramate (N = 896); and c) receiving both levetiracetam and topiramate (N = 47) compared to those not receiving levetiracetam and topiramate (N = 1072). Severe and serious TEAEs related to hostility and aggression were rare and occurred at a similar rate regardless of concomitant levetiracetam and/or topiramate therapy. Taken together, these results suggest that concomitant treatment with levetiracetam and/or topiramate has no appreciable effect on the occurrence of hostility- or aggression-related TEAEs in patients receiving perampanel. (C) 2017 The Authors. Published by Elsevier Inc.