Chung Steve, Williams Betsy, Dobrinsky Cindy, Patten Anna, Yang Haichen, Laurenza Antonio
Banner University Medical Center, Phoenix, AZ, USA.
Eisai Medical and Scientific Affairs, Eisai Inc., 100 Tice Blvd., Woodcliff Lake, NJ 07677, USA.
Epilepsy Behav. 2017 Oct;75:79-85. doi: 10.1016/j.yebeh.2017.06.038. Epub 2017 Aug 19.
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.
在4项III期注册试验中（3项针对部分性癫痫患者，N = 1480；1项针对全面性强直阵挛发作（PGTCS）患者，N = 163），对于已经正在接受1 - 3种抗癫痫药物（AEDs）治疗的患者，与安慰剂相比，服用吡仑帕奈在降低癫痫发作频率方面显示出统计学上更优的疗效。然而，在这些研究中使用吡仑帕奈与精神和行为不良反应风险相关，包括攻击行为、敌意、易怒、愤怒以及杀人意念和威胁。本研究是对这4项试验汇总数据的事后分析，以确定左乙拉西坦和/或托吡酯联合治疗是否会增加与敌意和攻击相关不良事件（AE）的风险。使用基于《监管活动医学词典》（MedDRA）标准MedDRA查询（SMQ）中与敌意和攻击相关事件的“狭义和广义”搜索来确定治疗中出现的不良事件（TEAEs）。在接受吡仑帕奈治疗的患者中，观察到与敌意和攻击相关的TEAEs发生率相似：a）接受左乙拉西坦的患者（N = 340）与未接受左乙拉西坦的患者（N = 779）相比；b）接受托吡酯的患者（N = 223）与未接受托吡酯的患者（N = 896）相比；c）同时接受左乙拉西坦和托吡酯的患者（N = 47）与未接受左乙拉西坦和托吡酯的患者（N = 1072）相比。与敌意和攻击相关的严重和重度TEAEs很少见，并且无论是否联合左乙拉西坦和/或托吡酯治疗，其发生率相似。综上所述，这些结果表明，左乙拉西坦和/或托吡酯联合治疗对接受吡仑帕奈治疗的患者中与敌意或攻击相关的TEAEs的发生没有明显影响。
