Psychiatric and behavioral side effects of antiepileptic drugs in adults with epilepsy
Psychiatric and behavioral side effects of antiepileptic drugs in adults with epilepsy
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DOI：
10.1016/j.yebeh.2017.08.039
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发表时间：
2017-11-01
影响因子：
2.6
通讯作者：
Detyniecki, Kamil
中科院分区：
文献类型：
--
作者：
Chen, Baibing;Choi, Hyunmi;Detyniecki, Kamil
目的：精神和行为副作用 (PBSE) 是与抗癫痫药物 (AED) 使用相关的常见不良反应。本研究的目的是在诊断为癫痫的患者的大型专业实践样本中比较较旧和较新的 AED 的 PBSE 概况。方法：作为哥伦比亚和耶鲁 AED 数据库项目的一部分，我们回顾了 4085 名新开始 AED 治疗的成年患者（年龄：18 岁）的患者记录，包括人口统计、病史、AED 使用和副作用。精神和行为副作用由病历中的患者或医生报告确定，其中包括抑郁情绪、精神病、焦虑、自杀念头、烦躁、攻击性和发脾气。首先使用逻辑回归从 83 个变量中确定 PBSE 率的显着非 AED 预测因子。然后在 18 种 AED 之间的 PBSE 和不可耐受 PBSE（导致剂量减少或停药的 PBSE）发生率的比较分析中控制预测因子。结果：17.2% 的患者出现精神和行为副作用，并导致 13.8% 的患者无法耐受。精神疾病史、继发性全面性癫痫发作、失神性癫痫发作和顽固性癫痫与 PBSE 发生率增加相关。左乙拉西坦 (LEV) 的 PBSE 率最高 (22.1%)。与其他 AED 的总和相比，这具有统计学意义（P < 0.001，OR = 6.87）。与其他 AED 的总和相比，左乙拉西坦还与较高的不耐受率 (17.7%)、剂量减少率 (9.4%) 和完全戒断率 (8.3%) 显着相关 (P < 0.001)。唑尼沙胺 (ZNS) 还与较高的 PBSE (9.7%) 和 IPBSE (7.9%，所有 P < 0.001) 发生率显着相关。另一方面，卡马西平 (CBZ)、氯巴占 (CLB)、加巴喷丁 (GBP)、拉莫三嗪 (LTG)、奥卡西平 (OXC)、苯妥英 (PHT) 和丙戊酸 (VPA) 与 PBSE 率降低显着相关 (P < 0.001)。与其他 AED 的总和相比，卡马西平、GBP、LTG、PHT 和 VPA 也与较低的 IPBSE 率相关。发现所有其他 AED 的发病率处于中等水平，与其他 AED 相比，既没有增加也没有减少。当将每种 AED 与 LTG 进行比较时，只有 CBZ 的 PBSE 率显着较低。这项研究的主要局限性在于，研究设计是回顾性的、非盲法，并且 AED 不是随机分配给患者的。结论：服用 LEV 和 ZNS 的患者比任何其他 AED 更容易出现精神和行为副作用，并导致不耐受率更高。服用 CBZ、CLB、GBP、LTG、OXC、PHT 和 VPA 的患者的 PBSE 率较低。我们的研究结果可能有助于促进 AED 选择过程。 (C) 2017 Elsevier Inc. 保留所有权利。
Purpose: Psychiatric and behavioral side effects (PBSEs) are common, undesirable effects associated with antiepileptic drug (AED) use. The objective of the study was to compare the PBSE profiles of older and newer AEDs in a large specialty practice-based sample of patients diagnosed with epilepsy.Methods: As part of the Columbia and Yale AED Database Project, we reviewed patient records including demographics, medical history, AED use, and side effects for 4085 adult patients (age: 18 years) newly started on an AED regimen. Psychiatric and behavioral side effects were determined by patient or physician report in the medical record, which included depressive mood, psychosis, anxiety, suicidal thoughts, irritability, aggression, and tantrum. Significant non-AED predictors of PBSE rate were first determined from 83 variables using logistic regression. Predictors were then controlled for in the comparison analysis of the rate of PBSEs and intolerable PBSEs (PBSEs that led to dosage reduction or discontinuation) between 18 AEDs.Results: Psychiatric and behavioral side effects occurred in 17.2% of patients and led to intolerability in 13.8% of patients. History of psychiatric condition(s), secondary generalized seizures, absence seizures, and intractable epilepsy were associated with increased incidence of PBSE. Levetiracetam (LEV) had the greatest PBSE rate (22.1%). This was statistically significant when compared with the aggregate of the other AEDs (P < 0.001, OR = 6.87). Levetiracetam was also significantly (P < 0.001) associated with higher intolerability rate (17.7%), dose decreased rate (9.4%), and complete cessation rate (8.3%), when compared with the aggregate of the other AEDs. Zonisamide (ZNS) was also significantly associated with a higher rate of PBSE (9.7%) and IPBSE (7.9%, all P < 0.001). On the other hand, carbamazepine (CBZ), clobazam (CLB), gabapentin (GBP), lamotrigine (LTG), oxcarbazepine (OXC), phenytoin (PHT), and valproate (VPA) were significantly associated with a decreased PBSE rates (P < 0.001). Carbamazepine, GBP, LTG, PHT, and VPA were also associated with lower IPBSE rates when compared individually with the aggregate of other AEDs. All other AEDs were found to have intermediate rates that were not either increased or decreased compared with other AEDs. When each AED was compared to LTG, only CBZ had a significantly lower PBSE rate. The main limitations of this study were that the study design was retrospective and not blinded, and the AEDs were not randomly assigned to patients.Conclusions: Psychiatric and behavioral side effects occur more frequently in patients taking LEV and ZNS than any other AED and led to higher rates of intolerability. Lower PBSE rates were seen in patients taking CBZ, CLB, GBP, LTG, OXC, PHT, and VPA. Our findings may help facilitate the AED selection process. (C) 2017 Elsevier Inc. All rights reserved.