Liu Jia, Wang Lu-Ning, Wang Yu-Ping
Department of Neurology, Xuanwu Hospital, Capital Medical University, Changchun Street 45, Beijing, China, 100053.
Cochrane Database Syst Rev. 2019 Jan 28;1(1):CD010008. doi: 10.1002/14651858.CD010008.pub4.
Topiramate is a newer broad-spectrum antiepileptic drug (AED). Some studies have shown the benefits of topiramate in the treatment of juvenile myoclonic epilepsy (JME). However, there are no current systematic reviews to determine the efficacy and tolerability of topiramate in people with JME. This is an update of a Cochrane Review first published in 2015, and last updated in 2017.
To evaluate the efficacy and tolerability of topiramate in the treatment of JME.
For the latest update, on 10 July 2018 we searched the Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group's Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid 1946- ), and ClinicalTrials.gov. We also searched ongoing trials registers, reference lists and relevant conference proceedings, and contacted study authors and pharmaceutical companies.
We included randomized controlled trials (RCTs) investigating topiramate versus placebo or other AED treatment for people with JME, with the outcomes of proportion of responders and proportion of participants experiencing adverse events (AEs).
Two review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted data, cross-checked the data for accuracy and assessed the methodological quality. We performed no meta-analyses due to the limited available data.
We included three studies with a total of 83 participants. For efficacy, a greater proportion of participants in the topiramate group had a 50% or more reduction in primarily generalized tonic-clonic seizures (PGTCS) compared with participants in the placebo group. There were no significant differences between topiramate and valproate in participants responding with a 50% or more reduction in myoclonic seizures or in PGTCS, or becoming seizure-free. Concerning tolerability, we ranked AEs associated with topiramate as moderate to severe, while we ranked 59% of AEs linked to valproate as severe complaints. Moreover, systemic toxicity scores were higher in the valproate group than the topiramate group.Overall we judged all three studies to be at high risk of attrition bias and at unclear risk of reporting bias. We judged all three studies to be at low to unclear bias for the remaining risk of bias domains (random sequence, allocation, blinding). We judged the quality of the evidence from the studies to be very low.
AUTHORS' CONCLUSIONS: We have found no new studies since the last version of this review was published in 2017. This review does not provide sufficient evidence to support topiramate for the treatment of people with JME. Based on the current limited available data, topiramate seems to be better tolerated than valproate, but has no clear benefits over valproate in terms of efficacy. Well-designed, double-blind RCTs with large samples are required to test the efficacy and tolerability of topiramate in people with JME.
托吡酯是一种较新的广谱抗癫痫药物(AED)。一些研究显示了托吡酯在治疗青少年肌阵挛性癫痫(JME)方面的益处。然而,目前尚无系统性综述来确定托吡酯在JME患者中的疗效和耐受性。这是Cochrane系统评价的更新版,首次发表于2015年,上次更新于2017年。
评估托吡酯治疗JME的疗效和耐受性。
为进行最新更新,我们于2018年7月10日检索了Cochrane研究注册库(CRS网络版),其中包括Cochrane癫痫小组专业注册库和Cochrane对照试验中央注册库(CENTRAL)、MEDLINE(Ovid 1946年起)及ClinicalTrials.gov。我们还检索了正在进行的试验注册库、参考文献列表及相关会议论文集,并联系了研究作者和制药公司。
我们纳入了针对JME患者比较托吡酯与安慰剂或其他AED治疗的随机对照试验(RCT),其结局指标为缓解者比例和发生不良事件(AE)的参与者比例。
两位综述作者独立筛选已识别记录的标题和摘要,选择纳入研究,提取数据,交叉核对数据准确性并评估方法学质量。由于可用数据有限,我们未进行Meta分析。
我们纳入了3项研究,共83名参与者。在疗效方面,与安慰剂组参与者相比,托吡酯组中有更大比例的参与者其原发性全面强直阵挛发作(PGTCS)减少了50%或更多。在肌阵挛发作或PGTCS减少50%或更多或无癫痫发作的参与者中,托吡酯与丙戊酸之间无显著差异。关于耐受性,我们将与托吡酯相关的AE评为中度至重度,而将与丙戊酸相关的AE中的59%评为严重不良事件。此外,丙戊酸组的全身毒性评分高于托吡酯组。总体而言,我们判断所有3项研究存在较高的失访偏倚风险,报告偏倚风险不明确。对于其余偏倚领域(随机序列、分配、盲法),我们判断所有3项研究存在低至不明确的偏倚。我们判断这些研究的证据质量非常低。
自本综述的上一版于2017年发表以来,我们未发现新的研究。本综述未提供足够证据支持托吡酯用于治疗JME患者。基于目前有限的可用数据,托吡酯似乎比丙戊酸耐受性更好,但在疗效方面与丙戊酸相比并无明显优势。需要设计良好、大样本的双盲RCT来测试托吡酯在JME患者中的疗效和耐受性。