拉莫三嗪治疗青少年肌阵挛癫有效性和安全性的系统评价

Systematic review of efficacy and safety of lamotrigine in the treatment of juvenile myoclonic epilepsy

目的系统评价拉莫三嗪单药治疗青少年肌阵挛癫的有效性和安全性。方法以juvenile myoclonic epilepsy、idiopathic generalized epilepsies、lamotrigine、antiepileptic drugs、random等英文词汇计算机检索1980年1月1日-2017年12月31日美国国立医学图书馆生物医学信息检索系统(PubMed)、荷兰医学文摘(EMBASE/SCOPUS)和Cochrane图书馆等数据库关于拉莫三嗪单药治疗青少年肌阵挛癫的临床指南、系统评价(包括Meta分析)、随机对照临床试验、病例对照研究、回顾性队列研究、病例观察研究等,采用Jadad量表、Cochrane系统评价手册和RevMan 5.3统计软件进行文献质量评价和Meta分析。结果共获得英文文献1220篇,经剔除重复和不符合纳入标准者,最终纳入6篇高质量(Jadad评分≥4分)文献共314例青少年肌阵挛癫患者(拉莫三嗪单药治疗组166例,丙戊酸钠单药治疗组148例),包括4项随机对照临床试验和2项病例观察研究。Meta分析结果显示,拉莫三嗪单药治疗组药物不良反应发生率低于丙戊酸钠单药治疗组(RR=0.540,95%CI:0.320～0.910;P=0.020),而癫发作频率减少>50%比例组间差异无统计学意义(RR=1.200,95%CI:0.870～1.650;P=0.260)。结论拉莫三嗪对青少年肌阵挛癫安全、有效,且疗效与丙戊酸钠相当、耐受性较好、不良反应较少,是青少年肌阵挛癫的首选药物,特别是女性患者尤其适用。但与其他抗癫药物联合应用的疗效尚待更高质量的临床研究证实。

Objective To evaluate the efficacy and safety of lamotrigine in the treatment of juvenile myoclonic epilepsy（JME）. Methods Retrieve relevant clinical guidelines, systematic review（including Meta-analysis）, randomized controlled clinical trials, case-control studies, retrospective cohort studies and case observation studies on lamotrigine treating JME from online databases（January 1, 1980-December 31, 2017） as PubMed, EBMASE/SCOPUS and Cochrane Library with key words： juvenile myoclonic epilepsy, idiopathic generalized epilepsies, lamotrigine, antiepileptic drugs, random. Jadad Scale,Cochrane System Evaluation Handbook and RevMan 5.3 statistical software were used for quality assessment and Meta-analysis. Results The research enrolled 1220 articles, from which 6 studies with Jadad score ≥ 4（4 randomized controlled clinical trials and 2 case observation studies） were chosen after excluding duplicates and those not meeting the inclusion criteria. A total of 314 JME patients（166 cases treated by lamotrigine and 148 cases treated by valproate） were enrolled in 6 studies. Meta-analysis showed the occurrence rate of adverse reaction in lamotrigine group was significantly lower than that in valproate group（RR = 0.540, 95% CI： 0.320-0.910; P = 0.020）, but there was no significant difference on rate of epileptic seizures decreasing 〉50%（RR = 1.200, 95% CI： 0.870-1.650; P = 0.260）. Conclusions Lamotrigine is safe and effective in the treatment of JME. It has better tolerance and less adverse reaction,and its effect is similar to that of valproate. It is the first choice for patients with JME, especially for adolescent female patients with JME. However, there is still lack of high-quality trials to confirm whether the combination with other drugs has any benefit in terms of efficacy.