丙戊酸钠联合拉莫三嗪治疗癫痫疗效及安全性的Meta分析

Efficacy and Safety of Sodium Valproate Combined with Lamotrigine in Epilepsy: a Meta Analysis

目的系统评价丙戊酸钠(VPA)联合拉莫三嗪(LTG)治疗癫痫的总有效率及不良反应,为临床癫痫的联合用药提供循证医学证据。方法 2015年12月,计算机检索PubMed、Cochrane Library、EMBase以及万方数据知识服务平台、维普网、中国知网(CNKI)、中国生物医学文献数据库(CBM)中收录的VPA联合LTG治疗癫痫疗效和安全性的随机对照试验,提取第一作者、发表时间、样本量、患者年龄、用药、疗程、癫痫类型、观察指标等资料,并采用改良的Jadad量表评价纳入文献的方法学质量。结果共纳入16篇文献,15篇中文文献,1篇英文文献,1 687例患者。分配方案的隐藏、盲法、选择性报道存在未知风险,纳入文献方法学质量较低。Meta分析显示,VPA联合LTG治疗癫痫的总有效率高于单用VPA[比值比(OR)=5.76,95%CI(3.78,8.78),P<0.001]或LTG[OR=2.80,95%CI(1.83,4.28),P<0.001],神经系统[危险差(RD)=-0.04,95%CI(-0.06,-0.02),P=0.002]、消化系统[RD=-0.05,95%CI(-0.08,-0.02)]、血液系统[RD=-0.03,95%CI(-0.05,-0.01),P=0.040]、皮肤附件[RD=-0.04,95%CI(-0.06,-0.01),P=0.008]不良反应发生率低于单用VPA或LTG。结论 VPA联合LTG治疗癫痫的临床疗效优于单用VPA或LTG,且耐受性好。受纳入文献方法学质量限制,该结论有待大样本、高质量的随机对照试验进一步证实。

Objective To systematically evaluate the overall efficacy and safety of sodium valproate（ VPA） combined with lamotrigine（ LTG） in epilepsy,so as to provide evidence-based reference for the combined medication for the disease.Methods We did a literature review of Pub Med, Cochrane Library, EMBase, Wanfang Data, VIP, CNKI and CBM to identify studies published as of December 2015,in which randomized controlled trials（ RTCs） of evaluating the efficacy and safety of VPA combined with LTG for patients with epilepsy were reported. We extracted the data of the articles＇ first author,time of publication,sample size,patients＇ age,medication,course of treatment,type of epilepsy,observation indexes and so on. The modified Jadad scale was used to assess the methodological quality of the included articles. Results A total of 16 articles were included,including 15 in Chinese and one in English,involving 1 687 patients. The methodological quality of the included articles was unsatisfactory due to unknown risks existing in the allocation concealment,blind method,and selective reporting. Results of meta-analysis showed that the efficacy of VPA combined with LTG was significantly better than that of VPA[OR = 5. 76,95% CI（ 3. 78,8. 78）,P〈0. 001]or that of LTG [OR = 2. 80,95% CI（ 1. 83,4. 28）,P〈0. 001],while the adverse reactions in nervous system [RD =-0. 04,95% CI（-0. 06,-0. 02）,P = 0. 002 ],digestive system[RD =-0. 05,95% CI（-0. 08,-0. 02） ],blood system [RD =-0. 03,95% CI（-0. 05,-0. 01）,P = 0. 040],and skin attachment system [RD =-0. 04,95% CI（-0. 06,-0. 01）,P = 0. 008]were less compared with those of VPA or LTG. Conclusion The effect of VPA combined with LTG is better than VPA or LTG along in epilepsy,and it has good tolerance. Due to limitations related to methodology of included studies,large-scale and high-quality RCTs are required for further validation of the conclusion.