左米那普仑缓释剂或左米那普仑控释剂治疗抑郁症安全性的系统评价

Systematic review of the safety of levomilnacipran extended or sustained-release agents in treating major depressive disorder

目的 系统评价左米那普仑缓释剂或左米那普仑控释剂（以下简称左米那普仑缓/控释剂）治疗抑郁症的安全性,为临床安全用药提供参考.方法 通过计算机检索Pubmed、EBSCO、OVID、荷兰医学文摘数据库（excerpt medica database,EMBASE）、Cochrane图书馆、万方医学网、中国知网及维普网,检索时间为从建库至2017年7月,收集有关左米那普仑缓/控释剂治疗抑郁症的临床随机对照试验研究文献;由2名研究者独立评阅纳入文献、筛选并予以文献质量评价.采用RevMan 5.0软件对效应指标进行Meta分析,Q检验进行异质性分析,并选择相应的效应模型进行系统评价.结果 共纳入5篇随机对照试验,文献质量均属高质量,偏倚风险低,患者共计2411例,其中试验组（左米那普仑缓/控释剂）1 538例,对照组（安慰剂）873例,Meta分析结果显示于治疗末,2组勃起功能障碍[RR=4.87,95％CI（2.74～8.65）,P＜0.01]、射精障碍[RR=26.94,95％CI（6.60～110.04）,P＜0.01]、尿不尽[RR=34.18,95％CI（6.60～177.16）,P＜0.01]及心率加快[RR=3.92,95％CI（1.33～11.56）,P=0.01]发生率差异均有统计学意义,上呼吸道感染发生率差异无统计学意义;次要安全性指标方面,2组在头痛、恶心、口干、多汗、呕吐发生率差异有统计学意义,头晕、失眠、腹泻、便秘、鼻咽炎及严重不良事件发生率差异无统计学意义.结论 左米那普仑缓/控释剂在胃肠道症状、神经系统症状的不良事件发生率较低,但有增加患者性功能障碍风险.

Objective To evaluate the safety of levomilnacipran extended or sustained-release agents in treatment of major depressive disorder.Methods Randomized controlled trial up to July 2017 for levomilnacipran extended/sustained-release agents against major depressive disorder was retrieved by Pubmed,EBSCO,OVID,EMBASE,Cochrane library,Wanfang Medical Network,CNKI and VIP.Two researchers independently reviewed the literature,performed screening and quality evaluation.RevMan 5.0 software was used to analysis the effect.Q test was used to analyze the heterogeneity of the effect index,and the corresponding effect model was selected for systematic evaluation.Results Five randomized controlled trial were included,and literature quality evaluation showed low risk of bias.Totally 2 411 patients with major depressive disorder were included,including 1 538 in levomilnacipran group and 873 in placebo control group.Meta-analysis results showed that,at the end of the treatment period higher rates of erectile dysfunction （RR=4.87,95%CI（2.74-8.65）,P〈0.01）,ejaculation disorder（RR=26.94,95%CI（6.60-110.04）,P〈0.01）,urinary hesitation （RR=34.18,95%CI （6.60-177.16）,P〈0.01） and increased heart rate （RR=3.92,95% CI （1.33-11.56）,P=0.01） were in levomilnacipram group and there was no difference on the upper respiratory tract infection between both groups.Other aspects of safety indicators,headache,nausea,dry mouth,hyperhidrosis,vomiting showed statistical significance,dizziness,insomnia,diarrhea,constipation,nasopharyngitis and severe adverse event showed no significant difference between both groups.Conclusion Extended/sustained-release levomilnacipran agent causes less gastrointestinal and nervous system symptoms,but it increases the risk of sexual dysfunction in the patients.