外源性褪黑素治疗阿尔茨海默病患者睡眠障碍有效性和安全性的随机临床试验的荟萃分析

Effectiveness and safety of exogenous melatonin for treating sleep disorders in patients with Alzheimer′s disease:a meta analysis of randomized clinical trials

目的评价外源性褪黑素治疗阿尔茨海默病(AD)患者睡眠障碍的疗效及安全性。方法计算机检索Pubmed、Cochrane数据库、中国知网、维普资讯中文期刊服务平台及万方数据知识服务平台等数据库,收集外源性褪黑素治疗AD患者睡眠障碍的随机对照试验,检索时间从建库至2018年5月。由2名研究者按Cochrane系统评价方法进行文献筛选、评价质量及提取资料,采用RevMan5.3软件进行荟萃分析、发表偏倚分析及敏感度分析等。结果共纳入6项研究,共340例患者。采用外源性褪黑素治疗对增加AD患者夜间总睡眠时间无显著影响[平均差(MD)=15.75,95%可信区间(95%CI):-6.17～37.67,P=0.16],其对减少白天与夜间睡眠的比例也无显著影响(MD=-0.12,95%CI:-0.26～0.02,P=0.09),对AD患者认知功能的改善同样不明显(MD=0.30,95%CI:-0.32～0.91,P=0.34),然而发生不良事件概率与安慰剂相似(优势比=1.67,95%CI:0.98～2.83,P=0.06)。结论褪黑素对改善AD患者睡眠质量及认知功能均无显著影响。

Objective To evaluate the efficacy and safety of exogenous melatonin for the treatment of sleep disorders in the patients with Alzheimer′s disease(AD). Methods The randomized controlled trials of exogenous melatonin in the treatment of sleep disorder in AD patients were collected by retrieving the databases of Pubmed,Cochrane database,Weipu Chinese Journal Database and Wanfang database.The retrieval time was from their database establishment to May 2018.The two researchers conducted the screening,evaluated the quality and extracted the data according to the Cochrane systematic evaluation method.The RevMan5.3 software was used for conducting the meta analysis,publication bias analysis and sensitivity analysis. Results Six researches were included,involving 340 patients.Adopting the exogenous melatonin treatment had no significant effect on increasing the total sleep time at night in the patients with AD [ MD =15.75,95% CI (-6.17-37.67), P =0.16],and also had no significant effect on reducing the proportion of daylight sleep to night sleep [ MD =-0.12,95% CI (-0.26-0.02), P =0.09],while had no obvious effect on improving the cognitive function in the AD patients [ MD =0.30,95% CI (-0.32-0.91), P =0.34].However,the probability of adverse events occurrence was similar to that of placebo [ OR =1.67,95% CI (0.98-2.83), P =0.06]. Conclusion Melatonin has no significant effect on improving the sleep quality and cognitive function in AD patients.