Yue Jing-Li, Chang Xiang-Wen, Zheng Jun-Wei, Shi Le, Xiang Ya-Jie, Que Jian-Yu, Yuan Kai, Deng Jia-Hui, Teng Teng, Li Yang-Yang, Sun Wei, Sun Hong-Qiang, Vitiello Michael V, Tang Xiang-Dong, Zhou Xin-Yu, Bao Yan-Ping, Shi Jie, Lu Lin
Peking University Sixth Hospital, Peking University Institute of Mental Health, Key of Mental Health, Ministry of Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China.
National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence, Peking University, Beijing, China; Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
Sleep Med Rev. 2023 Apr;68:101746. doi: 10.1016/j.smrv.2023.101746. Epub 2023 Jan 14.
Insomnia is one of the most common and burdensome disorders in adults. We compared and ranked insomnia medication on the basis of their efficacy and tolerability. We performed a systematic review and network meta-analysis of placebo-controlled or head-to-head randomized controlled trials for primary insomnia in adults comparing 20 drugs. We searched eight databases and seven trial registers from inception to March 1st, 2022. Primary outcomes included sleep latency (SL), awake time after sleep onset (WASO) and discontinuation for adverse events (AED), and secondary outcomes included total sleep time (TST), sleep efficiency (SE), sleep quality (SQ) and adverse events (ADE). Pooled standardized mean differences or odds ratios with 95% credible intervals were estimated using pairwise and network meta-analysis with random-effects. Differences among trial findings were explored in subgroup and sensitivity analyses. Confidence in evidence was assessed using GRADE. The PROSPERO registered number is CRD42020182144. We identified 22,538 records and included 69 studies (17,319 patients). Orexin receptor antagonists (ORAs) are more efficacious than benzodiazepine-like drugs (Z-drugs) and placebo for WASO and SE, and better than melatonin receptor agonists (MRAs) for SL, WASO and SE. ORAs ranked the best in SL (SUCRA value: 0.84), WASO (0.93), TST (0.86) and SE (0.96). Lemborexant and daridorexant (two ORAs) showed greater efficacy than placebo for SL, WASO, and TST, with good tolerability. Z-drugs were more efficacious than placebo for SL, WASO, TST and SE, but with higher risk to safety. Zaleplon and eszopiclone had better efficacy than placebo for TST and SQ respectively. MRAs may also be efficacious for sleep-onset insomnia with good safety. However, the long-term adverse effects of all medications are unclear. Insomnia medications differ in their efficacy and tolerability. ORAs have superior efficacy and tolerability. These findings should aid clinicians in matching risk/benefits of drugs available in their countries to insomnia symptoms.
失眠是成年人中最常见且负担最重的疾病之一。我们根据疗效和耐受性对失眠药物进行了比较和排名。我们对比较20种药物治疗成人原发性失眠的安慰剂对照或头对头随机对照试验进行了系统评价和网状Meta分析。我们检索了8个数据库和7个试验注册库，检索时间从数据库创建至2022年3月1日。主要结局包括睡眠潜伏期（SL）、睡眠开始后的清醒时间（WASO）以及因不良事件而停药（AED），次要结局包括总睡眠时间（TST）、睡眠效率（SE）、睡眠质量（SQ）和不良事件（ADE）。使用随机效应的成对和网状Meta分析估计合并标准化均数差或比值比及95%可信区间。在亚组分析和敏感性分析中探讨试验结果之间的差异。使用GRADE评估证据的可信度。PROSPERO注册号为CRD42020182144。我们识别出22538条记录，纳入了69项研究（17319例患者）。食欲素受体拮抗剂（ORA）在改善WASO和SE方面比苯二氮䓬类药物（Z类药物）和安慰剂更有效，在改善SL、WASO和SE方面比褪黑素受体激动剂（MRA）更有效。ORA在SL（累积排序曲线下面积值：0.84）、WASO（0.93）、TST（0.86）和SE（0.96）方面排名最佳。伦博瑞生和达利雷生（两种ORA）在改善SL、WASO和TST方面比安慰剂更有效，且耐受性良好。Z类药物在改善SL、WASO、TST和SE方面比安慰剂更有效，但安全性风险更高。扎来普隆和艾司佐匹克隆分别在改善TST和SQ方面比安慰剂更有效。MRA对入睡性失眠可能也有效，且安全性良好。然而，所有药物的长期不良反应尚不清楚。失眠药物在疗效和耐受性方面存在差异。ORA具有卓越的疗效和耐受性。这些研究结果应有助于临床医生将本国可用药物的风险/效益与失眠症状相匹配。
