Effectiveness of non-benzodiazepine hypnotics in treatment of adult insomnia: meta-analysis of data submitted to the Food and Drug Administration.
Effectiveness of non-benzodiazepine hypnotics in treatment of adult insomnia: meta-analysis of data submitted to the Food and Drug Administration.
复制标题
DOI：
10.1136/bmj.e8343
复制
发表时间：
2012-12-17
期刊：
影响因子：
--
通讯作者：
Siriwardena AN
中科院分区：
文献类型：
--
作者：
Huedo-Medina TB;Kirsch I;Middlemass J;Klonizakis M;Siriwardena AN
目的研究非苯二氮卓类催眠药（Z类药物）在成人中的有效性和相关的安慰剂反应，并在用于批准这些药物的数据集中评估有效性的潜在调节因素。设计系统综述和荟萃分析。数据来源美国食品药品监督管理局（FDA）。研究选择目前获批Z药物（右佐匹克隆、扎来普隆和唑吡坦）的随机双盲平行安慰剂对照试验。数据提取药物组和安慰剂组从基线到试验后的变化评分;药物疗效分析为两种变化评分的差异。多导睡眠图和主观睡眠潜伏期的加权原始和标准化平均差异及其随机效应假设下的置信区间，作为主要结局。次要结果包括入睡后醒来，醒来次数，总睡眠时间，睡眠效率和主观睡眠质量。采用加权最小二乘回归分析来解释药物效应的异质性。纳入了13项研究，其中包含65项按结局类型、药物类型和剂量进行的单独药物-安慰剂比较。这些研究包括来自不同国家的4378名参与者，他们的药物剂量、治疗时间和研究年限各不相同。与安慰剂相比，Z药物在我们的主要结局方面显示出显著的改善（减少）：多导睡眠潜伏期（加权标准化平均差异，95%置信区间-0.57至0.16）和主观睡眠潜伏期（-0.33，-0.62至0.04）。加权平均原始差异分析显示，与安慰剂相比，Z药物使多导睡眠潜伏期减少了22分钟（-33至-11分钟）。虽然在次要结局中未发现显著影响，但报告这些结局的研究不足，无法得出确切结论。主持人分析表明，在早期发表的研究中，使用较大的药物剂量、较长的治疗持续时间、较大比例的年轻和/或女性患者以及使用唑吡坦，睡眠潜伏期更有可能缩短。结论与安慰剂相比，Z类药物对主观睡眠潜伏期和多导睡眠潜伏期均有轻微改善，尤其是在大剂量时，且与药物类型无关。虽然药物效应和安慰剂反应相当小，临床重要性值得怀疑，但两者共同产生了相当大的临床反应。
Objectives To investigate the effectiveness of non-benzodiazepine hypnotics (Z drugs) and associated placebo responses in adults and to evaluate potential moderators of effectiveness in a dataset used to approve these drugs. Design Systematic review and meta-analysis. Data source US Food and Drug Administration (FDA). Study selection Randomised double blind parallel placebo controlled trials of currently approved Z drugs (eszopiclone, zaleplon, and zolpidem). Data extraction Change score from baseline to post-test for drug and placebo groups; drug efficacy analysed as the difference of both change scores. Weighted raw and standardised mean differences with their confidence intervals under random effects assumptions for polysomnographic and subjective sleep latency, as primary outcomes. Secondary outcomes included waking after sleep onset, number of awakenings, total sleep time, sleep efficiency, and subjective sleep quality. Weighted least square regression analysis was used to explain heterogeneity of drug effects. Data synthesis 13 studies containing 65 separate drug-placebo comparisons by type of outcome, type of drug, and dose were included. Studies included 4378 participants from different countries and varying drug doses, lengths of treatment, and study years. Z drugs showed significant, albeit small, improvements (reductions) in our primary outcomes: polysomnographic sleep latency (weighted standardised mean difference, 95% confidence interval −0.57 to −0.16) and subjective sleep latency (−0.33, −0.62 to −0.04) compared with placebo. Analyses of weighted mean raw differences showed that Z drugs decreased polysomnographic sleep latency by 22 minutes (−33 to −11 minutes) compared with placebo. Although no significant effects were found in secondary outcomes, there were insufficient studies reporting these outcomes to allow firm conclusions. Moderator analyses indicated that sleep latency was more likely to be reduced in studies published earlier, with larger drug doses, with longer duration of treatment, with a greater proportion of younger and/or female patients, and with zolpidem. Conclusion Compared with placebo, Z drugs produce slight improvements in subjective and polysomnographic sleep latency, especially with larger doses and regardless of type of drug. Although the drug effect and the placebo response were rather small and of questionable clinical importance, the two together produced to a reasonably large clinical response.
登录
查看更多内容
影响因子：
7
作者：
Huedo-Medina, Tania B.;Sanchez-Meca, Julio;Botella, Juan
通讯作者：
Botella, Juan
影响因子：
1.9
作者：
Duval, S;Tweedie, R
通讯作者：
Tweedie, R
影响因子：
7
作者：
Hedges, LV;Pigott, TD
通讯作者：
Pigott, TD
影响因子：
15.8
作者：
Kirsch, Irving;Deacon, Brett J.;Huedo-Medina, Tania B.;Scoboria, Alan;Moore, Thomas J.;Johnson, Blair T.
通讯作者：
Johnson, Blair T.
影响因子：
7.2
作者：
MacLean, CH;Morton, SC;Shekelle, PG
通讯作者：
Shekelle, PG