Risk of neuropsychiatric adverse events associated with varenicline: systematic review and meta-analysis.
Risk of neuropsychiatric adverse events associated with varenicline: systematic review and meta-analysis.
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DOI：
10.1136/bmj.h1109
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发表时间：
2015-03-12
期刊：
影响因子：
--
通讯作者：
Gunnell D
中科院分区：
文献类型：
--
作者：
Thomas KH;Martin RM;Knipe DW;Higgins JP;Gunnell D
目的 在随机对照试验中确定与安慰剂相比使用伐尼克兰相关的神经精神不良事件的风险。设计 使用固定效应模型、风险差异和 Peto 比值比中的两个汇总估计来比较研究效果的系统回顾和荟萃分析。数据来源 Medline、Embase、PsycINFO、Cochrane 对照试验中央注册库 (CENTRAL) 和 ClinicalTrials.gov。选择研究的资格标准 安慰剂对照组的随机对照试验，报告神经精神不良事件（抑郁、自杀意念、自杀企图、自杀、失眠、睡眠障碍、异常梦境、嗜睡、疲劳、焦虑）和死亡。不涉及人类参与者、未使用伐尼克兰最大推荐剂量（1 毫克，每日两次）以及交叉试验的研究被排除在外。结果 在 39 项随机对照试验（10 761 名受试者）中，没有证据表明自杀或自杀未遂（比值比 1.67，95% 置信区间 0.33 至 8.57）、自杀意念（0.58、0.28 至 1.20）、抑郁（0.96、0.75 至 1.22）、易怒风险增加与安慰剂使用者相比，伐尼克兰使用者的攻击性（0.98、0.81 至 1.17）、攻击性（0.91、0.52 至 1.59）或死亡（1.05、0.47 至 2.38）。伐尼克兰与睡眠障碍（1.63、1.29 至 2.07）、失眠（1.56、1.36 至 1.78）、异常梦（2.38、2.05 至 2.77）和疲劳（1.28、1.06 至 1.55）的风险增加相关，但焦虑风险降低（0.75、0.61 至0.93）。当报告风险差异时，也观察到了类似的结果。没有证据表明抑郁症和自杀意念因年龄组、性别、种族、吸烟状况、是否患有精神疾病以及研究赞助商类型（即制药行业或其他）而存在差异。结论 这项荟萃分析没有发现任何证据表明伐尼克兰会增加自杀或自杀未遂、自杀意念、抑郁或死亡的风险。这些发现为使用者和处方者关于伐尼克兰的神经精神安全性提供了一些保证。有证据表明伐尼克兰与失眠和异常梦等睡眠问题的风险较高有关。然而，这些副作用已被广泛认识。系统审评注册PROSPERO 2014：CRD42014009224。
Objective To determine the risk of neuropsychiatric adverse events associated with use of varenicline compared with placebo in randomised controlled trials. Design Systematic review and meta-analysis comparing study effects using two summary estimates in fixed effects models, risk differences, and Peto odds ratios. Data sources Medline, Embase, PsycINFO, the Cochrane Central Register of Controlled Trials (CENTRAL), and clinicaltrials.gov. Eligibility criteria for selecting studies Randomised controlled trials with a placebo comparison group that reported on neuropsychiatric adverse events (depression, suicidal ideation, suicide attempt, suicide, insomnia, sleep disorders, abnormal dreams, somnolence, fatigue, anxiety) and death. Studies that did not involve human participants, did not use the maximum recommended dose of varenicline (1 mg twice daily), and were cross over trials were excluded. Results In the 39 randomised controlled trials (10 761 participants), there was no evidence of an increased risk of suicide or attempted suicide (odds ratio 1.67, 95% confidence interval 0.33 to 8.57), suicidal ideation (0.58, 0.28 to 1.20), depression (0.96, 0.75 to 1.22), irritability (0.98, 0.81 to 1.17), aggression (0.91, 0.52 to 1.59), or death (1.05, 0.47 to 2.38) in the varenicline users compared with placebo users. Varenicline was associated with an increased risk of sleep disorders (1.63, 1.29 to 2.07), insomnia (1.56, 1.36 to 1.78), abnormal dreams (2.38, 2.05 to 2.77), and fatigue (1.28, 1.06 to 1.55) but a reduced risk of anxiety (0.75, 0.61 to 0.93). Similar findings were observed when risk differences were reported. There was no evidence for a variation in depression and suicidal ideation by age group, sex, ethnicity, smoking status, presence or absence of psychiatric illness, and type of study sponsor (that is, pharmaceutical industry or other). Conclusions This meta-analysis found no evidence of an increased risk of suicide or attempted suicide, suicidal ideation, depression, or death with varenicline. These findings provide some reassurance for users and prescribers regarding the neuropsychiatric safety of varenicline. There was evidence that varenicline was associated with a higher risk of sleep problems such as insomnia and abnormal dreams. These side effects, however,are already well recognised. Systematic review registration PROSPERO 2014:CRD42014009224.
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