Varenicline, Smoking Cessation, and Neuropsychiatric Adverse Events
Varenicline, Smoking Cessation, and Neuropsychiatric Adverse Events
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DOI：
10.1176/appi.ajp.2013.12121599
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发表时间：
2013-12-01
影响因子：
17.7
通讯作者：
Mann, J. John
中科院分区：
文献类型：
--
作者：
Gibbons, Robert D.;Mann, J. John
目的：2009年，美国食品和药物管理局针对伐尼克兰发布了有关神经精神事件的黑框警告。作者使用来自随机对照试验和国防部 (DOD) 大型观察性研究的数据来评估伐尼克兰的有效性和安全性。 方法：作者重新分析了辉瑞公司进行的 17 项安慰剂对照随机对照试验 (N=8,027) 的数据，使用完整的意向治疗个人水平纵向数据来评估戒烟情况，以及自杀想法和行为、抑郁、攻击性/激动和恶心的报告并比较患有（N=1,004）和不患有（N=7,023）精神疾病的患者的效果。作者还分析了 DOD 的大型数据集，以比较接受伐尼克兰或尼古丁替代疗法的患者 (N=35,800) 的神经精神不良事件的急性（30 天和 60 天）发生率，并评估焦虑、情绪和精神病症状和障碍、其他精神障碍以及自杀企图的报告。 结果：在随机对照试验中，伐尼克兰增加了恶心风险（比值比 = 3.69, 95%） CI=3.03-4.48），但不包括自杀事件、抑郁或攻击性/激动的发生率。它显着提高了戒断率，与安慰剂相比增加了 124%，与安非他酮相比增加了 22%。在接受治疗的患者和安慰剂患者中，当前或过去患有精神疾病会增加神经精神事件的风险。在 DOD 研究中，倾向评分匹配后，伐尼克兰的神经精神疾病总体发生率显着低于尼古丁替代疗法（2.28% 与 3.16%）。结论：该分析显示没有证据表明伐尼克兰与不良神经精神事件相关。证据支持伐尼克兰相对于安慰剂和安非他酮的优越疗效，表明对于近期有或没有精神疾病史的个体来说，在没有严重神经精神不良事件风险的证据的情况下，伐尼克兰具有相当大的益处。
Objective: In 2009, the U.S. Food and Drug Administration issued a black box warning for varenicline regarding neuropsychiatric events. The authors used data from randomized controlled trials and from a large Department of Defense (DOD) observational study to assess the efficacy and safety of varenicline.Method: The authors reanalyzed data from the 17 placebo-controlled randomized controlled trials (N=8,027) of varenicline conducted by Pfizer, using complete intent-to-treat person-level longitudinal data to assess smoking abstinence, and reports of suicidal thoughts and behavior, depression, aggression/agitation, and nausea and to compare effects in patients with (N=1,004) and without (N=7,023) psychiatric disorders. The authors also analyzed a large DOD data set to compare acute (30-day and 60-day) rates of neuropsychiatric adverse events in patients receiving varenicline or nicotine replacement therapy (N=35,800) and to assess reports of anxiety, mood, and psychotic symptoms and disorders, other mental disorders, and suicide attempt.Results: In the randomized controlled trials, varenicline increased the risk of nausea(odds ratio=3.69, 95% CI=3.03-4.48) but not rates of suicidal events, depression, or aggression/agitation. It significantly increased the abstinence rate, by 124% compared with placebo and 22% compared with bupropion. Having a current or past psychiatric illness increased the risk of neuropsychiatric events equally in treated and placebo patients. In the DOD study, after propensity score matching, the overall rate of neuropsychiatric disorders was significantly lower for varenicline than for nicotine replacement therapy (2.28% compared with 3.16%).Conclusions: This analysis revealed no evidence that varenicline is associated with adverse neuropsychiatric events. The evidence supports the superior efficacy of varenicline relative to both placebo and bupropion, indicating considerable benefit without evidence of risk of serious neuropsychiatric adverse events, in individuals with and without a recent history of a psychiatric disorder.