Hughes J R, Stead L F, Lancaster T
University of Vermont, Department of Psychiatry, 38 Fletcher Place, Burlington, Vermont 05401-1419, USA.
Cochrane Database Syst Rev. 2007 Jan 24(1):CD000031. doi: 10.1002/14651858.CD000031.pub3.
There are at least two theoretical reasons to believe antidepressants might help in smoking cessation. Nicotine withdrawal may produce depressive symptoms or precipitate a major depressive episode and antidepressants may relieve these. Nicotine may have antidepressant effects that maintain smoking, and antidepressants may substitute for this effect. Alternatively, some antidepressants may have a specific effect on neural pathways underlying nicotine addiction, (e.g. blocking nicotine receptors) independent of their antidepressant effects.
The aim of this review is to assess the effect of antidepressant medications in aiding long-term smoking cessation. The medications include bupropion; doxepin; fluoxetine; imipramine; moclobemide; nortriptyline; paroxetine; sertraline, tryptophan and venlafaxine.
We searched the Cochrane Tobacco Addiction Group trials register which includes trials indexed in MEDLINE, EMBASE, SciSearch and PsycINFO, and other reviews and meeting abstracts, in September 2006.
We considered randomized trials comparing antidepressant medications to placebo or an alternative pharmacotherapy for smoking cessation. We also included trials comparing different doses, using pharmacotherapy to prevent relapse or re-initiate smoking cessation or to help smokers reduce cigarette consumption. We excluded trials with less than six months follow up.
We extracted data in duplicate on the type of study population, the nature of the pharmacotherapy, the outcome measures, method of randomization, and completeness of follow up. The main outcome measure was abstinence from smoking after at least six months follow up in patients smoking at baseline, expressed as an odds ratio (OR). We used the most rigorous definition of abstinence available in each trial, and biochemically validated rates if available. Where appropriate, we performed meta-analysis using a fixed-effect model.
Seventeen new trials were identified since the last update in 2004 bringing the total number of included trials to 53. There were 40 trials of bupropion and eight trials of nortriptyline. When used as the sole pharmacotherapy, bupropion (31 trials, odds ratio [OR] 1.94, 95% confidence interval [CI] 1.72 to 2.19) and nortriptyline (four trials, OR 2.34, 95% CI 1.61 to 3.41) both doubled the odds of cessation. There is insufficient evidence that adding bupropion or nortriptyline to nicotine replacement therapy provides an additional long-term benefit. Three trials of extended therapy with bupropion to prevent relapse after initial cessation did not find evidence of a significant long-term benefit. From the available data bupropion and nortriptyline appear to be equally effective and of similar efficacy to nicotine replacement therapy. Pooling three trials comparing bupropion to varenicline showed a lower odds of quitting with bupropion (OR 0.60, 95% CI 0.46 to 0.78). There is a risk of about 1 in 1000 of seizures associated with bupropion use. Concerns that bupropion may increase suicide risk are currently unproven. Nortriptyline has the potential for serious side-effects, but none have been seen in the few small trials for smoking cessation. There were six trials of selective serotonin reuptake inhibitors; four of fluoxetine, one of sertraline and one of paroxetine. None of these detected significant long-term effects, and there was no evidence of a significant benefit when results were pooled. There was one trial of the monoamine oxidase inhibitor moclobemide, and one of the atypical antidepressant venlafaxine. Neither of these detected a significant long-term benefit.
AUTHORS' CONCLUSIONS: The antidepressants bupropion and nortriptyline aid long-term smoking cessation but selective serotonin reuptake inhibitors (e.g. fluoxetine) do not. Evidence suggests that the mode of action of bupropion and nortriptyline is independent of their antidepressant effect and that they are of similar efficacy to nicotine replacement. Adverse events with both medications are rarely serious or lead to stopping medication.
至少有两个理论依据表明抗抑郁药可能有助于戒烟。尼古丁戒断可能会产生抑郁症状或引发重度抑郁发作，而抗抑郁药可能会缓解这些症状。尼古丁可能具有维持吸烟行为的抗抑郁作用，抗抑郁药可能会替代这种作用。此外，一些抗抑郁药可能对尼古丁成瘾的神经通路有特定作用（例如阻断尼古丁受体），与其抗抑郁作用无关。
本综述的目的是评估抗抑郁药物在帮助长期戒烟方面的效果。这些药物包括安非他酮、多塞平、氟西汀、丙咪嗪、吗氯贝胺、去甲替林、帕罗西汀、舍曲林、色氨酸和文拉法辛。
我们于2006年9月检索了Cochrane烟草成瘾研究组的试验注册库，其中包括MEDLINE、EMBASE、SciSearch和PsycINFO索引的试验，以及其他综述和会议摘要。
我们纳入了将抗抑郁药物与安慰剂或用于戒烟的其他药物疗法进行比较的随机试验。我们还纳入了比较不同剂量、使用药物疗法预防复吸或重新开始戒烟或帮助吸烟者减少香烟消费量的试验。我们排除了随访时间少于6个月的试验。
我们对研究人群类型、药物疗法性质、结局指标、随机化方法和随访完整性进行了重复数据提取。主要结局指标是基线时吸烟的患者在至少6个月随访后戒烟的情况，以比值比（OR）表示。我们采用了各试验中可用的最严格的戒烟定义，如有可用的生化验证率则采用该率。在适当情况下，我们使用固定效应模型进行荟萃分析。
自2004年上次更新以来，共识别出17项新试验，使纳入试验总数达到53项。其中有40项安非他酮试验和8项去甲替林试验。当作为唯一的药物疗法使用时，安非他酮（31项试验，比值比[OR]为1.94，95%置信区间[CI]为1.72至2.19）和去甲替林（4项试验，OR为2.34，95%CI为1.61至3.41）使戒烟几率均增加了一倍。没有足够证据表明在尼古丁替代疗法中添加安非他酮或去甲替林能带来额外的长期益处。3项使用安非他酮进行延长治疗以预防初始戒烟后复吸的试验未发现有显著长期益处的证据。根据现有数据，安非他酮和去甲替林似乎同样有效，且与尼古丁替代疗法疗效相似。汇总3项比较安非他酮与伐尼克兰的试验显示，使用安非他酮戒烟的几率较低（OR为0.60，95%CI为0.46至0.78）。使用安非他酮有大约千分之一的癫痫发作风险。目前关于安非他酮可能增加自杀风险的担忧尚未得到证实。去甲替林有产生严重副作用的可能性，但在少数用于戒烟的小型试验中尚未观察到此类情况。有6项选择性5-羟色胺再摄取抑制剂试验；4项氟西汀试验、1项舍曲林试验和1项帕罗西汀试验。这些试验均未检测到显著的长期效果，汇总结果时也没有证据表明有显著益处。有1项单胺氧化酶抑制剂吗氯贝胺试验和1项非典型抗抑郁药文拉法辛试验。这两项试验均未检测到显著的长期益处。
抗抑郁药安非他酮和去甲替林有助于长期戒烟，但选择性5-羟色胺再摄取抑制剂（如氟西汀）则不然。证据表明，安非他酮和去甲替林的作用方式与其抗抑郁作用无关，且它们与尼古丁替代疗法疗效相似。两种药物的不良事件很少严重或导致停药。
