Antidepressants for smoking cessation

 

Abstract

Background

There are at least three 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. Finally, some antidepressants may have a specific effect on neural pathways (e.g. inhibiting monoamine oxidase) or receptors, (e.g. blockade of nicotinic-cholinergic receptors) underlying nicotine addiction.

Objectives

The aim of this review is to assess the effect of antidepressant medications to aid long-term smoking cessation. The medications include bupropion; doxepin; fluoxetine; imipramine; moclobemide; nortriptyline; paroxetine; selegiline; sertraline, tryptophan, venlafaxine and St. John's wort.

Search methods

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) which includes trials indexed in MEDLINE, EMBASE, SciSearch and PsycINFO, and other reviews and meeting abstracts, in June 2009.

Selection criteria

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.

Data collection and analysis

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 a risk ratio (RR). 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.

Main results

Thirteen new trials were identified since the 2006 update bringing the total number of included trials to 66. There were 49 trials of bupropion and nine trials of nortriptyline. When used as the sole pharmacotherapy, bupropion (36 trials, N = 11,140, risk ratio [RR] 1.69; 95% confidence interval [CI] 1.53 to 1.85) and nortriptyline (six trials, N = 975, RR 2.03; 95% CI 1.48 to 2.78) both significantly increased long term cessation. There is insufficient evidence that adding bupropion (6 trials, N = 1,106, RR 1.23; 95% CI 0.67 to 2.26) or nortriptyline (3 trials, N = 1,219, RR 1.29; 95% CI 0.97 to 1.72) to nicotine replacement therapy provides an additional 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 lower quitting with bupropion (N = 1,622, RR 0.66, 95% CI 0.53 to 0.82). There is a risk of about 1 in 1000 of seizures associated with bupropion use. Bupropion has been associated with suicide risk, but whether this is causal is unclear. Nortriptyline has the potential for serious side-effects, but none have been seen in the few small trials for smoking cessation. There was no evidence of a significant effect for selective serotonin reuptake inhibitors; fluoxetine 4 trials, N = 1,486, RR 0.92 (95% CI 0.68 to 1.24); paroxetine 1 trial, N = 224, RR 1.08 (95% CI 0.64 to 1.82); sertraline 1 trial, N = 134, RR 0.71 (95% CI 0.30 to 1.64). Significant effects were not detected for the monoamine oxidase inhibitors moclobemide (1 trial, N = 88, RR 1.57, 95% CI 0.67 to 3.68) or selegiline (3 trials, N = 250, RR 1.49, 95% CI 0.92 to 2.41) or the atypical antidepressant venlafaxine (N = 147, RR 1.22, 95% CI 0.64 to 2.32). No long term trials have been published for St John's Wort.

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 appear to be rarely serious or lead to stopping medication.

 

Plain language summary

Do medications used to treat depression help smokers who are trying to quit

Multiple trials of bupropion (Zyban) for smoking cessation show that it increases the number of successful quit attempts. The side effects of bupropion include insomnia, dry mouth and nausea and rarely (1:1000) seizures and perhaps psychiatric problems, but the last is unclear. The tricyclic antidepressant nortriptyline increases quit rates. The side effects of this medication include dry mouth, constipation, nausea, and sedation, and it can be dangerous in overdose. The efficacy of bupropion and nortriptyline appears to be similar to that for nicotine replacement and not restricted to people with a history of depression or depressive symptoms during smoking abstinence. Selective serotonin reuptake inhibitor antidepressants (for example, fluoxetine) have not been shown to help smoking cessation.

 

摘要

背景

抗憂鬱劑戒菸

抗精神病藥物對於戒菸有幫助有兩個理論上的理由。尼古丁戒斷可能造成憂鬱症狀或是促進重鬱發作而抗憂鬱劑可能減輕這些症狀。尼古丁可能有抗憂鬱的效果造成持續吸菸，而抗憂鬱劑可替換這個作用。此外，一些抗憂鬱劑可能會有獨立於抗憂鬱效果之外的對尼古丁成癮神經路徑有特別的作用(如：阻斷尼古丁感受器)

目標

這個回顧的目標是去評估抗憂鬱劑對戒除長期吸菸的幫助。藥物包括了bupropion；doxepin；fluoxetine；imipramine；moclobemide； nortriptyline；paroxetine； sertraline、tryptophan和 venlafaxine

搜尋策略

我們在2006年九月搜索了Cochrane Tobacco Addiction Group trials register包括了登記於MEDLINE、EMBASE、SciSearch 和PsycINFO的研究和其它回顧和會議的摘要

選擇標準

我們考慮了比較抗憂鬱劑和安慰劑或是替代的藥物治療對戒菸效果的隨機試驗. 我們納入比較不同的劑量，使用藥物防止復發或是重新開始吸菸的戒除或是幫助吸菸者減少香菸使用量的藥物治療。我們排除了少於六個月追蹤的試驗

資料收集與分析

我們重複的依據研究族群的類型，藥物治療的特性、結果評估、隨機化的方法和追蹤的完整性研究族群來擷取資料。主要的結果評估為至少從病患戒菸六個月為基準來陳述勝算比odds ratio (OR). 我們使用目前最嚴格戒除的定義在每個研究，假如有的話，使用生化方式來定義。若適當的話，我們使用固定效應模式來執行後設分析

主要結論

從2004最後一次更新後的17個新研究使得所有包含的研究數目增加為53個。有40個bupropion的研究和8個nortriptyline的研究。當單獨使用藥物治療時，bupropion (31 trials, odds ratio [OR] 1.94, 95% confidence interval [CI] 1.72 to 2.19)和nortriptyline (four trials, OR 2.34, 95% CI 1.61 to 3.41)均加倍了戒菸的勝算比。不充足的證據顯示加入bupropion或nortriptyline到尼古丁替代治療提供了額外長期的助益。3個在開始戒菸後加入bupropion防止復發的延伸研究並未發現有明顯的長期助益的證據。從可得到的資料中，bupropion和nortriptyline有相同效果也和尼古丁替代治療有類似的效果。將三個比較bupropion和varenicline研究合併發現bupropion戒煙有較低的勝算比(OR 0.60, 95% CI 0.46 to 0.78). 在bupropion使用上有一千分之一的癲癇的危險性。針對bupropion可能增加自殺機率目前尚未證實。Nortriptyline有嚴重副作用的可能,但並未在這幾個少數小型的戒煙研究中發現。有6個selective serotonin reuptake inhibitors的研究；四個為fluoxetine，一個為sertraline而一個為paroxetine。均未發現有明顯的長期效果，而當合併這些研究時，也無明顯助益的證據。有一個monoamine oxidase inhibitor moclobemide的試驗和一個非典型抗憂鬱劑venlafaxine的試驗。沒有一項有明顯的長期助益

作者結論

抗憂鬱劑bupropion和nortriptyline對長期戒菸有助益，但selective serotonin reuptake inhibitors (如fluoxetine)則無。證據顯示bupropion 和nortriptyline的作用方式獨立於他們的抗憂鬱的效果而他們與尼古丁替代的效果類似。 兩種藥物的副作用均極少為嚴重的或是會造成停止使用藥物

翻譯人

本摘要由彰化基督教醫院王智仁翻譯

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌

總結

兩種用來治療憂鬱症的藥物bupropion和nortriptyline幫助嘗試戒菸的吸菸者。bupropion (Zyban)用來戒菸的試驗指出他可以提高接近兩倍的戒菸勝算. bupropion的副作用包括失眠、口乾和嘔心。這個藥物也可造成癲癇; 在用於戒菸的劑量危險性約為1000分之一。三環抗憂鬱劑nortriptyline也提高戒菸率兩倍. 這藥物的副作用包括口乾、便秘、噁心和嗜睡，當他過量時也是危險的。bupropion 和nortriptyline的效果似乎與尼古丁替代療法相似且並未限於使用於有憂鬱症病史或是戒菸時有憂鬱症狀的病患。Selective serotonin reuptake inhibitor antidepressants (如fluoxetine)並無明確顯示對戒菸有幫助