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

Hughes JR, Stead LF, Lancaster T

Published Online:

August 10, 2011

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.

Abstract (click to read)

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 strategy:

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.

This record should be cited as:

Hughes JR, Stead LF, Lancaster T. Antidepressants for smoking cessation. Cochrane Database of Systematic Reviews 2007, Issue 1. Art. No.: CD000031. DOI: 10.1002/14651858.CD000031.pub3

Assessed as up to date:

July 30, 2009

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Primary Review Group:

Tobacco Addiction Group

PEARLS - Practical Evidence About Real Life Situations (click to read)

Clinical question:

Which antidepressants are effective in aiding long-term (>6 months) smoking cessation?

Bottom line:

Both bupropion and nortriptyline double the odds of cessation when compared to placebo (NNT = 7 and 10 respectively). 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. SSRIs, venlafaxine and moclobemide show no evidence of benefit.

Caveat:

Bupropion can cause insomnia, dry mouth, nausea and seizures (estimated risk = 1 in 1,000). Nortriptyline can cause dry mouth, constipation, nausea and sedation, and can be dangerous in overdose.

Context:

Smoking is the most preventable cause of premature death, accounting for about 17% of all deaths in developed countries

Cochrane Systematic Review:

Hughes JR et al. Antidepressants for smoking cessation. Cochrane Reviews, 2007, Issue 1. This review contains 40 Buproprion trials with study size ranging from 18 to 707 participants. There were 8 nortriptyline studies ranging from 103 to 214 participants.

Authored by:

Brian R McAvoy

Cochrane Primary Health Care Field

Health topics:

Lungs & airways > Smoking cessation > Pharmacological interventions

Tobacco, drugs, & alcohol dependence > Tobacco > Pharmacological interventions

Cochrane Summaries^beta

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

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