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Antidepressants for smoking cessation

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Abstract

Background

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, independent of their antidepressant effects.

Objectives

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.

Search methods

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 March 2004.

Selection criteria

We considered randomized trials comparing antidepressant medications to placebo or an alternative therapy for smoking cessation. We also included trials comparing different doses, using pharmacotherapy to prevent relapse or re‐initiate smoking cessation and using pharmacotherapy 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 an odds ratio (OR). We used the most rigorous definition of abstinence for each trial, and biochemically validated rates if available. Where appropriate, we performed meta‐analysis using a fixed effect model.

Main results

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. There were five trials of selective serotonin reuptake inhibitors; three of fluoxetine, one of sertraline and one of paroxetine. None of these detected significant effects, and there was no evidence of a significant benefit when results were pooled. There were 24 trials of bupropion and six trials of nortriptyline. When used as the sole pharmacotherapy, bupropion (19 trials, OR 2.06, 95% confidence intervals [CI] 1.77 to 2.40) and nortriptyline (four trials, OR 2.79, 95% CI 1.70 to 4.59) both doubled the odds of cessation. In one trial the combination of bupropion and nicotine patch produced slightly higher quit rates than patch alone, but this was not replicated in a second study. Two trials of extended therapy with bupropion to prevent relapse after initial cessation did not show a significant long‐term benefit. 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.

Authors' conclusions

The antidepressants bupropion and nortriptyline aid long term smoking cessation but selective serotonin reuptake inhibitors (e.g. fluoxetine) do not. The fact that only some forms of antidepressants aid cessation and that they do so regardless of depressive symptoms strongly suggests that their mode of action is independent of their antidepressant effect.

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Plain language summary

Two medications used to treat depression, bupropion and nortriptyline, help smokers who are trying to quit.

Trials of bupropion (Zyban) for smoking cessation indicate that it can double the chance of quitting, The side effects of bupropion include insomnia, dry mouth and nausea. This medication can also cause seizures; at the dose used for smoking cessation the risk is estimated to be 1 in 1000. The tricyclic antidepressant nortriptyline also doubles quit rates. The side effects of this medication include nausea and sedation. It may also cause urinary retention and can be dangerous in overdose. The efficacy of bupropion and nortriptyline does not appear to be restricted to people with a history of depression or depressive symptoms during smoking abstinence. Selective serotonin reuptake inhibitor antidepressants (for example, fluoxetine) have not consistently been shown to help smoking cessation.