Antidepressants for smoking cessation

Abstract

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. 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 March 2004. 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. 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. 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. 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.