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Background

Many placebo-controlled trials have demonstrated the efficacy of individual pharmacotherapies approved for smoking cessation. However, few direct or indirect comparisons of such interventions have been conducted. We performed a meta-analysis to compare the treatment effects of 7 approved pharmacologic interventions for smoking cessation.

Methods

We searched the US Centers for Disease Control and Prevention''s Tobacco Information and Prevention database as well as MEDLINE, EMBASE and the Cochrane Library for published reports of placebo-controlled, double-blind randomized controlled trials of pharmacotherapies for smoking cessation. We included studies that reported biochemically validated measures of abstinence at 6 and 12 months. We used a hierarchical Bayesian random-effects model to summarize the results for each intervention.

Results

We identified 70 published reports of 69 trials involving a total of 32 908 patients. Six of the 7 pharmacotherapies studied were found to be more efficacious than placebo: varenicline (odds ratio OR] 2.41, 95% credible interval CrI] 1.91–3.12), nicotine nasal spray (OR 2.37, 95% CrI 1.12–5.13), bupropion (OR 2.07, 95% CrI 1.73–2.55), transdermal nicotine (OR 2.07, 95% CrI 1.69–2.62), nicotine tablet (OR 2.06, 95% CrI 1.12–5.13) and nicotine gum (OR 1.71, 95% CrI 1.35–2.21). Similar results were obtained regardless of which measure of abstinence was used. Although the point estimate favoured nicotine inhaler over placebo (OR 2.17), these results were not conclusive because the credible interval included unity (95% CrI 0.95–5.43). When all 7 interventions were included in the same model, all were more efficacious than placebo. In our analysis of data from the varenicline trials that included bupropion control arms, we found that varenicline was superior to bupropion (OR 2.18, 95% CrI 1.09–4.08).

Interpretation

Varenicline, bupropion and the 5 nicotine replacement therapies were all more efficacious than placebo at promoting smoking abstinence at 6 and 12 months.Health Canada recently approved the use of varenicline as a pharmacotherapy for smoking cessation. Varenicline works by stimulating dopamine, which results in reduced cravings and withdrawal symptoms. The drug also blocks nicotine receptors, which prevents the dopamine release associated with nicotine consumption.¹ The drug has been examined in a few small randomized controlled trials.^2–5 Despite limited evidence concerning its use, varenicline is viewed by many clinicians and researchers as the most effective smoking cessation aid. Consequently, there is a need for a systematic assessment of the effectiveness of varenicline relative to placebo. Furthermore, there is a need to compare the efficacy of varenicline with that of existing pharmacotherapies, including sustained-release bupropion and approved nicotine replacement therapies.We undertook a meta-analysis of placebo-controlled randomized controlled trials of the efficacy of 7 pharmacotherapies approved for smoking cessation. We had 3 objectives: to summarize the efficacy of each pharmacotherapy; to undertake a direct comparison of varenicline and bupropion by analyzing trials that contained both varenicline and bupropion treatment arms; and to undertake an indirect comparison of all 7 pharmacotherapies using the results of the individual trials.