Clinical Question
Are antidepressants safe and effective for tobacco smoking cessation?
Evidence-Based Answer
Bupropion facilitates tobacco cessation reported at 6 months of follow-up compared with placebo or no pharmacological treatment (number needed to treat [NNT] with 150 to 300 mg of bupropion per day to yield one patient who stops smoking = 14; 95% CI, 13 to 17).1 (Strength of Recommendation: A, consistent, good-quality patient-oriented evidence.) More people discontinue using bupropion due to adverse effects than those using placebo or no pharmacological treatment (number needed to harm [NNH] with 150 to 300 mg of bupropion daily to result in one patient quitting = 33; 95% CI, 33 to 100). Nortriptyline might also be effective compared with placebo, but the evidence is not as strong as for bupropion. Bupropion is not as effective as varenicline (Chantix) alone or combination nicotine replacement therapy (e.g., nicotine patch plus nicotine gum or lozenges) at helping patients stay smoke-free 6 months after starting therapy.1
Practice Pointers
Cigarette smoking is the leading cause of preventable disease, disability, and death in the United States.2 Antidepressants offer an alternative to first-line smoking cessation medications. Further insight into the effectiveness and potential harms of antidepressants for smoking cessation is valuable because of the significant worldwide morbidity and mortality caused by tobacco smoking.
This Cochrane review included 124 randomized controlled trials (RCTs) and cluster RCTs in a meta-analysis of 48,832 participants.1 Only studies that tracked at least 6 months of smoking cessation rates after follow-up were included. Trials with additional, uncontrolled nonantidepressant interventions in only one study arm were excluded. Trials assessed different dosages, durations, and schedules of antidepressants, including 150 to 300 mg per day of bupropion and 75 to 100 mg per day of nortriptyline. Studies that included pregnant women and those that focused on smoking harm reduction or relapse prevention were excluded. Most participants were adults recruited from community settings in Asia, Australia, Europe, and North America.
High-certainty evidence found that 19% of participants taking bupropion were not smoking at 6 months of therapy compared with 12% of participants receiving placebo or nonpharmacological treatment (NNT = 15; 95% CI, 13 to 17; 50 studies; n = 18,577). There was no evidence that the effect depended on behavioral therapy or the presence of a psychiatric disorder. High-certainty evidence showed that 9% of participants dropped out due to bupropion therapy vs. 6% of those receiving placebo or nonpharmacological therapy (NNH = 33; 95% CI, 33 to 100; 25 studies; n = 12,346). Patients taking bupropion were not at increased risk of serious adverse effects.
Twice as many participants were not smoking at 6 months of follow-up with nortriptyline vs. placebo (20% vs. 10%, respectively; relative risk [RR] = 2.03; 95% CI, 1.48 to 2.78; six studies; n = 975). A smaller proportion of participants taking bupropion were not smoking at 6 months vs. those taking varenicline (18% vs. 24%; RR = 0.73; 95% CI, 0.67 to 0.80; nine studies; n = 7,564). Compared with patients taking bupropion, those receiving combination nicotine replacement therapy were more likely to be not smoking at 6 months (33% vs. 25%; RR = 0.74; 95% CI, 0.55 to 0.98; two studies; n = 720).
The U.S. Preventive Services Task Force recommendations include U.S. Food and Drug Administration–approved pharmacotherapy for nonpregnant adults.3 The National Institute for Health and Care Excellence guidelines on smoking cessation include bupropion and varenicline as pharmacotherapeutic options for nonpregnant adults 18 years and older.4
Editor's Note: All instances of NNT, NNH, and related 95% CIs in this review were calculated by the authors based on raw data provided in the original Cochrane review.
The practice recommendations in this activity are available at https://www.cochrane.org/CD000031.
