The effects of varenicline, bupropion, nicotine patch, and placebo on smoking cessation among smokers with major depression: A randomized clinical trial

IMPORTANCE: Improving treatment outcomes for smokers with Major Depressive Disorder (MDD) can have significant public health implications. OBJECTIVE: To evaluate the safety and efficacy of smoking cessation pharmacotherapy among smokers with MDD. DESIGN: Secondary analysis of a randomized, double-blind, active- (nicotine patch) and placebo-controlled trial of 12 weeks of either varenicline or bupropion with 12-week follow-up. PARTICIPANTS: Community volunteers 18-75 years of age; smoke 10+ cigarettes/day; with clinically stable MDD(N=2635) or no psychiatric disorder(N=4028), from 140 sites in 16 countries. INTERVENTION: 12 weeks of pharmacotherapy (placebo, PLA; nicotine replacement therapy, NRT; bupropion, BUP; varenicline, VAR) plus brief cessation counseling. MEASURE(S): Primary safety outcome: the occurrence of ≥ 1 treatment-emergent, moderate to severe Neuropsychiatric Adverse Event (NPSAE). Primary efficacy outcome: biochemically confirmed continuous abstinence (CA) during the final 4 weeks of treatment (Weeks 9–12). RESULTS: 6,653 participants (56% female; 39% MDD) ~47 years old. Risk of NPSAEs did not differ by medication for MDD. MDD had higher risk (p