Effects of Varenicline, Bupropion, Nicotine Patch, and Placebo on Treating Smoking Among Persons With Current or Past Major Depressive Disorder: Secondary Analysis of a Double-Blind, Randomized, Placebo-Controlled Trial

Objective: The aim of this study was to compare the safety and efficacy of the leading smoking cessation medications among individuals with current versus past major depressive disorder (MDD).

Methods: This was a secondary analysis of a randomized, double-blind trial over 12 weeks with varenicline or bupropion, followed by a 12-week assessment, in participants ages 18-75 with past (N=2,174) or current (N=451) MDD or without psychiatric disorders (N=4,028). Interventions included 12 weeks of pharmacotherapy with placebo, nicotine replacement therapy (NRT; nicotine patch), bupropion, or varenicline, and brief counseling. The primary safety outcome was occurrence of one or more moderate to severe neuropsychiatric adverse events. Efficacy was assessed as biochemically verified continuous abstinence during weeks 9-12.

Results: Among all 6,653 participants, the risk of neuropsychiatric adverse events did not differ by medication within the past-MDD, current-MDD, or nonpsychiatric cohorts. The MDD cohorts had higher risk difference (p<0.001) for neuropsychiatric adverse events compared with the nonpsychiatric cohort (past-MDD cohort, risk difference=-0.03, 95% CI=-0.05, -0.02; current-MDD cohort, risk difference=-0.02, 95% CI=-0.05, 0.00). Within the past-MDD cohort, the odds ratios compared with placebo were 3.0 (95% CI=2.0, 4.5) for varenicline, 2.1 (95% CI=1.6, 2.7) for bupropion, and 2.1 (95% CI=1.4, 3.2) for NRT. Within the current-MDD cohort, varenicline differed from placebo (odds ratio=2.67, 95% CI=1.2, 6.15) and NRT (odds ratio=2.93, 95% CI=1.2, 7.2).

Conclusions: All medications were generally safe in both MDD cohorts. NRT and bupropion were not more effective than placebo for those with current MDD. Varenicline plus counseling may be the best treatment for individuals with past or current MDD, given its greater efficacy, similar risk of adverse events, and, for those with current depression, reductions in anxiety and depression while trying to quit smoking.