Benefits of varenicline vs. bupropion for smoking cessation: a Bayesian analysis of the interaction of reward sensitivity and treatment

Rationale: We have shown that differences in the level of neural activation to stimuli associated with smoking vs. natural rewards, a biomarker related to reward sensitivity, predict treatment outcome. Objectives: This paper examined whether this biomarker moderates the impact of bupropion or varenicline on smoking cessation. Methods: Prior to treatment randomization, smokers (N = 180) in a placebo-controlled trial using bupropion and varenicline completed event-related potential recording (late positive potential, LPP) while viewing pleasant (P), cigarette (C)-related, and other pictures. We used Bayesian models to estimate the probability of interaction between treatment and the LPP for both efficacy and comparative effectiveness analyses. Results: Efficacy analysis showed that smokers with more neural activation to pleasant vs. cigarette-related stimuli (P > C) had a 98–99% chance of achieving greater abstinence than placebo (OR >1.00), using either medication from the end of treatment (EOT, primary outcome) through the 3-month follow-up. Relative to placebo, smokers with higher activation to cigarette-related vs. pleasant stimuli (C > P) had a 99% chance of increased benefit from varenicline at both time points (OR >1), but only 67 and 43% with bupropion at the EOT and 3-month follow-up, respectively. Comparative effectiveness analysis found that smokers with the C > P activation pattern had a 95–98% chance of benefit from varenicline vs. bupropion, while P > C smokers had a 50–58% chance of similar improvement with varenicline at the EOT and 3 months. Conclusions: Varenicline appears to be the treatment of choice for smokers with the C > P pattern of neural activation, while for those showing P > C, varenicline and bupropion have similar efficacy.