Using data from a multi-armed cessation trial that includes NRT, bupropion, combination pharmacotherapies, and placebo controls, we tested the hypotheses that: 1) individuals with CYP2A6 genotype-based fast nicotine metabolism are more likely to relapse sooner than individuals with slow metabolism when given placebo intervention, 2) the effect of active pharmacotherapy vs. placebo will vary (i.e., interact) with CYP2A6 genotype, and 3) the effects of NRT will differ (interact) with CYP2A6 genotype but the effects of bupropion will not. In addition, we examined whether the effects of CYP2A6 on smoking cessation outcome, and therapeutic response to NRT, are independent from those of CHRNA5, another gene associated with cessation outcomes and response to smoking cessation pharmacotherapy (1). This research was designed to reveal the genetic conditions under which the tested pharmacotherapies exert their optimal effects, a topic of clear relevance to a genetically informed, personalized approach to smoking cessation pharmacotherapy.
