Bupropion efficacy for smoking cessation is influenced by the DRD2 Taq1A polymorphism: Analysis of pooled data from two clinical trials

We analyzed pooled data from two comparable randomized placebo- controlled clinical trials of bupropion pharmacotherapy for smoking cessation for which data on DRD2 Taq1A genotype were available. A total of 722 smokers across the two trials were randomized to 10 weeks of sustained- release bupropion hydrochloride or placebo. General estimating equation analysis demonstrated a significant gene x drug interaction ( B=50.87, SE=0.34, p=.009). Smokers with the A2/A2 genotype using bupropion were more than three times as likely, relative to placebo, to be abstinent at end of treatment (35.2% vs. 15.1%; OR=3.25, 95% CI 2.00-5.28) and at 6 months of follow-up (26.7% vs. 12.2%; OR=2.81, 95% CI 1.66-4.77), which was attenuated by 12 months (16.3% vs. 10.7%; OR=1.70, 95% CI 0.95-3.05). We found no significant benefit of bupropion relative to placebo on smoking cessation outcomes at any time point in participants with A1/A1 or A1/A2 genotypes. These data suggest that bupropion may be effective for smoking cessation only in a subgroup of smokers with the DRD2 Taq1 A2/A2 genotype.