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 = 0.87, 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.
David
Sean P
SP
Brown University Center for Primary Care and Prevention, Primary Care Genetics and Translational Research Center, Memorial Hospital of Rhode Island, Pawtucket, RI 02860, USA. sean_david@brown.edu
Strong
David R
DR
Munafò
Marcus R
MR
Brown
Richard A
RA
Lloyd-Richardson
Elizabeth E
EE
Wileyto
Paul E
PE
Evins
Eden A
AE
Shields
Peter G
PG
Lerman
Caryn
C
Niaura
Raymond
R
D000328:Adult; D000368:Aged; D000483:Alleles; D016642:Bupropion / Q000008:administration & dosage* / Q000494:pharmacology; D016001:Confidence Intervals; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D016032:Randomized Controlled Trials as Topic; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D012189:Retrospective Studies; D012907:Smoking / Q000188:drug therapy* / Q000235:genetics*; D016540:Smoking Cessation / Q000379:methods; D014029:Tobacco Use Disorder / Q000188:drug therapy / Q000235:genetics; D016896:Treatment Outcome
D018765:Dopamine Uptake Inhibitors; D017448:Receptors, Dopamine D2; D016642:Bupropion