Pharmacogenetic clinical trial of sustained-release bupropion for smoking cessation

被引:70
作者
David, Sean P.
Brown, Richard A.
Papandonatos, George D.
Kahler, Christopher W.
Lloyd-Richardson, Elizabeth E.
Munafo, Marcus R.
Shields, Peter G.
Lerman, Caryn
Strong, David
McCaffery, Jeanne
Niaura, Raymond
机构
[1] Brown Univ, Ctr Primary Care & Prevent, Pawtucket, RI 02860 USA
[2] Primary Care Genet Lab & Translat Res Ctr, Providence, RI USA
[3] Butler Hosp, Brown Med Sch, Providence, RI USA
[4] Brown Univ, Behav & Prevent Med, Providence, RI USA
[5] Ctr Stat Sci, Providence, RI USA
[6] Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI USA
[7] Brown Univ, Ctr Behav & Prevent Med, Providence, RI USA
[8] Univ Bristol, Dept Expt Psychol, Bristol, Avon, England
[9] Georgetown Univ, Sch Med, Lombardi Comprehensive Canc Ctr, Washington, DC USA
[10] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA
关键词
D O I
10.1080/14622200701382033
中图分类号
R194 [卫生标准、卫生检查、医药管理];
学科分类号
摘要
This randomized, double-blinded, placebo-controlled trial examined genetic influences on treatment response to sustained-release bupropion for smoking cessation. Smokers of European ancestry (N5291), who were randomized to receive bupropion or placebo (12 weeks) plus counseling, were genotyped for the dopamine D2 receptor (DRD2Taq1A), dopamine transporter (SLC6A3 39 VNTR), and cytochrome P450 2B6 (CYP2B6 1459 C -> T) polymorphisms. Main outcome measures were cotinine-verified point prevalence of abstinence at end of treatment and at 2-, 6-, and 12-month follow-ups post quit date. Using generalized estimating equations, we found that bupropion, compared with placebo, was associated with significantly greater odds of abstinence at all time points (all p values <. 01). We found a significant DRD2xbupropion interaction (B=1.28, SE=0.59, p=.12) and a three-way DRD2 x bupropion x craving interaction on 6- month smoking cessation outcomes (B=-0.45, SE=0.22, p=.038), such that smokers with the A2/A2 genotype demonstrated the greatest craving reduction and the highest abstinence rates with bupropion. Furthermore, there was a significant DRD2 x CYP2B6 interaction (B=1.43, SE=0.56, p=.01), such that individuals with the DRD2-Taq1 A2/A2 genotype demonstrated a higher odds of abstinence only if they possessed the CYP2B6 1459 T/T or C/T genotype. Because the sample size of this study was modest for pharmacogenetic investigations, the results should be interpreted with caution. Although these results require replication, the data suggest preliminarily that the DRD2-Taq1A polymorphism may influence treatment response to bupropion for smoking cessation and, further, that exploration of gene x gene and gene x craving interactions in future, larger studies may provide mechanistic insights into the complex pharmacodynamics of bupropion.
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页码:821 / 833
页数:13
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