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Predictors of relapse in a bupropion trial for smoking cessation in recently-abstinent alcoholics: preliminary results using an aggregate genetic risk score.

ABSTRACT: INTRODUCTION:Rates of smoking in the US population have decreased overall, but rates in some groups, including alcoholic smokers, remain high. Many newly sober alcoholics are concerned about their smoking and some attempt to quit. However, quit rates in this population are low. Prior studies suggest risk for relapse in this population may be genetically influenced and that genetic factors may moderate response to treatment. METHODS:IN THIS EXPLORATORY STUDY, WE HAD TWO SPECIFIC AIMS: (1) to investigate associations between genetic risk and outcome; (2) to investigate whether genetic risk moderates the efficacy of a medication intervention. Data are from a subsample of 90 participants from a clinical trial of smoking cessation treatment for smokers with between 2 and 12 months of alcohol abstinence. Subjects were randomly assigned to bupropion or placebo. All subjects received counseling and nicotine patches. To examine the possibility that bupropion may have been efficacious in participants with a specific genetic profile (ie, a pharmacogenetic approach), an aggregate genetic risk score was created by combining risk genotypes previously identified in bupropion treatment studies. RESULTS:Although medication efficacy was not moderated by the aggregate genetic risk score, there was an interaction between nicotine dependence and genetic risk in predicting smoking abstinence rates at the end of treatment (10 weeks). CONCLUSIONS:Results suggest an aggregate genetic risk score approach may have utility in treatment trials of alcoholics who smoke. Additionally, these findings suggest a strategy for understanding and interpreting conflicting results for single genetic markers examined as moderators of smoking cessation treatment.

SUBMITTER: McGeary JE

PROVIDER: S-EPMC3460669 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Predictors of relapse in a bupropion trial for smoking cessation in recently-abstinent alcoholics: preliminary results using an aggregate genetic risk score.

McGeary John E JE Knopik Valerie S VS Hayes John E JE Palmer Rohan H RH Monti Peter M PM Kalman David D

Substance abuse : research and treatment 20120917

<h4>Introduction</h4>Rates of smoking in the US population have decreased overall, but rates in some groups, including alcoholic smokers, remain high. Many newly sober alcoholics are concerned about their smoking and some attempt to quit. However, quit rates in this population are low. Prior studies suggest risk for relapse in this population may be genetically influenced and that genetic factors may moderate response to treatment.<h4>Methods</h4>IN THIS EXPLORATORY STUDY, WE HAD TWO SPECIFIC AI ...[more]

PMID: 23032639

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Project description:BackgroundAlthough a relatively small proportion of women who become pregnant continue to smoke cigarettes, no smoking cessation medication has been shown to be effective for this subgroup of smokers. Bupropion, a nonnicotine-based medication, is approved for the promotion of smoking cessation in nonpregnant individuals. We chose to study it in pregnant smokers because, although pregnancy increases nicotine metabolism, it does not affect the metabolism of bupropion.ObjectiveWe evaluated the efficacy and safety of sustained-release bupropion for smoking cessation among pregnant women.Study designWe conducted a multiple site, placebo-controlled, randomized clinical trial of bupropion for tobacco use among pregnant women (N=129) (clinical trial number NCT02188459). We enrolled women during the second trimester and randomly assigned them to receive 10 weeks of treatment with either bupropion or placebo, accompanied by a total of 6 smoking cessation counseling sessions (4 during treatment and 2 postpartum). The primary outcome was 7-day point prevalence smoking abstinence, confirmed with breath carbon monoxide measurements, at the end of treatment (week 10) and at week 24. Group differences were assessed as a binary abstinence outcome using a repeated measure generalized estimating equations model with a logit link. Prolonged abstinence and smoking rates were secondary outcomes. Safety measures included maternal treatment-related adverse events, gestational age, the rate of overall and spontaneous preterm births and infant birthweight and size for gestational age, head circumference, and 5-minute Apgar scores.ResultsThere were no significant differences in the safety measures across the treatment arms and bupropion was not efficacious in promoting smoking cessation at the end of treatment (7-day point prevalence quit rates: bupropion, 11.0%; placebo, 18.5%) or week 24 (7-day point prevalence quit rates: bupropion, 9.4%; placebo, 21.5%) (P>.05). African American women and women with a lower severity of nicotine dependence had significantly higher quit rates overall and women with an opioid use disorder who were being treated with opioid agonist therapy had significantly lower quit rates overall, irrespective of the treatment group (all P values <.05).ConclusionAlthough bupropion use was not associated with an elevated risk for pregnancy complications when initiated in the second trimester, it did not increase the likelihood of smoking cessation in this cohort of pregnant women. Because smoking is the major preventable source of poor pregnancy outcomes and psychosocial interventions have only modest beneficial effects, additional studies are needed to identify safe and efficacious smoking cessation medications for pregnant women who continue to smoke.

Dataset Information

Predictors of relapse in a bupropion trial for smoking cessation in recently-abstinent alcoholics: preliminary results using an aggregate genetic risk score.

Publications

Predictors of relapse in a bupropion trial for smoking cessation in recently-abstinent alcoholics: preliminary results using an aggregate genetic risk score.

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