We found no evidence that genetic variation predicts a differential response to bupropion for smoking cessation in this sample of recently abstinent alcoholics. Despite the combination of patch plus bupropion vs. patch alone being largely ineffective for promoting smoking cessation in this population, an AGRS (created by examining genetic variation previously identified in at least two bupropion trials) interacted with nicotine dependence level to be associated with smoking cessation status at the end of treatment. Given that this AGRS does not interact with the medication condition, the implication may be that this AGRS by dependence interaction may actually be associated with the platform treatment of counseling + NRT (Nicotine Replacement Therapy). It is interesting that the candidates selected for inclusion in the AGRS were identified in pharmacogenetic trials of bupropion while the AGRS by dependence interaction moderated treatment response independently of medication condition. It is possible that a particular combination of alterations in the dopaminergic system may not only put one at risk for the development of comorbid alcohol and nicotine dependence, but also be related to response to standard smoking cessation treatments for individuals at varying levels of dependence.
