Can Pharmacogenetics Help Smokers Quit?

Abstract

Cigarette smoking is the largest preventable cause of death and morbidity in the USA, Europe and the rest of the developed world [1]. Despite decades of research to develop effective smoking cessation treatments, a large proportion of smokers who attempt to quit are doomed to fail [2]. Nicotine is the principal addictive chemical in tobacco smoke, but despite the addicting properties of nicotine there is nevertheless substantial interindividual variation in the level of nicotine dependence among cigarette smokers, as well as in therapeutic response to smoking cessation pharmacotherapies [2]. Therefore, the public health impact of cigarette smoking remains substantial, which means that any improvement in the currently modest success rates achieved by smokers attempting to quit would have the potential to afford a considerable improvement in public health. These observations have prompted a growing interest in pharmacogenetics research to determine whether the efficacy of different pharmacotherapies for the treatment of nicotine dependence is influenced by inherited variation in drug-metabolizing enzymes and drug targets [3,4]. To date, only a limited number of pharmacogenetic studies of smoking cessation pharmacotherapies have been published. Two studies have investigated nicotine replacement therapy (NRT), one an open-label trial of transdermal patch versus nasal spray [5–7], and the other a randomized controlled trial of transdermal patch versus placebo [8,9]. Three studies have investigated sustained-release bupropion, including two randomized controlled trials of bupropion versus placebo [5,10–12], and one open-label effectiveness trial [13]. Finally, one study has investigated venlafaxine versus placebo in a randomized controlled trial [14]. Based on the neurobiology of reward [15,16], these pharmacogenetic analyses have focused on genes in the dopamine pathway, the