While smoking cessation markedly reduces the risk of morbidity and premature death (1), sustained abstinence rates with the best available treatments (bupropion, nicotine replacement therapy or varenicline and behavioral counseling) do not exceed 50% by the end of treatment (2–5). Twin and family studies indicate that nicotine dependence and ability to quit smoking have genetic determinants (6–11). Candidate gene investigations of smoking cessation pharmacotherapies have reported associations between genetic variants in multiple pharmacodynamic (e.g., catecholamine, cholinergic, opioid receptors) and pharmacokinetic (e.g., cytochrome p450 [CYP] 2A6 & 2B6) pathways implicated in nicotine dependence and treatment response (12–16). Sustained-release bupropion hydrochloride, a first line treatment for smoking cessation, is an atypical antidepressant with dopaminergic (17) and noradrenergic (17) reuptake inhibition and cholinergic (18) properties and it is metabolized to hydroxybupropion and other active metabolites by CYP2B6 (19, 20).
