Sex heterogeneity in pharmacogenetic smoking cessation clinical trials

Approximately one-quarter of smokers who use treatments for nicotine dependence are able to achieve cessation. However, there is evidence that women do not respond as well to nicotine replacement therapy (NRT) and, perhaps, to bupropion, compared to men. In this contribution to the Special Issue of Drug and Alcohol Dependence concerning Women and Smoking, we begin with a brief overview of data supporting the role of sex in influencing response to NRT and bupropion. Next, we summarize the results of pharmacogenetic smoking cessation clinical trials which assessed sex as a moderator as well. A relatively small number of pharmacogenetic studies of nicotine dependence treatments have been conducted and five studies reported sex effects in these trials. Of these trials, sex moderated the association of genetic variation in drug pharmacokinetics or pharmacodynamics and treatment response. We conclude this paper with a summary and a brief discussion of the major caveats of this literature and priorities for future research.