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Biomarkers of Response to Smoking Cessation Pharmacotherapies: Progress to Date

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Abstract

For the past 30 years, research examining predictors of successful smoking cessation treatment response has focused primarily on clinical variables, such as levels of tobacco dependence, craving, and self-efficacy. However, recent research has begun to determine biomarkers (such as genotype, nicotine and metabolite levels, and brain imaging findings) that may have utility in predicting smoking cessation. For genotype, genes associated with nicotinic acetylcholine receptors (nAChRs) and related proteins have been found to predict response to first-line medications (e.g. nicotine replacement therapy [NRT], bupropion, or varenicline) or quitting over time without a controlled treatment trial. For nicotine and metabolite levels, function of the cytochrome P450 2A6 liver enzyme, which can be assessed with the nicotine metabolite ratio or via genotype, has been found to predict response, with slow nicotine metabolizers having less severe nicotine dependence and a greater likelihood of quitting with NRT than normal metabolizers. For brain imaging, decreased activation of brain regions associated with emotion regulation and increased connectivity in emotion regulation networks, increased responsiveness to pleasant cues, and altered activation with the Stroop effect have been found in smokers who quit with the first-line medications listed above or counseling. In addition, our group recently demonstrated that lower pre-treatment brain nAChR density is associated with a greater chance of quitting smoking with NRT or placebo. Several of these studies found that specific biomarkers may provide additional information for predicting response beyond subjective symptom or rating scale measures, thereby giving an initial indication that biomarkers may, in the future, be useful for guiding smoking cessation treatment intensity, duration, and type.

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Acknowledgments

This work was supported by grants from the National Institute on Drug Abuse (R01 DA20872), the Department of Veterans Affairs, Office of Research and Development (CSR&D Merit Review Award I01 CX000412), and the Tobacco-Related Disease Research Program (#23XT-0002) to Arthur L. Brody, and a grant from the National Institute on Drug Abuse (R21 DA33813) to Andrew W. Bergen. Michael Mamoun, Andrew W. Bergen, Arthur L. Brody, Jennifer Shieh and Anna Wiggins report no conflicts of interest.

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Authors and Affiliations

  1. Departments of Research and Psychiatry, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA

    Michael Mamoun & Arthur L. Brody

  2. Center for Health Sciences, SRI International, Menlo Park, CA, USA

    Andrew W. Bergen

  3. Department of Neurology, University of California at Los Angeles, Los Angeles, CA, USA

    Jennifer Shieh

  4. Department of Psychiatry, University of Southern California, Los Angeles, CA, USA

    Anna Wiggins

  5. Department of Psychiatry, University of California at Los Angeles, 300 UCLA Medical Plaza, Suite 2200, Los Angeles, CA, 90095, USA

    Arthur L. Brody

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  1. Michael Mamoun
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  5. Arthur L. Brody
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Correspondence to Arthur L. Brody.

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Mamoun, M., Bergen, A.W., Shieh, J. et al. Biomarkers of Response to Smoking Cessation Pharmacotherapies: Progress to Date. CNS Drugs 29, 359–369 (2015). https://doi.org/10.1007/s40263-015-0243-1

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