Could Metabolism Affect Smoking Cessation Efforts?
Researchers from the Perelman School of Medicine at the University of Pennsylvania, the Centre for Addiction and Health at the University of Toronto, the State University of New York, and The University of Texas MD Anderson Cancer Center recruited 1,246 treatment-seeking smokers for the study, which sorted participants into 2 groups. One group consisted of 662 “slow metabolizers,” while the remaining 584 were considered “normal” metabolizers.
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In order to differentiate between “slow” and “normal,” the researchers took participants’ blood samples, examining the ratio of 2 metabolites that are derived from smoking. According to the authors, this ratio is reflective of the activity of the major nicotine and cotinine-metabolizing enzyme in the liver—CYP2A6—which helps smokers to metabolize nicotine.
Participants were then randomized to 11 weeks of 1 of the following treatments: the nicotine patch plus a placebo bill, varenicline plus placebo path, or a placebo patch and pill. In addition, all participants received behavioral counseling. Patients’ smoking behaviors were then assessed at the end of the 11-week treatment period, and the authors followed up again at 6 and 12 months.
Among the normal metabolizers, nearly 40% of varenicline users had not relapsed, in comparison to 22% of patch users. The effectiveness of these 2 treatments was about the same among the slow metabolizers. This group, however, did report more overall side effects from taking varenicline, a finding the authors say suggests that slow metabolizers would benefit more from using the patch than from taking pills to help quit smoking.
In addition, quitting success had decreased by the time of the 6-month and 12-month follow-up periods. The authors anticipated as much, given the previous success rates reported in other smoking cessation studies. The ratios for normal and slow metabolizers using the patch and varenicline, however, remained.
While noting that this test is not currently available commercially, “the take-home message is that a one-size-fits-all approach to smoking cessation treatment does not account for the heterogeneity among smokers,” says Caryn Lerman, PhD, a professor in the department of psychiatry and Annenberg Public Policy Center at the University of Pennsylvania, and lead study author.
“A tailored approach is likely to be more effective,” says Lerman.
“We should have a commercially available test soon, which will be able to sort smokers on the basis of normal versus slow nicotine metabolism,” adds Tony George, MD, FRCPC, a professor of psychiatry and co-director of the division of brain and therapeutics at the University of Toronto, and a co-author of the study.
“This may have important treatment implications, in terms of choosing nicotine replacement versus non-nicotine treatments like varenicline,” says George. “That is, slow metabolizers respond better to nicotine replacement and normal metabolizers [respond better] to varenicline, and both treatments are well-tolerated. This will allow a ‘personalized medicine’ approach to smoking cessation.”
Lerman C, Schnoll R, et al. Use of the nicotine metabolite ratio as a genetically informed biomarker of response to nicotine patch or varenicline for smoking cessation: a randomised, double-blind placebo-controlled trial, The Lancet Respiratory Medicine. 2015.