Rate of Nicotine Metabolism and Smoking Cessation Outcomes in a Community-Based Sample of Treatment-Seeking Smokers

Addict Behav. 2015 Dec;51:93-9. doi: 10.1016/j.addbeh.2015.07.019. Epub 2015 Jul 26.


Background: In samples from controlled randomized clinical trials, a smoker's rate of nicotine metabolism, measured by the 3-hydroxycotinine to cotinine ratio (NMR), predicts response to transdermal nicotine. Replication of this relationship in community-based samples of treatment-seeking smokers may help guide the implementation of the NMR for personalized treatment for nicotine dependence.

Methods: Data from a community-based sample of treatment seeking smokers (N=499) who received 8weeks of transdermal nicotine and 4 behavioral counseling sessions were used to evaluate associations between the NMR and smoking cessation. Secondary outcomes included withdrawal and craving, depression and anxiety, side effects, and treatment adherence.

Results: The NMR was a significant predictor of abstinence (OR=.56, 95% CI: 0.33-0.95, p=.03), with faster metabolizers showing lower quit rates than slower metabolizers (24% vs. 33%). Faster nicotine metabolizers exhibited significantly higher levels of anxiety symptoms over time during treatment, vs. slower metabolizers (NMR x Time interaction: F[3,357]=3.29, p=.02). NMR was not associated with changes in withdrawal, craving, depression, side effects, and treatment adherence (p's>.05).

Conclusions: In a community-based sample of treatment-seeking smokers, faster nicotine metabolizers were significantly less likely to quit smoking and showed higher rates of anxiety symptoms during a smoking cessation treatment program, vs. slower nicotine metabolizers. These results provide further evidence that transdermal nicotine is less effective for faster nicotine metabolizers and suggest the need to address cessation-induced anxiety symptoms among these smokers to increase the chances for successful smoking cessation.

Keywords: Anxiety; Biomarker; Nicotine dependence; Nicotine metabolite ratio; Pharmacogenetics; Smoking cessation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Cutaneous
  • Analysis of Variance
  • Anxiety / complications
  • Anxiety / metabolism
  • Biomarkers / metabolism
  • Cotinine / analogs & derivatives
  • Cotinine / metabolism
  • Craving
  • Depression / complications
  • Depression / metabolism
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nicotine / administration & dosage
  • Nicotine / metabolism*
  • Smoking Cessation / statistics & numerical data*
  • Substance Withdrawal Syndrome / metabolism
  • Tobacco Use Disorder / complications
  • Tobacco Use Disorder / metabolism*
  • Tobacco Use Disorder / therapy*


  • Biomarkers
  • hydroxycotinine
  • Nicotine
  • Cotinine