title: Rate of nicotine metabolism and smoking cessation outcomes in a community-based sample of treatment-seeking smokers.
abstract: 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.
authors.affiliation: Department of Psychiatry, University of Pennsylvania, 3535 Market Street, Suite 4100, Philadelphia, PA 19104.
authors.forename: Amanda
authors.initials: A
authors.lastname: Kaufmann
authors.affiliation: Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, 680 N Lakeshore Drive, Chicago, IL 60611.
authors.forename: Brian
authors.initials: B
authors.lastname: Hitsman
authors.affiliation: Department of Psychiatry, University of Pennsylvania, 3535 Market Street, Suite 4100, Philadelphia, PA 19104.
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Goelz
authors.affiliation: Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, 680 N Lakeshore Drive, Chicago, IL 60611.
authors.forename: Anna
authors.initials: A
authors.lastname: Veluz-Wilkins
authors.affiliation: Department of Psychiatry, University of Pennsylvania, 3535 Market Street, Suite 4100, Philadelphia, PA 19104.
authors.forename: Sonja
authors.initials: S
authors.lastname: Blazekovic
authors.affiliation: Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, 680 N Lakeshore Drive, Chicago, IL 60611.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Powers
authors.affiliation: Pulmonary, Allergy, & Critical Care Division, University of Pennsylvania Presbyterian Medical Center, 51 N. 39th Street, Philadelphia, PA 19104.
authors.forename: Frank T
authors.initials: FT
authors.lastname: Leone
authors.affiliation: Department of Psychiatry, University of Pennsylvania, 3535 Market Street, Suite 4100, Philadelphia, PA 19104.
authors.forename: Peter
authors.initials: P
authors.lastname: Gariti
authors.affiliation: Centre for Addiction and Mental Health, 1 King's College Circle, University of Toronto, Toronto, Ontario, Canada, M5S 1A6; Department of Pharmacology & Toxicology, 1 King's College Circle, University of Toronto, Toronto, Ontario, Canada, M5S 1A6; Department of Psychiatry, 1 King's College Circle, University of Toronto, Toronto, Ontario, Canada, M5S 1A6.
authors.forename: Rachel F
authors.initials: RF
authors.lastname: Tyndale
authors.affiliation: Department of Psychiatry, University of Pennsylvania, 3535 Market Street, Suite 4100, Philadelphia, PA 19104. Electronic address: schnoll@mail.med.upenn.edu.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Schnoll
mesh_terms: D000279:Administration, Cutaneous; D000704:Analysis of Variance; D001007:Anxiety / Q000150:complications / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D003367:Cotinine / Q000031:analogs & derivatives / Q000378:metabolism; D066249:Craving; D003863:Depression / Q000150:complications / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000008:administration & dosage / Q000378:metabolism*; D016540:Smoking Cessation / Q000706:statistics & numerical data*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism; D014029:Tobacco Use Disorder / Q000150:complications / Q000378:metabolism* / Q000628:therapy*
chemical_list: D015415:Biomarkers; C001381:hydroxycotinine; D009538:Nicotine; D003367:Cotinine
keywords: Anxiety; Biomarker; Nicotine dependence; Nicotine metabolite ratio; Pharmacogenetics; Smoking cessation