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Escalating Doses of Transdermal Nicotine in Heavy Smokers: Effects on Smoking Behavior and Craving

Selby, Peter MBBS*†‡; Andriash, Katherine MSc§∥; Zawertailo, Laurie PhD*§∥; Persad, Desmond MSc*; Zack, Martin PhD§∥; Busto, Usoa E. PharmD§∥¶

Journal of Clinical Psychopharmacology: October 2013 - Volume 33 - Issue 5 - p 667–674
doi: 10.1097/JCP.0b013e31829a829d
Original Contributions

Abstract: Fixed-dose nicotine replacement therapy (NRT) is efficacious for smoking cessation in the general population of smokers. However, it is less effective in populations with psychiatric comorbidities and/or severe tobacco dependence where the percent nicotine replacement is suboptimal. The objective of this pilot study was to determine the effectiveness of nicotine patch dose titration in response to continued smoking in heavily dependent smokers with psychiatric comorbidity. In a single-arm, open-label study adult smokers (mean cigarettes per day, 25.4 ± 13.4; range, 14–43; n = 12) willing to quit were treated with escalating doses of transdermal nicotine and brief counseling intervention if they continued to smoke over a 9-week treatment period. Plasma nicotine and cotinine, along with expired carbon monoxide levels, and the subjective effects of smoking, urge to smoke, demand elasticity, and mood symptoms were also assessed. The mean NRT dose was 32.7 (SD, 16.4) mg/d (range, 7–56 mg/d). Smokers reported significant reductions in both cigarettes per day (mean decrease, 18.4 ± 11.5) confirmed by expired carbon monoxide (mean decrease, 13.5 ± 13.0) with no significant changes in plasma nicotine concentrations during the course of NRT dose titration. There were significant effects on the subjective effects of smoking and measures of smoking behavior. Most commonly reported adverse events were respiratory infections, skin irritation at patch site, nausea, and sleep disturbances, which were generally mild and transient. Titrating doses of NRT to effect with brief intervention hold promise as an effective clinical strategy to assist heavily dependent psychiatrically ill smokers to change their smoking behavior.

From the *Nicotine Dependence Clinic, Addictions Program, Centre for Addiction and Mental Health, †Ontario Tobacco Research Unit, ‡Department of Family and Community Medicine and Psychiatry and the Dalla Lana School of Public Health, §Clinical Neuroscience Section, Centre for Addiction and Mental Health, ∥Department of Pharmacology and Toxicology, and ¶Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.

Received May 17, 2012; accepted after revision January 4, 2013.

Reprints: Peter Selby, MBBS, Centre for Addiction and Mental Health, 33 Russell St, Toronto, Ontario, Canada M5S 2S1 (e-mail:

This work was conducted through the Nicotine Dependence Clinic at the Centre for Addiction and Mental Health in Toronto, Ontario, Canada, and was supported (to P.S.) by the Ontario Ministry of Health Promotion through the provision of nicotine patches purchased at a discounted rate from Pfizer Consumer Healthcare Canada (now McNeil Consumer Healthcare, Division of Johnson & Johnson Inc). K.A. was supported by the Ontario Tobacco Research Unit Ashley Studentship for Research in Tobacco Control. This study was also supported by the Canadian Institutes of Health Research New Emerging Team Grant to L.Z. and U.E.B. (grant ID 79919).

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© 2013 by Lippincott Williams & Wilkins.