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Immediate and delayed quitting during smoking cessation treatment with varenicline vs bupropion
David Gonzales, Senior Researcher and Co-Director, Smoking Cessation Research Center, Oregon Health & Science University, USA

Abstract
Nicotine binding at alpha-4 beta-2 nicotinic receptors stimulates dopamine release in the brains of smokers and is associated with some of the pleasurable and reinforcing effects of smoking. Abrupt reduction in nicotine binding due to smoking reduction or cessation results in a variety of withdrawal symptoms. The efficacy of varenicline for smoking cessation is believed to result from partial agonist and antagonist activity at the alpha-4 beta-2 receptors. Varenicline is thought to reduce craving and withdrawal by stimulating lower levels of dopamine release as well as reducing smoking satisfaction by blocking nicotine binding. We hypothesized that this unique mechanism of action may result in a more dynamic quitting process for some subjects that could continue beyond the target quit date (Week 1 visit). We analyzed quitting patterns from pooled data from 2 identically-designed randomized studies from the target quit date through 12 weeks of treatment with varenicline 1mg BID (n=692), bupropion SR 150mg BID (n=669), or placebo (n=684). Smoking status was assessed at weekly clinic visits through Week 12. The primary endpoint was carbon monoxide-confirmed continuous abstinence for Weeks 9¨C12 (last 4 weeks of drug treatment).

Subjects continuously abstinent for Weeks 9¨C12 were classified as either immediate quitters (ImQs; abstinent at all visits) or delayed quitters (DQs: smoking ¡Ý1 visits for Weeks 2¨C8). Those not continuously abstinent for Weeks 9-12 were classified as either intermittent quitters (IntQs: abstinent ¡Ý1 visits from the target quit date to Week 12); or non-quitters (NQs: not abstinent at any visit). Overall continuous abstinence rates for Week 9¨C12 were 44.2% for varenicline versus 29.7% for bupropion SR (p<0.0001) or 17.7% for placebo (p<0.0001). Of these, 24.1% were ImQs for varenicline, 18.1% for bupropion SR and 10.2% for placebo. DQs were 20.1% for varenicline 11.7% for bupropion SR and 7.5% for placebo. Of those not continuously abstinent for Weeks 9¨C12, IntQs were 24.3%, 25.6%, and 14.2% for varenicline, bupropion SR, and placebo, respectively. There were fewer NQs for varenicline (31.5%) than for bupropion SR (44.7%) or placebo (68.1%). These data show that, regardless of treatment, a proportion of quitting is dynamic and occurs beyond the target quit date, suggesting that smokers unable to quit immediately should continue taking medication and attempting to quit. The more robust effects on immediate quitting and on delayed quitting for those on varenicline may represent additional evidence of the dual partial agonist and antagonist mechanism of action.

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Biography
David Gonzales, PhD is a Senior Researcher and Co-director of the OHSU Smoking Cessation Center, Division of Pulmonary and Critical Care Medicine at Oregon Health & Science University in Portland, Oregon USA where he directs the clinical trials and training programs section. Since 1988 he has been providing treatment to smokers and researching pharmacologic and behavioural interventions for nicotine dependence treatment. He has conducted clinical trials of pharmacotherapies such as nicotine replacement, bupropion, rimonabant, dopamine receptor antagonists, a nicotine vaccine and varenicline. Much of his work has focused on translating leading edge research findings into clinical practice through professional education and community training programs.

He has investigated smoking and quitting patterns, pharmacology use and re-use patterns, gender response to interventions and spirituality as an aid to abstinence for smokers. He provides consultation to national, state and local tobacco control programs, the National Tobacco Cessation Leadership Network, Native American and Alaskan Native Area Health Boards, and Native American tribal health clinics throughout the US. He conducts professional education programs for health care, mental health and pharmacy professionals in a variety of academic and community settings throughout the United States.

David Gonzales
Smoking Cessation Research Center
Oregon Health & Science University
Portland
OR 97239-3098
USA

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