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Effect of varenicline and bupropion on craving, nicotine withdrawal symptoms, and rewarding effects of smoking during a quit attempt
Robert West, Professor of Health Psychology and Director of Tobacco Studies at the Cancer Research UK Health Behaviour Research Centre, University College London

Abstract
Varenicline was designed to bind with high affinity to the alpha4beta2 NAch receptor 1) to block nicotine from binding thereby reducing the rewarding effect of cigarettes, and 2) to increase activity in neural pathways downstream thus diminishing craving and withdrawal. Published data from two Phase III clinical trials support this hypothesis but allow room for doubt about the interpretation because data were averaged over 7 weeks and analyses of craving and withdrawal symptoms used data from both abstinent and non-abstinent smokers. Hence subjective effects could have been secondary to effects on abstinence. We analyzed the pooled data from two clinical trials comparing varenicline, bupropion and placebo using ratings of craving, withdrawal, and the rewarding effects of cigarettes smoked in the first week after the quit date, separating out abstinent and non-abstinent subjects. One week was used as the follow-up point because withdrawal symptoms would be at their most severe during that time and the number of subjects who were abstinent from the quit date would be greatest. Craving was less in subjects receiving varenicline and bupropion than in those receiving placebo in both the abstinent and non-abstinent. Those receiving varenicline reported less craving than those receiving bupropion but the difference was only significant in non-abstinent subjects. Among abstinent subjects, those receiving varenicline and bupropion reported significantly less negative affect than those receiving placebo, but varenicline did not differ from bupropion. Neither medication reduced restlessness, insomnia or appetite in abstainers. Ratings of satisfaction and psychological reward following the first cigarette smoked after the quit date were significantly lower in those receiving varenicline than either bupropion or placebo. The greater efficacy of varenicline compared with bupropion in aiding abstinence seems to be largely due to its effect on r!
educing nicotine reward. Varenicline’s lack of efficacy in reducing insomnia, restlessness, and increased appetite in this analysis suggests that receptors other than the alpha4beta2 NAch subtype are implicated in these withdrawal symptoms.

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Biography
Robert West is Director of Tobacco Studies at the Cancer Research UK Health Behaviour Unit, Department of Epidemiology and Public Health, University College London. He started researching tobacco and nicotine use in 1982 under the direction of Michael Russell. His early research focused on the nicotine withdrawal syndrome but since then he has also contributed to clinical trials of behavioural and pharmacological aids to cessation, population surveys and cohort studies of smokers looking at patterns of smoking and smoking cessation, as well as surveys of health professionals examining attitudes, knowledge and behaviour's relating to smoking cessation. He has also contributed to the development of national and international clinical practice guidelines on smoking cessation. He is Editor-in-Chief of the journal, Addiction. He has been an author on more than 250 scientific works and has recently written a book developing a new, comprehensive theory of motivation and its!
application to addiction. More information can be found at www.rjwest.co.uk.

Robert West
Cancer Research UK Health Behaviour Unit
University College London
London
WC1E 6BT

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