Combination Treatment With Varenicline and Bupropion in an Adaptive Smoking Cessation Paradigm

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2014-06-17

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OBJECTIVE The authors assessed the efficacy and safety of combination treatment with varenicline and sustained-release bupropion for smokers who, based on an assessment of initial smoking reduction prior to the quit date, were deemed unlikely to achieve abstinence using nicotine patch treatment. METHOD In a randomized, double-blind, parallel-group adaptive treatment trial, the authors identified 222 cigarette smokers who failed to show a reduction of more than 50% in smoking after 1 week of nicotine patch treatment. Smokers were randomly assigned to receive 12 weeks of varenicline plus bupropion or varenicline plus placebo. The primary outcome measure was continuous smoking abstinence at weeks 8-11 after the target quit date. RESULTS Both treatments were well tolerated. Participants who received the combination treatment had a significantly higher abstinence rate than those who received varenicline plus placebo (39.8% compared with 25.9%; odds ratio=1.89; 95% CI=1.07, 3.35). Combination treatment had a significantly greater effect on abstinence rate in male smokers (odds ratio=4.26; 95% CI=1.73, 10.49) than in female smokers (odds ratio=0.94; 95% CI=0.43, 2.05). It also had a significantly greater effect in highly nicotine-dependent smokers (odds ratio=3.51, 95% CI=1.64, 7.51) than in smokers with lower levels of dependence (odds ratio=0.71, 95% CI=0.28, 1.80). CONCLUSIONS Among smokers who did not show a sufficient initial response to prequit nicotine patch treatment, combination treatment with varenicline and bupropion proved more efficacious than varenicline alone for male smokers and for smokers with a high degree of nicotine dependence.

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10.1176/appi.ajp.2014

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Rose, JE, and FM Behm (2014). Combination Treatment With Varenicline and Bupropion in an Adaptive Smoking Cessation Paradigm. American Journal of Psychiatry. 10.1176/appi.ajp.2014 Retrieved from https://hdl.handle.net/10161/9020.

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Scholars@Duke

Rose

Jed Eugene Rose

Professor Emeritus in Psychiatry and Behavioral Sciences

We are pursuing three main lines of research:

1) Brain imaging of the effects of nicotine and cigarette smoking: We have used Positron Emission Tomography (PET) methods to analyze regional cerebral blood flow responses to nicotine, administered either intravenously or inhaled in cigarettes. Our aim is to identify brain substrates mediating the addictive properties of nicotine. Preliminary results have shown alterations in the pattern of regional cerebral blood flow, involving frontal cortex, amygdala and other brain regions. We will continue to delineate the similarities and differences between the effects of nicotine and other drugs on regional brain activity, and plan to monitor the changes in response to nicotine after smoking cessation with nicotine antagonist treatment.

2) Analysis of airway sensory components of smoking reinforcement: We have continued the study the role of sensorimotor aspects of cigarette smoking in relieving craving for cigarettes and regulating smoke intake. We completed a study of the effects of intravenous nicotine presented alone or in combination with the sensorimotor aspects of smoking using de-nicotinized cigarette smoke. Craving for cigarettes was relieved more effectively by the de-nicotinized smoke than by the intravenous nicotine. Current studies underway at the Clinical Research Unit will further investigate the subjective effects of i.v. nicotine and de-nicotinized cigarette smoke, using a wider range of nicotine doses. Possible predictors of clinical outcome following nicotine skin patch treatment will be identified based on acute responses to the pharmacologic effects of nicotine in the laboratory.

We are also continuing to further the clinical application of these findings by developing substitutes that provide the airways sensory effects of smoking (e.g. citric acid aerosol).


3) Agonist/antagonist combination treatment for drug dependence: In a double blind smoking cessation trial using mecamylamine, a nicotinic antagonist, in combination with nicotine skin patches, we found that addition of the antagonist substantially increases smoking abstinence throughout the 1 year follow-up. Two additional studies that we conducted support the view that pre-treatment with mecamylamine prior to smoking cessation may be a critical factor in achieving high success rates. By blocking reinforcing effects of nicotine, smoking behavior may be partially extinguished, thereby facilitating subsequent smoking cessation. We recently completed a Phase II FDA trial evaluating a transdermal patch delivering nicotine and mecamylamine, which replicated our previous results. It is anticipated that an NDA pertaining to the new skin patch will be submitted in 1997. Continuing studies in our program will determine the optimal dose and duration of treatment. We also have initiated studies to extend this approach to the treatment of other drug dependencies, including cocaine.


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