Efficacy and Safety of Varenicline for Smoking Cessation
Section snippets
Overview of development and mechanism of action of varenicline
The positive reinforcing effects of nicotine and the presence of craving and withdrawal symptoms associated with tobacco cessation are important factors that prevent smokers from achieving long-term tobacco abstinence. Addressing both the positive reinforcing effects of nicotine and the withdrawal symptoms with a single drug would be expected to improve the efficacy of tobacco dependence treatment. Varenicline was developed to achieve both of these aims.
A basic understanding of the
Design
To establish the safety, efficacy, and appropriate dose of varenicline, 2 multicenter, randomized, double-blind, placebo-controlled phase 2 clinical trials were conducted in cigarette smokers (Table 1).22, 23, 24, 25, 26 In both trials, smoking abstinence was determined by self-report and verified by measurement of exhaled carbon monoxide ≤10 ppm at weekly visits. Patients were provided with educational material on smoking cessation and up to 10 minutes of smoking cessation counseling at each
Phase 3 clinical trials with varenicline
Three large phase 3 trials were designed to test the hypothesis that varenicline 1 mg twice daily is safe and efficacious in the treatment of tobacco dependence; 2 of the 3 trials evaluated varenicline as an aid to cessation compared with placebo and bupropion-SR.24, 25 The third trial was designed to determine whether maintenance therapy with varenicline after an initial 12 weeks of varenicline treatment would result in reduced or delayed relapse to smoking compared with varenicline treatment
Varenicline: place in therapy
Varenicline is the first in a new class of agents for smoking cessation, the α4β2 nAChR partial agonists. Thus, varenicline offers a new therapeutic option for patients trying to achieve smoking cessation. Consistent with its mechanism of action, this agent appears to offer improvement over placebo and bupropion-SR for nicotine craving and withdrawal measures, and for reducing smoking satisfaction and reward in subjects who lapse. These pharmacologic differences between varenicline and other
Summary
Tobacco use continues to be the most important cause of preventable premature death in the United States and an increasing cause of morbidity and mortality throughout the world. Effective therapy for current smokers is needed to reduce the substantial predicted morbidity and mortality related to smoking. Currently recommended treatments are efficacious, but long-term abstinence rates are less than optimal. Varenicline, a novel α4β2 nAChR partial agonist, is efficacious for the treatment of
Author disclosures
J. Taylor Hays, MD, has served as an unpaid consultant on an advisory board for Pfizer Inc; and has received grant/research support from Pfizer Inc.
Jon O. Ebbert, MD, has no financial arrangement or affiliation with a corporate organization or a manufacturer of a product discussed in this supplement.
Amit Sood, MD, has no financial arrangement or affiliation with a corporate organization or a manufacturer of a product discussed in this supplement.
Acknowledgment
Editorial support was provided by Darlene Benson, BSPharm, of Medesta Publications Group, and funded by Pfizer Inc.
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Statement of conflict of interest: Please see Author Disclosures section at the end of this article.