Efficacy and Safety of Varenicline for Smoking Cessation

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Abstract

Effective treatment of nicotine addiction is essential for reducing the substantial current and predicted morbidity and mortality associated with tobacco smoking. Despite the availability of effective treatments for smoking cessation, such as nicotine replacement therapy and bupropion sustained-release (SR), abstinence rates remain less than optimal. Varenicline is the first in a new class of agents for smoking cessation, the α4β2 nicotinic acetylcholine receptor (nAChR) partial agonists. Nicotine addiction is mediated by stimulation of central α4β2 nAChRs by nicotine, which causes the release of dopamine, ultimately leading to the pleasurable effects of smoking. As a nAChR partial agonist, varenicline attenuates the craving and withdrawal symptoms that occur with abstinence from nicotine and also reduces the rewarding effects of nicotine obtained from smoking in patients who lapse. Thus, varenicline offers a new therapeutic option for the treatment of nicotine addiction. Clinical trials have demonstrated superior efficacy of this agent over placebo and bupropion-SR for achieving abstinence from smoking, and varenicline has also been shown to significantly delay smoking relapse. As the newest agent approved for smoking cessation, the mechanism of action, efficacy, and safety of varenicline.

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.

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