Varenicline Outperforms Zyban in Smoking-Cessation Trial
November 22, 2005
Investigational smoking-cessation drug varenicline has showed promising results. In a clinical study comparing varenicline with Zyban, participants receiving varenicline were more likely to be smoke-free at 12 weeks than participants taking Zyban (bupropion) or placebo. However, results suggest that varenicline may not offer significant longer-term advantages.
Study results, reported by Serena Tonstad, MD, PhD, of the University of Oslo at the American Heart Association meeting, were summarized in a report by MedPage Today on 15 November 2005.
Study Outcomes
Results showed that, at 12 weeks, 44% of smokers receiving varenicline had quit, compared with 30% of smokers receiving Zyban and 17.7% receiving placebo (P<0.001). However, after one year, only 20% of smokers receiving varenicline were still smoke-free.
Dr Tonstad said that varenicline was well tolerated. The major side-effect was nausea, but this was mild and caused no participant to stop taking varenicline. Because the study used Zyban as a comparator, it excluded people who had a history of bipolar depression, seizure disorder or panic attacks.
Altogether, Dr Tonstad reported results from two clinical trials that involved about 2,000 participants and used the same design. Participants were randomized to receive wither varenicline (1 mg/bid), Zyban (150 mg/bid) or placebo.
How Varenicline Works
Varenicline's mechanism of action is to partially block the brain's alpha4-beta2 nicotinic receptor, the main nicotine receptor, according to Dr Tonstad. When someone smokes, nicotine attaches to this receptor within 10-19 seconds of a single cigarette puff. The receptor, in turn, triggers large increases in dopamine, which provide the smoker with a pleasurable sensation.
Varenicline attaches to this receptor and, by occupying it, prevents nicotine from attaching to it. This can break the cycle of addiction by blocking the reward-reinforcement associated with large increases in dopamine, according to Dr Tonstad.
Dr Tonstad noted that varenicline would not work in combination with nicotine-replacement drugs, as varenicline would also block the activity of such drugs.
Perceptions of Varenicline
During an American Heart Association (AHA) press conference Timothy Gardner, MD, who is chairman of the program committee, noted that the study's absolute numbers are "a little disappointing," according to MedPage Today.
In a later interview, Dr Gardner noted that the one-year cessation rate was 22.1% for participants receiving varenicline, versus 16.4% for those receiving Zyban and 10% for those receiving placebo.
He called these rates "underwhelming," particularly since the participants were presumably "motivated to quit, since they entered a smoking cessation study." He also pointed out that the study participants were not "really heavy smokers, since they smoked only about a pack a day."
Raymond J Gibbons, MD, Mayo Clinic cardiologist and president-elect of the AHA, commented that, if varenicline receivers FDA approval, it may be a useful addition to the range of available treatments for nicotine addiction, but "it is no magic bullet." He noted that the lack of long-term smoking cessation highlights the "difficulty of treating smoking addiction, which means that we need to focus our efforts on prevention - we need to target kids so that they never start smoking."
Varenicline is being developed by Pfizer.
Sources:
AHA:
Investigational Smoking-Cessation Drug May Offer Short-Term
Help, MedPage Today, 15 November 2005.
Smoking
cessation and efficacy of an alpha-4 beta-2 nicotinic receptor
partial agonist-results from varenicline in cessation therapy:
optimizing results. Tonstad S et al, presented at the American
Heart Association's Scientific Sessions 2005, 15 November 2005.
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