Varenicline is a partial agonist of nicotinic acetylcholine receptors. Partial agonists exert both agonist and antagonistic effects.
As an agonist, it binds to the receptors to alleviate symptoms of craving and withdrawal. As an antagonist, it competes with nicotine at the receptor binding sites resulting in a reduction of the rewarding and reinforcing effects of smoking.
The efficacy of varenicline has been studied in three clinical trials involving chronic cigarette smokers (>10 cigarettes per day).
Two identical double-blind studies1,2 involving 1,022 and 1,023 subjects, respectively, compared varenicline 1mg twice daily with bupropion sustained-release 150mg twice daily, and placebo. Patients were treated for 12 weeks and were followed for 40 weeks post-treatment. At weekly visits, patients received smoking cessation counselling and abstinence from smoking was determined by patient self-report and verified by exhaled carbon monoxide (CO). Patients set a target quit date (TQD), with dosing starting one week prior to this date.
Subjects treated with varenicline had a superior rate of CO-confirmed abstinence during weeks 9 to 12 (44% in both studies) compared to those treated with bupropion (30% in both studies) or placebo (17% in one study, and 18% in the other).
In addition, a greater proportion of the varenicline group was continuously abstinent from one week after TQD through the end of treatment (29% in both studies) compared with the bupropion group (23% in one study, and 21% in the other) and the placebo group (12% in one study, and 11% in the other).
The third randomised study, involving 1,927 smokers3, assessed the effect of an additional 12 weeks of varenicline therapy on long-term abstinence. Patients were treated with varenicline 1mg twice daily for 12 weeks. Those who had stopped smoking by week 12, received further treatment with either varenicline or placebo for an additional 12 weeks, and were then observed for 28 weeks post-treatment.
The abstinence rate from weeks 13 to 24 was 70% for patients continuing treatment with varenicline, compared with 50% for patients switching to placebo. Superiority of varenicline over placebo was maintained during 28 weeks post-treatment follow-up (54% continuous abstinence rate in the varenicline group compared with 39% in the placebo group).
Overall, varenicline was well tolerated. The most commonly reported adverse event was nausea (29.4% in one study, and 28.1% in the other), which was mostly mild and tolerable.
1. Gonzales D, Rennard S, Nides M et al. Varenicline, an α4β2 Nicotinic Acetylcholine Receptor Partial Agonist, vs Sustained-Release Bupropion and Placebo for Smoking Cessation. JAMA, 2006: Vol 296 (No.1); 47-55.
2. Jorenby D, Hays J, Rigotti N et al. Efficacy of Varenicline, an α4β2 Nicotinic Acetylcholine Receptor Partial Agonist, vs Placebo or Sustained-Release Bupropion for Smoking Cessation. JAMA 2006: Vol 296 (No.1); 56-63.
3. Tonstad S, Tonnesen P, Hajek P et al. Effect of Maintenance Therapy With Varenicline on Smoking Cessation. JAMA 2006: Vol 296 (No.1); 64-71.
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