New Drug for Smoking Cessation

Varenicline might be more effective than bupropion.

A new drug for smoking cessation, varenicline (Chantix), was approved by the FDA in May 2006. As a partial agonist of a nicotinic acetylcholine receptor, the drug presumably reduces nicotine craving and withdrawal; as a partial antagonist, it presumably blocks the effect of smoked nicotine. In three industry-sponsored trials, investigators addressed varenicline's efficacy. The research teams included several employees of the sponsoring manufacturer.

In the first trial, 1025 smokers (age range, 18–75; ≥10 cigarettes daily) were randomized to receive 12 weeks of twice-daily varenicline (1 mg), sustained release bupropion (up to 150 mg), or placebo. For weeks 9–12, continuous abstinence rates were significantly better for varenicline than for bupropion or placebo (44% vs. 30% and 18%, respectively). For weeks 9–52, continuous abstinence rates remained significantly higher for varenicline (23% vs. 15% and 10%, respectively). Study completion rates were 55%–60% in all groups. The most common side effects were nausea (28%) for varenicline and insomnia (22%) for bupropion. In a similar multisite study, researchers randomized 1027 smokers to the same treatments and found similar rates of short- and long-term continuous abstinence.

In a third study, 1236 adult smokers who had stopped smoking by the last week of a 12-week, open-label trial of varenicline were randomized to continue on varenicline (1 mg twice daily) or placebo. Continuous abstinence rates for weeks 13–52 were significantly different — 44% and 37%, respectively.

Editorialists urge caution in interpreting these results because of the highly controlled nature of such trials, as well as some other statistical and methodologic concerns. In addition, the difference between varenicline and placebo narrowed to 13 percentage points after 1 year in the first two studies. Nonetheless, these studies deserve replication in community-based trials to evaluate real-world effectiveness.

Reference:

Gonzales D et al. Varenicline, an {alpha}4ß2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: A randomized controlled trial. JAMA 2006 Jul 5; 296:47-55.

Jorenby DE et al. Efficacy of varenicline, an {alpha}4ß2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: A randomized controlled trial. JAMA 2006 Jul 5; 296:56-63.

Tonstad S et al. Effect of maintenance therapy with varenicline on smoking cessation: A randomized controlled trial. JAMA 2006 Jul 5; 296:64-71.

Klesges RC et al. Varenicline for smoking cessation: Definite promise, but no panacea. JAMA 2006 Jul 5; 296:94-5.