Oxford, UK - Smokers who were given varenicline (Chantix, Pfizer), a nicotine receptor agonist, to help them stop smoking were three times more likely to quit than those who got an antidepressant or no treatment at all, according to a new database review of six large trials [1].

The study, which included 4924 smokers, 2451 of whom used varenicline, was published in the Cochrane Database of Systemic Reviews on January 24, 2007.

"The main adverse effect of varenicline is nausea, but this is mostly at mild to moderate levels and tends to reduce with habituation," the study's lead author, Kate Cahill (Oxford University, UK), reported.

Licensed for use in the UK in December 2006, varenicline is the first antismoking drug in the past 10 years and only the third (after nicotine replacement therapy [NRT] and bupropion [Wellbutrin, Zyban, GlaxoSmithKline]) to be licensed in the US for smoking cessation.

"In trials conducted so far, varenicline appears to outperform both NRT and bupropion. However, although it seems to be well-tolerated and effective, we don't know yet about its long-term safety," Cahill said in an interview with heartwire.

Researchers included six studies that compared varenicline with placebo and three that did a head-to-head comparison with the antidepressant bupropion.

The drug has a two-pronged attack to help smokers kick the habit: it taps the dopamine receptors, prompting them to release more of the "feel-good" hormone, thereby reducing withdrawal symptoms, and it blocks nicotine absorption, making puffing less satisfying.

To review the efficacy and tolerability of nicotine receptor partial agonists (varenicline and cytisine) for smoking cessation, investigators used the Cochrane Tobacco Addiction Group's register for trials, searching for terms (in the title, abstract, or keywords) that included varenicline, cytisine, Tabex, nicotine receptor partial agonist, or smoking.

"We included randomized controlled trials that compared the treatment drug with placebo. We also included comparisons with bupropion where available," she said.

If the trials were shorter than six months, they were excluded.

The pooled odds ratio for continuous abstinence at 12 months for varenicline vs placebo was 3.22 (95% CI 2.43-4.27). The OR for varenicline vs bupropion was 1.66 (95% CI 1.28-2.16).

Two trials followed smokers beyond the standard 12 weeks and found the drug to "be well-tolerated and effective during long-term use," the investigators reported.

In addition, the one cytisine trial found that more participants taking cytisine stopped smoking than with placebo at a two-year follow-up (OR of 1.77; 95% CI 1.30-2.40).

The study did not examine "what sort of smokers had the most trouble taking the drug or quitting. And I don't know how you would discover who was suited for the drug and who was not. The trials report only on participants, who may not necessarily be typical of smokers in the general population," she told heartwire.

Cahill noted that the effectiveness of varenicline as an aid to relapse prevention has not been clearly established, and there is still "a need for independent trials of varenicline vs placebo, to test the early findings."

In addition, direct comparisons with nicotine-replacement therapy and bupropion need to be done to establish how the antismoking strategies stack up against one another, she added.