Nicotine-Receptor Partial Agonist Found Better Butt-Beater

OXFORD, England, Jan. 24 -- Efforts to quit smoking with Chantix (varenicline), the nicotine receptor partial agonist, seems to be more successful than with Zyban (bupropion), according to a Cochrane review.

Successful long-term smoking cessation was about threefold more likely with Chantix than with unassisted quit attempts and about 1.5-times more likely compared with Zyban, said Kate Cahill, B.A., of the University of Oxford, and colleagues in a review published online in The Cochrane Library.

Although the six trials included in the review--all sponsored by Chantix maker Pfizer--established efficacy for the agent, the next step is to see how the drug measures up in independent trials, particularly against nicotine replacement therapy, the authors said.

"Direct comparisons with nicotine replacement therapy and further comparisons with bupropion would establish varenicline's relative effectiveness and safety," they wrote.

Chantix is a nicotine-free drug that acts as a partial agonist and partially stimulates nicotinic acetylcholine receptors to release low levels of dopamine, thus counteracting withdrawal symptoms. It was approved as a smoking cessation aid by the FDA last May and has also been approved in Europe.

Zyban, which is also sold as the antidepressant Wellbutrin, is the only other nicotine-free drug FDA-approved to help smokers quit.

The researchers examined all the randomized, controlled trials of Chantix published or presented since trial data began to be published in 2006. Overall, these six trials encompassed nearly 5,000 participants.

Three of the trials compared Chantix with Zyban as well as placebo. One compared Chantix with placebo for relapse prevention. All six were multicenter trials set in the United States, or including American patients, and used a regimen of 1 mg of Chantix or 150 mg of Zyban twice daily. Two trials tested other doses and titration strategies as well and most included a few brief smoking cessation counseling sessions.

The primary outcome measure was a minimum of six months abstinence, with most trials defining this as "continuous" abstinence verified by exhaled carbon monoxide levels.

The pooled odds ratio findings for continuous abstinence at one year were:

• 3.22 for Chantix versus placebo (95% confidence interval 2.43 to 4.27),
• 1.66 for Chantix versus Zyban (95% CI 1.28 to 2.16), and
• 1.59 for Chantix versus Zyban (95% CI 1.21 to 2.10) excluding a trial that included previous Zyban users.

The pooled odds ratios for continuous abstinence at the end of treatment were:

• 4.07 for 12 weeks (95% CI 3.28 to 5.05).
• 3.53 for 24 weeks (95% CI 2.74 to 4.54) ,
• 6.71 for seven-day point prevalence abstinence at 52 weeks (95% CI 3.35 to 13.45).

In the one trial that included a 12-week extension randomizing successful quitters to Chantix or placebo, the drug again came out significantly superior to placebo for continuous abstinence (OR 1.34, 95% CI 1.06 to 1.69).

Comparing tobacco cessation methods based on these and other meta-analyses, the researchers found the number-needed-to-treat was:

• Eight for Chantix (95% CI 5 to 11),
• 15 for Zyban (95% CI 11 to 20), and
• 20 for all types of nicotine replacement therapy (95% CI 17 to 23).

The evidence so far indicates Chantix is safe and well tolerated regardless of dose or duration of use, the researchers said. Adverse events with the drug were most commonly nausea (29% to 40%), insomnia, headache, and abnormal dreams. Nausea was "generally mild to moderate, diminished over time, and was associated with low discontinuation rates."

The review also included a seventh study of the nicotine receptor partial antagonist cytisine from which Chantix was developed. It is widely used in central and eastern Europe for smoking cessation under the trade name Tabex.

In the trial, 1.5 mg Tabex for 20 days compared with placebo improved self-reported abstinence significantly at six months (OR 2.30, 95% CI 1.75 to 3.04) and at two years (OR 1.77, 95% CI 1.30 to 2.40).

"The evidence on cytisine is limited at present, and no firm conclusions can yet be drawn about its effectiveness as an aid to quitting," the researchers wrote.

They noted that further study will be needed and are under way for both Chantix and Tabex. One of the Chantix studies will include direct comparison with nicotine replacement therapy and others are looking at special populations such as patients with cardiovascular disease and chronic obstructive pulmonary disease.

The researchers reported no potential conflict of interest, though all the reviewed Chantix trials were funded and managed by Pfizer, the manufacturers of Chantix.