*** NOTE: The drug varenicline, also known as Chantix, is a partial "nicotinic" receptor agonist that targets "nicotine receptors" not "protein receptors" as recently was inaccurately reported in the media. ***

OHSU Smoking Cessation Center researcher publishes results of pivotal nationwide clinical trial that tested whether a new drug could help smokers quit

Researchers in the Smoking Cessation Center in the Oregon Health & Science University School of Medicine report the nonnicotine drug varenicline is more effective than a placebo and bupropion SR in helping smokers quit and remain abstinent from smoking. Three papers on the pivotal multi-center Phase III clinical trials of varenicline were published in the July 5 issue of JAMA (Journal of the American Medical Association).

"It has been several years since a new smoking cessation medication has been approved," said David Gonzales, Ph.D., lead author of one of the papers and clinical investigator in medicine (pulmonary and critical care medicine) in the Smoking Cessation Center, OHSU School of Medicine. "Many smokers who have been unsuccessful in the past have exhausted medication options. The approval of varenicline means that patients and health care providers will have a new and unique smoking cessation medication to add to the current ones to help smokers quit. Varenicline is the first smoking cessation medication developed to target specific nicotine sub-receptors linked to dopamine release and opens up an entire new direction for medication research for smoking cessation."

Nearly 41 percent of smokers try to quit smoking each year, but only about 10 percent succeed. The unpleasant effects of nicotine withdrawal account, in part, for low success rates, according to the study. Other therapies approved to treat nicotine dependence, such as nicotine replacement therapy and bupropion SR, have had only moderate success, with reported rates of quitting about twice those of a placebo.

Gonzales and colleagues at 19 centers around the United States evaluated the efficacy of varenicline compared with bupropion SR (marketed as Zyban or Wellbutrin) and a placebo in 1,025 smokers from June 2003 to April 2005. Varenicline is thought to increase the chances for smoking cessation by stimulating the release of lower levels of the chemical dopamine in the brain, compared with nicotine, to reduce craving and withdrawal symptoms when a smoker quits, while at the same time blocking nicotine from binding in the brain should the smoker have a slip or relapse. Most other smoking cessation therapies are nicotine replacement products with bupropion SR being the only other nonnicotine medication approved for smoking cessation. It has been a number of years since a new medication has been approved for smoking cessation, and smoking remains the leading cause of preventable death.

Study participants were aged 18 to 75 and had smoked 10 or more cigarettes a day with fewer than three months of smoking abstinence during the past year. Participants were randomly assigned to receive brief counseling plus either varenicline twice per day, bupropion SR twice per day or a placebo orally for 12 weeks, with 40 weeks of nondrug follow-up.

The researchers assessed the nonsmoking status of participants by measuring exhaled carbon monoxide and through voluntary reporting. For study weeks 9 through 12, the rate of abstinence was 44 percent for varenicline compared with 29.5 percent for buproprion SR and 17.7 percent for the placebo; for weeks 9 to 24 the abstinence rate was 29.5 percent for varenicline compared with 20.7 percent for bupropion and 10.5 percent for the placebo; and for weeks 9 through 52, the continuous abstinence rate was 21.9 percent for varenicline compared with 16.1 percent for bupropion SR and 8.4 percent for the placebo.

Varenicline was more effective than a placebo at all time points and more effective than bupropion SR at the end of 12 weeks of drug treatment and at six months.

At the conclusion of this large clinical trial, the researchers found that varenicline reduced craving and withdrawal and, for those who smoked while receiving study drug, also reduced smoking satisfaction. Varenicline was found to be safe and generally well tolerated. The most common side effect for participants receiving varenicline was nausea and for those receiving bupropion SR, insomnia.

The study was supported by Pfizer Inc., which provided funding, study drug and placebo, and monitoring. For the financial disclosures of the authors, please see the JAMA article.