Varenicline, also known as Chantix, a pill prescribed for those who want to quit smoking has been sold in United States from August 2006, after it was approved in May 2006. Since its introduction, Chantix generated about $600 million in sales.

In November last year the U.S. Food and Drug Administration revealed that it had received reports of mood disorder and erratic behavior among patients using Chantix.

FDA advised doctors to closely supervise their patients and report whether they have any behavior changes.

Also, last month, Pfizer updated the Chantix label in US by including a new warning that says the patients who are taking this drug should be observed for serious neuropsychiatric symptoms, including changes in behavior, agitation, depressed mood, suicidal ideation and suicidal behavior.

In its yesterday advisory, FDA said that a the agency's review of the adverse event reports proceeds, it appears increasingly likely that there may be an association between Chantix and serious neuropsychiatric symptoms.

As a result, FDA has requested that Pfizer elevate the prominence of this safety information to the warnings and precautions section of the Chantix prescribing information, or labeling.

"While Chantix has demonstrated clear evidence of efficacy, it is important to consider these safety concerns and alert the public about these risks. Patients should talk with their doctors about this new information and whether Chantix is the right drug for them, and health care professionals should closely monitor patients for behavior and mood changes if they are taking this drug," said  Bob Rappaport, M.D., director of the FDA's Division of Anesthesia, Analgesia and Rheumatology Products.

"We've become increasingly concerned as we've seen there are a number of compelling cases that truly look as if they are the result of exposure to the drug," he added.

Varenicline relieves withdrawal symptoms and tobacco craving associated with smoking cessation by acting as an agonist for α₄β₂ nicotine receptors in the brain, which are associated with nicotine dependence. At the same time, if a person smokes a cigarette while receiving treatment, Champix acts as an antagonist to inhibit nicotine from binding to α₄β₂ nicotine receptors, restricting the patient’s sense of satisfaction associated with smoking.

“Health care professionals, patients, patients' families, and caregivers should be alert to and monitor for changes in mood and behavior in patients treated with Chantix. Symptoms may include anxiety, nervousness, tension, depressed mood, unusual behaviors and thinking about or attempting suicide. In most cases, neuropsychiatric symptoms developed during Chantix treatment, but in others, symptoms developed following withdrawal of varenicline therapy,” noted FDA in its advisory.

Although it has agreed to include the warning since November, Pfizer officials repeatedly said that there is no scientific evidence linking Champix to depression.

“A causal relationship between Chantix and these reported symptoms has not been established. In some reports, however, an association could not be excluded. More specifically, some reports may have been complicated by the symptoms of nicotine withdrawal in patients who stopped smoking, but not all patients with these symptoms had quit smoking,” Pfizer said in statement released last month.

In December last year, the European Medicines Agency (EMEA) said Pfizer’s Champix, (the European name of Chantix), should carry a warning about the high risk of suicide attempts among patients. The Committee for Medicinal Products has closely monitored the safety of the drug for Human Use (CHMP) since it was first authorized in the European Union in September 2006.

Meanwhile, on January 25, Pfizer Japan announced that the company received manufacturing and marketing authorization for Champix.