When Pfizer’s anti-smoking pill Chantix came on the market 18 months ago, it was touted as more effective than existing treatments at helping break the deadly nicotine addiction.
Propelled by a multimillion-dollar advertising campaign and aggressive marketing to doctors, the drug already has been used by 5.5 million patients, helped an estimated 1 million people quit smoking, and brought in $883 million in sales last year.
But the widespread use of the drug has led to unexpected side effects, possibly including suicidal behavior, raising concerns at the Food and Drug Administration and within the medical and smoking treatment communities.
Chantix is the latest example of the pitfalls associated with promising new medicines that are tested on a small number of carefully screened patients in a controlled environment, then mass-marketed to a much broader and potentially more vulnerable population.
“The drug companies go from zero to a hundred miles an hour promoting their new drugs,” said Arthur Levin, director of the nonprofit Center for Medical Consumers. “They rush to expose so many people to a drug based on results from a very few people, and that is why surprises occur all the time.”
A DIFFERENT APPROACH
Chantix is a new kind of treatment, one that contains no nicotine but interacts with the same brain receptors as nicotine, reducing the cravings and symptoms of withdrawal.
Prior to Chantix, smokers who wanted to quit had limited options, including products containing nicotine such as patches, chewing gums and sprays, as well as the antidepressant Zyban, which is sold as a smoking-cessation treatment. The nicotine products are designed to replace the nicotine in cigarettes, curbing the desire to smoke and minimizing the effects of withdrawal as doses are gradually reduced over time.
Earlier this month, the FDA said it had received reports of serious psychiatric symptoms among Chantix users, such as suicide and suicidal behavior, agitation and depression, which required new safety warnings on the label.
Martina Flammer, a senior medical director for Pfizer, said the company takes the reports seriously and changed its labeling as a precaution, but insisted there has been no demonstrated link between use of Chantix and suicide or suicidal behavior.
The FDA said it is not clear whether Chantix is responsible for these side effects because smoking cessation, with or without treatment, is associated with nicotine withdrawal symptoms and the worsening of underlying psychiatric illness.
“However, not all patients described in these cases had pre-existing psychiatric illness, and not all had discontinued smoking,” the FDA said.
A PATIENT WHO DIED
The FDA got involved after the death of folk-rock musician Carter Albrecht, who was shot by a neighbor in Dallas after a night of uncharacteristically violent behavior. Family members said Chantix may have caused the rage that ultimately led to Albrecht’s death, although his blood-alcohol level was highly elevated.
New York magazine recently published a story titled “My Brain on Chantix” by Derek de Koff, who chronicled his experience on the medication, including strange dreams, intense paranoia and self-destructive fantasies.
Robert Klesges, a professor of preventive medicine at the University of Tennessee Health Sciences Center, said the clinical evidence shows Chantix improves the chances of stopping smoking. But he said the FDA alert “raises a bit of a red flag,” and reinforces his belief that the first line of treatment should be the nicotine-replacement products, which have a long safety record.
Ponni Subbiah, Pfizer’s vice president of medical affairs, said Chantix has risks like all medications, but emphasized it has proven effective in helping people stop smoking and in helping control “a huge public health epidemic” that causes death and sickness.
More than 44 million adult Americans smoke cigarettes, with 8.6 million suffering from at least one serious smoking-related illness, including cancer and heart disease. Some 438,000 Americans die annually because of tobacco use.
Pfizer conducted a half-dozen clinical trials involving more than 5,000 chronic smokers to win FDA approval for Chantix in 2006. At the end of the 12-week treatment that included counseling, 44 percent of the patients using Chantix stopped smoking, compared with 30 percent using Zyban and 17 percent on a placebo. After one year, however, the former Chantix users who had given up cigarettes had dropped to 22 percent.
Pfizer said there were no suicides attributed to the drug during the clinical trials, and no differences in behavior, agitation, depression or suicidal behavior between users of Chantix and those given the placebo. The company said patients with schizophrenia, bipolar disorder and other major depressive disorders did not participate in the trials.
Numerous studies have shown that smokers have substantially higher rates of suicide and mental illness than nonsmokers.
ONE MAN’S PRAISE
Chantix isn’t the first big-selling medicine to run into safety problems after being cleared for sale by the FDA. Within the past year, the widely used GlaxoSmithKline diabetes drug Avandia added stern label warnings about the risk of heart attacks; Bayer suspended marketing of Trasylol, a drug used to control bleeding during heart surgery, because of the increased risk of death, and Sanofi-Aventis had to greatly limit the use of the antibiotic Ketek because of unacceptable liver injuries.
One enthusiastic Chantix adherent is 60-year-old Roger West of Monroe Township, who smoked for 45 years and had been unsuccessfully trying to quit for the last six. After trying hypnosis from “a mad Russian in Massachusetts” and the nicotine patch, he started on Chantix five months ago, along with a counseling program.
“I don’t like to take pills, but frankly I found Chantix to be a miracle drug. It has worked for me,” said West.
West said he will be entering his sixth and final month of taking the drug, having stopped smoking after the third week and now feeling no urge to resume.
Not everyone has experienced the same outcome, judging from comments posted on a blog written by clinical psychologist Jonathan Foulds, the director of the University of Medicine and Dentistry of New Jersey School of Public Health Tobacco Dependence Program in New Brunswick.
A woman identified as Rachel wrote of a relative with no previous psychiatric problems who committed suicide on New Year’s Eve after having been on Chantix for a few months. “It seemed to be working quite well, then his behavior began to change,” she wrote.
In an anonymous posting in September, another writer described severe “mood problems” while using the drug.
“I was not depressed before I took this drug for 6 days in February, and upon stopping it … I had a complete mental melt down of depression, crying for no reason, suicidal thoughts, panic,” the writer said. “I did not make it to the stop smoking date, so nicotine withdrawal would also not be a factor in my case.”
UMDNJ’s Foulds has been an advocate for Chantix and is paid by Pfizer as a promotional speaker for the drug. He said the clinical trials had outstanding results, as have many patients at the New Brunswick treatment center, but “when you look at the blog and see people tell their stories, it makes you think maybe something is going on here.
“We have to take these reports seriously,” said Foulds. “Health professionals who prescribe this medicine for people to quit smoking need to monitor patients closely. They can’t just have them then pick up a script and let them go on.”