Stop-Smoking Aid Chantix Sparks Safety Concerns

Researchers Focus on 26 Reports of Chantix and Aggression or Violence; Drugmaker Says No Cause-Effect Evidence Exists

By Kathleen Doheny
WebMD Health News

Reviewed by Louise Chang, MD

July 27, 2010 -- Evidence is accumulating that the stop-smoking drug Chantix is linked with unprovoked acts and thoughts of aggression and violence, according to a new report.

The drug is so potentially dangerous that its use should be restricted to exclude police, military, and similar occupations in which workers carry weapons, says Thomas J. Moore, senior scientist for drug safety and policy at the Institute for Safe Medication Practices in Horsham, Pa. Moore is one of three co-authors of the new report on the drug, published in the Annals of Pharmacotherapy.

"My colleagues and I have been concerned about the safety profile of [Chantix] since our first report [warning of adverse events] in 2008," Moore tells WebMD.

But others, including a smoking cessation researcher and a spokesperson for Pfizer, which makes Chantix, disagreed strongly. They point out that the number of adverse events is far outweighed by the benefits of the drug, which has helped countless people give up cigarettes and the health risks associated with tobacco use.

One co-author of the report, Joseph Glenmullen, MD, of Harvard Medical School, has been retained as a potential consultant in legal cases involving Chantix. He often provides expert testimony on the side effects of psychiatric medications.

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About Chantix

Chantix was approved by the FDA in May 2006 as a smoking cessation treatment. It targets nicotine receptors in the brain, blocking nicotine from getting to them.

Smokers begin at a low dose and then increase it, continuing to smoke until the eighth day, when they are instructed to quit. They continue the drug for 12 weeks and in some cases an additional 12.

In late 2007, concern surfaced after an episode in which a Dallas musician taking the drug displayed aggressive, abusive behavior and was shot dead while trying to kick in the door of a girlfriend's neighbor, the researchers write.

Since the drug came on the market, the FDA has received adverse event reports and then issued communication about the possible risks, and required a medication guide be given to each patient and with each refill. On the package insert, a boxed warning says that some people have had changes in behavior as well as hostility, agitation, suicidal thoughts, and other problems. Patients are advised to stop the drug and get medical help if that happens.

Chantix: A Closer Look

Moore and his colleagues gathered information on 78 adverse event reports received by the FDA as well as four other cases reported in clinical trials and three others from published literature. Moore suspects that the 78 cases are just a fraction of existing reports and that some adverse events are unreported.

The researchers used assessment tools to home in on 26 of the cases to look at more closely. Of these 26:

• 10 involved assault
• 9 involved homicidal thoughts
• 7 cases included other thoughts or acts of aggression or violence

In a sampling of the cases, the researchers reported that:

• A 24-year-old woman on the drug woke up her boyfriend and started beating him, then attempted to kill herself.
• A 21-year-old woman threatened her mother with a shotgun.
• A 46-year-old man reported he had ''crazy thoughts'' of killing himself and his parents.
• A 42-year-old man punched a stranger while at a bowling alley.

The symptoms typically began soon after starting the drug, Moore and his colleagues say, occurring a median of two days after starting.

They found that when the drug was stopped, the symptoms and other adverse effects resolved in most all cases.

Moore and his colleague note that nearly 40% of patients on Chantix were also on tranquilizers, antidepressants, or antipsychotic drugs, according to the FDA. The adverse events, the researchers write, may be more or less likely when another medication is also being taken.

The acts are not likely part of nicotine withdrawal, the researchers say, as they say the effects aren't noticed in other smoking cessation products. The problems may be confined to a small, susceptible group, they say.

Chantix: Other Views

The new report shouldn't turn people automatically against the drug, says Serena Tonstad, MD, PhD, a professor of health promotion and education at the Loma Linda University School of Public Health in Loma Linda, Calif., who reviewed the report for WebMD.

She has served on the advisory board and has been a consultant for Pfizer.

''I wouldn't advise people not to try it [Chantix] based on this report," she says. "The benefit of quitting smoking is most important.'' And, she says, the drug has proven effective in helping people to quit.

She does agree that people on the drug need to be monitored, and people with bipolar disorder should be especially closely monitored, she says. In her experience, they seem to be more at risk for difficulties than people with other psychiatric problems. ''With depressed people, I like their depression to be controlled before putting them on smoking cessation," she says.

MacKay Jimeson, a spokesman for Pfizer, issued this statement: “Pfizer takes the safety of all of its medicines seriously. All post-marketing reports of adverse events are reviewed by Pfizer, and reported to regulators, including FDA. The currently approved Chantix label contains a boxed warning regarding reports of serious neuropsychiatric events reported in some patients. If these neuropsychiatric symptoms are observed by the physician, patient or caregiver, patients should stop taking Chantix and notify their healthcare provider immediately. There is no reliable scientific evidence demonstrating that Chantix causes these events."

Clinical studies are under way, he says, "to help us further characterize the benefit risk profile of Chantix in different smokers. As studies complete, the results will be published.”

From May, 2006 until late last year, Jimeson says, more than 12 million prescriptions for Chantix had been written worldwide. More than 6 million in the U.S. have been prescribed the drug, according to the drug's web site.

SOURCES:
MacKay Jimeson, spokesman, Pfizer Inc.
Serena Tonstad, PhD, MD, professor of health promotion and education, Loma Linda University School of Public Health, Loma Linda, Calif.; consultant and advisory board member, Pfizer Inc.
Thomas J. Moore, senior scientist, drug safety and policy, Institute for Safe Medication Practices.
Moore, T. The Annals of Pharmacotherapy, online July 20, 2010.
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