First of Two Parts

Wendy Wolfson
Newswire21.org

Still smoking? Wanna quit? Then those recent ads for the antismoking drug Chantix probably caught your attention.

The ads, which seemed ubiquitous as Americans tried to stick with their New Year's resolutions during January, claimed the drug was about twice as effective as sugar pills in helping people stay away from cigarettes during trials. The announcer in the commercials also rattles off a litany of possible side effects.

What the ads don't tell you is that Chantix and a competing antismoking drug, Zyban, together have generated more than 14,000 complaints to the Food and Drug Administration since 2006 based on problems ranging from nausea to agitation, depression and, in at least some cases, suicidal thoughts and suicide.

 At least some of those smokers who experienced severe side effects out of the blue. They didn't have a prior psychiatric history, or were still smoking cigarettes, so effects couldn't be blamed on nicotine withdrawal.  

While that may not seem like many complaints considering Chantix alone has been prescribed over 6 million times in the U.S.,  it was enough to prompt the drug agency to slap warnings onto both Chantix, known generically as varenicline, and Zyban, a drug made by Glaxosmithkline known as bupropion. Bupropion also has been marketed widely for years as an antidepressant under the brand name Wellbutrin. 

The FDA warning came 14 months after the FAA barred air traffic controllers and airline pilots from using either drug on the job.

To be sure, smoking is dangerous and quitting can be hard. While most smokers end up going cold turkey, others have trouble giving it up without help from counseling and drugs. The trick comes in balancing the benefits of quitting with the side effects of drugs that help you quit.

"It is important to keep in mind that all medicines have both benefits and potential risks."  Dr. Marina Brodsky, a Medical Team Leader at Pfizer, wrote in an email to Newswire21. "When considering the use of Chantix for their patients, healthcare providers should discuss the risks of smoking, the health benefits of quitting, the patient's medical history and the product's efficacy and safety profile."

Of the complaints received by the FDA, 9,111 were for Chantix and 5,152 were for Zyban.  But it's difficult to know from those crude numbers how many problems were directly tied to the drugs or how many other problems went unreported. 

An Iceberg's Tip?
The FDA's reports, gathered from patients, their families, doctors, and hospitals, is haphazard. So events reported after a drug passes clinical trials and comes on the market may represent the tip of the iceberg. For example, there's no accounting of the number of new complaints generated after Pfizer launched its New Year's advertising blitz.

One confounder is that people who smoke are simply more vulnerable to problems than non-smokers. Quitting often makes people depressed and irritable.

"The symptoms of nicotine/smoking withdrawal would certainly include depression and sometimes other psychiatric events." noted Marina Picciotto, professor of psychiatry at Yale University Medical School, who received funding from Pfizer to study depression among people taking Chantix. "In addition, there is high co-morbidity between smoking and psychiatric illness."

A study in 2000 published in the Journal of American Medicine by Dr. Karen Lasser and colleagues estimated that people with psychiatric illness smoke at twice the rate of healthy people. A 2004 study in the Archives of General Psychiatry by Dr. Bridget Grant and colleagues estimated that about a third of cigarettes smoked in the US were consumed by people with mental disorders such as schizophrenia and depression.

Self-Medicating
People with ADHD also smoke at a rate higher than the general population.  "People are medicating themselves" said Athina Markou, a professor of Psychiatry at the UCSD School of Medicine. According to Markou, there is also a high correlation between smoking and alcohol.

In 2008, the Veterans Administration was roundly criticized after it recruited combat veterans for Chantix clinical trials, and then waited three months to tell them about the drugs' safety concerns. Even then, the VA didn't mention the suicide risk in its initial warning, although combat veterans have a high rate of psychiatric problems such as post traumatic stress disorder. It finally told the soldiers about the risk in a second warning.

According to Brodsky, the neuropsychiatric adverse events that have been reported are in a different category than those events documented in clinical trials. Problems could also be caused by background events seen in the smoking population and effects potentially associated with drug treatment.

"Since all three may be present simultaneously and due to the limitations of spontaneous adverse event reporting described above, separating them is very difficult." Brodsky noted.