Chantix: Do Risks Outweigh Benefits?
Until two years ago, only two classes of smoking cessation drugs were available: nicotine replacement therapy (NRT) with multiple delivery methods (gum, patch, inhaler, spray, lozenge) and the mild antidepressant bupropion. All approximately double the rate of cessation when compared to placebo. Chantix (Varenicline) is the first new agent for smoking cessation approved in almost a decade and represents a third class of drug with a different mechanism of action than either nicotine replacement therapy or bupropion.
Studies done to date demonstrate that Chantix is associated with higher smoking cessation rates than placebo and produces better cessation rates than bupropion.
Chantix is a partial agonist that binds to a specific nicotinic receptor, resulting in a limited release of dopamine. Chantix also has a competitive antagonist effect on nicotine which blocks nicotine from binding to the receptors. These receptors play a principal role in mediating reinforcement and dependence producing effects of nicotine. The urge to smoke is therefore significantly reduced.
Chantix is suggested for anyone who currently smokes cigarettes. Treatment should be initiated one week before the target quit date. The recommended dose is 1mg twice daily for 12 weeks including an initial week of titration (0.5mg each day for 3 days then 0.5mg twice daily for 4 days). For those who are successful in quitting smoking at the end of 12 weeks, an additional 12 weeks of treatment is recommended to reduce the chance of relapse. Patients who cannot tolerate side effects from Chantix (nausea, insomnia, abnormal dreams, headaches and flatulence are the most commonly reported side effects) can have the dose temporarily or permanently lowered, as Chantix is available in 1mg and 0.5mg tablets.
Currently, there are 5.5 million people on Chantix in this country alone and 6.5 million world-wide. This medication has no contraindications and very few untoward side effects. However, a troubling list of central nervous system related events have been reported by Chantix users, such as depression, aggressive behavior, sudden drowsiness, and, most ominously, suicidality. Even though these reports are very few in number, they have resulted in exceedingly negative press and patient and doctor fears.
In November, the Food and Drug Administration began investigating reports of psychiatric events such as suicidal thoughts associated with Chantix. That prompted Pfizer to update the drug's labeling that patients should be monitored for unusual behavior and patients with a history of mental illness who are considering taking Chantix should let their doctors know of their condition.
In mid-May, a report was released by an organization called the “Institute for Safe Medication Practices” (ISMP) which claimed to have safety concerns about Chantix. The report summarized the most frequent side effects reported from using Chantix. By far the most common was nausea, which was more than twice as common as any other reported symptom. It was also notable that among the most commonly reported adverse effects, many are also recognized nicotine withdrawal symptoms (symptoms known to occur during smoking cessation, particularly without any treatment medication), such as depression, insomnia, anxiety, and weight increase.
The Executive Summary of the report made two main recommendations:
- Chantix should be avoided or used with caution by persons operating aircraft, motor vehicles or other machines where a lapse in alertness or motor control could have serious consequences.
- Patients and doctors should exercise caution in the use of Chantix and “consider the use of alternative approaches to smoking cessation.”
These are strong recommendations, and have immediately resulted in the Federal Aviation Authority (FAA) and Federal Motor Carrier Safety Administration (FMCSA) adding varenicline to their list of drugs that should not be used by pilots or truck drivers.
There are a number of fundamental problems with the quality of the data, analysis and interpretation in the ISMP report. The report fails to consider the frequency of the use of the drug when considering the number of adverse events being reported. The report also fails to adequately consider the possibility that some of the reported adverse events may have been caused by nicotine withdrawal. It is entirely plausible that many of these reported symptoms were caused by nicotine withdrawal rather than Chantix. In fact in the placebo-controlled trials of Chantix, withdrawal symptoms were reduced in those using Chantix!
In addition, the report does not adequately consider that a high proportion of patients using smoking cessation medications are already suffering from or at very high risk for smoking-caused illnesses, including some mentioned as adverse events in the report (cardiac arrhythmias). The report inaccurately characterizes the relative efficacy of varenicline versus other treatments.
The ISMP report states that Chantix has similar long term quit rates to nicotine gum. This statement contradicts the findings of the new US Public Health Service Clinical Practice Guideline on Treating Tobacco Use and Dependence, which found that quit rates with varenicline are significantly greater than with the nicotine patch or gum.
The Guideline, written after the recent labeling changes for varenicline, concluded that “Varenicline is an effective smoking cessation treatment that patients should be encouraged to use.” When added to the other problems of interpretation mentioned above, it seems most prudent to rely on the recommendation of the US Clinical Practice Guideline, which resulted from a very thorough review of the available scientific evidence.
Pfizer stated that it did not see an increase in psychiatric events in patients taking Chantix compared with placebo during its own clinical trials.
Pfizer recently announced that it is conducting additional studies in several patient populations, including people suffering from schizophrenia, heart disease, emphysema, as well as adolescents. Also, the company plans on publishing the results later this year of an in-depth analysis of the psychiatric events seen in patients taking Chantix.
It is imperative that health care professionals and tobacco users weigh the risks of continued smoking against those of any treatment. Thus far, the adverse reports regarding Chantix are anecdotal. There is no doubt about the risks of tobacco use!
UPDATE: The VA is sending letters to more than 30,000 veterans who are taking the smoking-cessation drug Chantix, warning them of the drug's possible side effects, including suicide. The move comes a few days after ABC News and the Washington Times reported that the agency had waited months before notifying vets taking Chantix as part of a study that the drug was associated with psychiatric side effects in some patients.
The vets in the study had PTSD and were trying to quit smoking. On a conference call yesterday, VA secretary James Peake suggested the drug didn't seem to be associated with suicidal thoughts in the study in question, the AP reports. Two percent of the vets who took the drug experienced thoughts of suicide, compared to 4.4% of those in the study who didn't take the drug. The letter urges patients who are experiencing side effects or are worried about the drug to consult with their doctor. Overall, Peake said, agency doctors are not seeing serious problems or trends and will continue to prescribe the Pfizer drug, which has recently been beset by safety questions. "This is a very important drug for our clinicians to be able to use when appropriate for patients," he said.
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