And so, the debate over Chantix continues. Two weeks after the FDA finished reviewing two epidemiological studies and decided that the benefits of the Pfizer pill continue to outweigh the risks, yet another study comes out and declares that the safety profile of the controversial smoking-cessation drug makes it unsuitable for first-line use.
The latest study found that Chantix was the primary suspect in 92 percent of suicides reported to the FDA for smoking cessation drugs over a period stretching nearly 13 years, and accounted for 10 times more reports of suicidal behavior and depression than the Zyban antidepressant, which is also used to treat smoking habits and is sold by GlaxoSmithKline. Another nugget: after adjusting for seven possible confounding factors, Chantix was 8.4 times more likely to result in a report to the FDA of suicidal behavior or depression than other nicotine replacement products.
The study, which was published yesterday in PLoS One, analyzed 3,249 case reports of serious injury in the FDA’s Adverse Event Reporting System from 1998 through September 2010 for self-injurious behavior or depression linked to Chantix, Zyban and nicotine replacement products. They found 2,925, or 90 percent, of the cases of suicidal behavior or depression were linked to Chantix, while 229, or 7 percent, were listed for Zyban. The remaining 3 percent were cited for nicotine replacement products (here is the study).
The findings, essentially, contradict the conclusion reached by the FDA just last month. The agency had sponsored two observational studies of neuropsychiatric adverse events with Chantix, and decided that neither one found a difference in risk of neuropsychiatric hospitalizations between Chantix and nicotine replacement therapy (back story).
The proclamation was the second such win for Pfizer, which has struggled to make a success of Chantix. The European Medicines Agency recently ruled that Chantix benefits outweigh any heart risks (see this and this), although psychiatric issues have generated the most controversy. And in addition to concerns about suicide, studies have also suggested Chantix can be responsible for violent behavior (look here and here). Meanwhile, Chantix is banned for use by pilots, air traffic controllers, military missile crews and pilots, and is also restricted for truck drivers.
As for the PLoS researchers, they are unapologetic. The "two newly released, but unpublished FDA studies of psychiatric hospitalizations provide little useful safety information, because the serious psychiatric side effects of smoking cessation treatment do not normally result in hospitalization. Notably suicide, aggression, depression, and assault would not normally result in hospitalization," study co-author Thomas Moore, a senior scientist with the Institute for Safe Medication Practices and who serves as a consulting expert in the civil litigation regarding Chantix, writes us in an e-mail. "In all, 82.2 percent of serious psychiatric side effects for (Chantix) that were reported to the FDA did not result in hospitalization and would have been overlooked in the two FDA studies.
We should note that Moore has co-authored previous studies examining Chantix links to violent behavior. Another co-author, Joseph Glenmullen of the Department of Psychiatry-Cambridge Hospital, Harvard Medical School, is also an expert witness for plaintiffs in Chanitx litigation. And yet another co-author, Sonal Singh of Johns Hopkins University, has released a meta-analysis concluding Chantix is linked to cardiovascular risk.
As for Pfizer, a spokesman sends us this: "Based upon the limited data we have seen, the conclusions of the authors are inconsistent with both the FDA’s statement of last week ...The analysis does not appear to contain any new information with respect to Chantix. These same authors persist in publishing analyses based on a review of spontaneous reports. It is important to remember that post-marketing reports do not establish a cause and effect relationship between a medicine and a reported adverse event.
"Also, it is not appropriate to draw conclusions based on comparisons between different drugs and reporting rates. Post-marketing reports can come from any source ranging from patients to healthcare providers, and from phone calls to internet postings and lawyers. Often these reports lack sufficient medical information to enable meaningful assessment. Because of the many limitations of post-marketing reports, the conclusions made by the authors are not supported by the data."
Pfizer, by the way, is conducting a large, double blind placebo controlled safety clinical trial to assess neuropsychiatric safety in patients with and without psychiatric disorders. However, results are not expected until 2017.
cig smoke thx to jo naylor on flickr