long-awaited study has found that two smoking-cessation pills do not appear to increase the risk of suicidal behavior, an issue that has plagued the medicines and caused considerable controversy for years.
The study, which involved more than 8,100 people, was ordered by the US Food and Drug Administration following ongoing reports of neuropsychiatric side effects for Pfizer’s Chantix and Zyban, which is made by GlaxoSmithKline. The agency had previously required Black Box warnings – the most serious type of safety alerts – on product labeling for both pills.
“The findings show that it is highly unlikely that (the medicines) contribute to neuropsychiatric adverse events,” the study authors wrote in the Lancet, which published the study late last week. Moreover, the study also provided what the authors called “the first definitive evidence” that the pills are effective in helping people with psychiatric disorders to quit smoking. The study also found about 22 percent of those on Chantix were not smoking six months later versus 16 percent for Zyban and a nicotine patch, and 9 percent on a placebo.
The results may be a boon for Pfizer, which has struggled for a decade to transform Chantix into a blockbuster product, but instead has encountered negative publicity, expensive litigation, and stalled sales.
Shortly after Chantix was approved in 2006, the pill became associated with a stream of stories about suicide and violence, which dampened use. Sales fell to $671 million last year from $846 million in 2008. And Pfizer spent hundreds of millions of dollars to settle hundreds of lawsuits. Two years ago, several consumer groups petitioned the FDA to add stiffer warnings about psychiatric side effects.
Now, however, Pfizer plans to ask the FDA to remove the Black Box. A company spokesman wrote us that the “available scientific evidence concerning neuropsychiatric events in patients attempting to quit smoking does not support a boxed warning in the Chantix label.” He added that the drug maker plans to discuss the data with the FDA and regulators in other countries.
An FDA spokesman wrote us that the agency will review the findings along with additional scientific evidence “as we continue to evaluate this issue.” Zyban, by the way, is no longer actively marketed by Glaxo since its patent expired about 10 years ago and is available as a generic. A Glaxo spokeswoman says the trial data was shared with the FDA and the “next step is up to FDA.”
Pfizer had previously attempted to have the Black Box warning about psychiatric side effects removed from the Chantix labeling. In 2014, the drug maker cited a meta-analysis of five studies and four observational studies showing its drug did not show an increase in suicidal activity. An FDA advisory panel, however, voted to recommend that the warning remain in place.
The latest study involved 8,144 adult participants between the ages of 18 and 75 who, on average, smoked more than 10 cigarettes a day. And 82 percent had previously made at least one attempt to quit smoking. Of these, about half — or 4,116 participants — had a history of a previous or currently stable psychiatric condition. About half of these people were taking a psychotropic medicine.
Among the participants who did not have psychiatric problems, the risk of suicidal thoughts or behavior was low and statistically the same: about 1.3 percent for those taking Chantix and 2.2 percent taking Zyban. The results were similar for those using a nicotine patch – about 2.5 percent — and those given a placebo — 2.4 percent.
Among those with psychiatric problems, those risks were higher for all of the participants — 6.5 percent for Chantix, 6.7 percent for Zyban, 5.2 percent for a nicotine patch, and nearly 5 percent for a placebo. None of the trial participants committed suicide, although one person using Zyban and two people given placebos did make attempt suicide.
Not everyone was convinced the study supports the findings.
“It would be a mistake to claim this study proves that severe psychiatric side effects don’t occur with Chantix,” said Thomas Moore, a senior scientist with the Institute for Safe Medicines Practices, a nonprofit that tracks drug safety issues and has previously released reports detailing Chantix side effects.
“With eight different treatment arms, the number of patients in each may not be enough to capture the severe psychiatric side effects for which the drug is known. The study’s severity assessments were subjective judgments, and the combined endpoint included many psychiatric side effects that Chantix is not suspected of causing,” he added.
“Given that this is a manufacturer-sponsored study conducted in 140 centers in 16 countries, it would benefit from an independent event review,” Moore said. “Distinctive, early onset cases of psychosis, aggression, and suicidal behaviors have been observed by regulators in many countries, far outnumbering those reported for other smoking treatments.”