FDA announced yesterday afternoon that the smoking cessation drugs Chantix (varenicline) and Zyban (bupropion) must bear black box warnings for serious mental health symptoms, including changes in behavior, hostility, depression, and attempted suicide.

In addition to being used in smoking cessation, buproprion is also marketed as an atypical antidepressant under the brand name Wellbutrin, as well as in a generic form. All these products will receive increased warnings highlighting the risks for mental health events. (The drugs already carry black box warnings for suicidality.)

According to FDA, symptoms have occurred in patients with and without histories of psychiatric illness, and tend to occur shortly after medication starts and end when treatment is stopped. But there have been instances reported where side effects continue even after the patient stops taking the drug.

According to raw FDA numbers, 98 people taking Pfizer’s Chantix committed suicide, while 14 people took their lives while on GlaxoSmithKline’s Zyban. One hundred eighty-eight people attempted suicide on Chantix, and 17 tried while taking Zyban.

“It has been difficult to evaluate some of these cases, as we are working off adverse event reports,” said Bob Rappaport, director, Division of Anesthesia, Analgesia and Rheumatology Products, CDER. “People who stopped smoking without using medication may also report similar symptoms in nicotine withdrawal. However, we examined some cases where people were using the products under discussion and also had the adverse events while smoking.”

Rappaport admitted in a teleconference that both smoking cessation aids are effective, and possible risks should be weighed against the health benefits of quitting smoking.

Both companies can continue to advertise the drugs, but additional warnings must be added to the risk statements. However, they will no longer be allowed to run reminder ads.

About Time or Too Late?
Chantix came under fire last year in the blogosphere and media as hundreds of consumers began posting on Web forums that they had become increasingly depressed while on the smoking cessation drug.

Minutes after FDA announced the call for increased warnings, Pfizer released a statement saying that it would update its labeling to add the black box warning and adjust the current warning. Pfizer wouldn’t comment whether recent public scrutiny has affected sales, or whether the company will retool its sales force in light of the new warnings.

Zyban, Really?
The black box for Zyban, however, is a bit of a surprise.

“We looked at three products [including nicotine replacement treatments] to get some sort of idea if Chantix would stick out,” Rappaport said. “We were surprised to find that Zyban seemed out to have the same characteristic of [adverse] reporting and the same reporting rates. So this is a new thing for Zyban.”

Pfizer and GSK are being required to conduct clinical trials to determine incidents of mental health symptoms in people trying to quit smoking, including people with and without pre-existing mental conditions.

FDA said that it doesn’t expect the results of the trials to be revealed for several years.