July 1 (Bloomberg) -- Pfizer Inc. and GlaxoSmithKline Plc’s quit-smoking treatments must carry the strictest U.S. warning about psychiatric side effects, including the risk of suicide.

The Food and Drug Administration is adding the warnings, which will be highlighted in a black box, to the prescribing information of Pfizer’s Chantix and Glaxo’s Zyban. The agency has received a combined 317 reports of suicides and attempted suicides among patients taking the drugs, said Curtis Rosebraugh, director of the FDA’s Office of Drug Evaluation II, in a conference call today with reporters.

Pfizer said it stands by the safety of Chantix and Glaxo said it doesn’t believe there is enough evidence to prove a link. The FDA warned in January that Chantix may increase the risk of suicide or erratic behavior, and the Federal Aviation Administration banned its use in pilots. Chantix sales plunged 36 percent to $177 million in the first quarter, Pfizer said.

“In someone on these drugs trying to quit smoking, you need to watch them for these events,” said Bob Temple, director of the FDA’s Office of Drug Evaluation I. “We don’t want to scare people off from using the medications to stop smoking, we just want them to be monitored.”

The medicines may cause a change in behavior, depressed mood, hostility and suicidal thoughts, the FDA said.

Pfizer, based in New York, and London-based Glaxo will be required to conduct a clinical trial to determine how often psychiatric side effects occur, the FDA said.

Pfizer Response

Pfizer hasn’t been able to determine whether the reported behavior changes are related to quitting smoking or a result of the drug, Briggs Morrison, head of medicines development for Pfizer’s primary care business unit, said today in a conference call. Pfizer saw no reported suicides in its clinical trials.

Glaxo hasn’t seen enough evidence to show a link between Zyban and suicides when used for smoking, said spokeswoman Mary Anne Rhyne in an e-mailed statement. Zyban’s active ingredient, bupropion, is available in generic form and used to treat depression under the brand-name Wellbutrin. Wellbutrin already carries a boxed warning for suicides.

The FDA said it first received an alert about Chantix and behavior changes from European regulators about two years ago. The agency began investigating a possible risk from Chantix in September 2007 when Carter Albrecht, a keyboard player for Edie Brickell and the New Bohemians, was killed after taking Chantix.

Musician’s Death

Albrecht was shot as he tried to kick in the door of his girlfriend’s next-door neighbor in Dallas. He had more than three times the legal driving limit of alcohol in his system when he died, the Dallas Morning News reported. The singer’s girlfriend told the newspaper his behavior was uncharacteristic and that he had begun acting strangely shortly after he started taking Chantix to quit smoking.

While studying Chantix suicide reports, the agency saw a similar trend in reports among people taking Zyban, the FDA’s Rosebraugh said. Nicotine replacement products, such as gums and patches, don’t appear to have the same side effect, he said.

The FDA said it has received reports of 98 suicides and 188 attempted suicides in Chantix users since it came on the market in May 2006. Among those taking Zyban, there are 14 reports of suicides and 17 attempted suicides, according to the agency. Zyban has been on the market since 1997.

It is common for people to experience behavior changes when quitting smoking, though the agency became concerned when it saw suicide reports in people still smoking while taking the drug or whose symptoms stopped after going off the medication, Rosebraugh said.

Chantix affects dopamine, a chemical in the brain involved in controlling mood and behavior. Because dopamine triggers a positive mood response, regulating its levels can remove some of the pleasure derived from smoking.

The most common side effects of the drug, tested in 4,500 people before its FDA approval, were nausea, headache, vomiting, insomnia, abnormal dreams and a change in taste perception.

To contact the reporters on this story: Shannon Pettypiece in New York at spettypiece@bloomberg.net;

Last Updated: July 1, 2009 14:52 EDT