FDA Calls for Warnings on 10 Antidepressant Drugs

The Food and Drug Administration warned doctors, patients and their families Monday that 10 popular antidepressants could cause deepening depression and even suicide. It also directed the manufacturers to put warnings of such possible side effects on the drugs’ labels.

The agency also alerted those involved with the drugs to look out for agitation, hostility, mania and other forms of sometimes violent behavior that have been associated with them.

The drugs -- Prozac, Zoloft, Paxil, Luvox, Celexa, Lexapro, Effexor, Wellbutrin, Serzone and Remeron -- are taken by 30 million Americans, according to some estimates. The first seven are in the drug category known as “serotonin reuptake inhibitors,” and their sales in 2003 exceeded those of any other drug class except the group of painkillers that includes codeine.

The speed and scope of the FDA’s action reflected its concerns about the breadth of the potential damage the drugs could cause. “Our hope is that the new language and labeling will result in closer observation of patients who are being prescribed these drugs,” said Dr. Thomas P. Laughren, leader of the FDA’s psychiatric drug products team.

The warnings came after an FDA advisory panel heard testimony last month from dozens of patients and family members who blamed the drugs for suicide attempts, suicides and violent acts by children among patients taking them.

Testimony at that meeting showed that patients on the medications had become more depressed or even suicidal or more agitated and violent, and their doctors were doing nothing about it, Laughren said.

The FDA hopes that with the new warnings, doctors will know when to reassess treatments and possibly discontinue the drugs, he added.

The FDA said it was not yet clear whether antidepressants contributed to the emergence of suicidal tendencies and behavior. But at the urging of the advisory panel, the agency decided to issue the warnings now, before it completed a reexamination of 25 clinical trials of various drugs on children.

This summer, when that review is done, the FDA may have more to say on the issue, Laughren said.

Drug companies played down the warnings and stressed that the FDA had not shown a link between the drugs and suicide.

“Depression is a serious public health issue -- and it takes great courage for patients to begin treatment in the first place,” said Jennifer Yoder, spokeswoman for Eli Lilly and Co., which makes Prozac. “Patents should not stop treatment without first talking to their doctors.”

Dr. Cathryn Clary, a vice president of Pfizer, maker of Zoloft, said her company was “working closely with the FDA” to change the drug’s labeling.

Concerns about a possible link between the drugs and suicide were raised in the media and by some psychiatrists in 1990. The FDA convened an advisory panel on the topic but opted not to issue any warnings.

“It’s 14 years later, and finally the FDA -- albeit tentatively -- is doing the right thing,” said Dr. Joseph Glenmullen, a Harvard Medical School psychiatrist, who wrote a book about the side effects of antidepressants.

The FDA’s warning is important, he said, because many doctors and patients are not aware that suicidal and violent behavior are possible side effects.

Glenmullen, who prescribes the drugs to his patients, said the warning sent a direct message to doctors: “You can’t give a patient one of these drugs and tell them to come back in two or three months. You have to monitor them closely.”

Dr. Matthew Rudorfer, the National Institute of Mental Health psychiatrist who chairs the FDA advisory panel, said the group did not believe that the risks of the medications ruled out their use.

“But we think such warnings are required to elevate the level of concern and attention that practitioners use in prescribing them,” Rudorfer said.

The FDA said patients should be monitored especially carefully at the beginning of treatment and when doses are increased or decreased.

Thomas J. Moore, a health policy analyst at George Washington University, said the FDA’s warnings were more confusing than the message from the British government, which in December said children and teenagers should not take the drugs because of the possible increased risk of suicide.

“The drawback to what the FDA did today is that it still failed to acknowledge the relationship of the suicidal, violent and manic behaviors to the drug,” Moore said.

With the possible exception of Prozac, there is not enough evidence that the drugs are beneficial to children to justify the risks of dangerous side effects, he said.

Prozac is the only antidepressant in the group that the FDA has approved for use by children.

Neither the FDA nor the drug companies try to estimate how many Americans take the drugs. Britain’s North Wales Department of Psychological Medicine estimates that as many as 30 million Americans take antidepressants.

Generic drugs are available in the U.S. for three of the drugs: fluoxetine for Prozac, paroxetine for Paxil and bupropion for Wellbutrin.

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Take with care

The antidepressants covered by the government’s warning:

Celexa, Effexor, Lexapro, Luvox, Paxil, Prozac, Remeron, Serzone, Wellbutrin, Zoloft