FDA Panels Urge Strong Warnings on Antidepressants

Two Food and Drug Administration advisory committees recommended Tuesday that the agency warn doctors, patients and their families that antidepressants can increase the risk of suicidal thought and behavior among children.

The panels called for placing the warning in a black box on the detailed information that manufacturers provide to physicians. The panels also agreed that packages should be accompanied by warnings for patients and caregivers that medication designed to help severely depressed children could instead endanger their lives.

Of the 23 panel members who voted, 15 urged the black boxes, which are the most prominent warnings that the FDA can require. Drug companies must include them in advertisements for their drugs. Many doctors are reluctant to prescribe medicines with black-box warnings.

The panels -- whose members include psychiatrists, pediatricians, statisticians and pharmacists -- stopped short of recommending that the agency ban the drugs for children. Many doctors say the drugs are effective with some patients, and panel members did not want to take away one of the few forms of treatment for a sometimes disabling condition.

“I think the purpose of the black box is to make [doctors] think twice about prescribing the drugs,” said Dr. P. Joan Chesney, chairwoman of the FDA’s pediatric advisory committee.

“Suicide is a life-threatening complication of major depressive disorder. What the treatment appears to do is to add a 2% to 3% increase in the risk of suicide” for children, she said.

Dr. Wayne K. Goodman, a psychiatrist and chairman of the FDA’s psychopharmacologic drugs advisory committee, said, “I’m not ready, given what we know, to ban antidepressants.”

Tuesday’s recommendations were the latest events in a drama that began with emotional pleas from parents that the FDA act against the pills that they believed had caused their children’s suicides.

It is up to the FDA to decide whether to accept the panels’ advice. The agency is not obliged to follow the recommendations of its advisory committees, but generally it does.

Dr. Robert Temple, director of the FDA’s office of drug evaluation, said the agency would probably move quickly, given the intense public attention on the issue. Some action can be expected within a few months, he said.

In March, the FDA warned doctors, patients and families of the risks of depression among people taking antidepressants, especially in the first weeks on the drugs or after a change in dosage. But the agency did not single out children, nor did it indicate the drugs cause suicidal behavior.

Doctors wrote about 15 million prescriptions for nine antidepressants for children and teenagers last year, according to data from IMS Health, a pharmaceutical information and consulting company, and the FDA. Patients typically receive several prescriptions a year.

The FDA has released no information on the overall number of children taking antidepressants who commit suicide, although experts believe about 15% of people who suffer major depressive disorder ultimately kill themselves.

Fluoxetine hydrochloride, marketed as Prozac by Eli Lilly & Co., is the only antidepressant approved for use in children, because it meets the FDA’s standard for showing effectiveness in clinical trials.

But doctors routinely prescribe other antidepressants for young patients, and the FDA doesn’t prohibit them from doing so.

Zoloft is the drug most frequently prescribed for children, according to the FDA. Prozac has moved into second place.

The FDA advisory panels were responding to a recent examination by Columbia University and FDA experts of incidents of suicidal thought and behavior in clinical trials of nine relatively new antidepressants, which include most of the drugs currently prescribed.

In addition to Prozac and Zoloft, the other antidepressants that were the focus of the FDA’s analysis were Celexa, Effexor, Luvox, Paxil, Remeron, Serzone and Wellbutrin.

Their analysis found that two or three children out of 100 on antidepressants experienced an increased risk of suicidal thought or behavior, compared with young people taking sugar pills, or placebos.

“We have very strong evidence of harm and really not very good evidence of efficacy,” said Dr. Thomas Newman, a member of the FDA pediatric advisory committee and a professor at the UC San Francisco School of Medicine.

He said doctors should talk to young patients’ parents or caregivers about the risks of the drugs before prescribing them. “It would not be that bad if use of these drugs were diminished,” he said.

The panels debated whether to exclude some of the nine antidepressants from the warnings, and they also discussed whether to extend the warning to older antidepressants, which are not widely prescribed, or to any drugs that may be developed. They opted to recommend that the FDA direct the warning to all antidepressants.

Sales of antidepressants for all ages rose about 7% in the first six months of this year compared with the first six months of last year, according to the FDA. Adolescents and children have consistently accounted for 7% to 8% of all prescriptions.

The data from the recent trials of antidepressants helped show a stronger connection between the drugs and suicidal behavior in children than in adults.