New Warnings Sought on Antidepressants
September 12, 2004
By Gardiner Harris, New York Times

When the Food and Drug Administration opens an advisory committee hearing tomorrow into the safety of antidepressants, several committee members will push for tougher warnings saying that a child or teenager given the drugs can become suicidal in the first weeks of therapy, they said in interviews.

"I want the warning strengthened," said Dr. Richard Gorman, a member of the committee and a pediatrician from Ellicott City, Md. "I would also like the pharmaceutical companies to send out letters to doctors saying that, in kids, this stuff doesn't work."

Dr. James McGough, another committee member and a professor of clinical psychiatry at the University of California, Los Angeles, also said he wanted stronger warnings.

For more than a year, agency officials have struggled to find the appropriate balance between warning patients about the possible suicide risk of antidepressants and reassuring those patients that drug therapy can be an effective and safe remedy.

Along the way, the agency has been the object of intense scrutiny and criticism, in part because its own employees, reflecting differences outside the agency, have disagreed about the appropriate course. A safety reviewer for the agency, Dr. Andrew Mosholder, wrote memorandums recommending that doctors be discouraged from prescribing the drugs for children; his bosses thought him alarmist and barred him from speaking about his conclusions at a public meeting in February.

Dr. Mosholder is now scheduled to speak at the hearing tomorrow, and this time agency officials have said they will allow him to do so. The committee has about 30 members.

But to bolster its point that there could be grave consequences if patients are afraid to seek drug therapy, the agency has also scheduled speakers to discuss the devastating effects of depression among teenagers and children.

In 2001, some 1,611 teenagers committed suicide, making it the third leading cause of death among 15- to-19-year-olds. By the age of 18, one out of five teenagers has suffered a period of intense depression, studies show.

Still, agency officials will also discuss the results of 22 clinical trials of antidepressants showing that teenagers and children given the pills were almost twice as likely to become suicidal as those given placebos. And few of the trials show that the drugs cured depression any better than placebos.

The studies were sponsored by drug companies and largely kept secret from the public. The controversy surrounding the trials has led most pharmaceutical companies to promise to make public the results of all future human trials, and it has spurred Congress to propose mandating that all human trials be disclosed on government Web sites.

Other tests may also prove crucial to the committee's deliberations. The most important is one financed by the National Institute of Mental Health that found that Prozac was far more effective than talk therapy, or one-on-one counseling, in ameliorating the symptoms of depression in teenagers and children. Another study recently published in The Journal of the American Medical Association found that those taking antidepressants were most likely to become suicidal in the first nine days of treatment. After that, the risk of suicide, which is quite rare in any case, declines sharply.

Together, the two studies suggest that the benefits of taking Prozac far outweigh the risks, and that the risks can be managed if patients are observed closely in the first two weeks of therapy, several experts said.


"This study shows that the drug is definitely worth the risk," said Dr. Thomas R. Insel, director of the National Institute of Mental Health. "And after all the work that went into the study, the clear results we got out of it, I would hate to see those findings ignored."

But studies are only part of the story. As it did in earlier proceedings, the committee will hear from family members of those who committed suicide while taking antidepressants. In the past, the heartbreaking anecdotes have shaken many committee members and led them to push for stronger warnings than agency officials originally suggested.

That dynamic may play out again. The agency has already promised to include in the inserts in antidepressants' packaging a summary of its analysis of the 22 trials. Two agency officials acknowledged privately that the committee was also likely to press the agency to strengthen the labels' suicide warnings. The F.D.A. generally follows the recommendations of its advisory committees. In the only recent public testimony by agency officials regarding the controversy, Dr. Janet Woodcock, the agency's acting deputy commissioner for operations, explained before a House subcommittee on Thursday why the agency had refused to bar doctors from prescribing most antidepressants to children, as British health authorities did late last year.

The British decided on the prohibition because, authorities there said, none of the drugs except Prozac had proved beneficial in fighting depression in teenagers and children, and several studies appeared to show that they may increase the risk of suicide. With no benefit to recommend the drugs, the British concluded that they were not worth their risks.

By contrast, Dr. Woodcock said the FDA was keenly aware that, without antidepressants, physicians had few tools with which to treat pediatric depression. And she said that the agency's decision to force all of the drugs to include a general warning about the risk of suicide was an appropriate course.

"This is what we know," she said. "We have several positive trials with Prozac. We know these drugs are effective in adults. We know they have not been effective in some trials, in a number of trials." She later added: "And we know the information about suicidality. That is the state of the science."