Testifying before two FDA advisory committees, the officials said that a recent study contracted by the FDA and conducted by Columbia University confirmed the findings of an internal analysis early this year: In clinical trials, the drugs almost doubled the incidence of suicidal behavior in children.
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More than 4,000 children ages 6 to 18 participated in the clinical trials. None of the children killed themselves, although hundreds experienced suicidal behavior or thoughts.
The agency, under mounting criticism for its approach to regulating antidepressants for children, is seeking advice from the two committees on the need for further regulation. The committees are expected to announce their suggestions today at the culmination of a two-day meeting.
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 issued no warnings. Anecdotal evidence of such a link continued to accumulate, and last December the British counterpart of the FDA effectively prohibited physicians from prescribing a range of antidepressants to children, citing an increased risk of suicide.
In March, after hearings where parents told of the effects these drugs had on their children, the FDA ordered manufacturers of 10 frequently prescribed antidepressants — Prozac, Zoloft, Paxil, Luvox, Celexa, Lexapro, Effexor, Wellbutrin, Serzone and Remeron — to include warnings about an increased risk of deepening depression or even suicide on product labels and urged patients and their families to report any changes in behavior to their doctors.
Members of Congress from both parties have joined parents in criticizing the FDA for suppressing the results of the internal study, which showed a clear link between the drugs and suicidal behavior in youths. That study became public after it was leaked to the news media.
But Temple said he was not sorry about waiting for the Columbia study before concluding that the data suggested a clear link between the drugs and suicidal behavior among children.
It would be dangerous, he said, to prematurely rule out these drugs as possible treatment for childhood depression because there are few medical remedies available for the illness. Depression plays a significant role in suicide, the third leading cause of death in teens.
"We've thought all along, it is extremely important to get as right an answer on this as we can," Temple told reporters.
Fluoxetine hydrochloride, marketed by Eli Lilly & Co. as Prozac, is the only antidepressant approved by the FDA for use in children, because it meets the agency's standard of effectiveness in clinical trials. Doctors regularly prescribe several of the other drugs to young patients, however.
Dr. Tarek Hammad, the FDA's senior medical reviewer, said that 2% to 3% of the children treated with the antidepressants in the most recent study experienced increased suicidal behavior or thought.
The FDA analyzed 26 trials of nine antidepressants. (Lexapro was not included in these trials.) Data from 25 trials conducted by drug manufacturers were reexamined by Columbia scientists, while independent researchers conducted the 26th trial.
Dr. Andrew Mosholder, the FDA researcher who produced the earlier internal analysis showing a connection between the drugs and suicidal behavior in children, said the new report "reproduced" his findings. Mosholder's superiors had prohibited him from presenting his findings at a February FDA advisory committee meeting on the same topic.
After a morning of dispassionate scientific presentations, the committee heard from family members of children who committed acts of violence, including suicide, while taking the drugs. In emotional appeals, the relatives urged the FDA to ban the drugs.
"The senior leadership at FDA drag their feet and make Orwellian statements such as 'Just because these drugs have not been proven to be effective does not necessarily mean they're ineffective,' " said Thomas Woodward, a businessman from North Wales, Pa., whose 17-year-old daughter killed herself after taking Zoloft for seven days. The FDA officials "know the truth and therefore have blood on their hands," he said.
Raul Laguerre of Newburgh, N.Y., said his son may spend most of his life in prison because of a violent act he committed while taking one of the drugs.
"Before he took these drugs he was a gentle, lovable kid who never hurt himself or any other person," said Laguerre, who did not want to give his son's name or details of his violent acts because he has not yet stood trial. "The FDA needs to step up and protect the consumer and crack down on these drug companies before more lives are lost."
But drug companies and some doctors stressed the importance of keeping the medicines available for treating children.
Dr. David Fassler, testifying on behalf of the American Psychiatric Assn., said each of the antidepressants was effective for some young patients.
"Most clinicians believe, and I would concur, that for children and adolescents who suffer from depression, the potential benefit from these medicines far outweighs the risk," said Fassler, whose organization represents more than 35,000 psychiatrists.
Representatives from the drug companies did not agree on whether the FDA should consider the drugs individually or as a class, taking the same action toward all of them.
Dr. Steven Romano of Pfizer Inc. urged the panel, when it decides what regulatory action to take against an individual drug, to consider suicidal behavior more seriously than suicidal thought.
In the data analyzed by Columbia and the FDA, his company's product, Zoloft (sertraline hydrochloride), was linked to more instances of serious suicidal thought than suicidal behavior.
The risk or benefit of antidepressant use "should be assessed on an individual product basis," he said.
But Dr. Joseph Camardo of Wyeth Pharmaceuticals argued that the data were not detailed enough to justify treating any antidepressant differently from another. He urged the agency to change the labeling requirements for all of the drugs.
"The information should be consistent for all of the antidepressants," he said.
Of all the drugs studied, patients taking his company's product, Effexor (venlafaxine hydrochloride), had the highest ratio of serious suicidal behavior or thought compared with patients taking placebos in the clinical trials.
