WP: FDA Confirms Antidepressants Raise Children's Suicide Risk

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FDA Confirms Antidepressants Raise Children's Suicide Risk

By Shankar Vedantam

Washington Post Staff Writer

Tuesday, September 14, 2004; Page A01

Two to 3 percent of children treated with antidepressants had suicidal

thoughts or behavior as a result of the drugs, officials said yesterday

based on the Food and Drug Administration's most comprehensive analysis of

past clinical trials of the widely used drugs.

In a sharp departure from a decade-old position, agency officials said the

increase in suicidal tendencies was not a result of the children's

underlying depression but was caused by the medications themselves.

" Out of 100 patients treated, we may expect to see two to three patients

[who] will experience increases in suicidality due to short-term treatment, "

said Tarek A. Hammad, the FDA analyst who conducted the latest review. The

increase, he said, " is beyond the suicidality as a result of the disease

being treated. "

Senior FDA officials acknowledged that the results of the new analysis were

substantially the same as the conclusions more than seven months ago of an

agency scientist who also found an increase in suicidal tendencies in

children taking the medications. At the time, the agency declined to make

the conclusions of staff scientist D. Mosholder public, citing a lack

of confidence in his results.

Hammad spoke at a meeting of an FDA expert advisory board that began a

two-day hearing yesterday on the controversy over the reported risks of

prescribing the widely used antidepressants to young people.

J. Temple, the FDA's associate director for medical policy, defended

the decision to hold off presenting Mosholder's controversial conclusions in

March.

" Obviously people can disagree, " he said. At a news briefing that included

Mosholder and Hammad, Temple added: " We are cognizant that taking these

drugs might increase suicidal ideation. But depression alone is a cause of

potential suicide, so scaring people needlessly and overdoing it is

worrisome also. "

Parents and other critics of the agency had accused senior officials of

turning a blind eye to the worrisome data. But Temple, Hammad and Mosholder

agreed that the studies lent themselves to differing interpretations, in

part because they were not originally designed to answer questions about

suicidal tendencies. While individual clinical trials sometimes contradicted

each other, the FDA officials said a broad pattern of evidence had emerged

that, on average, children taking the medications had about twice the risk

of developing suicidal behavior or thoughts as children receiving sugar

pills, or placebos.

" It's very consistent, " Temple said, adding that regulators would examine

today whether the drugs' labeling should be modified and whether some drugs

for children should be recommended to physicians ahead of others.

The controversy over the drugs is the subject of several congressional

inquiries. Physicians and families have complained that pharmaceutical

companies kept secret the results of more than half the trials that found

the drugs were no more effective than placebos.

Prozac is so far the only medicine approved by the FDA specifically to treat

children's depression, but physicians routinely prescribe other drugs of the

same type, called selective serotonin reuptake inhibitors.

Experts had previously said that studies of Prozac found no increase in

suicidal tendencies, but its unique status came into question yesterday.

Hammad testified that a recent government-sponsored study, which researchers

had described as convincing evidence of Prozac's effectiveness, found that

it carried the same risk of triggering suicidal behavior as other drugs.

In an exchange with the head of the government advisory panel meeting at the

Holiday Inn in Bethesda, the lead investigator of the new Prozac study also

said it might not have been considered a success by the strict criteria of

the FDA. The drug proved superior to placebos in three out of four criteria,

said March of Duke University, but " by the technical definition of the

FDA, it would require the study be considered negative. "

FDA officials declined to say whether they would have ruled the trial

positive or negative, saying only that a number of factors are usually taken

into account.

Prozac is so far the only antidepressant that has been shown to be more

effective than placebos in two separate studies -- the FDA's standard for

approval -- but supporters of the medications and senior FDA officials have

said that does not mean the others are ineffective.

In March, the FDA officials issued an advisory to physicians reminding them

to be vigilant to the possibility of suicide in children and adults taking

the drugs. The data presented yesterday suggested that the increased

suicidal tendencies seen in the trials may be unique to children.

Pharmaceutical company representatives offered conflicting recommendations

to the panel.

J. Romano of Pfizer Inc., which makes Zoloft, said the agency should

warn patients selectively about those medications that showed a higher risk

in the studies. The FDA advisory in March applied to the entire group of

medications.

" Approaching this as a class effect may potentially jeopardize potentially

beneficial treatments for children with major depressive disorder, " he told

the panel.

ph S. Camardo of Wyeth Pharmaceuticals immediately disagreed. Wyeth's

drug, Effexor, showed the highest risks of suicidal behavior and thoughts,

but Camardo said all the drug studies were small and used varying criteria.

While agreeing that physicians should be informed of the results of all

trials, he said the FDA should not issue warnings about some medications and

not others.

Until the new Prozac study came out, Camardo pointed out, everyone had

assumed there was no problem with that drug. " Everyone thought Prozac had a

risk below 1, " he said, referring to a statistical benchmark. " There is

uncertainty in the results of these trials. "

Fassler of the American Psychiatric Association cautioned that the FDA

should not scare patients away from treatment. " Half of all kids who suffer

from depression will attempt suicide at least once, and at least 7 percent

will die as a result, " he said.

The advisory panel is expected to issue recommendations today on how the

agency should respond to the new analysis. The agency is not bound to follow

the recommendations but frequently does.

© 2004 The Washington Post Company