Parents to tell their stories to FDA review panel

Outcome could hurt the billion-dollar antidepressant market
Sunday, September 12, 2004
Star-Ledger Staff

During the next two days, a simmering national dialogue about the safety of antidepressants will play out in a drab Holiday Inn ballroom in Bethesda, Md.

That is where a Food and Drug Administration advisory panel will review clinical-trial data showing links between these widely used medicines -- which include Zoloft, Prozac, Paxil and Effexor -- and suicide in children younger than 18.

The event promises to be an unusual mix of scientific debate about bone-dry statistics and extraordinary high drama.

Tomorrow, four hours are set aside just so dozens of parents can publicly describe the affects these drugs had on their children. And Tuesday, the panel will spend all day reviewing data before making recommendations about what steps, if any, should be taken by regulators.

The bottom line for drug makers, families and doctors is the extent to which the panel finds one or more antidepressants do trigger suicidal behavior.

"This is really a very complicated question with no easy answers," said David Fassler, a University of Vermont psychiatry professor and American Psychiatric Association trustee who has pushed drug makers to disclose more clinical-trial data.

"There will be a lot of strong feelings and opinions expressed. But I don't expect we will get definitive answers. We need more research to really help us better understand which kids are at risk for particular side effects and which can be helped by specific treatments."

The issue is coming to a head after more than a year of fractious debate, which was triggered after U.K. regulators warned doctors not to prescribe the medicines to children. And it was fueled by revelations that drug makers didn't publish data showing negative results.

The controversy is crucial to the pharmaceutical industry. Last year, the retail market for antidepressants topped $11 billion. Any move to restrict prescriptions would crimp revenue and, given concerns about side effects, raise potential liability for drug makers.

But as families across the country began demanding the FDA take action, the agency last February held a special panel meeting to review scientific data. Yet, rather than resolve the debate, the effort only accelerated it.

An FDA medical reviewer, Andrew Mosholder, wasn't allowed by the FDA to recommend tight restrictions on the use of antidepressants in children. Only Prozac is approved for children. But doctors are free to prescribe any drug, a practice known as off-label prescribing. In 2002, nearly 11 million antidepressant prescriptions were written for children, according to the FDA.

Instead of taking the same action as their U.K. counterparts, the FDA opted to seek still more evaluation. So the agency last spring commissioned Columbia University researchers to review drug-company clinical trials for evidence of links to suicidal behavior.

Meanwhile, the FDA urged drug makers to issue label warnings that doctors monitor all patients taking antidepressants -- children and adults -- for signs of suicidal behavior.

At the same time, the FDA told Wyeth, which sells Effexor, to soften a stronger warning the company placed on its label in 2003. The agency took this step so that all labels for antidepressants contained similar language.

As it turns out, the results of the Columbia University analysis are very similar to what Mosholder concluded earlier this year, according to an Aug. 16 memo written by Paul Seligman, acting director of the FDA's Office of Drug Safety.

In addition, a more recent FDA analysis also appeared to confirm the findings of the Columbia team. The FDA reviewer who conducted this newer analysis reportedly believes all antidepressants, including Prozac, shouldn't be prescribed for children.

Throughout the debate, FDA officials argue their primary goal is to ensure patients and doctors have useful treatments and weigh them against the risks of taking those medications. The task is made more difficult because depression can lead to suicide.

"We're trying to wrestle with the scientific questions about the potential benefits and risks," said Janet Woodcock, the FDA's acting deputy commissioner for operations, before a congressional committee last week. "The jury is still out on the effectiveness of these drugs."

Woodcock, who was criticized by the committee for not providing requested documents about clinical trials, went on to say the issue will be explored at this week's meeting. But she gave no indication a resolution is at hand.

Some parents are looking for closure. Lisa Van Syckel of Raritan Township, who will speak at the meeting tomorrow, intends to tell the FDA panel about the day her daughter attempted suicide while taking GlaxoSmithKline's Paxil.

"These medications can't be regulated, because prescribing off- label is not illegal," said Van Syckel, who has filed a lawsuit against Glaxo. "But tougher warnings will not be enough. At this point, I want them all banned for anyone who is under 18."

Ed Silverman can be reached at (973) 392-1542 or esilverman@starled

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