Scientific advisers to the Food and Drug Administration next week are expected to recommend tougher warning labels or other restrictions on antidepressants linked to suicidal behavior in children.
More than 1 million U.S. children take the pills. A re-analysis of studies, released last month, confirmed that those on antidepressants may be nearly twice as likely to become suicidal as kids given sugar pills, and some drugs appear to raise the risk much more than others.
There were no suicides in the 4,250 children studied, but experts think a "wait and see" approach isn't likely.
"They're going to have to do something," says Graham Emslie, child and adolescent psychiatrist at University of Texas Southwestern Medical Center in Dallas. "The horror stories have been just too horrible, and their advisory committee is going to be influenced."
Dozens of parents testified at a February FDA hearing that antidepressants had caused their children to kill themselves. Similar testimony is expected at the hearings in Bethesda, Md., starting Monday. The following day, the FDA's advisory panel may recommend new labeling. The agency usually, but not always, does what its scientific advisers suggest.
In March, the FDA put stronger warning labels on 10 antidepressants after its expert panel recommended the step. But critics derided that move as "too little, too late," considering that, in December, British drug regulators had advised doctors to prescribe only Prozac for depressed kids.
Prozac is the only FDA-approved drug for childhood depression among a newer class of antidepressants called selective serotonin reuptake inhibitors (SSRIs). Other SSRIs, such as Zoloft and Celexa, haven't been proven safe or effective in depressed kids. They are approved for adults and can still be legally prescribed, off-label, to children.
After March, there was a sharp drop in pediatric users of antidepressants, according to an analysis for USA TODAY by Medco, a large pharmaceutical benefit management firm. Records show a 10% decline in patients under 18 taking the drugs in the three months after the March warnings, says spokeswoman Jennifer Leone.
Still, "the data are not black and white" on whether the drugs can make kids more suicidal, says a memo sent last month to the FDA advisory panel by Thomas Laughren, the agency's team leader for psychiatric drugs. But risky signals have been raised for some drugs in some studies, he says.
The FDA, like the British, could advise doctors to prescribe no antidepressants, with the exception of Prozac, for kids. That's possible, but viewed as unlikely. The agency also could put a "black box" warning on a few of the drugs, a much stronger warning than the agency called for in March. This step is considered somewhat more likely.
Tougher label warnings might add the fact that "after clinical trials," all of the drugs (except Prozac) haven't been found to work for kids. Since most drugs haven't been studied in children, "pediatricians assume, in the absence of data, the drug just hasn't been studied. This would tell them it has, and hasn't been found to work," says University of Pennsylvania pediatrician Robert Nelson, an advisory panel member.
The FDA also might send out new "Dear Dr." letters confirming a suicidal risk -- the March advisory said no risk had been proven -- or require pharmacists to give a printed warning of possible suicidal behavior to every adult picking up a child's prescription.
Regulating the drugs has been tricky because major depression increases the risk of childhood suicide about 12-fold. In studies of children who killed themselves, most weren't on medication, says psychiatrist Frederick Goodwin of George Washington University.
But in real-life medical practice, kids with minor adjustment problems too often get antidepressants, some psychiatrists say. And many doctors say the drugs occasionally trigger a frenzied, impulsive agitation that can lead to suicide.
There's rising concern about kids with undiagnosed bipolar disorder (manic-depression) on antidepressants because doctors think they have ordinary depression. Studies suggest up to half of teens with major depression symptoms are manic-depressives, and most with pre-puberty depression become bipolar, Goodwin says. In these kids, SSRIs can trigger suicidal mania. Goodwin thinks the FDA should warn doctors to ask about signs of future bipolar disease -- mood swings, impulsiveness, aggression -- before prescribing antidepressants.
Phyllis Day of Boca Raton, Fla., wishes her 9-year-old daughter, Hallie, hadn't been put on Zoloft a year and a half ago. "She became angrier, more openly violent and suicidal," Day says. One particularly scary time, the little girl struggled to pull her hand out of her mother's so that she could run into heavy traffic.
She was taken off the drug after several months and diagnosed as bipolar a few months later. Now on different medication, Hallie is much improved, Day says. "We're very unhappy that doctors are giving Zoloft to kids who are bipolar. It was a nightmare."
It's a serious challenge for the FDA to weigh the potential benefits of antidepressants for kids against risks because there is relatively little research on each drug, experts say, and emotions run so high. About all everyone can agree on is that the FDA is likely to be criticized no matter what it does.
A timeline of concern about children taking antidepressant drugs:
* June 2003: FDA advises doctors not to prescribe Paxil for kids under 18 because of possible rise in suicide risk.
* August 2003: Wyeth tells doctors that studies show hostility and thoughts of suicide increase in children 6 to 17 taking Effexor and Effexor XR. Advises careful monitoring and possibly reconsidering use of the drugs in kids.
* October 2003: FDA sends a "Dear Dr." letter saying studies can't rule out increased suicidal thinking and attempts in children on the antidepressants, urges caution in prescribing.
* November 2003: FDA decides to ask Columbia University team to take an independent look at incidents called "suicidal" in pediatric studies of antidepressants, checking to see if these incidents are bona fide suicide-related thoughts and behaviors.
* December 2003: British drug regulators advise doctors to use none of the antidepressants except for Prozac with children, saying it's the only one whose benefits outweigh risks.
* February 2004: FDA holds public hearings on suicide/depression link. Many parents testify that antidepressants prompted their children's suicides. FDA advisory panel recommends stronger warning labels on the drugs.
* March 2004: FDA tells drug companies to relabel 10 antidepressants, warning that patients should be closely watched for worsening depression, suicidal behavior and anxiety. The drugs: Prozac, Zoloft, Paxil, Luvox, Celexa, Lexapro, Wellbutrin, Effexor, Serzone and Remeron.
* August 2004: Using the new Columbia report on suicidal events, FDA's re-analysis confirms more suicidal behavior by children taking antidepressants than those on sugar pills. Studies originally showed an 89% higher risk; the new report says 78% higher. No suicides in any of the studies.
* September 13-14, 2004: FDA will get public input at hearings and ask its advisory panel if more labeling changes or other restrictions on the drugs are needed.
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