Strong warnings expected on antidepressants for kids

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Strong warnings expected on antidepressants for kids

By Marilyn Elias, USA TODAY

http://www.usatoday.com/news/health/2004-09-08-drug-warning-usat_x.htm

 

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. "

 

Suicide timeline

 

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.

 

 

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, Laughren 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 seen as 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 sheets warning of possible suicidal behavior to every

adult picking up a child's prescription.

 

Regulating the drug 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.