add news- 2-16-04

Detroit Free Press, 2/16/04

ANTIDEPRESSANTS' USE ON KIDS RAISES ISSUES

by Chris Adams and Alison Young

WASHINGTON -- As US regulators debate whether a popular class of antidepressant drugs causes suicidal behavior in children, their review is also raising questions about whether the drugs are effective.

The use of antidepressants to treat depression or other conditions, such as attention-deficit disorder, in children is growing rapidly even though there are few credible studies showing they work.

The drugs under review by the Food and Drug Administration include such blockbusters as Prozac, Paxil and Zoloft as well as other antidepressants. The drugs are generally approved for treating depression and many other conditions in adults.

The FDA-approved uses in children, however, are far more limited. Only Prozac is approved for major childhood depression and obsessive-compulsive disorder, and Zoloft and Luvox are approved for obsessive-compulsive disorder in children.

Doctors, however, are free to prescribe a drug approved for one condition -- say, depression in adults -- to any patient, of any age, for any condition.

Such off-label prescribing is common. In the treatment of depression, it is fueled by doctors' belief that if the drugs help adults, they should also help children. Further, insurers often won't pay for psychotherapy for depressed children but will pay for drug therapy.

The FDA said that in 2002 nearly 11 million prescriptions for antidepressants were written for children, spread among several different diagnoses, including depression, anxiety, attention-deficit disorder and obsessive-compulsive disorder.

According to a January FDA memo, drugmakers have submitted 15 studies designed to test the effectiveness of these drugs in treating depression in children. Three came back positive, two were statistically inconclusive, and 10 were negative.

"These are sobering findings and certainly raise a question about the benefits of these drugs in pediatric depression," the FDA's Dr. Thomas Laughren wrote in the memo. "The overall success rate for positive studies...is clearly a concern."

Laughren cautioned in the memo that the failure of the trials doesn't necessarily mean antidepressants are ineffective in children. Trials could have failed due to poor design, and the FDA does "not view negative studies as proof of no benefit," he wrote.

This year, however, the FDA has plunged into a thorny debate about whether antidepressants can cause suicidal thoughts or behaviors in children after British regulators kick-started the issue in June.

British officials issued the first in a series of alerts to doctors in the United Kingdom, advising them not to use the British version of Paxil and similar drugs to treat depressed children because of an increased risk of suicide and suicidal thinking. They also found higher rates of self-harm and agitation.

British regulators made an exception for Prozac, which they concluded had evidence of effectiveness in treating childhood depression.

Canadian regulatory agency Health Canada, following up on earlier alerts, urged families there this month to consult with their doctors to confirm that the benefits of these drugs for children outweigh their potential risks.

It's unclear why these drugs may increase the risk of suicide, although some experts theorize that the first few weeks on an antidepressant may give a patient enough energy to act on pre-existing suicidal thoughts. But the FDA's efforts to determine the risk is confounded by data from studies that weren't designed to answer the suicide question.

"There is some concern there might be a risk, but it has not been clearly shown," said Dr. James McGough, a member of the FDA's expert panel and an associate professor of clinical psychiatry at the University of California, Los Angeles Neuropsychiatric Institute. "Carefully monitoring patients is the watchword at this time."

Drugmakers have long said that their products prevent suicide, and that any suicidal thoughts during treatment are a result of depression, not the drugs. But some companies have recently issued warnings.

GlaxoSmithKline, the maker of Paxil, sent a letter in July to Canadian doctors advising them that the drug shouldn't be used to treat children because of a possible increased risk of suicide-related adverse events. A letter to U.S. doctors informed them of the FDA's ongoing suicide review, but it didn't advise them not to prescribe the drug to children.

Wyeth, the maker of Effexor, warned doctors in August of a similar risk of increased hostility and suicidal thoughts in children, especially among those taking the drug for depression.

If the drugs don't work, there's little reason to take even a small risk in prescribing them.

"People shouldn't jump to the immediate conclusion that these medications are not for kids," said Dr. Boris Birmaher, a professor of psychiatry at the University of Pittsburgh School of Medicine. "But people should be careful with their use."

It's not only the drugs' use for depression that has caused concern.

An FDA review of prescribing data for children younger than 12 indicates that 18 percent of the antidepressant prescriptions were for patients who had attention-deficit disorder, or the related attention-deficit/hyperactivity disorder (ADHD). None of the drugs are approved to treat attention-deficit disorders. Dr. Josephine Elia of the University of Pennsylvania School of Medicine and the Children's Hospital of Philadelphia, a key researcher on the issue, said the main class of drugs under review "are not effective in treating ADHD."

Contact Chris Adams at cadams@krwashington.com and Alison Young at ayoung@krwashington.com.

Copyright © 2004 Detroit Free Press Inc.