Archive for Sunday, February 15, 2004

FDA challenges usefulness of antidepressants in children

February 15, 2004

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— As U.S. 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 that 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's 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 the antidepressants were written for children, spread among several different diagnoses, including depression, attention-deficit disorder, anxiety and obsessive-compulsive disorder.

According to a January FDA memo, drug makers 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 didn't necessarily mean antidepressants were 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.

The public seldom learns that there have been so many negative studies. Pharmaceutical companies perform multiple studies on their drugs and have a great deal of control over when -- or if -- the results are made public.

Suicidal tendencies

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.

"Having looked at the evidence -- and it's the most comprehensive body of evidence available -- the balance of risks and benefits for taking these drugs for treating depressive illness was not favorable" for children, Steve Ryan, a spokesman for the Medicines and Healthcare products Regulatory Agency in London, said this past week.

The one exception that British regulators made was for Prozac, which they concluded had evidence of effectiveness in treating childhood depression.

Health Canada, the Canadian regulatory agency, following up on earlier alerts, this month urged families there 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.

Attention-deficit disorder

It's not only the drugs' use for depression that's 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 is "not effective in treating ADHD."

In a separate review of prescribing data, George Washington University researcher Thomas J. Moore also found a high percentage of use for what he defined as "attention deficit and conduct disorders" among boys ages six to 12. Moore concluded that the use of antidepressants in children has expanded rapidly -- "primarily for off-label use for which little or no scientific evidence exists."

"To expose so many boys to a medical treatment without clinical trials evidence of safety or efficacy represents an uncontrolled experiment in hundreds of thousands of youths where the risks are unknown and benefits may not exist," Moore wrote.

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