Study supports pairing Prozac, therapy – Duke research focuses on kids — (The News and Observer)

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The News and Observer

Modified: Aug 18, 2004 7:57 AM

By SARAH AVERY, Staff Writer

Pairing Prozac with talk therapy works best to curb depression in children, according to research published today by Duke University scientists.

But the researchers also found that a small number of children on the antidepressant showed an increased risk of harming themselves or others. However, the researchers did not not draw a causal effect.

The findings come at a time when the use of Prozac and other antidepressants for children is being questioned by many psychiatrists, patients’ advocates and parents. At issue is whether the pills cause some children to suddenly flare with aggressiveness, self-injury and even become suicidal.

Earlier this year, the Food and Drug Administration began holding hearings to determine whether it should put the drugs under stronger regulatory control. Already, it has issued a warning to doctors that the antidepressants might cause harmful side effects in some children.

Prozac,  MANUFACTURER: Eli Lilly and Co.

SCIENTIFIC NAME: Fluoxetine hydrochloride

AVAILABILITY: Prescription only

INTRODUCED: 1986

TREATS: Depression, obsessive compulsive disorder, bulimia nervosa, panic disorder

PATIENTS: Only antidepressant approved for adolescents

OTHER ANTIDEPRESSANTS: Effexor, Paxil, Tryptizol, Cipramil, Zispin, Lustral

ELI LILLY AND CO.

In addition to Prozac, the antidepressants in question include Paxil, Effexor, Zoloft and Celexa. They belong to a class of drugs called selective serotonin reuptake inhibitors, or SSRIs, named for the way they improve the flow of serotonin, a brain chemical linked to mood.

In 2002, 11 million prescriptions for antidepressants were dispensed to children, according to the FDA.

Only Prozac, the oldest of the blockbuster drugs, has been approved for use in children. The others are legally prescribed for children “off label” as an extension of their approval to treat depression and other psychiatric conditions in adults.

One of the studies the FDA will use in deciding the appropriateness of drugs in treating children is the Duke research reported today in the Journal of the American Medical Association. The study examined 439 youngsters ages 12 to 17 who had been diagnosed with major depression.

The children were randomly assigned to one of four treatment groups:

* Prozac and cognitive behavioral therapy together.

* Prozac alone.

* Talk therapy alone.

* Sugar pill that looked like Prozac.

Children in all the groups improved, but researchers found that the combination treatment of Prozac and talk therapy worked best to reduce depression. A spokesman at Eli Lilly, which makes Prozac, said that finding reinforces the company’s treatment goal: “We believe that monitoring with a physician should be part of the process along with drug treatment.”

What is likely to grab more attention, however, is the study’s finding that the children who received Prozac — whether with cognitive behavioral therapy or not — had higher incidents of harmful behaviors.

Twenty-two children, or 10 percent of those assigned to take Prozac, did something to harm themselves, such as cutting themselves without trying to commit suicide. Fifteen of the children on Prozac — 7 percent of the group — had worsening suicidal thoughts or made a suicide attempt. None of the children involved in the study died.

By comparison, 11 children in the therapy or placebo groups, or 5 percent, had harmful incidents, with nine of them, or 4 percent, demonstrating suicidal behavior.

“There is a slight increase of risk,” for harmful behaviors with Prozac, said Dr. John S. March, a Duke psychiatrist and lead author of the study. “But the rates of these events are relatively low.”

When the drugs were combined with cognitive behavioral therapy, however, the risk of harmful behaviors diminished, although they remained slightly elevated. March said Prozac also caused an increase in agitation among youths — a side effect that has been reported in adults.

“These are known side effects of drugs — all medicines cause some level of side effects,” March said.

But the down sides to antidepressants such as Prozac had, for years, been underplayed, according to patient advocates who are now pushing to reduce their use among children.

Jennifer Tierney of Kernersville said her daughter, Jame, nearly died after taking the antidepressant Effexor in 2000 when it was prescribed for migraine headaches. Jame became withdrawn, angry, agitated and suicidal within days of starting the drug.

“It was hell on Earth,” Jennifer Tierney said, noting that she and her husband didn’t know what was wrong with their bright, engaging daughter until reading about similar cases on the Internet.

With a doctor’s help, they spent the next year trying to wean Jame from the drug amid vomiting, muscle cramps and electrical zapping sensations in the brain.

Jame recently testified to the FDA, and her mother plans to testify at hearings in September.

“I am mad beyond anything you can imagine,” Jennifer Tierney said. Her anger stems in large part from the lack of information provided to her about the side effects of the drugs. She and others contend that the pharmaceutical companies hid negative research results from public scrutiny.

That contention forms the basis of a lawsuit filed this summer by the New York attorney general against GlaxoSmithKline, maker of Paxil. The lawsuit alleges that GSK publicized the results of one study showing Paxil’s benefits, while suppressing others that found little or no efficacy, or a possible increase in suicidal thinking. GSK has since posted the research on its corporate Web site.

But a definitive link between the antidepressants and suicide is difficult to make, in part because depression often leads to suicide, creating a chicken-and-the-egg dilemma: Was it the illness or the drug that prompted suicidal behavior?

“Really all that existed was some very compelling individual cases and anecdotal reports about people who did things to themselves or others that were uncharacteristic,” said Dr. Jeffrey A. Lieberman, a psychiatrist and researcher at UNC-Chapel Hill. “But that could not be regarded as any kind of conclusive or definitive evidence.”

Other psychiatrists said the Duke study reinforces the need for talk therapy in treating depression, noting that it is not enough to prescribe drugs. But the current health-care market works against the best practice, said Dr. John Diamond, director of the division of child and adolescent psychiatry at East Carolina University and president of the N.C. Council of Child and Adolescent Psychiatry.

“Managed care is not yet willing to pay for psychotherapy,” Diamond said, leading to situations where family physicians and pediatricians are prescribing the drugs, often with little follow-up.

Staff writer Sarah Avery can be reached at 829-4882 or savery@newsobserver.com.