April 8, 2004 — Should antidepressants be prescribed to children and teens? The FDA is currently reviewing the safety of the drugs that are increasingly being used to treat depression in kids. Now a new study questions their effectiveness.

In their review of some of the largest published trials on the efficacy of newer antidepressants in children and adolescents, psychiatric researchers say that the reported benefits of these drugs to treat depression in children have been exaggerated. They say that children in these studies that received placebo routinely achieved responses that were similar to children treated with antidepressants.

Researcher Jon N. Jureidini, MD, PhD, tells WebMD that even when the effectiveness of an active antidepressant was reported as significantly greater than the placebo, the difference did not necessarily translate into a clinical advantage.

Jureidini, tells WebMD that one large trial involving the antidepressant Zoloft was mathematically determined to have an advantage over placebo. “But the advantage amounted to just a 2- or 3-point improvement on a 100-point variation scale. From a clinical point of view this was most likely trivial.”

But one child psychiatry expert tells WebMD that antidepressants can be very helpful and even lifesaving when used appropriately.

FDA Warning

Last month the FDA issued a warning about the possibility that antidepressant use might be linked to a worsening of depression or an increase in suicidal thoughts, especially among children and teens.

The agency sent letters to the manufacturers of 10 antidepressants, requesting that they alter their drugs’ labels to warn of possible suicide, worsening depression, anxiety, and panic attacks in adults and children. The drugs that are the focus of this labeling change request are Prozac (sold generically as fluoxetine), Zoloft, Paxil, Luvox, Celexa, Lexapro, Wellbutrin, Effexor, Serzone, and Remeron.

In a March 22 press statement, FDA officials reported that it was not yet clear whether antidepressants contribute to the emergence of suicidal thinking and behavior. But they urged clinicians and those close to antidepressant users to closely monitor behavioral changes, especially at the beginning of drug treatment or when the doses are increase or decreased.

The results of an independent review of the safety data from 25 studies of antidepressant use among children and adolescents are expected to be made public this summer, at which time an FDA advisory panel will consider new recommendations regarding their use. But Do They Work?

In the latest analysis, published in the April 10 issue of the British Medical Journal, Jureidini and colleagues reviewed six previously published trials that included 940 young patients. Roughly half were treated with the antidepressants Paxil, Effexor, Zoloft, or Prozac and the other half got a placebo.

The researchers say that biased reporting in the mostly drug manufacturer-funded trials commonly led to overstatements of the effectiveness of various antidepressants.

They say that of the 42 behavioral measures used to determine efficacy of antidepressants in children and teens, only 14 measurements were shown to improve with treatment. They also say that of 10 measures that rely on children or parents reporting a change with treatment no change was seen with drug treatment. They say that claims of effectiveness were based entirely on ratings by doctors.

“These results make a major benefit from newer antidepressants unlikely, but a small benefit remains possible,” Jureidini and colleagues wrote.

Jureidini says interventions that have been proven effective in the treatment of children and teens with depression, such as behavioral therapies, are being replaced by drug treatments because prescribing pills is easy and takes little time.

“If our health care system is set up so that there is a strong bias toward using the prescription pad instead of demonstrably more effective interventions, then we should take a careful look at that system,” he tells WebMD.

‘Still Learning’

Child psychiatrist David Fassler, MD, tells WebMD that a major challenge is to better identify which children and adolescents are most likely to respond to antidepressant drugs.

“We are still learning about depression in the young, and we may find that it is not just one disorder but a number of them,” he says. “A drug treatment may be very effective for some kids with depression, but not for others.”

Fassler testified before an FDA panel earlier this year, calling for independent studies designed to clarify the role of drugs in the treatment of depressed children and teens. He is a spokesman for the American Psychiatric Association and the American Academy of Child and Adolescent Psychiatry.

He says parents and other caregivers must act as advocates for depressed children by learning as much as they can about the diagnosis and treatment options, and making sure that a child taking antidepressants is closely monitored.

“The good news is that we really can help most of these kids,” he says. “Medication can be extremely helpful and even lifesaving. But medication alone is rarely an adequate or appropriate treatment for complex child psychiatric disorders like depression.”