Washington Editor

BETHESDA, Md. - Some FDA regulators believe drug companies might need to conduct large, randomized, controlled studies to ascertain whether antidepressants prompt suicide or thoughts of suicide in kids. Such opinions were aired Monday before the FDA's psychopharmacologic and pediatric advisory panels concerning the use of selective serotonin reuptake inhibitors (SSRIs) in children.

Panel members heard analyses from the FDA and a committee of experts assembled by Columbia University to review trials involving kids with major depressive disorder (MDD) and other psychiatric disorders who might take products like Zoloft, Paxil or Prozac. Prozac, made by Eli Lilly and Co., of Indianapolis, is the only FDA-approved antidepressant in the pediatric population. The others are used off-label.

Indeed, the FDA, as well as the House Energy Commerce Committee, initiated investigations into the use of antidepressants in children following a report released in June 2003 suggesting that paroxetine (generic for GlaxoSmithKline plc's Paxil) appeared to increase the risk of suicidal thoughts and actions in children. (See BioWorld Today, Sept. 10, 2004.)

Speaking to the panels Monday, Dianne Murphy, the FDA's director, office of pediatric therapeutics, said the medical community's knowledge of pediatric therapeutics is in its infancy, admitting that pharmacokinetics in children are more variable than anticipated. She believes larger studies are needed. (Previous studies have been designed for efficacy and not large enough to find differences in some adverse events.)

But for Wyeth Pharmaceuticals, located in Collegeville, Pa., the maker of Effexor (venlafaxine), signs of danger did surface in pediatric trials, said Joseph Camardo, senior vice president of medical affairs in the Collegeville office, who told the panels that there were increased reports of hostility and suicide-related events, such as suicidal ideation and self-harm, in his firm's pediatric trials.

"We at Wyeth updated our label and provided our pediatric safety information to over 450,000 health care professionals in 2003 in a Dear Health Care Provider' letter," he said. "Studies with other antidepressants carried out by other pharmaceutical companies in pediatric patients have shown similar adverse events."

Many of the 70 people, including patient advocates and families of attempted suicide or suicide victims, who spoke during the panel's four-hour public hearing demanded everything from removing SSRIs from the market to better label warnings. Marion Goff, the mother of twins, said her 9-year-old daughter was prescribed Zoloft (made by New York-based Pfizer Inc.) for a condition that ended up being Lyme disease. Past clinical trials dealing with depressed youth have been plagued in many cases by adverse events not considered suicidal, therefore incorrectly classified.

On behalf of the Columbia University analysis, Kelly Posner said trials have been challenged by a lack of conceptual clarity about suicidal behavior and corresponding lack of well-defined terminology, a lack of systemic or standardized language used to define suicidal behavior in the 25 industry antidepressant trials and a difficulty in interpreting the meaning of reported adverse events that occurred in those trials.

Tom Woodward, whose 17-year-old daughter committed suicide within days of starting Zoloft, quoted scientists who said the chances of suicide are higher in the first few days of taking SSRIs. When asked whether Forest Laboratories Inc. had compared suicide rates in the first few days of treatment to determine whether incidence was higher, Jeffrey Jonas, a vice president with the New York-based company, said no.

However, he said pediatric trials of Forest products Celexa (citalopram) and Lexapro (escitalopram) revealed no evidence that adverse events experienced in the beginning of the trial would escalate to serious adverse events. Patients with severe adverse events generally are considered poor responders. A recent study funded by the National Institute for Mental Health found that the most effective treatment for adolescent depression is a combination of medication (one SSRI) and a form of psychotherapy (cognitive behavioral therapy), according to the National Mental Health Association in Alexandria, Va.

No Comments