U.S.
Food and Drug Administration
FDA Consumer magazine
January-February 2003
Table of Contents
By Floyd R. Sallee, M.D., Ph.D.
Psychotic illnesses are very debilitating. They are developmental in origin and frequently have their beginnings in childhood. As division director of the psychiatry program at Cincinnati Children's Hospital Medical Center, I have witnessed the ongoing crisis in child mental health care.
When I am on call over a weekend, I can expect to receive 20 to 30 calls from our emergency room per night. I will have to decide, from more than a dozen boys and girls needing acute psychiatric care, which ones will be admitted to our unit and which ones will wait on a medical floor until transfer.
My experience is based on the fact that our hospital has 3,000 mental health-related emergency room visits involving children each year and will admit more than 6,000 children for acute psychiatric care. These admissions are mostly for psychotic illness, typified by early-onset manic-depressive illness and thought disorder.
As a result of this crisis, child psychiatrists and other experts in pediatric psychopharmacology are routinely using the newer antipsychotic agents termed "atypical neuroleptics" to quickly stabilize school-age children with severe mental illness. These agents are "atypical" in that they have reduced nervous system side effects, and rely on complex pharmacologies to achieve their sometimes remarkable and rapid reversal of psychosis-related thought disorder and cognitive impairment. Examples of drugs in this class include Zyprexa, Geodon, Seroquel, Risperdal, and Abilify.
In my view, safety information should be a primary goal of the application of the FDA's pediatric rule and other initiatives that encourage the study of drugs in children. (See "Drug Research and Children.") As a researcher, I believe it is important for the FDA to consider the actual use patterns for drug classes as we move forward with increasing pediatric research.
While the atypical neuroleptics are intended for treating schizophrenia, pediatric practitioners and child psychiatrists are using these agents for early forms of disorders that have not yet reached full expression. These mental health professionals rarely see children who meet full criteria for schizophrenia.
There is, therefore, a significant gap in knowledge, particularly concerning safety, since the drugs' adult-based labeling does not address clinical use in children. The objective in applying the pediatric rule must be to provide safety information that addresses the way the drug is actually used.
Several FDA-approved, randomized controlled trials with atypical neuroleptics are either in the planning stages or currently underway. We need to ensure that the studies do not contain criteria that are so restrictive that they interfere with completion of the research, favor adolescents over younger children, or result in data that cannot be applied generally to the current landscape of clinical use in children.
The Best Pharmaceuticals Act for Children and the pediatric rule have had a major impact on the rapidly developing field of pediatric psychopharmacology. I believe that these initiatives have had more of an impact on the study of early-onset psychotic illness, such as bipolar disorder and schizophrenia, than any other area.
The effects have been far reaching and include child-friendly design of drug trials, clinical symptom rating scales sensitive to a child's development, and sophisticated technology for conducting pediatric trials, as well as new measurement tools to help quantify quality of life issues.
Before these initiatives, the number of children participating in drug studies was small. The reliability and validity of pediatric rating instruments for psychiatric symptoms in children were largely unknown.
Pharmaceutical-based clinical trials as a rule largely were focused on how well drugs worked in the short term, with little opportunity to examine long-term risks and benefits. And no quality of life measures were available, even if the study ran long enough to make them relevant.
These issues become extremely important when psychotic illness is involved. We know that for children experiencing their first psychotic episode, it can take months, if not years, for their impairment to become fully realized.
Children may indeed be at greatest risk from the atypical neuroleptic drug class, not just because of a rapidly developing brain, but also potential sensitivities to certain cardiac arrhythmias and the well-documented weight gain associated with this drug class. Given the increased risk of type 2 diabetes in children due to rising obesity generally over the last decade, attention to safety should be a major goal of pediatric research initiatives.
Floyd R. Sallee, M.D., Ph.D., is a child psychiatrist and director of the pediatric pharmacology research unit at Cincinnati Children's Hospital Medical Center.