Is There a Role for Clozapine in the Treatment of Children and Adolescents?

Abstract

Robert L. Findling, M.D. The question of whether clozapine is ever appropriate to use in the pediatric population is an important one. At present, according to the U.S. Food and Drug Administration (FDA), clozapine is indicated for patients with treatment-resistant schizophrenia and may be prescribed for patients with psychotic illnesses to lower the risk of suicidal behavior. The reason that clozapine is reserved for use with patients who are not responsive to other interventions is because clozapine therapy can lead to agranulocytosis, seizures, and myocarditis. Clozapine is currently not approved for use in pediatric patients. Despite these facts, treatment with clozapine is considered for some children and adolescents who are suffering from severe, disabling psychopathology who do not respond to or cannot tolerate firstor even secondline medication interventions for which clozapine therapy may be considered. Although the use of clozapine has been described in several pediatric patient populations, the best evidence supporting its use in children or adolescents are in youths with treatmentresistant psychotic illnesses or in young people with treatment-resistant bipolar illness (Findling et al., 2005). It should be emphasized that the use of clozapine has not been rigorously studied in aggressive youths with primary diagnoses of disruptive behavior disorders. Because of this lack of evidence and the side effect profile of clozapine, use in aggressive patients with primary diagnoses of disruptive behavior disorders is not recommended. Although some of the data relating to clozapine_s use in the young may not be methodologically stringent or extensive, what information is available does suggest that clozapine may be helpful when reserved for use in some seriously ill patients with treatmentresistant schizophrenia or bipolar illness. In short, the answer to the question posed is Byes.[ Clozapine therapy may be appropriate for some pediatric patients with psychotic disorders or bipolar illnesses who do not respond to other forms of pharmacotherapy. Now that the diagnoses of the patients for whom clozapine therapy may be beneficial have been This is a case vignette created to exemplify a complex clinical problem and does not refer to any specific patient. This column aims to discuss practical approaches to everyday issues in pediatric pharmacotherapy. The cases and discussions specifically target aspects of clinical care related to psychopharmacology for which we do not have adequate applicable controlled trials. Given the need to address symptoms in youths with complex, severe, and comorbid disorders, recommendations are likely to be ‘‘off label’’ from the perspective of the U.S. Food and Drug Administration. While it is important that clinicians address psychosocial issues in the evaluation and treatment of their patients, such discussion is beyond the specific scope of this feature. These are not meant to be practice guidelines, but rather examples of thought processes that may go into pharmacotherapy decision making. Accepted September 28, 2006. Dr. Kratochvil is with the Department of Psychiatry, University of Nebraska Medical Center, Omaha; Dr. Findling is with Departments of Psychiatry and Pediatrics, University Hospitals of Cleveland/Case Western Reserve University; Dr. Frazier is with the Department of Psychiatry, Harvard Medical School, Boston; Dr. Gerbino-Rosen is with the Department of Psychiatry and Behavioral Science, Albert Einstein College of Medicine and the Bronx Children_s Psychiatric Center, New York; Dr. Kranzler is with the Department of Psychiatry, Albert Einstein College of Medicine and the Bronx Children_s Psychiatric Center, New York; and Dr. Kumra is with the Department of Psychiatry, University of Minnesota, Minneapolis. Correspondence to Dr. Christopher J. Kratochvil, University of Nebraska Medical Center, 985581 Nebraska Medical Center, Omaha, NE 68198-5581; e-mail: ckratoch@unmc.edu. 0890-8567/07/4603-0423 2007 by the American Academy of Child and Adolescent Psychiatry. DOI: 10.1097/chi.0b013e3180ed94e P S Y CHOPHARMACOLOGY P E R S P E CT I V E S Assistant Editor: Christopher J. Kratochvil, M.D.