Clozapine Treatment of Children and Adolescents with Bipolar Disorder and Schizophrenia: A Clinical Case Series

Abstract

Ten consecutive severely ill child and adolescent inpatients (aged 6–15 years), who had either multiple trials of typical neuroleptics and antimanic agents with inadequate symptom remission or side effect intolerance, were treated with open-label clozapine. Five patients had bipolar mood disorder (mixed type) and four had schizophrenia; one had psychotic disorder NOS. Weekly ratings of global functioning, estimated retrospectively by the treating physicians, were obtained for the 3 weeks before and 6 weeks during clozapine treatment. The mean daily clozapine dose was 3.2 mg/kg or 128 mg (range 75–225 mg). Seven of 10 patients received concurrent lithium therapy throughout the study. All of these 10 patients had psychotic symptoms and all 9 of the male patients had aggressive symptoms that required treatment. On the Clinical Global Impression Scale (CGI), there was a 42% decrease in the Severity of Illness score during the 6-week treatment (p < 0.004). All patients were rated as "severely ill" before clozapine, but 7 of the 10 patients were rated as being "moderately ill" or better following treatment. There were also significant improvements in the CGI Improvement subscale (57% increase) and the mean CGAS score (change from 22 to 54) during the 6-week treatment. Apparent improvements were generally evident after 1–2 weeks. Clozapine also seemed particularly helpful in treating aggressive behavior and psychotic symptoms in both bipolar and schizophrenic patients. Adverse effects were common but mild. Safety and efficacy cannot be assessed without controls, but these clinical trials suggest that highly treatment-resistant patients could show clinically meaningful improvement without problematic side effects during short-term clozapine treatment. These preliminary data also suggest that clozapine might have antipsychotic/antimanic properties in some youths with early-onset bipolar disorder.