CLOZAPINE TREATMENT OF CHILDREN AND ADOLESCENTS WITH BIPOLAR DISORDERAND SCHIZOPHRENIA - A CLINICAL CASE SERIES

Ten consecutive severely ill child and adolescent inpatients (aged 6-1 5 years), who had either multiple trials of typical neuroleptics and a ntimanic agents with inadequate symptom remission or side effect intol erance, were treated with open-label clozapine. Five patients had bipo lar mood disorder (mixed type) and four had schizophrenia; one had psy chotic disorder NOS. Weekly ratings of global functioning, estimated r etrospectively by the treating physicians, were obtained for the 3 wee ks before and 6 weeks during clozapine treatment. The mean daily cloza pine dose was 3.2 mg/kg or 128 mg (range 75-225 mg). Seven of 10 patie nts received concurrent lithium therapy throughout the study. All of t hese 10 patients had psychotic symptoms and all 9 of the male patients had aggressive symptoms that required treatment. On the Clinical Glob al Impression Scale (CGI), there was a 42% decrease in the Severity of Illness score during the 6-week treatment (p < 0.004). All patients w ere rated as ''severely ill'' before clozapine, but 7 of the 10 patien ts were rated as being ''moderately ill'' or better following treatmen t. There were also significant improvements in the CGI Improvement sub scale (57% increase) and the mean CGAS score (change from 22 to 54) du ring the 6-week treatment. Apparent improvements were generally eviden t after 1-2 weeks. Clozapine also seemed particularly helpful in treat ing aggressive behavior and psychotic symptoms in both bipolar and sch izophrenic patients. Adverse effects were common but mild. Safety and efficacy cannot be assessed without controls, but these clinical trial s suggest that highly treatment-resistant patients could show clinical ly meaningful improvement without problematic side effects during shor t-term clozapine treatment. These preliminary data also suggest that c lozapine might have antipsychotic/antimanic properties in some youths with early-onset bipolar disorder.