Clozapine treatment of childhood-onset schizophrenia

The first double-blind controlled trial of an atypical neuroleptic, ln children and adolescents has just been completed at the NIMH. In this study the efficacy and safety of clozapine vs. haloperidol was examined in children and adolescents with the onset of schizophrenia by age 12. Twenty-one patients who were either intolerant or nonresponders to at least two different neuroleptics (age 14.0 ± 2.3 years, male 11, female 10) participated in this parallel design study. Clozapine significantly reduced total BPRS symptoms scores (p<0.04), Bunney Hamburg total score (p<0.02), negative symptoms of schizophrenia, SAPS (p<0.01) and positive symptoms of schizophrenia, SAPS (p<0.01) in comparison with haloperidol. Of the ten patients in the clozapine group, 5 (50%) met a priori responder criteria. However, toxicity was a major concern. patients in the clozapine group had to be withdrawn from the study; 2 patients developed neutropenia and failed rechallenge with clozapine, and 1 patient developed intractable seizures. An additional patient on clozapine developed epileptiform changes requiring prophylactic anticonvulsant treatment. In summary, the judicious use of clozapine for severely ill schizophrenic children and adolescents, who are nonresponders to typical agents is warranted. Due to the possibly increased toxicity of this drug in pediatric populations, patients must be carefully monitored for adverse effects.