Childhood-onset schizophrenia: A double-blind clozapine-haloperidol comparison

Sanjiv Kumra, Jean A. Frazier, Leslie K. Jacobsen, Kathleen McKenna, Charles T. Gordon, Marge C. Lenane, Susan D. Hamburger, Amy K. Smith, Kathleen E. Albus, Javad Alaghband-Rad, Judith L. Rapoport

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348 Scopus citations


Background: Childhood-onset schizophrenia is a rare but severe form of the disorder that is often treatment-refractory. In this study, the efficacy and adverse effects of clozapine and haloperidol were compared for children and adolescents with early-onset schizophrenia. Methods: Twenty-one patients (mean [±SD] age, 14.0±2.3 years) with onset of Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition-defined schizophrenia that began by age 12 years and who had been nonresponsive to typical neuroleptics participated in the study. Patients were randomized to a 6-week double-blind parallel comparison of clozapine (mean [±SD] final dose, 176±149 mg/d), or haloperidol, (16±8 mg/d). Results: Clozapine was superior to haloperidol on all measures of psychosis (P=.04-.002). Positive and negative symptoms of schizophrenia improved. However, neutropenia and seizures were major concerns. To date, one third of the group has discontinued using clozapine. Conclusions: Clozapine has striking superiority for positive and negative symptoms in treatment-refractory childhood-onset schizophrenia. However, due to possibly increased toxic effects in this pediatric population, close monitoring for adverse events is essential.

Original languageEnglish (US)
Pages (from-to)1090-1097
Number of pages8
JournalArchives of General Psychiatry
Issue number12
StatePublished - Jan 1 1996

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