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A Double-blind Clozapine-Haloperidol Comparison

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

Arch Gen Psychiatry. 1996;53(12):1090-1097.

Abstract
Background
Childhood-onset schizophrenia is a rare but severe form of the disorder that is often treatmentrefractory. 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.

Author Affiliations
From the Child Psychiatry Branch, National Institute of Mental Health, Bethesda, Md (Drs Kumra, Jacobsen, Alaghband-Rad, and Rapoport and Mss Lenane, Hamburger, Smith, and Albus); Harvard University School of Medicine, Boston, Mass (Dr Frazier); Northwestern University School of Medicine, Chicago, Ill (Dr McKenna); and University of Maryland School of Medicine, Baltimore (Dr Gordon).

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