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

Kumra S.; Frazier J.A.; Jacobsen L.K.; McKenna K.; Gordon C.T.; Lenane M.C.; Hamburger S.D.; Smith A.K.; Albus K.E.; Alaghband-Rad J.; Rapoport J.L.

Child Psychiatry Branch, NIMH, Bldg 10, 9000 Rockville Pike, Bethesda, MD 20892, USA

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.

Keywords: schizophrenia (link) drug therapy; adolescent; article; child; chronic disease; clinical article; clinical trial; double blind procedure; drowsiness (link) side effect; drug efficacy; extrapyramidal symptom (link) side effect; extrapyramidal symptom (link) prevention; extrapyramidal symptom (link) drug therapy; female; human; hypersalivation (link) side effect; insomnia (link) side effect; liver toxicity (link) side effect; male; neuroleptic malignant syndrome (link) side effect; neutropenia (link) side effect; onset age; psychopharmacotherapy; psychosis (link) drug therapy; seizure (link) side effect; seizure (link) drug therapy; seizure (link) prevention

ARCH. GEN. PSYCHIATRY 53/12 (1090-1097) 1996