Clozapine and "high-dose" olanzapine in refractory early-onset schizophrenia: a 12-week randomized and double-blind comparison.

Author(s): Kumra S, Kranzler H, Gerbino-Rosen G, Kester HM, De Thomas C, Kafantaris V, Correll CU, Kane JM

Affiliation(s): Department of Child and Adolescent Psychiatry, University of Minnesota, Minneapolis, Minnesota 55454-1495, USA. kumra002@umn.edu

Publication date & source: 2008-03-01, Biol Psychiatry., 63(5):524-9. Epub 2007 Jul 25.

Publication type: Comparative Study; Multicenter Study; Randomized Controlled Trial

BACKGROUND: The present study evaluated the effectiveness and safety of clozapine versus "high-dose" olanzapine in treatment-refractory adolescents with schizophrenia. METHODS: Children, ages 10-18 years, who met DSM-IV criteria for schizophrenia and who were resistant or intolerant to at least two antipsychotic drugs were randomized to receive 12 weeks of double-blind flexibly dosed treatment with clozapine (n = 18) or "high-dose" olanzapine (up to 30 mg/day) (n = 21). The primary efficacy measure was response (improvement), defined as a decrease of 30% or more in total Brief Psychiatric Rating Scale score from baseline and a Clinical Global Impression Scale improvement rating of "1" (very much improved) or "2" (much improved). RESULTS: Significantly more clozapine-treated adolescents met response criteria (66%) compared with olanzapine-treated subjects (33%). Clozapine was superior to olanzapine in terms of reduction of the psychosis cluster scores and negative symptoms from baseline to end point. However, both treatments were associated with significant weight-gain and related metabolic abnormalities. CONCLUSIONS: This double-blind randomized comparison of two second-generation antipsychotic drugs for treatment-refractory adolescents with schizophrenia supports clozapine as the agent of choice. The development of interventions to limit weight gain and metabolic side effects are needed to enhance the risk-benefit profile for both study treatments.