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

Biol Psychiatry. 2008 Mar 1;63(5):524-9. doi: 10.1016/j.biopsych.2007.04.043. Epub 2007 Jul 25.


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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Age Factors
  • Antipsychotic Agents / administration & dosage*
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / pharmacology
  • Benzodiazepines / administration & dosage*
  • Benzodiazepines / adverse effects
  • Benzodiazepines / pharmacology
  • Child
  • Clozapine / administration & dosage*
  • Clozapine / adverse effects
  • Clozapine / pharmacokinetics
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Olanzapine
  • Psychiatric Status Rating Scales
  • Schizophrenia / blood
  • Schizophrenia / diagnosis
  • Schizophrenia / drug therapy*
  • Schizophrenic Psychology*


  • Antipsychotic Agents
  • Benzodiazepines
  • Clozapine
  • Olanzapine