title: Clozapine and "high-dose" olanzapine in refractory early-onset schizophrenia: a 12-week randomized and double-blind comparison.
abstract: 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.
authors.affiliation: Department of Child and Adolescent Psychiatry, University of Minnesota, Minneapolis, Minnesota 55454-1495, USA. kumra002@umn.edu
authors.forename: Sanjiv
authors.initials: S
authors.lastname: Kumra
authors.forename: Harvey
authors.initials: H
authors.lastname: Kranzler
authors.forename: Ginny
authors.initials: G
authors.lastname: Gerbino-Rosen
authors.forename: Hana M
authors.initials: HM
authors.lastname: Kester
authors.forename: Courtney
authors.initials: C
authors.lastname: De Thomas
authors.forename: Vivian
authors.initials: V
authors.lastname: Kafantaris
authors.forename: Christoph U
authors.initials: CU
authors.lastname: Correll
authors.forename: John M
authors.initials: JM
authors.lastname: Kane
mesh_terms: D000293:Adolescent; D000367:Age Factors; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D001569:Benzodiazepines / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D002648:Child; D003024:Clozapine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D000077152:Olanzapine; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D003024:Clozapine; D000077152:Olanzapine