Clozapine and "high-dose" olanzapine in refractory early-onset schizophrenia: a 12-week randomized and double-blind comparison.
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.
Kumra
Sanjiv
S
Department of Child and Adolescent Psychiatry, University of Minnesota, Minneapolis, Minnesota 55454-1495, USA. kumra002@umn.edu
Kranzler
Harvey
H
Gerbino-Rosen
Ginny
G
Kester
Hana M
HM
De Thomas
Courtney
C
Kafantaris
Vivian
V
Correll
Christoph U
CU
Kane
John M
JM
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
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D003024:Clozapine; D000077152:Olanzapine