Clozapine Versus “High-Dose” Olanzapine in Refractory Early-Onset Schizophrenia: An Open-Label Extension Study

OBJECTIVE: A recent 12-week controlled comparison demonstrated the superiority of clozapine to "high-dose" olanzapine in adolescents with treatment-refractory schizophrenia. In the present study, the authors conducted a 12-week, open-label, follow-up study to examine changes in lipid and glucose metabolism in youths maintained on clozapine and to determine whether patients who were previously randomized to high-dose olanzapine (up to 30 mg/day) responded to clozapine. METHOD: Thirty three (14 clozapine, 19 olanzapine) (85%) of 39 patients were available for the present 12-week, open-label extension study. Extended safety data using an intention-to-treat analysis from the 14 subjects treated with clozapine for a total of 24 weeks are presented. In addition, we report the clinical outcomes for 10 of 19 olanzapine-treated patients who were switched after 12 weeks to clozapine due to treatment nonresponse. Clinical response was defined as a decrease of 30% or more in total Brief Psychiatric Rating score from week 12 and a Clinical Global Impression-Improvement rating of 1 (very much improved) or 2 (much improved). RESULTS: The incidence of hypertriglyceridemia (defined as fasting triglycerides >125 mg/dL) (10/14 = 71%) and the incidence of "prediabetes" (defined as fasting blood glucose > or =100) (4/14 = 29%) at week 24 in the clozapine-treated subjects were notable. Seven (70%) of 10 of young patients with schizophrenia who failed treatment with "high-dose" olanzapine were found to respond to a 12-week, open-label clozapine trial. CONCLUSIONS: Clinicians and caregivers need to be aware of potential metabolic adverse events of long-term clozapine treatment. Adolescents with a poor response to olanzapine may do better on clozapine.