Olanzapine Versus Placebo in Adolescents With Schizophrenia: A 6-Week, Randomized, Double-Blind, Placebo-Controlled Trial

Objective: To assess olanzapine's efficacy and tolerability in adolescents with schizophrenia. Method: One hundred seven inpatient and outpatient adolescents (olanzapine, n = 72, mean age 16.1 years; placebo, n = 35, mean age 16.3 years) with schizophrenia participated in this randomized (2:1), international, multisite, industry-sponsored trial. All patients met DSM-IV-TP criteria for schizophrenia, and they were treated for up to 6 weeks with flexible doses of olanzapine (2.5-20.0 mg/day) or placebo. Last-observation-carried-forward mean changes from baseline to endpoint on the anchored version of the Brief Psychiatric Rating Scale for Children, Clinical Global Impression Scale-Severity of Illness, and Positive and Negative Syndrome Scale (PANSS) were assessed. Results: More olanzapine-treated versus placebotreated patients completed the trial (68.1% versus 42.9%, p = .020). Compared with placebo-treated patients, olanzapine-treated adolescents had significantly greater improvement in Brief Psychiatric Rating Scale for Children total (p = .003), Clinical Global Impressions Scale-Severity of Illness (p = .004), PANSS total (p = .005), and PANSS positive scores (p = .002). Olanzapine-treated patients gained significantly more baseline-to-endpoint weight (4.3 kg versus 0.1 kg, p < .001). Significantly more olanzapine-treated versus placebo-treated patients gained 7% or greater of their body weight at any time during treatment (45.8% versus 14.7%, p = .002). Prolactin and triglyceride mean baseline-to-endpoint changes were significantly higher in olanzapine-treated versus placebo-treated adolescents. The incidence of treatment-emergent significant changes in fasting glucose, cholesterol, or triglycerides did not differ between the groups at endpoint, but significantly more olanzapine-treated patients had high triglycerides at any time during treatment. Conclusions: Olanzapine-treated adolescents with schizophrenia experienced significant symptom improvement. Significant increases in weight, triglycerides, uric acid, most liver function tests, and prolactin were observed during olanzapine treatment. J. Am. Acad. Child Adolesc. Psychiatfy, 2009;48(1):60-70.