The Safety of Olanzapine in Adolescents With Schizophrenia or Bipolar I Disorder: A Pooled Analysis of 4 Clinical Trials

Objective: To describe the safety of olanzapine treatment in adolescents (aged 13­17 years) with schizophrenia or bipolar I disorder, and to compare these data with those of olanzapine-treated adults.

Data Sources and Study Selection: Placebo-controlled database, adolescents: acute phase of 2 double-blind, placebo-controlled trials (3­6 weeks; olanzapine, N=179, mean age=15.5 years; placebo, N=89, mean age=15.7 years); overall adolescent olanzapine exposure database, adolescents: 4 trials (e.g., the 2 aforementioned studies, each with a 26-week open-label extension phase, and 2 open-label, 4.5- and 24-week trials; N=454, mean age=15.9 years); and adult database: 84 clinical trials of up to 32 weeks.

Data Synthesis: The mean daily dosage of olanzapine was 10.6 mg/day (exposure=48,946 patient days). In the overall adolescent olanzapine exposure database, the most common adverse events included increased weight (31.7%), somnolence (19.8%), and increased appetite (17.4%). In up to 32 weeks of treatment, when compared with adults, adolescents from the overall adolescent olanzapine exposure database gained statistically significantly more weight (7.4 kg vs. 3.2 kg, p<.001); statistically significantly more adolescents gained ≥7% of their baseline weight (65.1% vs. 35.6%, p<.001). Adolescents experienced statistically significant within-group baseline-to-endpoint changes in fasting glucose (p<.001), total cholesterol (p=.002), triglycerides (p=.007), and alanine aminotransferase (p<.001). Two patients from the overall adolescent olanzapine exposure database (0.4%) attempted suicide; 13 (2.9%) had suicidal ideation. In the placebo-controlled database, adolescents had statistically significant baseline-to-endpoint increases in prolactin (11.4 micrograms/L, p<.001); 47.4% had high prolactin levels.

Conclusion: The types of adverse events in olanzapine-treated adolescents appear to be similar to those of adults. The magnitude and incidence of weight and prolactin changes were greater in adolescents.

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