The safety of olanzapine in adolescents with schizophrenia or bipolar I disorder: a pooled analysis of 4 clinical trials

J Clin Psychiatry. 2009 Feb;70(2):247-58. doi: 10.4088/jcp.08m03538. Epub 2009 Feb 10.

Abstract

Objective: To describe the safety of olanzapine treatment in adolescents (aged 13-17 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 (3-6 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 > or = 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.

Conclusions: 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.

Trial registration: clinicaltrials.gov Identifiers: NCT00051298, NCT00050206, and NCT00113594.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Adverse Drug Reaction Reporting Systems
  • Age Factors
  • Antipsychotic Agents / adverse effects*
  • Antipsychotic Agents / therapeutic use
  • Benzodiazepines / adverse effects*
  • Benzodiazepines / therapeutic use
  • Bipolar Disorder / diagnosis
  • Bipolar Disorder / drug therapy*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug-Related Side Effects and Adverse Reactions
  • Female
  • Humans
  • Male
  • Meta-Analysis as Topic
  • Olanzapine
  • Randomized Controlled Trials as Topic / statistics & numerical data
  • Schizophrenia / diagnosis
  • Schizophrenia / drug therapy*

Substances

  • Antipsychotic Agents
  • Benzodiazepines
  • Olanzapine

Associated data

  • ClinicalTrials.gov/NCT00050206
  • ClinicalTrials.gov/NCT00051298
  • ClinicalTrials.gov/NCT00113594