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 13-17 years) with schizophrenia or bipolar I disorder, and to compare these data with those of olanzapine-treated adults.


METHODS
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.


RESULTS
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.


BACKGROUND
clinicaltrials.gov Identifiers: NCT00051298, NCT00050206, and NCT00113594.
Kryzhanovskaya
Ludmila A
LA
Lilly Research Laboratories, Eli Lilly and Co, Indianapolis, IN 46285-6156, USA. kryzhanovskayalu@lilly.com
Robertson-Plouch
Carol K
CK
Xu
Wen
W
Carlson
Janice L
JL
Merida
Karen M
KM
Dittmann
Ralf W
RW
D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000367:Age Factors; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001569:Benzodiazepines / Q000009:adverse effects* / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D000077152:Olanzapine; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D000077152:Olanzapine