The safety of olanzapine in adolescents with schizophrenia or bipolar I disorder: a pooled analysis of 4 clinical trials.
ABSTRACT 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.
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.
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.
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.
clinicaltrials.gov Identifiers: NCT00051298, NCT00050206, and NCT00113594.
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ABSTRACT: To assess the efficacy and safety of olanzapine/fluoxetine combination (OFC) for the acute treatment of bipolar depression in children and adolescents. Patients 10 to 17 years of age with bipolar I disorder (BP-I), depressed episode, baseline Children's Depression Rating Scale-Revised (CDRS-R) total score ≥40, Young Mania Rating Scale (YMRS) total score ≤15, and YMRS-item 1 ≤2 were randomized to OFC (6/25-12/50 mg/day olanzapine/fluoxetine; n = 170) or placebo (n = 85) for up to 8 weeks of double-blind treatment. The primary efficacy measure was mean change in CDRS-R using mixed-model repeated-measures methodology. Baseline-to-week-8 least-squares mean change in CDRS-R total score was greater for OFC-treated patients than for placebo-treated patients (-28.4 versus -23.4, p = .003; effect size = .46), with between-group differences statistically significant at week 1 (p = .02) and all subsequent visits (all p < .01). Rates of and times to response and remission were statistically significantly greater for OFC- than for placebo-treated patients. The most frequent treatment-emergent adverse events in the OFC group were weight gain, increased appetite, and somnolence. Mean weight gain at patient's endpoint was significantly greater for OFC- than for placebo-treated patients (4.4 kg versus 0.5 kg, p < .001). Treatment-emergent hyperlipidemia was very common among OFC-treated patients. Abnormal increases in hepatic analytes, prolactin, and corrected QT interval (QTc) were also common or very common but generally not clinically significant. In this study, OFC was superior to placebo, and has been approved by the US Food and Drug Administration (FDA) for the acute treatment of bipolar I depression in patients 10 to 17 years of age. Benefits should be weighed against the risk of adverse events, particularly weight gain and hyperlipidemia. Clinical trial registration information-A Study for Assessing Treatment of Patients Ages 10-17 with Bipolar Depression; http://clinicaltrials.gov; NCT00844857. Copyright © 2015 American Academy of Child & Adolescent Psychaitry. Published by Elsevier Inc. All rights reserved.Journal of the American Academy of Child & Adolescent Psychiatry 12/2014; 54(3). DOI:10.1016/j.jaac.2014.12.012 · 6.35 Impact Factor
61st Meeting of American Academy of Child and Adolescent Psychiatry; 10/2014
Article: Olanzapine[Show abstract] [Hide abstract]
ABSTRACT: Olanzapine is an atypical antipsychotic that, in addition to its use in adults, is now indicated for the treatment of schizophrenia, and manic or mixed episodes associated with bipolar I disorder in adolescents aged 13–17 years. In a randomized, double-blind, multicentre, 6-week trial in adolescents aged 13–17 years with schizophrenia, the least squares mean reduction from baseline to 6 weeks in the Brief Psychiatric Rating Scale for Children (BPRS-C) total score (primary endpoint) was significantly greater with olanzapine than with placebo. In a randomized, double-blind, multicentre, 3-week trial in adolescents, aged 13–17 years, with manic or mixed episodes associated with bipolar I disorder, the mean reduction from baseline to 3 weeks in the Adolescent Structured Young Mania Rating Scale (YMRS) total score (primary endpoint) was significantly greater with olanzapine than with placebo. In extensions of each of the pivotal placebo-controlled trials in schizophrenia and bipolar mania, open-label treatment with olanzapine for up to 26 weeks produced significant reductions from baseline to end-point in BPRS-C and YMRS total scores, respectively. Oral olanzapine was generally well tolerated in adolescents with schizophrenia or bipolar mania. Sedation and weight gain were the most common adverse events in placebo-controlled trials. Extrapyramidal symptoms were reported by 10% of olanzapine recipients compared with 6% of placebo recipients. Olanzapine-treated adolescents were likely to experience greater increases in bodyweight, sedation, blood lipids, serum prolactin and liver transaminase levels than olanzapine-treated adults. Therefore, careful consideration of risk-benefit is recommended before using olanzapine in adolescents.Drugs 01/2010; 64(23). DOI:10.2165/00003495-200464230-00006 · 4.13 Impact Factor