Olanzapine/Fluoxetine combination in children and adolescents with bipolar I depression: a randomized, double-blind, placebo-controlled trial.

Abstract

OBJECTIVE:

To assess the efficacy and safety of olanzapine/fluoxetine combination (OFC) for the acute treatment of bipolar depression in children and adolescents.

METHOD:

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.

RESULTS:

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.

CONCLUSION:

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.

• Authors: Holland C Detke, Melissa P DelBello, John Landry, Roland W Usher
• Journal: Journal of the American Academy of Child and Adolescent Psychiatry (J Am Acad Child Adolesc Psychiatry) Vol. 54 Issue 3 Pg. 217-24 (Mar 2015) ISSN: 1527-5418 [Electronic] United States
• PMID: 25721187 (Publication Type: Clinical Trial, Phase IV, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 American Academy of Child & Adolescent Psychaitry. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antipsychotic Agents
• Drug Combinations
• olanzapine-fluoxetine combination
• Fluoxetine
• Benzodiazepines

Topics

• Adolescent
• Antipsychotic Agents (administration & dosage, adverse effects)
• Benzodiazepines (administration & dosage, adverse effects)
• Bipolar Disorder (drug therapy)
• Child
• Double-Blind Method
• Drug Combinations
• Female
• Fluoxetine (administration & dosage, adverse effects)
• Humans
• Male
• Psychiatric Status Rating Scales
• Severity of Illness Index
• Suicide, Attempted (statistics & numerical data)
• Treatment Outcome
• United States