title: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.affiliation: Eli Lilly and Co., Indianapolis. Electronic address: detkehc@lilly.com.
authors.forename: Holland C
authors.initials: HC
authors.lastname: Detke
authors.affiliation: Division of Bipolar Disorders Research, University of Cincinnati College of Medicine, Cincinnati.
authors.forename: Melissa P
authors.initials: MP
authors.lastname: DelBello
authors.affiliation: Eli Lilly Canada Inc., Toronto.
authors.forename: John
authors.initials: J
authors.lastname: Landry
authors.affiliation: Eli Lilly and Co., Indianapolis.
authors.forename: Roland W
authors.initials: RW
authors.lastname: Usher
mesh_terms: D000293:Adolescent; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001569:Benzodiazepines / Q000008:administration & dosage* / Q000009:adverse effects; D001714:Bipolar Disorder / Q000188:drug therapy*; D002648:Child; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D013406:Suicide, Attempted / Q000706:statistics & numerical data*; D016896:Treatment Outcome; D014481:United States
chemical_list: D014150:Antipsychotic Agents; D004338:Drug Combinations; C492572:olanzapine-fluoxetine combination; D005473:Fluoxetine; D001569:Benzodiazepines
keywords: bipolar; depression; olanzapine fluoxetine combination