A 7-week, randomized, double-blind trial of olanzapine/fluoxetine combination versus lamotrigine in the treatment of bipolar I depression

J Clin Psychiatry. 2006 Jul;67(7):1025-33. doi: 10.4088/jcp.v67n0703.

Abstract

Objective: Determine the efficacy and tolerability of olanzapine/fluoxetine combination (OFC) for treatment of acute bipolar I depression compared with lamotrigine.

Method: The 7-week, acute phase of a randomized, double-blind study compared OFC (6/25, 6/50, 12/25, or 12/50 mg/day; N = 205) with lamotrigine ([LMG] titrated to 200 mg/day; N = 205) in patients with DSM-IV-diagnosed bipolar I disorder, depressed. The study was conducted from November 2003 to August 2004.

Results: Completion rates were similar between treatments (OFC, 66.8% vs. LMG, 65.4%; p = .835). OFC-treated patients had significantly greater improvement than lamotrigine-treated patients in change from baseline across the 7-week treatment period on the Clinical Global Impressions-Severity of Illness scale (primary outcome) (p = .002, effect size = 0.26), Montgomery-Asberg Depression Rating Scale (MADRS) (p = .002, effect size = 0.24), and Young Mania Rating Scale total scores (p = .001, effect size = 0.24). Response rates did not significantly differ between groups when defined as > or = 50% reduction in MADRS score (OFC, 68.8% vs. LMG, 59.7%; p = .073). Time to response was significantly shorter for OFC-treated patients (median days [95% CI] = OFC, 17 [14 to 22] vs. LMG, 23 [21 to 34]; p = .010). There was a significant difference in incidence of "suicidal and self-injurious behavior" adverse events (OFC, 0.5% vs. LMG, 3.4%; p = .037). Somnolence, increased appetite, dry mouth, sedation, weight gain, and tremor occurred more frequently (p < .05) in OFC-treated patients than lamotrigine-treated patients. Weight, total cholesterol, and triglyceride levels were significantly elevated in OFC-treated patients compared with lamotrigine-treated patients (all p < or = .001).

Conclusions: Patients with acute bipolar I depression had statistically significantly greater improvement in depressive and manic symptoms, more treatment-emergent adverse events, greater weight gain, and some elevated metabolic factors with OFC than lamotrigine. Treatment differences were of modest size.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anticonvulsants / adverse effects
  • Anticonvulsants / therapeutic use
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use
  • Benzodiazepines / adverse effects
  • Benzodiazepines / therapeutic use
  • Bipolar Disorder / chemically induced
  • Bipolar Disorder / diagnosis
  • Bipolar Disorder / drug therapy*
  • Bipolar Disorder / psychology
  • Depressive Disorder / diagnosis
  • Depressive Disorder / drug therapy
  • Depressive Disorder / psychology
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Fluoxetine / adverse effects
  • Fluoxetine / therapeutic use*
  • Humans
  • Lamotrigine
  • Male
  • Olanzapine
  • Psychiatric Status Rating Scales / statistics & numerical data
  • Self-Injurious Behavior / chemically induced
  • Serotonin Uptake Inhibitors / adverse effects
  • Serotonin Uptake Inhibitors / therapeutic use
  • Severity of Illness Index
  • Treatment Outcome
  • Triazines / adverse effects
  • Triazines / therapeutic use*

Substances

  • Anticonvulsants
  • Antipsychotic Agents
  • Serotonin Uptake Inhibitors
  • Triazines
  • Fluoxetine
  • Benzodiazepines
  • Olanzapine
  • Lamotrigine