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

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.

• Authors: Eileen B Brown, Susan L McElroy, Paul E Keck Jr, Ahmed Deldar, David H Adams, Mauricio Tohen, Douglas J Williamson
• Journal: The Journal of clinical psychiatry (J Clin Psychiatry) Vol. 67 Issue 7 Pg. 1025-33 (Jul 2006) ISSN: 0160-6689 [Print] United States
• PMID: 16889444 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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