A randomized, double-blind comparison of olanzapine/fluoxetine combination, olanzapine, and fluoxetine in treatment-resistant major depressive disorder.

Abstract

OBJECTIVE:

Two parallel, 8-week double-blind studies compared olanzapine/fluoxetine combination, olanzapine, and fluoxetine in outpatients with treatment-resistant depression (TRD).

METHOD:

Treatment-resistant depression was defined as a documented history of current-episode antidepressant failure plus a prospective failure on fluoxetine. Following an 8-week fluoxetine lead-in, 605 nonresponders with DSM-IV major depressive disorder were randomly assigned to olanzapine/fluoxetine combination, olanzapine, or fluoxetine. The primary outcome measure was baseline-to-endpoint mean change on the Montgomery-Asberg Depression Rating Scale (MADRS). The study was conducted from April 2002 to May 2005.

RESULTS:

After 8 weeks of double-blind treatment, Study 1 revealed no statistically significant therapy differences in MADRS mean change (olanzapine/fluoxetine combination: -11.0, fluoxetine: -9.4, olanzapine: -10.5). In Study 2, olanzapine/fluoxetine combination demonstrated significantly greater MADRS improvement (-14.5) than fluoxetine (-8.6, p < .001) and olanzapine (-7.0, p < .001). Pooled study results revealed significant differences for olanzapine/ fluoxetine combination (-12.7) versus fluoxetine (-9.0, p < .001) and olanzapine (-8.8, p < .001). Pooled remission rates were 27% for olanzapine/ fluoxetine combination, 17% for fluoxetine, and 15% for olanzapine. Adverse events were consistent with previous studies. Cholesterol mean change (mg/dL) was +15.1 for olanzapine/ fluoxetine combination, +0.8 for fluoxetine, and +2.7 for olanzapine. Mean weight change (kg) was +4.9 for olanzapine/fluoxetine combination, +0.4 for fluoxetine, and +5.5 for olanzapine. Nonfasting glucose mean change (mg/dL) was +11.4 for olanzapine/fluoxetine combination, +4.9 for fluoxetine, and +9.9 for olanzapine.

CONCLUSION:

Patients with TRD (defined as treatment failure on 2 antidepressants) taking olanzapine/fluoxetine combination demonstrated significantly greater improvement in depressive symptoms than patients taking olanzapine or fluoxetine in 1 of 2 studies and in the pooled analysis. When considered within the context of all available evidence, olanzapine/fluoxetine combination is an efficacious therapy for patients with TRD.

CLINICAL TRIALS REGISTRATION:

ClinicalTrials.gov identifier: NCT00035321.

• Authors: Michael E Thase, Sara A Corya, Olawale Osuntokun, Michael Case, David B Henley, Todd M Sanger, Susan B Watson, Sanjay Dubé
• Journal: The Journal of clinical psychiatry (J Clin Psychiatry) Vol. 68 Issue 2 Pg. 224-36 (Feb 2007) ISSN: 1555-2101 [Electronic] United States
• PMID: 17335320 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antipsychotic Agents
• Serotonin Uptake Inhibitors
• Fluoxetine
• Benzodiazepines
• Olanzapine

Topics

• Adolescent
• Adult
• Aged
• Antipsychotic Agents (administration & dosage, adverse effects, therapeutic use)
• Benzodiazepines (administration & dosage, adverse effects, therapeutic use)
• Depressive Disorder, Major (drug therapy)
• Double-Blind Method
• Drug Resistance
• Drug Therapy, Combination
• Female
• Fluoxetine (administration & dosage, adverse effects, therapeutic use)
• Humans
• Male
• Middle Aged
• Olanzapine
• Selective Serotonin Reuptake Inhibitors (administration & dosage, adverse effects, therapeutic use)
• Treatment Failure