Olanzapine/fluoxetine combination in patients with treatment-resistant depression: Rapid onset of therapeutic response and its predictive value for subsequent overall response in a pooled analysis of 5 studies

Mauricio Tohen, Michael Case, Madhukar H. Trivedi, Michael E. Thase, Scott J. Burke, Todd M. Durell

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Objective: To characterize response profiles of olanzapine/fluoxetine combination therapy in treatment-resistant depression (TRD) and to investigate predictive relationships of early improvement with olanzapine/fluoxetine combination for subsequent response/remission during the acute phase of treatment. Method: Results were pooled from 5 outpatient studies comparing oral olanzapine/fluoxetine combination, fluoxetine, or olanzapine for a maximum of 8 weeks in patients with TRD who had at least 1 historical antidepressant treatment failure during the current episode and who failed a prospective antidepressant therapy during the study lead-in period. Mean Montgomery-Asberg Depression Rating Scale (MADRS) total and core mood items scores from the 8-week evaluation period were compared across treatment groups. Positive and negative predictive values (PPVs, NPVs) were computed from olanzapine/fluoxetine combination-treated patients demonstrating response and remission based on whether they demonstrated early improvement. Results: Mean olanzapine/fluoxetine combination MADRS score reductions were significantly greater than fluoxetine by week 0.5 and olanzapine by week 1. Significantly more olanzapine/fluoxetine combination patients demonstrated MADRS onset of response compared with fluoxetine and olanzapine patients (P < .001 for both MADRS total and core mood items). In olanzapine/fluoxetine combination patients, 38.1% exhibited MADRS total score response versus 26.9% of fluoxetine patients (P < .001) and 22.2% of olanzapine patients (P < .001). NPVs for MADRS total and core mood items response and remission ranged from 85.7% to 92.1%; PPVs ranged from 29.9% to 45.1%. Conclusions: Olanzapine/fluoxetine combination is superior to fluoxetine and olanzapine in producing early improvement in patients with TRD. The absence of early improvement is highly predictive for overall response failure. Trial Registration: clinicaltrials.gov Identifier: NCT00035321

Original languageEnglish (US)
Pages (from-to)451-462
Number of pages12
JournalJournal of Clinical Psychiatry
Volume71
Issue number4
DOIs
StatePublished - Apr 1 2010

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ASJC Scopus subject areas

  • Psychiatry and Mental health

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