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
J Clin Psychiatry 2010;71(4):451-462
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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
J Clin Psychiatry
Submitted: December 23, 2008; accepted October 19, 2009.
Online ahead of print: February 23, 2010.
Corresponding author: Mauricio Tohen, MD, DrPH, MBA, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229 (firstname.lastname@example.org).