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
ABSTRACT 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.
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.
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%.
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.
clinicaltrials.gov Identifier: NCT00035321.
SourceAvailable from: Cyril Höschl[Show abstract] [Hide abstract]
ABSTRACT: Current studies suggest that an early improvement of depressive symptoms and the reduction of prefrontal theta cordance value predict the subsequent response to antidepressants. The aim of our study was (1) to compare the predictive abilities of early clinical improvement defined as ≥20 % reduction in Montgomery and Åsberg Depression Rating Scale (MADRS) total score at week 1 and 2, and the decrease of prefrontal theta cordance at week 1 in resistant depressive patients and (2) to assess whether the combination of individual predictors yields more robust predictive power than either predictor alone. Eighty-seven subjects were treated (≥4 weeks) with various antidepressants chosen according to the judgment of attending psychiatrists. Areas under curve (AUC) were calculated to compare predictive effect of defined single predictors (≥20 % reduction in MADRS total score at week 1 and 2, and the decrease of cordance at week 1) and combined prediction models. AUCs of all three predictors were not statistically different (pair-wise comparison). The model combining all predictors yielded an AUC value 0.91 that was significantly higher than AUCs of each individual predictor. The results indicate that the combined predictor model may be a useful and clinically meaningful tool for the prediction of antidepressant response in patients with resistant depression.European Archives of Psychiatry and Clinical Neuroscience 05/2014; 265(1). DOI:10.1007/s00406-014-0506-8 · 3.36 Impact Factor
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ABSTRACT: The effectiveness of prefrontal theta cordance and early reduction of depressive symptoms in the prediction of antidepressant treatment outcome in patients with resistant depression: analysis of naturalistic dataEuropean Archives of Psychiatry and Clinical Neuroscience 01/2014; · 3.36 Impact Factor
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