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.
Author(s): Tohen M, Case M, Trivedi MH, Thase ME, Burke SJ, Durell TM.
Affiliation(s): University of Texas Health Science Center at San Antonio, San Antonio, TX 78229,
USA. tohen@uthscsa.edu
Publication date & source: 2010, J Clin Psychiatry. , 71(4):451-62
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.
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