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. Academic Article uri icon

start page

  • 451

end page

  • 462

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.Copyright 2010 Physicians Postgraduate Press, Inc.

date/time value

  • April 2010

Digital Object Identifier (DOI)

  • 10.4088/JCP.08m04984gre

PubMed Identifier

  • 20361905

volume

  • 71

number

  • 4

keywords

  • Adolescent
  • Adult
  • Aged
  • Antipsychotic Agents
  • Benzodiazepines
  • Depressive Disorder
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Approval
  • Drug Therapy, Combination
  • Female
  • Fluoxetine
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Psychiatric Status Rating Scales
  • Randomized Controlled Trials as Topic
  • Serotonin Uptake Inhibitors
  • Severity of Illness Index
  • Treatment Outcome