title: 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: 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.
  
  
  METHODS
  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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00035321.
authors.affiliation: University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA. tohen@uthscsa.edu
authors.forename: Mauricio
authors.initials: M
authors.lastname: Tohen
authors.forename: Michael
authors.initials: M
authors.lastname: Case
authors.forename: Madhukar H
authors.initials: MH
authors.lastname: Trivedi
authors.forename: Michael E
authors.initials: ME
authors.lastname: Thase
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Burke
authors.forename: Todd M
authors.initials: TM
authors.lastname: Durell
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D017277:Drug Approval; D004359:Drug Therapy, Combination; D005260:Female; D005473:Fluoxetine / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D011379:Prognosis; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D005473:Fluoxetine; D000077152:Olanzapine; D017367:Selective Serotonin Reuptake Inhibitors