title: Olanzapine augmentation of milnacipran for stage 2 treatment-resistant major depression: an open study.
abstract: OBJECTIVE
  Olanzapine augmentation of fluoxetine, a selective serotonin reuptake inhibitor, is an effective augmentation therapy for treatment-resistant depression (TRD). However, studies of olanzapine augmentation of other antidepressants are few. We investigated the efficacy and safety of olanzapine augmentation of milnacipran, a serotonin-norepinephrine reuptake inhibitor, for TRD.
  
  
  METHODS
  This study covered patients with stage 2 TRD, defined by Thase and Rush. Olanzapine was added to milnacipran, and its dosage was adjusted according to each patient. Previous treatments were continued, but no new treatments were allowed. Response was measured using Hamilton Depression Rating Scale (HAMD) and Clinical Global Impression at weeks 0, 1, 2, 3, 4, and 8.
  
  
  RESULTS
  Eleven patients aged 53.2 ± 24.0 years received olanzapine at 5.0 ± 1.9 mg/day with milnacipran. HAMD and Clinical Global Impression scores improved significantly from baseline to endpoint. This improvement occurred in week 1. At endpoint, seven of 11 (64%) were responders on HAMD (≥ 50% reduction). Four patients (36%) discontinued the trial because of no efficacy. No severe adverse effect occurred.
  
  
  CONCLUSIONS
  Olanzapine augmentation of milnacipran for stage 2 TRD might be effective and well tolerated. However, our study is open label and uncontrolled. Therefore, a double-blind controlled trial is necessary to confirm our results.
authors.affiliation: Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo, Japan. shuboku@med.hokudai.ac.jp
authors.forename: Shuken
authors.initials: S
authors.lastname: Boku
authors.forename: Takeshi
authors.initials: T
authors.lastname: Inoue
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Honma
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Honma
authors.forename: Shin
authors.initials: S
authors.lastname: Nakagawa
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Koyama
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001569:Benzodiazepines / Q000008:administration & dosage*; D003521:Cyclopropanes / Q000008:administration & dosage*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000453:epidemiology / Q000523:psychology*; D061218:Depressive Disorder, Treatment-Resistant / Q000188:drug therapy* / Q000453:epidemiology / Q000523:psychology*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000078764:Milnacipran; D000077152:Olanzapine; D055815:Young Adult
chemical_list: D003521:Cyclopropanes; D001569:Benzodiazepines; D000078764:Milnacipran; D000077152:Olanzapine