A randomized, double-blind, placebo-controlled, duloxetine-referenced, fixed-dose study comparing the efficacy and safety of Lu AA21004 in elderly patients with major depressive disorder

Int Clin Psychopharmacol. 2012 Jul;27(4):215-23. doi: 10.1097/YIC.0b013e3283542457.


The efficacy and tolerability of Lu AA21004 at 5 mg/day, a novel multimodal antidepressant, were assessed in elderly patients with recurrent major depressive disorder. Patients were randomly assigned (1:1:1) to Lu AA21004 5 mg/day, duloxetine 60 mg/day (reference) or to placebo in an 8-week double-blind study. The primary efficacy measure was the 24-item Hamilton Depression Scale (HAM-D(24)) total score (analysis of covariance, last observation carried forward). Patients (mean age 70.6 years) had a mean baseline HAM-D(24) score of 29.0. Lu AA21004 showed significantly (P = 0.0011) greater improvement on the primary efficacy endpoint compared with placebo at week 8 (3.3 points). Duloxetine also showed superiority to placebo at week 8, thereby validating the study. HAM-D(24) response (53.2 vs. 35.2%) and HAM-D(17) remission (29.2 vs. 19.3%) rates at endpoint were higher for Lu AA21004 than for placebo. Lu AA21004 showed superiority to placebo in cognition tests of speed of processing, verbal learning and memory. The withdrawal rate due to adverse events was 5.8% (Lu AA21004), 9.9% (duloxetine) and 2.8% (placebo). Whereas nausea was the only adverse event with a significantly higher incidence on treatment with Lu AA21004 (21.8%) compared with placebo (8.3%), the incidence of nausea, constipation, dry mouth, hyperhidrosis and somnolence was higher for duloxetine. In conclusion, Lu AA21004 was efficacious and well tolerated in the treatment of elderly patients with recurrent major depressive disorder.

Trial registration: ClinicalTrials.gov NCT00811252.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antidepressive Agents / adverse effects*
  • Antidepressive Agents / therapeutic use*
  • Cognition Disorders / drug therapy*
  • Depressive Disorder, Major / complications
  • Depressive Disorder, Major / drug therapy*
  • Double-Blind Method
  • Duloxetine Hydrochloride
  • Female
  • Humans
  • Male
  • Piperazines / adverse effects*
  • Piperazines / therapeutic use*
  • Placebos
  • Psychiatric Status Rating Scales / statistics & numerical data
  • Sulfides / adverse effects*
  • Sulfides / therapeutic use*
  • Thiophenes / therapeutic use*
  • Vortioxetine


  • Antidepressive Agents
  • Piperazines
  • Placebos
  • Sulfides
  • Thiophenes
  • Vortioxetine
  • Duloxetine Hydrochloride

Associated data

  • ClinicalTrials.gov/NCT00811252