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.