The efficacy, safety, and tolerability of Lu AA21004 vs. placebo using 
venlafaxine XR as active reference in patients with DSM-IV-TR major depressive 
disorder (MDD) were evaluated. Lu AA21004 is a novel antidepressant that is a 
5-HT3 and 5-HT7 receptor antagonist, 5-HT1A receptor agonist, 5-HT1B receptor 
partial agonist and inhibitor of the 5-HT transporter in recombinant cell lines. 
In this 6-wk, multi-site study, 429 patients were randomly assigned (1:1:1:1) to 
5 or 10 mg Lu AA21004, placebo or 225 mg venlafaxine XR. All patients had a 
baseline Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≥ 30. The 
primary efficacy analysis was based on the MADRS total score adjusting for 
multiplicity using a hierarchical testing procedure starting with the highest 
dose vs. placebo. Lu AA21004 was statistically significantly superior to placebo 
(n=105) in mean change from baseline in MADRS total score at week 6 (p<0.0001, 
last observation carried forward), with a mean treatment difference vs. placebo 
of 5.9 (5 mg, n=108), and 5.7 (10 mg, n=100) points. Venlafaxine XR (n=112) was 
also significantly superior to placebo at week 6 (p<0.0001). In total, 30 
patients withdrew due to adverse events (AEs)--placebo: four (4%); 5 mg Lu 
AA21004: three (3%); 10 mg Lu AA21004: seven (7%); and venlafaxine: 16 (14%). 
The most common AEs were nausea, headache, hyperhidrosis, and dry mouth. No 
clinically relevant changes over time were seen in the clinical laboratory 
results, vital signs, weight, or ECG parameters. In this study, treatment with 5 
mg and 10 mg Lu AA21004 for 6 wk was efficacious and well tolerated in patients 
with MDD.