PMID- 21767441
OWN - NLM
STAT- MEDLINE
DCOM- 20120906
LR  - 20220419
IS  - 1469-5111 (Electronic)
IS  - 1461-1457 (Print)
IS  - 1461-1457 (Linking)
VI  - 15
IP  - 5
DP  - 2012 Jun
TI  - A double-blind, randomized, placebo-controlled, active reference study of Lu 
      AA21004 in patients with major depressive disorder.
PG  - 589-600
LID - 10.1017/S1461145711001027 [doi]
AB  - 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-Asberg 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.
FAU - Alvarez, Enric
AU  - Alvarez E
AD  - Servei de Psiquiatria, Hospital de Sant Pau, Universidat Autonoma de Barcelona, 
      Barcelona, Spain.
FAU - Perez, Victor
AU  - Perez V
FAU - Dragheim, Marianne
AU  - Dragheim M
FAU - Loft, Henrik
AU  - Loft H
FAU - Artigas, Francesc
AU  - Artigas F
LA  - eng
SI  - ClinicalTrials.gov/NCT00839423
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20110718
PL  - England
TA  - Int J Neuropsychopharmacol
JT  - The international journal of neuropsychopharmacology
JID - 9815893
RN  - 0 (Antidepressive Agents, Second-Generation)
RN  - 0 (Cyclohexanols)
RN  - 0 (Piperazines)
RN  - 0 (Placebos)
RN  - 0 (Sulfides)
RN  - 112692-38-3 (Receptor, Serotonin, 5-HT1A)
RN  - 3O2K1S3WQV (Vortioxetine)
RN  - 7D7RX5A8MO (Venlafaxine Hydrochloride)
SB  - IM
MH  - Adult
MH  - Antidepressive Agents, Second-Generation
MH  - Cyclohexanols/*administration & dosage/adverse effects
MH  - Depressive Disorder, Major/*drug therapy
MH  - Diagnostic and Statistical Manual of Mental Disorders
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Piperazines/*administration & dosage/adverse effects
MH  - Placebos
MH  - Psychiatric Status Rating Scales
MH  - Receptor, Serotonin, 5-HT1A/physiology
MH  - Sulfides/*administration & dosage/adverse effects
MH  - Treatment Outcome
MH  - Venlafaxine Hydrochloride
MH  - Vortioxetine
PMC - PMC3349292
EDAT- 2011/07/20 06:00
MHDA- 2012/09/07 06:00
CRDT- 2011/07/20 06:00
PHST- 2011/07/20 06:00 [entrez]
PHST- 2011/07/20 06:00 [pubmed]
PHST- 2012/09/07 06:00 [medline]
AID - S1461145711001027 [pii]
AID - 00102 [pii]
AID - 10.1017/S1461145711001027 [doi]
PST - ppublish
SO  - Int J Neuropsychopharmacol. 2012 Jun;15(5):589-600. doi: 
      10.1017/S1461145711001027. Epub 2011 Jul 18.