PMID- 22048884
OWN - NLM
STAT- MEDLINE
DCOM- 20130121
LR  - 20151119
IS  - 1461-7285 (Electronic)
IS  - 0269-8811 (Linking)
VI  - 26
IP  - 5
DP  - 2012 May
TI  - Efficacy, safety, and tolerability of a triple reuptake inhibitor GSK372475 in 
      the treatment of patients with major depressive disorder: two randomized, 
      placebo- and active-controlled clinical trials.
PG  - 653-62
LID - 10.1177/0269881111424931 [doi]
AB  - GSK372475 is a triple reuptake inhibitor with approximately equipotent inhibition 
      of serotonin, norepinephrine, and dopamine transporters. Two randomized, placebo- 
      and active-controlled, double-blind studies examined the efficacy and safety of 
      GSK372475 in outpatients (aged 18-64 years) with a diagnosis of major depressive 
      episode associated with major depressive disorder (MDD). Patients were randomized 
      1:1:1 to placebo, GSK372475 (1-2 mg/d), or active control (Study 1: venlafaxine 
      XR 150-225 mg/d; Study 2: paroxetine 20-30 mg/d). GSK372475 did not significantly 
      differ from placebo on any of the key efficacy endpoints (six-item Bech scale, 
      IDS-Clinician Rated, MADRS) in either study. Both active controls demonstrated 
      significant antidepressant activity compared with placebo on both primary and 
      secondary endpoints. The most common adverse effects (AEs) with GSK372475 were 
      dry mouth, headache, insomnia, and nausea. AEs were more frequent for GSK372475 
      versus placebo for sleep, anxiety-related, gastrointestinal, and tachycardia 
      events. Increases in mean change from baseline in heart rate and sitting blood 
      pressure were greater for GSK372475 than observed for either placebo or active 
      control groups. Completion rates were lower for GSK372475 (49%, 58%) compared 
      with placebo (67%, 74%), venlafaxine XR (63%), or paroxetine (77%). GSK372475 was 
      neither efficacious nor well tolerated in patients with MDD in two 10-week 
      studies.
FAU - Learned, Susan
AU  - Learned S
AD  - Neurosciences Discovery Medicine, Research Triangle Park, NC, USA.
FAU - Graff, Ole
AU  - Graff O
FAU - Roychowdhury, Suraja
AU  - Roychowdhury S
FAU - Moate, Rachel
AU  - Moate R
FAU - Krishnan, K Ranga
AU  - Krishnan KR
FAU - Archer, Graeme
AU  - Archer G
FAU - Modell, Jack G
AU  - Modell JG
FAU - Alexander, Robert
AU  - Alexander R
FAU - Zamuner, Stefano
AU  - Zamuner S
FAU - Lavergne, Agnes
AU  - Lavergne A
FAU - Evoniuk, Gary
AU  - Evoniuk G
FAU - Ratti, Emiliangelo
AU  - Ratti E
LA  - eng
SI  - ClinicalTrials.gov/NCT00420641
SI  - ClinicalTrials.gov/NCT00448058
PT  - Clinical Trial
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20111102
PL  - United States
TA  - J Psychopharmacol
JT  - Journal of psychopharmacology (Oxford, England)
JID - 8907828
RN  - 0 (Antidepressive Agents)
RN  - 0 (Cyclohexanols)
RN  - 0 (GSK372475)
RN  - 0 (Neurotransmitter Uptake Inhibitors)
RN  - 0 (Placebos)
RN  - 0 (Tropanes)
RN  - 41VRH5220H (Paroxetine)
RN  - 7D7RX5A8MO (Venlafaxine Hydrochloride)
SB  - IM
MH  - Adult
MH  - Antidepressive Agents/adverse effects/pharmacokinetics/*therapeutic use
MH  - Cyclohexanols/therapeutic use
MH  - Depressive Disorder, Major/*drug therapy/metabolism
MH  - Double-Blind Method
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Male
MH  - Neurotransmitter Uptake Inhibitors/adverse effects/pharmacokinetics/*therapeutic 
      use
MH  - Paroxetine/therapeutic use
MH  - Placebos
MH  - Tropanes/adverse effects/pharmacokinetics/therapeutic use
MH  - Venlafaxine Hydrochloride
EDAT- 2011/11/04 06:00
MHDA- 2013/01/23 06:00
CRDT- 2011/11/04 06:00
PHST- 2011/11/04 06:00 [entrez]
PHST- 2011/11/04 06:00 [pubmed]
PHST- 2013/01/23 06:00 [medline]
AID - 0269881111424931 [pii]
AID - 10.1177/0269881111424931 [doi]
PST - ppublish
SO  - J Psychopharmacol. 2012 May;26(5):653-62. doi: 10.1177/0269881111424931. Epub 
      2011 Nov 2.