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Triple reuptake inhibitor GSK372475 fails.

Posted by SLS on November 10, 2011, at 6:42:27

Hi.

I found this extremely disappointing.

I don't know what pre-clinical tests were used to indicate antidepressant activity for this drug. Perhaps these tests ought to be re-appraised.


- Scott


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http://www.ncbi.nlm.nih.gov/pubmed?term=Efficacy%2C%20safety%2C%20and%20tolerability%20of%20a%20triple%20reuptake%20inhibitor%20GSK372475


J Psychopharmacol. 2011 Nov 6. [Epub ahead of print]

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.

Learned S, Graff O, Roychowdhury S, Moate R, Krishnan KR, Archer G, Modell JG, Alexander R, Zamuner S, Evoniuk G, Ratti E.
Source

Neurosciences Discovery Medicine, Research Triangle Park, NC, USA; Neurosciences Discovery Medicine, Verona Italy.
Abstract

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.


Some see things as they are and ask why.
I dream of things that never were and ask why not.

- George Bernard Shaw

 

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poster:SLS thread:1002099
URL: http://www.dr-bob.org/babble/20111110/msgs/1002099.html