title: 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.
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.
authors: Neurosciences Discovery Medicine, Research Triangle Park, NC, USA.
authors: Susan
authors: S
authors: Learned
authors: Ole
authors: O
authors: Graff
authors: Suraja
authors: S
authors: Roychowdhury
authors: Rachel
authors: R
authors: Moate
authors: K Ranga
authors: KR
authors: Krishnan
authors: Graeme
authors: G
authors: Archer
authors: Jack G
authors: JG
authors: Modell
authors: Robert
authors: R
authors: Alexander
authors: Stefano
authors: S
authors: Zamuner
authors: Agnes
authors: A
authors: Lavergne
authors: Gary
authors: G
authors: Evoniuk
authors: Emiliangelo
authors: E
authors: Ratti
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003511:Cyclohexanols / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D014179:Neurotransmitter Uptake Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017374:Paroxetine / Q000627:therapeutic use; D010919:Placebos; D014326:Tropanes / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D000069470:Venlafaxine Hydrochloride
chemical_list: D000928:Antidepressive Agents; D003511:Cyclohexanols; C577569:GSK372475; D014179:Neurotransmitter Uptake Inhibitors; D010919:Placebos; D014326:Tropanes; D017374:Paroxetine; D000069470:Venlafaxine Hydrochloride