New 'multimodal' antidepressant effective in the elderly

The investigational antidepressant vortioxetine has shown promising results in elderly patients.

Depression in the elderly is widespread and undertreated  | SCIENCE PHOTO LIBRARY
Depression in the elderly is widespread and undertreated | SCIENCE PHOTO LIBRARY

Data from a multicentre phase III trial published in International Clinical Psychopharmacology show that the drug reduces symptoms in patients aged 65 years and over with recurrent major depressive disorder.

Dual mechanism of action

Vortioxetine displays two complementary mechanisms of action in vitro: inhibition of serotonin reuptake and modulation of serotonin receptor activity. In addition to blocking the serotonin transporter protein, vortioxetine acts as antagonist at 5-HT3 and 5-HT7 receptors, a partial agonist at 5-HT1B receptors and an agonist at 5-HT1A.

This multimodal activity may be useful in patients with major depressive illness that is unresponsive to traditional SSRI or SNRI antidepressants.

Positive results

The 8-week study enrolled 452 patients, who were randomised to receive daily doses of vortioxetine (5mg), duloxetine (60mg) or placebo. 

Patients who received vortioxetine experienced a significantly greater reduction in HAM-D-24 (24-item Hamilton Depression Rating Scale) score at study end than those given placebo (3.3 points; p=0.0011). They also showed better cognitive function than placebo-treated patients.

Withdrawal rates due to adverse events were higher for vortioxetine than for placebo (5.8% vs 2.8%, respectively), although the difference only reached significance for nausea (21.8% vs 8.3%).

Licence application

In 8 out of 10 phase III studies, vortioxetine reduced depression symptoms to a significantly greater extent than placebo. Lundbeck has announced plans to submit an application in the second half of 2012 to market the drug in the EU.

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