Positive Results Reported for Vortioxetine (Brintellix) in Adult Patients With Major Depression
Drug significantly more effective than comparator, agomelatine (Apr. 8)
Positive results have been reported from a European study of vortioxetine (Brintellix, Lundbeck) versus agomelatine in adults with major depression (MDD) who changed antidepressant treatment after an inadequate response to selective serotonin reuptake inhibitor (SSRI) or serotonin–norepinephrine reuptake inhibitor (SNRI) therapy.
The objective of this double-blind, randomized study was to compare the efficacy and tolerability of flexible-dose treatment with vortioxetine versus agomelatine in patients with MDD. Agomelatine was chosen as the comparator because of its different mode of action from that of conventional SSRI/SNRI drugs.
In the REVIVE trial, the primary efficacy endpoint was the change from baseline to week 8 in the Montgomery–Åsberg Depression Rating Scale (MADRS) total score. Secondary endpoints included assessments of anxiety symptoms (Hamilton Anxiety Scale [HAM-A]); global clinical judgment (Clinical Global Impressions Scale–Severity [CGI-S] and Clinical Global Impressions Scale–Improvement [CGI-I]); and overall functioning (Sheehan Disability Scale [SDS]). Patients were randomly assigned to receive vortioxetine (10 to 20 mg/day) or agomelatine (25 to 50 mg/day) for 12 weeks.
On the primary efficacy endpoint, vortioxetine (n = 252) was significantly superior to agomelatine (n = 241) by 2.2 MADRS points (P < 0.05). Significant differences in favor of vortioxetine were also found for MADRS, HAM-A, CGI-S, CGI-I, and SDS from week 4 onwards (P < 0.05).
Vortioxetine was well tolerated, with fewer patients withrawing from the vortioxetine group (5.9%) versus the agomelatine group (9.5%). Nausea was more common in vortioxetine-treated patients than in those given agomelatine (16% vs. 9%, respectively).
Vortioxetine is under investigation as a multimodal antidepressant that is thought to work through a combination of two complementary mechanisms of action: receptor activity modulation and reuptake inhibition. In vitro studies demonstrated that vortioxetine is a 5-HT3,5-HT7, and 5-HT1D receptor antagonist; a 5-HT1B receptor partial agonist; a 5-HT1A receptor agonist; and a serotonin transporter (SERT) inhibitor. In addition, in vivo nonclinical studies have shown that vortioxetine modulates neuronal firing and neurotransmitter release in multiple systems, resulting in enhanced levels of serotonin, noradrenaline, dopamine, acetylcholine, and histamine in specific areas of the brain.
The multimodal activity profile of vortioxetine differs from the activity profiles of currently available antidepressant drugs.
In 2012, vortioxetine (formerly known as Lu AA21004) was filed for regulatory approval for the treatment of MDD in the U.S.
Source: Lundbeck; April 8, 2013.