Efficacy and safety of vortioxetine (Lu AA21004), 15 and 20 mg/day: a randomized, double-blind, placebo-controlled, duloxetine-referenced study in the acute treatment of adult patients with major depressive disorder

Boulenger, Jean-Philippea; Loft, Henrikb; Olsen, Christina Kurreb

International Clinical Psychopharmacology: May 2014 - Volume 29 - Issue 3 - p 138–149
doi: 10.1097/YIC.0000000000000018
Original Articles

This study assessed the efficacy, tolerability and safety of vortioxetine versus placebo in adults with recurrent major depressive disorder. This double-blind, randomized, placebo-controlled study included 608 patients [Montgomery–Åsberg Depression Rating Scale (MADRS) total score≥26 and Clinical Global Impression – Severity score≥4]. Patients were randomly assigned (1 : 1 : 1 : 1) to vortioxetine 15 mg/day, vortioxetine 20 mg/day, duloxetine 60 mg/day or placebo. The primary efficacy endpoint was change from baseline in MADRS total score at week 8 (mixed model for repeated measurements). Key secondary endpoints were: MADRS responders; Clinical Global Impression – Improvement scale score; MADRS total score in patients with baseline Hamilton Anxiety Rating Scale ≥20; remission (MADRS≤10); and Sheehan Disability Scale total score at week 8. On the primary efficacy endpoint, both vortioxetine doses were statistically significantly superior to placebo, with a mean difference to placebo (n=158) of −5.5 (vortioxetine 15 mg, P<0.0001, n=149) and −7.1 MADRS points (vortioxetine 20 mg, P<0.0001, n=151). Duloxetine (n=146) separated from placebo, thus validating the study. In all key secondary analyses, both vortioxetine doses were statistically significantly superior to placebo. Vortioxetine treatment was well tolerated; common adverse events (incidence≥5%) were nausea, headache, diarrhea, dry mouth and dizziness. No clinically relevant changes were seen in clinical safety laboratory values, weight, ECG or vital signs parameters. Vortioxetine was efficacious and well tolerated in the treatment of patients with major depressive disorder.

aUniversity Department of Adult Psychiatry, CHU de Montpellier, Montpellier, France

bH. Lundbeck A/S, Copenhagen, Denmark

Trial Registration: This study has the ClinicalTrials.gov identifier NCT01140906.

Correspondence to Jean-Philippe Boulenger, MD, University Department of Adult Psychiatry, Hôpital La Colombiere, CHRU de Montpellier, 39 Avenue Charles Flahault, F-34295 Montpellier Cedex 5, France Tel: +33 4673 39753; fax: +33 4673 39660; e-mail: jp-boulenger@chu-montpellier.fr

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/3.0.

Received July 10, 2013

Accepted October 17, 2013

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins