The International Journal of Neuropsychopharmacology

Research Article

A randomized, double-blind, placebo-controlled 6-wk trial of the efficacy and tolerability of 5 mg vortioxetine in adults with major depressive disorder  *

Rakesh Jaina1a2, Atul R. Mahableshwarkara3, Paula L. Jacobsena3, Yinzhong Chena3 and Michael E. Thasea4 c1

a1 R/D Clinical Research Inc., Lake Jackson, TX, USA

a2 University of Texas Medical School at Houston, Houston, TX, USA

a3 Takeda Global Research and Development Center, Deerfield, IL, USA

a4 University of Pennsylvania, Philadelphia, PA, USA


Vortioxetine (Lu AA21004) is a multi-modal antidepressant in clinical development for the treatment of major depressive disorder (MDD). The current study evaluated the efficacy and tolerability of 5 mg vortioxetine compared to placebo after 6 wk of treatment in adults with MDD in an out-patient setting. Adults aged 18–75 yr, with a diagnosis of MDD and a baseline Montgomery–Asberg Depression Rating Scale (MADRS) total score ⩾30, were randomized to receive either 5 mg vortioxetine or placebo over 6 wk, followed by a 2-wk medication-free discontinuation period. The primary efficacy measure was change from baseline in Hamilton Rating Scale for Depression (HAMD)-24 total score at week 6 compared to placebo. Additional measures included response and remission rates, Clinical Global Impression Scale – Improvement scores, HAMD-24 total score in subjects with baseline Hamilton Anxiety Scale (HAMA) >19 and MADRS-S total score. Adverse events (AEs) were assessed throughout the study. A total of 600 adults were randomized. There were no significant differences in efficacy measures between subjects in the 5 mg vortioxetine and placebo groups at week 6. HAMD-24 total score in subjects with baseline HAMA >19 in the 5 mg vortioxetine group was improved at weeks 3–6 compared to the placebo group (nominal p value <0.05). The most common AEs for the vortioxetine and placebo groups were nausea (19.1 and 9.4%), headache (17.1 and 15.1%) and diarrhoea (11.4 and 7.0%), respectively. In this study of adults with MDD, 5 mg vortioxetine did not differ significantly from placebo in reducing depression symptoms after 6 wk of treatment.

(Received February 28 2012)

(xxxMay 10 2012)

(Revised May 31 2012)

(Accepted June 07 2012)

(Online publication September 11 2012)

Key words

  • vortioxetine;
  • multi-modal;
  • randomized clinical trial


c1 Address for correspondence: M. E. Thase, MD, Department of Psychiatry, Mood and Anxiety Disorders Treatment and Research Program, University of Pennsylvania, 3535 Market Street, Suite 670, Philadelphia, PA 19104-3309, USA. Tel.: 215 746 6680 Fax: 215 573 0759 Email:


*  This trial has been registered at #NCT00672958.