Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Pharmacol. Mar 9, 2015; 4(1): 17-30
Published online Mar 9, 2015. doi: 10.5497/wjp.v4.i1.17
Levomilnacipran and vortioxetine: Review of new pharmacotherapies for major depressive disorder
Mei T Liu, Megan E Maroney, Evelyn R Hermes-DeSantis
Mei T Liu, Megan E Maroney, Evelyn R Hermes-DeSantis, Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, Rutgers, the State University of New Jersey, Piscataway, NJ 08854, United States
Author contributions: Liu MT, Maroney ME, Hermes-DeSantis ER all contributed to this paper.
Conflict-of-interest: The authors have nothing to declare.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Mei T Liu, PharmD, BCPP, Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, Rutgers, the State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854, United States.
Telephone: +1-848-4456487 Fax: +1-732-4452533
Received: July 9, 2014
Peer-review started: July 9, 2014
First decision: August 14, 2014
Revised: January 6, 2015
Accepted: January 18, 2015
Article in press: January 20, 2015
Published online: March 9, 2015

Major depressive disorder (MDD) is a common psychiatric disorder with an estimated lifetime prevalence rate in the range of 13% to 16% in the United States population. Patients with MDD often have symptoms such as depressed mood, loss of interest or pleasure in usual activities, changes in eating or sleeping patterns, fatigue, difficulty concentrating and thoughts of suicide. Although many pharmacotherapy treatment options are available for MDD, antidepressants can often cause adverse effects that could affect adherence to the medication. Additionally, it is estimated that MDD is unremitting in 15% of patients and 35% can have recurrent episodes. Given the high rate of recurrence and the adverse effects associated with existing medications, new treatment options for depression are needed. Both levomilnacipran and vortioxetine are new antidepressants that were approved by the food and drug administration in 2013 for the treatment of MDD in adults. Levomilnacipran is a serotonin norepinephrine reuptake inhibitor that was effective in several short term studies and sustained efficacy and tolerability was demonstrated in a 48-wk extension study. Vortioxetine is a multi-modal antidepressant and it is thought to work via inhibition of the serotonin (5-HT) transporter, 5-HT3A, 5-HT7 and 5-HT1D antagonist, a 5-HT1B partial agonist, and a 5-HT1A agonist. Vortioxetine was effective in the treatment of MDD in both short-term trials as well as in the prevention of relapse in a 24-36 wk trial. Sustained efficacy and tolerability was demonstrated in several long-term open-label trials. Further studies comparing levomilnacipran and vortioxetine to other currently available antidepressants are needed to establish its place in therapy.

Keywords: Levomilnacipran, Vortioxetine, Adult, Major depressive disorder, Antidepressive agents

Core tip: Levomilnacipran and vortioxetine are the two newest antidepressant medications to join the armamentarium of treatment choices for major depressive disorder. Levomilnacipran, a serotonin norepinephrine reuptake inhibitor, is an enantiomer of the previously approved fibromyalgia agent milnacipran. Vortioxetine is a multimodal antidepressant with a unique mechanism of action, affecting several serotonin receptors as well as inhibiting serotonin reuptake. This review summarizes the clinical trial data as well as pharmacokinetic, dosing and safety concerns with these two new agents.