Vortioxetine in major depressive disorder: from mechanisms of action to clinical studies. An updated review

Expert Opin Drug Saf. 2022 May;21(5):673-690. doi: 10.1080/14740338.2022.2019705. Epub 2021 Dec 29.

Abstract

Introduction: Vortioxetine is a multimodal-acting antidepressant that provides improvements on cognitive function aside from antidepressants and anxiolytic effects. Vortioxetine has been found to be one of the most effective and best tolerated options for major depressive disorder (MDD) in head-to-head trials.

Areas covered: The present review intends to gather the most relevant and pragmatic data of vortioxetine in MDD, specially focusing on new studies that emerged between 2015 and 2020.

Expert opinion: Vortioxetine is the first antidepressant that has shown improvements both in depression and cognitive symptoms, due to the unique multimodal mechanism of action that combine the 5-HT reuptake inhibition with modulations of other key pre- and post-synaptic 5-HT receptors (agonism of 5-HT1A receptor, partial agonism of 5-HT1B receptor, and antagonism of 5-HT3, 5-HT1D and 5-HT7 receptors). This new mechanism of action can explain the dose-dependent effect and can be responsible for its effects on cognitive functioning and improved tolerability profile. Potential analgesic and anti-inflammatory properties observed in preclinical studies as well as interesting efficacy and tolerability results of clinical studies with specific target groups render it a promising therapeutic option for patients with MDD and concomitant conditions (as menopause symptoms, pain, inflammation, apathy, sleep and/or metabolic abnormalities).

Keywords: Antidepressant; cognition; efficacy; interactions; major depressive disorder; neurotransmission; pharmacology; safety; vortioxetine.

Publication types

  • Review

MeSH terms

  • Antidepressive Agents / adverse effects
  • Depressive Disorder, Major* / drug therapy
  • Female
  • Humans
  • Piperazines / pharmacology
  • Serotonin / therapeutic use
  • Sulfides / pharmacology
  • Sulfides / therapeutic use
  • Vortioxetine / adverse effects

Substances

  • Antidepressive Agents
  • Piperazines
  • Sulfides
  • Serotonin
  • Vortioxetine