Vortioxetine in major depressive disorder: from mechanisms of action to clinical studies. An updated review
Open accessAbstract
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).
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Vortioxetine works as a 5-HT3, 5-HT7 and 5-HT1D receptor antagonist, a partial 5-HT1B receptor agonist, a 5-HT1A receptor agonist, and a SERT inhibitor.
“Vortioxetine works as a 5-HT3, 5-HT7 and 5-HT1D receptor antagonist, a partial 5-HT1B receptor agonist, a 5-HT1A receptor agonist, and a 5-hydroxytryptamine transporter (SERT) inhibitor, combining the 5-HT reuptake inhibition with modulations of other key 5-HT receptors.42”
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- Authors
- De Diego-Adeliño, J., Crespo, J. M., Mora, F., Neyra, A., Iborra, P., Gutiérrez-Rojas, L., & Salonia, S. F.
- Affiliations
- Department of Psychiatry, Hospital de La Santa Creu I Sant Pau, Institut d’Investigació Biomèdica Sant Pau (Iib-sant Pau), Universitat Autònoma de Barcelona (Uab), Centro de Investigación Biomédica En Red de Salud Mental (Cibersam), Spain
- Complejo Hospitalario Universitario de Ferrol (ES)
- Hospital Universitario Infanta Leonor (ES)
- Hospital Universitario de Gran Canaria Doctor Negrín (ES)
- Hospital Universitari Sant Joan D'Alacant (ES)
- Department of Psychiatry, San Cecilio University Hospital, Granada, Spain
- Department of Psychiatry, CSM Yecla-Jumilla, Spain
- Venue
- Expert Opinion on Drug Safety
- Publisher
- Informa UK Limited
- Published
- 2021-12-29
- Volume
- 21
- Issue
- 5
- Pages
- 673-690
- ISSN
- 1474-0338 (ISSN-L)
- 1744-764X
- OpenAlex
- W4200299146
- Cited by
- 67
- References
- 129
- Citations by year
- 2026: 16 · 2025: 17 · 2024: 19 · 2023: 12 · 2022: 3
- FWCI
- 1.08
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Expert Opinion on Drug Safety (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Dipòsit Digital de Documents de la UAB (Universitat Autònoma de Barcelona) (submittedVersion, cc-by-nc-nd)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- vortioxetine, major depressive disorder, 5-HT1A receptor agonism, 5-HT3 receptor antagonism, cognitive enhancement, antidepressant tolerability, menopausal symptoms, sleep disorders, metabolic abnormalities, apathy
- MeSH terms
- Vortioxetine, Antidepressive Agents, Major Depressive Disorder, Depressive Disorder, Major, Female, Humans, Piperazines, Serotonin, Sulfides
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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