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Meta-Analysis
. 2025 Feb;39(2):92-105.
doi: 10.1177/02698811241309612. Epub 2025 Feb 1.

The efficacy of vortioxetine in the acute treatment of major depressive disorder: A systematic review and meta-analysis

Affiliations
Meta-Analysis

The efficacy of vortioxetine in the acute treatment of major depressive disorder: A systematic review and meta-analysis

Isabella Berardelli et al. J Psychopharmacol. 2025 Feb.

Abstract

Background: Among the available pharmacological treatments for acute major depressive disorder (MDD), vortioxetine, a serotonin transporter inhibitor (SERT), has been widely used for its multimodal action on serotonin neurotransmission, which produces essential changes also on glutamate, gamma amino butyric acid (GABA), norepinephrine, acetylcholine, and dopamine.

Aim: This systematic review and meta-analysis aimed to evaluate the acute efficacy of vortioxetine across multiple dosing and to evaluate whether there is a dose-response effect and as well there is a dose-response issue with respect to side effects in acute depression.

Methods: According to PRISMA guidelines, we systematically searched three major electronic databases (PubMed/MEDLINE, PsycINFO, and Cochrane Central Register of Controlled Trials) for Randomized Controlled Trial (RCT) studies published between January 2013 and April 2024. Twenty-four studies were included in the review and two meta-analyses were conducted to determine whether the mean Montgomery-Asberg Depression Rating Scale (MADRS) scale values in the placebo groups differ significantly from the mean MADRS scale values in the group receiving vortioxetine 10 mg or vortioxetine 20 mg.

Results: Vortioxetine significantly improved acute depression severity, anxiety symptoms, and cognitive function, with high response and remission rates in acute MDD. It was also well tolerated with a relatively low occurrence of severe or serious treatment-emergent adverse events (TEAEs). Observing the results of the meta-analysis, the effect was significant for both vortioxetine 10 and 20 mg, with a greater effect size for vortioxetine 20 mg.

Conclusion: Vortioxetine should be considered efficacious as a first- and second-line therapy.

Keywords: Acute depression; efficacy; meta-analysis; vortioxetine.

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Conflict of interest statement

Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: M Pompili wishes to disclose that in the last 5 years, he has received lectures and advisory board honoraria or has engaged in clinical trial activities with Angelini Pharma, Allergan, Janssen, Lundbeck, Merck Sharp and Dohme, Otsuka, Rovi, Pfizer Inc, Fidia, Viatris, Recordati, Boehringer Ingelheim, Newron, GSK, and Teva, all of which are unrelated to this article. Roger S McIntyre has received research grant support from CIHR/GACD/National Natural Science Foundation of China (NSFC) and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Neurawell, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. Roger S McIntyre is the CEO of Braxia Scientific Corp. I Berardelli disclosed that in the last 5 years, she has received consultant fees and/or lectures or has engaged in clinical trial activities with Angelini Pharma, Janssen Pharmaceuticals, Lundbeck, and Rovi, all unrelated to this article. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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