Background: Vortioxetine (VRX) is a multimodal antidepressant that acts as serotonin (5HT)
transporter inhibitor as well as 5HT3A and 5HT7 receptors antagonist, 5HT1A and 5HT1B receptors partial
agonist. It was recently approved in the US and the EU for the treatment of adult patients with Major
Depressive Disorder (MDD).
Objective: The present article aims at systematically reviewing findings of the published and unpublished
research on the pharmacological properties, efficacy, safety and tolerability of oral VRX in the
treatment of MDD.
Method: A systematic review, in accordance with the Cochrane Collaboration and the PRISMA guidelines,
was conducted searching the electronic databases MEDLINE, by combining the following
keyterms: ((vortioxetine OR LU AA21004 OR brintellix) AND (antidepressant OR depression OR major
depressive disorder), without language/time restrictions. Further studies were retrieved from reference
listing of relevant articles or manual search. Preclinical and clinical studies (RCT and open label
trials) were here retrieved.
Results: Several placebo-controlled and active-treatment studies demonstrated the antidepressant efficacy
and tolerability of VRX in adult patients affected with MDD. In addition, VRX seems to own procognitive
activity. VRX seems generally well tolerated, without significant cardiovascular or weight
gain effects. The most common adverse events reported included nausea, vomiting, hyperhidrosis,
headache, dizziness, somnolence, diarrhoea and dry mouth.
Conclusion: Overall, placebo controlled and active treatment trials support that VRX is effective and
well tolerated in MDD. Its combined serotonin reuptake inhibition with agonism, partial agonism and
antagonism of a number of receptors might provide a broader spectrum of antidepressant activity than
currently available agents.