Pharmacology and clinical potential of vortioxetine in the treatment of major depressive disorder

Abstract

Enric Alvarez,1,2 Victor Perez,4,2 Francesc Artigas3,2 1Department of Psychiatry, Hospital de Sant Pau, Universitat Autonoma de Barcelona, Institut de Recerca Biomedica Sant Pau, Barcelona, Spain; 2Ministry of Science and Innovation, CIBERSAM, Madrid, Spain; 3Institut d’Investigacions Biomediques de Barcelona, CSIC, Barcelona, Spain; 4Institut de Neuropsiquiatria I Adiccions, Universitat Autonoma de Barcelona, Hospital del Mar, Barcelona, Spain Abstract: Vortioxetine is a new multimodal action antidepressant with two types of action: serotonin transporter (SERT) blockade and a strong affinity for several serotoninergic receptors. It is an antagonist of the 5-HT3 and 5-HT7 receptors, a partial agonist of 5-HT1B, and an agonist of 5-HT1A. Its combined action on SERT and four subtypes of serotoninergic receptors increases the extracellular concentration of serotonin, dopamine, and noradrenaline. Twelve ­clinical trials have been carried out, nine of which had positive results versus placebo. When active comparators were included in the study design, no significant differences were found except in one study in which the efficacy of vortioxetine was superior to the comparator (agomelatine) in depression resistant to selective serotonin reuptake inhibitors (SSRI)/serotonin–norepinephrine reuptake inhibitors (SNRI) treatment. Tolerability studies indicate that the drug does not cause any important problems on blood tests, vital signs, or on electrocardiography. The lack of weight gain and induction of metabolic syndrome and the lack of significant changes in the QTc are especially important. The incidence rate of sexual dysfunction is low and similar to placebo in various trials. Similarly, cognitive function remains intact with vortioxetine. Keywords: depression, clinical trial, efficacy