La vortioxetine (Brintellix®, 1-[2-(2,4-dimethylphenyl-sulfanyl)-phenyl]-piperazine), un nouvel antidépresseur (AD) multimodal avec un mécanisme d’action innovant, a obtenu l’autorisation de mise sur le marché de la Food and Drug Administration (FDA) et de la European Medicines Agency (EMA) en 2013. La vortioxetine est présentée comme antidépresseur multimodal puisque c’est non seulement un inhibiteur du transporteur de la sérotonine (SERT), mais aussi un antagoniste des récepteurs sérotoninergiques 5-HT_1D, 5-HT₃, 5-HT₇, un agoniste partiel des récepteurs 5-HT_1B et un agoniste des récepteurs 5-HT_1A. Son profil pharmacologique particulier lui permet à la fois de moduler les neurotransmissions sérotoninergiques et noradrenergiques centrales, mais aussi les systèmes histaminergiques, cholinergiques, GABAergiques et glutamatergiques. Ainsi, en plus de son activité antidépressive et anxiolytique, la vortioxetine semble apporter un réel bénéfice cognitif dans différents modèles animaux. La synthèse de ces données démontre que, même si des travaux complémentaires restent à réaliser, notamment dans le domaine de la réponse insuffisante à un 1^er traitement antidépresseur, la vortioxetine représente d’ores et déjà une nouvelle option thérapeutique pour le traitement des épisodes dépressifs majeurs.

Selective Serotonin Reuptake Inhibitors (SSRIs) are extensively used for the treatment of major depressive disorder (MDD). SSRIs are defined as indirect receptor agonists since the activation of postsynaptic receptors is a consequence of an increase in extracellular concentrations of serotonin (5-HT) mediated by the blockade of serotonin transporter. The activation of some serotoninergic receptors (5-HT_1A, post-synaptic, 5-HT_1B post-synaptic, 5-HT_2B, and 5-HT₄), but not all (5-HT_1A, pre-synaptic, 5-HT_1B pre-synaptic, 5-HT_2A, 5-HT_2C, 5-HT₃, and probably 5-HT₆), induces anxiolytic/antidepressive – like effects. Targetting specifically some of them could potentially improve the onset of action and/or efficacy and/or prevent MD relapse. Vortioxetine (Brintellix®, 1- [2-(2,4-dimethylphenyl-sulfanyl)-phenyl]-piperazine) is a novel multi-target antidepressant drug approved by the Food and Drug Administration (FDA) and by European Medicines Agency. Its properties are markedly different from the extensively prescribed SSRIs. Compared to the SSRIs, vortioxetine is defined as a multimodal antidepressant drug since it is not only a serotonin reuptake inhibitor, but also a 5-HT_1D, 5-HT₃, 5-HT₇ receptor antagonist, 5-HT_1B receptor partial agonist and 5-HT_1A receptor agonist. This specific pharmacological profile enables vortioxetine to affect not only the serotoninergic and noradrenergic systems, but also the histaminergic, cholinergic, gamma-butyric acid (GABA) ergic and glutamatergic ones. Thus, vortioxetine not only induces antidepressant-like or anxiolytic-like activity but also improves cognitive parameters in several animal models. Indeed, vortioxetine was shown to improve working memory, episodic memory, cognitive flexibility and spatial memory in young adult rodents and also in old animal models. These specific effects of the vortioxetine are of interest considering that cognitive dysfunction is a common comorbidity to MDD. Altogether, even though this molecule still needs to be investigated further, especially in the insufficient-response to antidepressant drugs, vortioxetine is already an innovative therapeutic option for the treatment of major depression.