Vortioxetine: First Global Approval

Abstract

Vortioxetine is an orally administered small molecule developed by Lundbeck A/S for the once-daily treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD). Vortioxetine received its first global approval for MDD in the USA in September 2013 and regulatory approval for its use in this indication in the EU (where it has received a positive opinion) and Canada is awaited. The drug is a bis-aryl-sulphanyl amine compound that combines serotonin (5-HT) reuptake inhibition with other characteristics, including receptor activity modulation. In vitro studies indicate that vortioxetine is an inhibitor of the 5-HT transporter and is a 5-HT(1D), 5-HT₃ and 5-HT₇ receptor antagonist, a 5-HT(1A) receptor agonist and a 5-HT(1B) receptor partial agonist. Animal and in vitro studies indicate that several neurotransmitter systems may be impacted by vortioxetine, with the drug enhancing levels of 5-HT, noradrenaline, dopamine, acetylcholine and histamine in certain areas of the brain, as well as modulating γ-aminobutyric acid and glutamate neurotransmission. Phase III trials of vortioxetine in both MDD and GAD have been conducted worldwide. This article summarizes the milestones in the development of vortioxetine leading to this first approval for MDD.

Sexual Dysfunction, Depression and Antidepressants: A Translational Approach

“…Although a statistically significant decrease in libido was reported, no or minimal differences were reported in sexual side effects in pooled data from three randomized, double-blind, placebo-controlled studies in almost 500 depressed adult patients [19][20][21]. Vortioxetine is an SSRI that also exerts agonistic activity at 5-HT 1A and 5-HT 1B receptors and antagonistic activity at 5-HT 3 , 5-HT 7 , and 5-HT 1D receptors [22,23]. Vortioxetine is an efficient antidepressant and has a low sexual side effect profile [21,22].…”

A Sensitive Precolumn Derivatization Method for Determination of Piperazine in Vortioxetine Hydrobromide Using a C8 Column and High-Performance Liquid Chromatography–Mass Spectrometry

“…[2][3][4] VT was jointly developed by the pharmaceutical companies Lundbeck A/S and Takeda Pharmaceutical Company Ltd. to treat major depressive disorders. [5][6][7] Piperazine is used as a starting material in the synthesis of VT and may represent a residual compound in the active pharmaceutical ingredient (API) product.…”

Vortioxetine: a meta-analysis of 12 short-term, randomized, placebo-controlled clinical trials for the treatment of major depressive disorder

“…6,[11][12][13][14] The development of vortioxetine, an antidepressant with a novel mechanism of action, which was approved by the U.S. Food and Drug Administration (FDA) in September 2013 for the treatment of MDD, is timely. 15 Vortioxetine is a selective serotonin reuptake inhibitor (SSRI) that binds to the presynaptic serotonin reuptake site, increasing the level of serotonin (5-HT) in the neuronal synapse and selectively binding to a variety of other serotonin receptors. It selectively binds to and acts as an antagonist of 5-HT 3 , 5-HT 1D , and 5-HT 7 receptors; as a partial agonist to 5-HT 1B receptors; and as an agonist of 5-HT 1A receptors.…”