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.