Vortioxetine: a comprehensive update on a new-generation antidepressant

Abstract

The combined mechanisms of action of new-generation antidepressants may provide greater therapeutic benefits (14).New-generation antidepressants were designed with the goal of optimizing treatment efficacy and tolerability. Vortioxetine is one of the new antidepressants with multimodal activity (10). It is the first mixed serotonin agonist and antagonist antidepressant (7). It has been approved for the treatment of MDD in many countries, including European nations (15) and the United States (16). The antidepressant mechanism of action of vortioxetine combines serotonin transporter (5-HTT) inhibition and direct modulation of serotonin receptor activity; it is a 5-HT1A receptor agonist; a 5-HT1B receptor partial agonist; a 5-HT3, 5-HT7, and 5-HT1D receptor antagonist; and a 5-HTT inhibitor (14,17,18). These additional serotonin receptor targets distinguish vortioxetine from other SSRIs and SNRIs, and this activity may provide unique clinical benefits for symptomatic recovery in MDD patients ( 7). Vortioxetine increases the extracellular concentration of various neurotransmitters, such as dopamine, histamine, noradrenaline, and acetylcholine, in addition to providing a regulatory effect on serotonin receptors and 5-HTT (14,18). The serotonin system has a positive effect on mood, affect, and cognition. Vortioxetine also modulates key neurotransmitters involved in cognitive regulation, such as glutamate, acetylcholine, histamine, dopamine, and noradrenaline (17). Dose and PharmacokineticsVortioxetine is available in 5-, 10-, and 20-mg tablets. Vortioxetine was found to be less effective at low doses of 2.5-5 mg, while a dose range of 5-20 mg is effective (17). The maximum dose of 20 mg vortioxetine has demonstrated a better clinical response than lower doses (19)(20)(21)(22). However, the 20-mg dose has also been associated with a higher risk of side effects ( 14). An initial 10-mg dose once a day may be increased to 20 mg according to tolerability and clinical response (14). The pharmacokinetics of vortioxetine are linear and dose-proportional (23). Since the binding rate of vortioxetine to plasma proteins is 80-90%, it has a wide distribution volume (steady-state distribution volume of approximately 2600 L) (14,23). It has been reported that vortioxetine at higher doses (20 mg) was significantly superior to a placebo ( 14). It takes 3-16