A review of the clinical efficacy, safety and tolerability of the antidepressants vilazodone, levomilnacipran and vortioxetine

As a leading cause of disability, major depressive disorder (MDD) is characterized by reduced quality of life and altered functioning. Current pharmaceutical treatment options are limited in their success by modest effects and adverse events that often lead to discontinuation. One current trend in antidepressant development is to combine inhibition of the serotonin transporter with other pharmacological targets, including the norepinephrine transporter or different serotonin receptors.In a span of < 3 years, the FDA approved three new antidepressants for the treatment of MDD: vilazodone in January 2011, levomilnacipran in July 2013 and vortioxetine in September 2013. This article reviews the efficacy, safety and tolerability of these three drugs mainly from the Phase III trial data.All three drugs are effective in the treatment of MDD, but data comparing them to other antidepressants is currently lacking. Vilazodone was proposed to produce a more rapid onset and have fewer sexual side effects but neither effect has been conclusively shown. Levomilnacipran appears to be effective in improving functional impairment, including both social and work functioning. Vortioxetine is currently the only drug of the three with proven efficacy in elderly patients. It also appears to have cognitive enhancing properties which are largely independent of improved depressive symptoms. Overall, these drugs represent a promising step forward in antidepressant drug development.