Abstract
Background: Vilazodone is the latest US Food and Drug Administration approved antidepressant agent available in the USA. Its putative mechanism of antidepressant action enhances the release of serotonin across the brain’s serotonergic pathways specifically by inhibiting the serotonin transporter, similar to a selective serotonin reuptake inhibitor (SSRI), and simultaneously stimulating serotonin-1a receptors via partial agonism, similar to the anxiolytic buspirone. This combined activity in the single vilazodone agent has been termed by the authors as being a serotonin partial agonist and reuptake inhibitor or (SPARI).
Methods: A MEDLINE and Internet search was conducted and the resultant preclinical and clinical evidence was reviewed. The authors attempt to review laboratory data, animal model data and human trial data to develop a translational theory on the mechanism of antidepressant action of this agent and also its adverse effect potential.
Results: Randomized, controlled empirical data for vilazodone have gained it approval for treating major depressive disorder. It combines two well known pharmacodynamic mechanisms of serotonergic action into a novel agent. Although no head-to-head studies against other antidepressants have been published, the efficacy data for vilazodone appear comparable to other known antidepressants, with similar gastrointestinal side effects to SSRI or serotonin norepinephrine reuptake inhibitor (SNRI) antidepressants, but possibly with a lower incidence of sexual side effects and weight gain.
Discussion: Vilazodone will lend itself to the current armamentarium in the treatment of major depressive disorder and may hold promise for patients who cannot tolerate other antidepressants. Its unique SPARI mechanism of action could also be efficacious for patients who do not respond to SSRI or SNRI antidepressant monotherapies.