The discovery and development of vilazodone for the treatment of depression: a novel antidepressant or simply another SSRI?

Introduction: Vilazodone is the newest serotonergic antidepressant to be approved by the FDA for the treatment of major depressive disorder (MDD). Vilazodone is a combined serotonin specific reuptake inhibitor (SSRI) and 5-HT1A receptor partial agonist. It was originally designed based on the premise that negative feedback circuitry mediated through somatodendritic 5-HT1 autoreceptors, limits the acute SSRI-induced enhancements in serotonergic neurotransmission. Therefore, the combination of SSRI with 5-HT1A receptor agonism should temporally enhance the neuroplastic adaptation and subsequently hasten therapeutic efficacy compared to current treatments. Areas covered: This review provides the history and preclinical development of vilazodone, highlighting the available data on its putative mechanism of action, potential clinical profile and possible areas for differentiation. These preclinical hypotheses will be contextualised with an overview of the key findings from the current clinic data on vilazodone. Expert opinion: Preclinical data packages on vilazodone have clearly demonstrated its SSRI activity. In isolated in vitro systems, 5-HT1A receptor agonism has been demonstrated, but the recapitulation of this activity in vivo has been inconclusive. This uncertainty of its in vivo profile has largely translated to the clinical scenario with efficacy and adverse event profiles being similar to that seen with SSRIs in MDD. More in-depth evaluation of the two Phase III studies have also provided some early evidence of differentiation on onset of therapeutic benefit, anxiety measures and improvements in sexual function. Further evaluation of MDD and anxiety patient outcomes is essential to demonstrate if vilazodone is truly a novel therapeutic.