title: The discovery and development of vilazodone for the treatment of depression: a novel antidepressant or simply another SSRI?
abstract: BACKGROUND
  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-HT(1A) 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-HT(1A) receptor agonism should temporally enhance the neuroplastic adaptation and subsequently hasten therapeutic efficacy compared to current treatments.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  Preclinical data packages on vilazodone have clearly demonstrated its SSRI activity. In isolated in vitro systems, 5-HT(1A) 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.
authors.affiliation: Neuroscience & General Medicines Product Creation Unit, Eisai, Ltd. , Hatfield, Herts, AL10 9SN , UK +0845 676 5261 ; +020 8600 1401 ; Lee_Dawson@eisai.net.
authors.forename: Lee A
authors.initials: LA
authors.lastname: Dawson
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001572:Benzofurans / Q000494:pharmacology / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy*; D055808:Drug Discovery; D006801:Humans; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D058825:Serotonin 5-HT1 Receptor Agonists / Q000627:therapeutic use*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D000069503:Vilazodone Hydrochloride
chemical_list: D000928:Antidepressive Agents; D001572:Benzofurans; D007211:Indoles; D010879:Piperazines; D058825:Serotonin 5-HT1 Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D000069503:Vilazodone Hydrochloride