title: The Preclinical and Clinical Effects of Vilazodone for the Treatment of Major Depressive Disorder.
abstract: BACKGROUND
  Major depressive disorder (MDD) is the leading cause of disability worldwide, and according to the STAR*D trial, only 33% of patients with MDD responded to initial drug therapy. Augmentation of the leading class of antidepressant treatment, selective serotonin reuptake inhibitors (SSRIs), with the 5-HT1A receptor agonist buspirone has been shown to be effective in treating patients that do not respond to initial SSRI therapy. This suggests that newer treatments may improve the clinical picture of MDD. The US Food and Drug Administration (FDA) approved the antidepressant drug vilazodone (EMD 68843), a novel SSRI and 5-HT1A receptor partial agonist. Vilazodone has a half-life between 20-24 hours, reaches peak plasma concentrations at 3.7-5.3 hours, and is primarily metabolized by the hepatic CYP450 3A4 enzyme system.
  
  
  METHODS
  The authors review the preclinical and clinical profile of vilazodone. The roles of serotonin, the 5-HT1A receptor, and current pharmacotherapy approaches for MDD are briefly reviewed. Next, the preclinical pharmacological, behavioral, and physiological effects of vilazodone are presented, followed by the pharmacokinetic properties and metabolism of vilazodone in humans. Last, a brief summary of the main efficacy, safety, and tolerability outcomes of clinical trials of vilazodone is provided.
  
  
  CONCLUSIONS
  Vilazodone has shown efficacy versus placebo in improving depression symptoms in several double-blind, placebo-controlled trials. The long-term safety and tolerability of vilazodone treatment has also been established. Further studies are needed that directly compare patients treated with an SSRI (both with and without an adjunctive 5-HT1A partial agonist) versus patients treated with vilaozodone.
authors.affiliation: a Department of Psychiatry and Neuroscience Program , Harvard Medical School, McLean Hospital , Belmont , MA , USA.|b School of Medicine , American University of Beirut , Beirut , Lebanon.
authors.forename: Zeyad T
authors.initials: ZT
authors.lastname: Sahli
authors.affiliation: c Forest Research Institute , Jersey City , NJ , USA , an affiliate of Allergan Inc.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Banerjee
authors.affiliation: a Department of Psychiatry and Neuroscience Program , Harvard Medical School, McLean Hospital , Belmont , MA , USA.
authors.forename: Frank I
authors.initials: FI
authors.lastname: Tarazi
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D006801:Humans; D058825:Serotonin 5-HT1 Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000069503:Vilazodone Hydrochloride / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000928:Antidepressive Agents; D058825:Serotonin 5-HT1 Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D000069503:Vilazodone Hydrochloride
keywords: 5-HT1A receptor; clinical trials; generalized anxiety disorder; major depressive disorder; serotonin transporter; sexual dysfunction; vilazodone