title: The US Food and Drug Administration's perspective on the new antidepressant vortioxetine.
abstract: OBJECTIVE
  This article summarizes the US Food and Drug Administration's (FDA's) review of the New Drug Application for vortioxetine, especially the clinical efficacy and safety data. It emphasizes the issues that were important to the FDA's approval decision, particularly the difference in the effective dose in domestic and foreign studies, and notes several new labeling features, specifically, description of time course of treatment response and detailed sexual dysfunction evaluation.
  
  
  METHODS
  The data sources were the original raw data sets for all clinical trials included in the development program for vortioxetine, as well as the sponsor's original analyses of these data. Data were available from 51 human trials involving vortioxetine, and included a total of 7,666 healthy volunteers and patients with a diagnosis of major depressive disorder (MDD) or generalized anxiety disorder who were exposed to at least 1 dose of vortioxetine for a total of 2,743 patient-years.
  
  
  RESULTS
  Vortioxetine was effective in treating MDD in the United States at a dose of 20 mg/d. The recommended starting dose is 10 mg once daily without regard to food, with increase to 20 mg/d if the 10 mg/d dose is tolerated. For patients who do not tolerate 20 mg/d, 10 mg/d can be used and 5-mg/d dose can be considered. Vortioxetine can be discontinued abruptly, but it is recommended that doses of 15 mg/d or 20 mg/d be reduced to 10 mg/d for 1 week prior to full discontinuation to avoid potential withdrawal symptoms. Although the non-US maintenance study showed that maintenance doses of 5 to 10 mg/d were effective, a clinical judgment needs to be made to decide the maintenance dose in the United States. The applicant has agreed to conduct a US maintenance dose-response study covering the US-approved dose range. Vortioxetine's adverse event profile is similar to that of other selective serotonin reuptake inhibitors (SSRIs). Nausea is the most common adverse event and is dose dependent. No dose adjustment is needed based on age, gender, or the presence of renal or mild to moderate hepatic impairment. The maximum recommended dose is 10 mg/d in known cytochrome P450 2D6 poor metabolizers.
  
  
  CONCLUSIONS
  Vortioxetine is a new treatment for MDD, and its adverse event profile is similar to that of other SSRIs.
authors.affiliation: Division of Psychiatry Products, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave, Silver Spring, MD 20993 jing.zhang@fda.hhs.gov.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Mitchell V
authors.initials: MV
authors.lastname: Mathis
authors.forename: Jenn W
authors.initials: JW
authors.lastname: Sellers
authors.forename: George
authors.initials: G
authors.lastname: Kordzakhia
authors.forename: Andre J
authors.initials: AJ
authors.lastname: Jackson
authors.forename: Antonia
authors.initials: A
authors.lastname: Dow
authors.forename: Peiling
authors.initials: P
authors.lastname: Yang
authors.forename: Linda
authors.initials: L
authors.lastname: Fossom
authors.forename: Hao
authors.initials: H
authors.lastname: Zhu
authors.forename: Hiren
authors.initials: H
authors.lastname: Patel
authors.forename: Ellis F
authors.initials: EF
authors.lastname: Unger
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Temple
mesh_terms: D000328:Adult; D001008:Anxiety Disorders / Q000188:drug therapy; D018849:Controlled Clinical Trials as Topic; D003865:Major Depressive Disorder / Q000188:drug therapy*; D017277:Drug Approval; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D013440:Sulfides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D014481:United States; D014486:United States Food and Drug Administration / Q000592:standards*; D000078784:Vortioxetine
chemical_list: D010879:Piperazines; D017367:Selective Serotonin Reuptake Inhibitors; D013440:Sulfides; D000078784:Vortioxetine