title: Inclusion/exclusion criteria in placebo-controlled studies of vortioxetine: Comparison to other antidepressants and implications for product labeling.
abstract: BACKGROUND
  We recently conducted a comprehensive review of the psychiatric inclusion/exclusion criteria used in 170 placebo-controlled antidepressant efficacy trials (AETs) published during the past 20 years and found that the criteria of more recent studies were significantly more restrictive than prior studies. Vortioxetine is the most recently approved medication for the treatment of major depressive disorder (MDD). We compared the inclusion/exclusion criteria of the vortioxetine studies to the criteria used in other AETs, and discuss the broader issue of the generalizability of AETs and the implications this might have for the labeling of antidepressants receiving FDA approval.
  
  
  METHODS
  We conducted a comprehensive literature review of placebo-controlled AETs published from January, 1995 through December, 2014. We identified 170 AETs published during this 20 year period and compared the inclusion/exclusion criteria used in the 12 studies of vortioxetine to those used in the nonvortioxetine studies. A second analysis compared vortioxetine to the 3 antidepressants most recently approved prior to vortioxetine (desvenlafaxine, levomilnacipran extended release, vilazodone).
  
  
  RESULTS
  Compared to the nonvortioxetine AETs, the vortioxetine studies significantly more often excluded patients with any comorbid Axis I disorder (p<.001) and more often required the current depressive episode to be longer than the DSM minimum symptom duration requirement of 2 weeks (p<.01). The cutoff on the Montgomery Asberg Depression Rating Scale required for inclusion in the vortioxetine studies was higher than the cutoff used in the other AETs (p<.01).
  
  
  CONCLUSIONS
  A limitation of the present analysis is that it was based on published placebo-controlled studies of antidepressants.
  
  
  CONCLUSIONS
  The inclusion/exclusion criteria in the studies of vortioxetine were more restrictive than the criteria used in other AETs. Inconsistent with FDA guidelines on the labeling of medications, the label of vortioxetine does not include a description of the limits to the group of patients with MDD for whom the medication has been shown to be effective.
authors.affiliation: Department of Psychiatry and Human Behavior, Brown Medical School, Rhode Island Hospital, Providence, RI, United States. Electronic address: mzimmerman@lifespan.org.
authors.forename: Mark
authors.initials: M
authors.lastname: Zimmerman
authors.affiliation: Department of Psychiatry and Human Behavior, Brown Medical School, Rhode Island Hospital, Providence, RI, United States.
authors.forename: Heather L
authors.initials: HL
authors.lastname: Clark
authors.affiliation: Department of Psychiatry and Human Behavior, Brown Medical School, Rhode Island Hospital, Providence, RI, United States.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Multach
authors.affiliation: Department of Psychiatry and Human Behavior, Brown Medical School, Rhode Island Hospital, Providence, RI, United States.
authors.forename: Emily
authors.initials: E
authors.lastname: Walsh
authors.affiliation: Department of Psychiatry and Human Behavior, Brown Medical School, Rhode Island Hospital, Providence, RI, United States.
authors.forename: Lia K
authors.initials: LK
authors.lastname: Rosenstein
authors.affiliation: Department of Psychiatry and Human Behavior, Brown Medical School, Rhode Island Hospital, Providence, RI, United States.
authors.forename: Douglas
authors.initials: D
authors.lastname: Gazarian
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000145:classification / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000379:methods*; D003866:Depressive Disorder / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D018579:Patient Selection; D010879:Piperazines / Q000145:classification / Q000627:therapeutic use*; D011356:Product Labeling / Q000706:statistics & numerical data*; D011569:Psychiatric Status Rating Scales; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D013440:Sulfides / Q000145:classification / Q000627:therapeutic use*; D000078784:Vortioxetine
chemical_list: D000928:Antidepressive Agents; D010879:Piperazines; D013440:Sulfides; D000078784:Vortioxetine
keywords: Antidepressant efficacy trials; Antidepressants; Exclusion criteria; External validity; FDA; Generalizability; Vortioxetine