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).
LIMITATIONS: A limitation of the present analysis is that it was based on 
published placebo-controlled studies of antidepressants.
CONCLUSION: 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.