Have Treatment Studies of Depression Become Even Less Generalizable? A Review of the Inclusion and Exclusion Criteria Used in Placebo-Controlled Antidepressant Efficacy Trials Published During the Past 20 Years.
OBJECTIVE
To compare the inclusion and exclusion criteria used in antidepressant efficacy trials (AETs) published during the past 5 years with those used in studies published during the previous 15 years.


METHODS
We conducted a comprehensive literature review of placebo-controlled AETs published from January 1995 through December 2014. We included trials whether or not the medication has received regulatory approval for the treatment of depression. We compared the inclusion and exclusion criteria of studies published during the past 5 years (2010-2014) with those of studies published during the previous 15 years (1995-2009).


RESULTS
We identified 170 placebo-controlled AETs published during the past 20 years, 56 of which were published during the past 5 years. The more recent studies were significantly more likely to exclude patients with comorbid Axis I disorders and personality disorders, patients with the episode duration either too long or too short, and patients who had made a suicide attempt in the past. The severity threshold on depression rating scales required for inclusion was higher in the more recent studies.


CONCLUSIONS
The inclusion and exclusion criteria of AETs have become more stringent over the past 5 years, thereby suggesting that AETs may be even less generalizable than they were previously (when concerns about their generalizability had already been raised).
Department of Psychiatry and Human Behavior, Brown University School of Medicine, Rhode Island Hospital, Providence. Electronic address: mzimmerman@lifespan.org.
Mark
M
Zimmerman
Department of Psychiatry and Human Behavior, Brown University School of Medicine, Rhode Island Hospital, Providence.
Heather L
HL
Clark
Department of Psychiatry and Human Behavior, Brown University School of Medicine, Rhode Island Hospital, Providence.
Matthew D
MD
Multach
Department of Psychiatry and Human Behavior, Brown University School of Medicine, Rhode Island Hospital, Providence.
Emily
E
Walsh
Department of Psychiatry and Human Behavior, Brown University School of Medicine, Rhode Island Hospital, Providence.
Lia K
LK
Rosenstein
Department of Psychiatry and Human Behavior, Brown University School of Medicine, Rhode Island Hospital, Providence.
Douglas
D
Gazarian
D002986:Clinical Trials as Topic; D003866:Depressive Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D018579:Patient Selection; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome
D017367:Selective Serotonin Reuptake Inhibitors