Have Treatment Studies of Depression Become Even Less Generalizable? Applying the Inclusion and Exclusion Criteria in Placebo-Controlled Antidepressant Efficacy Trials Published over 20 Years to a Clinical Sample

Abstract

Background: Antidepressants are amongst the most frequently prescribed medications. More than a decade ago, our clinical research group applied a prototypic set of inclusion/exclusion criteria used in an antidepressant efficacy trial (AET) to patients presenting for treatment in our outpatient practice and found that most patients would not qualify for the trial. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, we apply the psychiatric inclusion/exclusion criteria used in 158 placebo-controlled studies to a large sample of depressed patients who presented for outpatient treatment to determine the range and extent of the representativeness of samples treated in AETs and whether this has changed over time. Method: We applied the inclusion and exclusion criteria used in 158 AETs to 1,271 patients presenting to an outpatient practice who received a principal diagnosis of major depressive disorder. The patients underwent a thorough diagnostic evaluation. Results: Across all 158 studies, the percentage of patients that would have been excluded ranged from 44.4 to 99.8% (mean = 86.1%). The percentage of patients that would have been excluded was significantly higher in the studies published in 2010 through 2014 compared to the studies published from 1995 to 2009 (91.4 vs. 83.8%, t(156) = 3.74, p < 0.001). Conclusions: Only a minority of depressed patients seen in clinical practice are likely to be eligible for most AETs. The generalizability of AETs has decreased over time. It is unclear how generalizable the results of AETs are to patients treated in real-world clinical practice.