Applying the inclusion/exclusion criteria in placebo-controlled studies to a clinical sample: A comparison of medications

Abstract

BackgroundWe previously compared the inclusion/exclusion criteria in the studies of vortioxetine to other antidepressants and found that they were significantly more restrictive in the vortioxetine studies. In the present study, we tested the hypothesis that the differences in psychiatric inclusion/exclusion criteria used in the studies of some antidepressants resulted in differences in generalizability to clinical samples. MethodsWe applied the inclusion and exclusion criteria used in 161 antidepressant efficacy trials 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. We compared the percentage of patients that would be excluded in studies of different medications. ResultsThe percentage of patients that would have been excluded was significantly higher in the vortioxetine studies than other medications. For the 15 medications that were included in at least 5 trials, we computed the mean percentage of patients that would be excluded. The values ranged from 76.0% (for fluoxetine) to 99.1% (for quetiapine). LimitationsWhile our calculations were based on the exclusion criteria stated in the published articles, we have no way of knowing how these criteria were actually applied. ConclusionStudies of different medications vary in how representative the samples are of patients in clinical practice. The variability in the inclusion/exclusion criteria used to select samples for antidepressant efficacy trials, and the evidence that studies of different medications vary in their generalizability, makes it more difficult to interpret network analyses comparing the relative efficacy of medications.