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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

      Abstract

      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.

      Patients and 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.

      Conclusion

      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).

      Abbreviations and Acronyms:

      AET (antidepressant efficacy trial), DSM (Diagnostic and Statistical Manual), HAMD (Hamilton Rating Scale for Depression), MADRS (Montgomery-Asberg Depression Rating Scale), MDD (major depressive disorder)
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      Linked Article

      • Hard-Wired Bias: How Even Double-Blind, Randomized Controlled Trials Can Be Skewed From the Start
        Mayo Clinic ProceedingsVol. 90Issue 9
        • Preview
          Well-designed, adequately powered randomized controlled trials (RCTs) are rightfully considered the highest form of evidence on which to base treatment and diagnostic decisions, minimizing potential biases, particularly confounding, that plague nonrandomized evidence.1-3 At the same time, simply using an RCT is not sufficient to ensure that conclusions are free from bias. In recent years, sponsors and trialists have incorporated subtle design choices into RCTs that have skewed the final trial results.
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