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).
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.
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)
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Mayo Clinic Proceedings
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- Symptomatic volunteers: another patient dimension for clinical trials.J Clin Pharmacol New Drugs. 1973; 13: 89-98
- Solicitations of elderly depressives for treatment outcome research: a comparison of referral sources.J Consult Clin Psychol. 1985; 53: 552-554
- A comparison of patients with major depressive disorder recruited through newspaper advertising versus consultation referrals for clinical drug trials.Psychopharmacol Bull. 1997; 33: 69-73
- A comparison of descriptive variables for clinical patients and symptomatic volunteers with depressive disorders.J Clin Psychopharmacol. 1996; 16: 242-246
- Symptomatic volunteers in multicenter drug trials.Prog Neuropsychopharmacol. 1979; 3: 521-533
- Patients excluded from an antidepressant efficacy trial.J Clin Psychiatry. 1996; 57: 572-575
- How many subjects with major depressive disorder meet eligibility requirements of an antidepressant efficacy trial?.J Clin Psychiatry. 2003; 64: 1091-1093
- Are subjects in pharmacological treatment trials of depression representative of patients in routine clinical practice.Am J Psychiatry. 2002; 159: 469-473
- The generalizability of antidepressant efficacy trials to routine psychiatric out-patient practice.Psychol Med. 2011; 41: 1353-1363
- Can phase III trial results of antidepressant medications be generalized to clinical practice? A STAR∗D report.Am J Psychiatry. 2009; 166: 599-607
- Relevance of exclusion criteria in antidepressant clinical trials: a replication study.J Clin Psychopharmacol. 2007; 27: 295-301
- Exclusion criteria used in antidepressant efficacy trials: consistency across studies and representativeness of samples included.J Nerv Ment Dis. 2004; 192: 87-94
- Does the probability of receiving placebo influence clinical trial outcome? A meta-regression of double-blind, randomized clinical trials in MDD.Eur Neuropsychopharmacol. 2009; 19: 34-40
- Randomized, placebo-controlled trials of antidepressants for acute major depression: thirty-year meta-analytic review.Neuropsychopharmacology. 2012; 37: 851-864
- A rating scale for depression.J Neurol Neurosurg Psychiatry. 1960; 23: 56-62
- A new depression scale designed to be sensitive to change.Br J Psychiatry. 1979; 134: 382-389
- Symptom severity and exclusion from antidepressant efficacy trials.J Clin Psychopharmacol. 2002; 22: 610-614
- Antidepressant drug effects and depression severity: a patient-level meta-analysis.JAMA. 2010; 303: 47-53
- Severity of depression and response to antidepressants and placebo: an analysis of the Food and Drug Administration database.J Clin Psychopharmacol. 2002; 22: 40-45
- Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration.PLoS Med. 2008; 5: e45
- Major depressive disorder and Axis I diagnostic comorbidity.J Clin Psychiatry. 2002; 63: 187-193
- Selective publication of antidepressant trials and its influence on apparent efficacy.N Eng J Med. 2008; 358: 252-260
- Agomelatine efficacy and acceptability revisited: systematic review and meta-analysis of published and unpublished randomised trials.Br J Psychiatry. 2013; 203: 179-187
- Antidepressant efficacy of agomelatine: meta-analysis of published and unpublished studies.BMJ. 2014; 348: g1888
Published online: August 12, 2015
For editorial comment, see page 1171
© 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.
ScienceDirectAccess this article on ScienceDirect
- Hard-Wired Bias: How Even Double-Blind, Randomized Controlled Trials Can Be Skewed From the StartMayo Clinic ProceedingsVol. 90Issue 9
- PreviewWell-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.