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Many patients ineligible for antidepressant registration trials due to inclusion, exclusion criteria

Inclusion and exclusion criteria commonly used in antidepressant registration trials excludes a significant proportion of patients, suggesting that results from these trials may not seamlessly translate into clinical practice.

To investigate the effects of inclusion and exclusion criteria on study enrollment, Sheldon H. Preskorn, MD, of the University of Kansas School of Medicine-Wichita, and colleagues applied inclusion and exclusion criteria commonly used in antidepressant registration trials to the population treated in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. The STAR*D study cohort was used as a representative for the general population of individuals with major depressive disorder.

Sheldon H. Preskorn

“We chose to use the STAR*D study for our investigation for the following reasons: (1) it was large (n = 4041), (2) it was designed to be more inclusive than usual [antidepressant registration trials] (it enrolled nonpsychotic patients with major depression and did not exclude most comorbid medical conditions or concomitant medications), and (3) data on how inclusion and exclusion criteria affected enrollment were systematically collected,” Preskorn and colleagues wrote.

Researchers reviewed the 10 most recent antidepressant registration trials conducted at their institution between 2010 and 2014 to determine “usual” inclusion and exclusion criteria for antidepressant registration. Inclusion criteria included:

• Study participants aged 18 to 65 years;
• A minimum score of at least 18 on the 17-item Hamilton Depression Rating Scale at baseline;
• Current depressive episode duration of at least 2 months; and
• Use of reliable contraception among female study participants of child-bearing age.

Exclusion criteria included:

• Clinically significant or unstable illness, including hepatic, renal, gastroenterological, respiratory, cardiovascular, endocrine, hematologic, neurological, genitourinary, musculoskeletal, and/or psychiatric condition;
• Use of mood stabilizers, monoamine oxidase inhibitors, antipsychotics, herbal or over-the-counter treatment for mood symptoms;
• Presence of a clinically significant Axis II disorder that majorly impacts the patient’s current psychiatric status; and
• Participants considered to pose an imminent risk to self or others.

When this inclusion and exclusion criteria was applied to the STAR*D study cohort, 82% of study participants would have been excluded from the study because they did not meet at least one of the inclusion or exclusion criteria.

Fourteen percent of study participant were excluded due to the age requirement; 15% were excluded by the Hamilton Depression Rating Scale inclusion criteria; 12% were excluded by the required duration of current depressive episode; 21% of female participants were excluded for lack of appropriate contraception; more than 20% were excluded due to a clinically significant or unstable general medical condition; 3% were excluded for suicidality; 2% were excluded for an Axis II disorder and less than 1% were excluded for use of concomitant medications.

“From a clinical perspective, the data presented here graphically illustrate for prescribers the restricted nature of the population likely to be enrolled in [antidepressant registration trials] relative to the patients whom they treat in day-to-day clinical practice,” the researchers concluded. – by Amanda Oldt

Disclosure: Preskorn has received grants/research support from or has served as a consultant, on the advisory board, or on the speakers bureau for Assurex Health, Cambridge Isotope Laboratories, Cubist/Trius, Eisai, EnViVo, GlaxoSmithKline, Forum, Johnson & Johnson, Merck, Naurex, National Institute of Mental Health, Pfizer, Stanley Medical Research Institute, and Sunovion. Please see the full study for a list of all other authors’ relevant financial disclosures.