Symptom severity and exclusion from antidepressant efficacy trials

Area of Science:

• Psychiatry and Clinical Psychology
• Clinical Trial Design and Generalizability

Background:

• Standard practice in antidepressant efficacy trials (AETs) involves excluding major depressive disorder (MDD) patients with low Hamilton Rating Scale for Depression (HAM-D) scores.
• The impact of varying HAM-D cutoff scores on the generalizability of AETs remains unclear.

Purpose of the Study:

• To determine the proportion of MDD patients in an outpatient setting who would be excluded from AETs due to insufficient symptom severity (low HAM-D scores).
• To assess the impact of diverse HAM-D cutoff scores on patient exclusion rates in AETs.

Main Methods:

• Evaluated 1500 individuals at psychiatric outpatient intake using semistructured interviews.
• Identified 503 patients with a principal diagnosis of nonbipolar, nonpsychotic MDD.
• Reviewed 39 AETs from leading journals, applying their HAM-D inclusion cutoffs to the identified MDD patient sample.

Main Results:

• Exclusion rates varied significantly, with 11.3% to 71.0% of MDD patients failing to meet AET inclusion criteria based on HAM-D scores.
• The two most frequently used HAM-D cutoffs would exclude nearly half of the study's MDD patient sample.
• AETs predominantly recruit MDD patients with moderate to severe symptoms, excluding a considerable number with mild MDD.

Conclusions:

• Current HAM-D score inclusion criteria in AETs lead to the exclusion of a substantial proportion of patients with MDD, particularly those with milder symptom presentations.
• The variability in HAM-D cutoffs significantly influences exclusion rates, raising concerns about the generalizability of findings from AETs to the broader MDD population.