Fewer Study Participants Needed to Demonstrate Superior Antidepressant Efficacy When Using the Hamilton Melancholia Subscale (HAM-D₆) as Outcome Measure

J Affect Disord. 2016 Jan 15;190:842-845. doi: 10.1016/j.jad.2014.10.047. Epub 2014 Nov 7.

Abstract

Background: In the development of new antidepressant treatments, the failed study has unfortunately become a prevalent problem. The number of failed studies could probably be reduced significantly by applying more informative outcome measures. Previous studies have indicated that the 6-item melancholia subscale (HAM-D6) of the 17-item Hamilton Depression Rating Scale (HAM-D17) may be more informative than other scales, due to its superior psychometric properties. In the present study we investigated whether the HAM-D6 had higher informativeness than the HAM-D17 based on data from a randomized placebo-controlled trial (RCT) testing the effect of erythropoietin (EPO) as augmentation therapy in patients with treatment-resistant depression.

Methods: We assessed the scalability (Mokken analysis of unidimensionality), responsiveness (item responsiveness analysis) and ability to show drug-placebo separation (estimation of sample size needed to detect statistically significant difference between EPO and placebo) of the HAM-D6 and the HAM-D17.

Results: The HAM-D6 demonstrated higher scalability, higher responsiveness, and better drug-placebo separation compared to the HAM-D17. As a consequence, only 39 participants per group would be required to detect a statistically significant difference between EPO and placebo when using the HAM-D6 as outcome measure, whereas the required group size for HAM-D17 would be 146 participants.

Limitations: The EPO RCT was not originally designed to investigate the research questions addressed in this study.

Conclusions: Both for ethical and financial reasons it is of interest to minimize the number of participants in clinical trials. Therefore, we suggest employing the HAM-D6 as outcome measure in clinical trials of depression.

Keywords: Depressive disorder; Erythropoeitin; Psychiatric status rating scales; Treatment-resistant.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Antidepressive Agents / therapeutic use*
  • Depressive Disorder, Treatment-Resistant / drug therapy*
  • Depressive Disorder, Treatment-Resistant / psychology
  • Erythropoietin / therapeutic use*
  • Female
  • Humans
  • Male
  • Outcome Assessment, Health Care / methods*
  • Psychiatric Status Rating Scales*
  • Psychometrics
  • Reproducibility of Results

Substances

  • Antidepressive Agents
  • Erythropoietin