title: Fewer study participants needed to demonstrate superior antidepressant efficacy when using the Hamilton melancholia subscale (HAM-D₆) as outcome measure.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Research Department P, Aarhus University Hospital, Risskov, Denmark; The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus and Copenhagen, Denmark.
authors.forename: Søren Dinesen
authors.initials: SD
authors.lastname: Østergaard
authors.affiliation: Psychiatric Research Unit, Psychiatric Center North Zealand, Copenhagen University Hospital, Hillerød, Denmark. Electronic address: Per.bech@regionh.dk.
authors.forename: Per
authors.initials: P
authors.lastname: Bech
authors.affiliation: Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Kamilla Woznica
authors.initials: KW
authors.lastname: Miskowiak
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D061218:Depressive Disorder, Treatment-Resistant / Q000188:drug therapy* / Q000523:psychology; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D017063:Outcome Assessment, Health Care / Q000379:methods*; D011569:Psychiatric Status Rating Scales; D011594:Psychometrics; D015203:Reproducibility of Results
chemical_list: D000928:Antidepressive Agents; D004921:Erythropoietin
keywords: Depressive disorder; Erythropoeitin; Psychiatric status rating scales; Treatment-resistant