title: Comparing HAMD(17) and HAMD subscales on their ability to differentiate active treatment from placebo in randomized controlled trials.
abstract: BACKGROUND
  The 17-item Hamilton depression rating scale (HAMD(17)) is the standard efficacy outcome in antidepressant clinical trials. It is criticized for multidimensionality and poorly discriminating treatment from placebo. HAMD subscales may overcome these limitations and reduce the sample size of clinical trials. This study compared the discriminative performance of the HAMD(17) and three established HAMD subscales (Bech, Maier-Philipp, Gibbons) across a range of antidepressants with different mechanisms of action.
  
  
  METHODS
  We analyzed data from 24 clinical trials including 3692 patients randomized to tricyclic or tetracyclic antidepressants (TCAs or TeCAs), selective serotonin reuptake inhibitors (SSRIs) or placebo. Data were analyzed using a mixed model for repeated measurements (MMRM). Standardized effect sizes for the HAMD(17) and subscales were derived for every time-point, and their effect on sample size was evaluated.
  
  
  RESULTS
  For TCAs and TeCAs vs. placebo, the HAMD(17) consistently provided the highest standardized effects. The sample size to establish efficacy at week six was >25 percent smaller than for any of the subscales. However, for SSRIs vs. placebo, the HAMD(17) provided slightly smaller standardized effects and was the least efficient outcome. There were no relevant differences between the subscales.
  
  
  CONCLUSIONS
  Data were derived exclusively from mirtazapine trials. Conclusions are restricted to clinical trial settings.
  
  
  CONCLUSIONS
  Comparative performance of the HAMD(17) and various subscales strongly depends on type of antidepressant. Results support using HAMD(17) as primary endpoint in clinical trials, but it will be beneficial to pro-actively include subscales as additional endpoints to successfully establish treatment effects of new antidepressants.
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, PO Box 85500, 3508 GA, Utrecht, The Netherlands. R.Boessen-2@umcutrecht.nl
authors.forename: Ruud
authors.initials: R
authors.lastname: Boessen
authors.forename: Rolf H H
authors.initials: RH
authors.lastname: Groenwold
authors.forename: Mirjam J
authors.initials: MJ
authors.lastname: Knol
authors.forename: Diederick E
authors.initials: DE
authors.lastname: Grobbee
authors.forename: Kit C B
authors.initials: KC
authors.lastname: Roes
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011569:Psychiatric Status Rating Scales; D016032:Randomized Controlled Trials as Topic; D015203:Reproducibility of Results
chemical_list: D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D010919:Placebos