The Validity of the Different Versions of the Hamilton Depression Scale in Separating Remission Rates of Placebo and Antidepressants in Clinical Trials of Major Depression

Abstract

Our objective was to validate the different versions of the Hamilton Depression Scale (HAM-D) both psychometrically (scalability) and clinically in discriminating antidepressants from placebo in terms of remission rates in an 8-week clinical trial in the acute treatment of major depression. The traditional HAM-D17 version was compared with the shorter HAM-D6 and the longer HAM-D21 or HAM-D24 in a fixed-dose placebo-controlled vortioxetine study. Clinical Global Impression of Severity scores were used to establish standardized cutoff scores for remission across each scale. Using these cutoff scores, we compared the ability of each scale to separate drug-placebo remission rates, evaluated by the number needed to treat for clinical evidence. The HAM-D6 was superior to HAM-D17 in separating drug-placebo remission rates at the end point, defined as number needed to treat of less than 10. More items in the longer HAM-D versions indicated smaller discriminating validity over placebo. The HAM-D6 indicated a dose effect on remission for vortioxetine in both moderate and severe major depression. The brief HAM-D6 was thus found superior to HAM-D17, HAM-D21, and HAM-D24 both in terms of scalability and in discriminating antidepressants from placebo.

A Systematic Review of the Clinimetric Properties of the 6-Item Version of the Hamilton Depression Rating Scale (HAM-D₆)

“…Both Ruhe et al [20] and Kyle et al [21] found that a score <5 on the HAM-D 6 or <8 on the HAM-D 17 was obtained using CGI-S as reference for remission. These remission cut-off scores are important when using remission rates as outcome in treatment studies.…”

The Major Depressive Disorder Hierarchy: Rasch Analysis of 6 Items of the Hamilton Depression Scale Covering the Continuum of Depressive Syndrome

“…The Major Depressive Disorder Hierarchy PLOS ONE | DOI:10.1371/journal.pone.0170000 January 23,2017patients. This means that they are able to differentiate both the less and the most severe patients in this setting.…”

“…This subscale has been called the "melancholia subscale", or HAM-D 6 [21], and has demonstrated that it can meet the criteria for unidimensionality. It is also clinically meaningful, more psychometrically robust, and less likely to mistake side effects of drugs for improvement or worsening in depression [22,23]. Furthermore, even when applied in non-melancholic patients, the HAM-D 6 has shown that it can provide larger effect sizes in clinical trials [24] and even a need for fewer study participants to demonstrate superior antidepressant efficacy [25] in comparison to HDRS-17.…”

Do not blame the SSRIs: blame the Hamilton Depression Rating Scale

“…The subscale defined by these six items is now commonly referred to as 'Hamilton-6' (HDRS 6 ) (5). As opposed to the HDRS, the psychometric validity of the HDRS 6 has been confirmed numerous times (8)(9)(10)(11)(12)(13)(14)(15) since its derivation from the HDRS in 1975 (6). Importantly, when using the total score on the HDRS 6 as outcome measure in RCTs of SSRIs (and related antidepressants) versus placebo, the effect sizes are markedly larger than those obtained when using the total score of the HDRS as outcome measure (17)(18)(19)(20).…”

“…In two landmark studies from 1975 (6) and 1981 (7), respectively, Bech et al demonstrated that the original HDRS met none of these two criteria. This lack of psychometric validity of the HDRS has been confirmed in a large number of studies since then (8)(9)(10)(11)(12)(13)(14)(15). Therefore, the total score of the HDRS cannot be considered as a clinically valid measure of the severity of depression (5,16).…”