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

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-D-17 version was compared with the shorter HAM-D-6 and the longer HAM-D-21 or HAM-D-24 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-D-6 was superior to HAM-D-17 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-D-6 indicated a dose effect on remission for vortioxetine in both moderate and severe major depression. The brief HAM-D-6 was thus found superior to HAM-D-17, HAM-D-21, and HAM-D-24 both in terms of scalability and in discriminating antidepressants from placebo.