Relative sensitivity of the Montgomery-Asberg Depression Rating Scale, the Hamilton Depression rating scale and the Clinical Global Impressions rating scale in antidepressant clinical trials.

Abstract

Although early antidepressant clinical trials simply relied on a clinician's judgment as to whether a depressed patient clinically improved or not, the Hamilton Depression (HAM-D) rating scale has become the 'gold standard' to assess the efficacy of new antidepressants. The alternative Montgomery-Asberg Depression Rating Scale (MADRS) has not achieved general acceptance. However, its ease of use warrants evaluation as to whether it is comparable to HAM-D in its sensitivity in detecting antidepressant-placebo differences in antidepressant clinical trials. A retrospective chart review was performed on the records of 208 depressed adult patients that participated in eight randomized, placebo-controlled, double-blind antidepressant clinical trials at the Northwest Clinical Research Center between 1996 and 2000. We compared the effect sizes of the HAM-D, MADRS and Clinical Impressions Rating Scale (CGI-S for severity and CGI-I for improvement) for patients assigned to placebo or an established antidepressant. The effect size (measured as the mean change in rating with antidepressants minus the mean change for placebo divided by the pooled SD of change, adjusted for age, gender and initial scores) was 0.49 with MADRS, 0.53 with HAM-D, 0.55 with CGI-S and 0.59 with CGI-I. The four rating scales had similar effect sizes regardless of the type of antidepressant evaluated. These data suggest that MADRS is as sensitive an instrument as HAM-D for detecting antidepressant efficacy in clinical trials. Thus, MADRS may be a desirable tool in large-scale, pivotal antidepressant clinical trials.