Hamilton scale and MADRS are interchangeable in meta-analyses but can disagree at trial level.

Background And Objective: Major depressive disorder is a multidimensional disease, in which demonstrating the efficacy of treatments is difficult. The Hamilton Rating Scale for Depression (HRSD) and the Montgomery-Asberg Depression Rating Scale (MADRS) cover different domains but are used interchangeably as primary measures of the outcome in trials and-with standardized measures-in meta-analyses. We aimed at understanding (i) whether the choice of the outcome measurement tool can influence the outcome of a trial, and if so, (ii) whether one systematically outperforms the other, and (iii) whether using standardized measures of the effect in meta-analysis is justified.

Methods: Short-term randomized trials in patients with major depressive disorder that used both the scales were systematically searched and the results were collected. To quantify the differences in the results-both in terms of the standardized mean difference (SMD) and odds ratio (OR) for response-and their range, data were analyzed and plotted with the Bland-Altman method.

Results: 161 comparisons from 80 studies were included, involving a total of 18,189 patients. Neither of the two scales appears systematically more sensitive to the treatment effect than the other in terms of SMDs (P-value = 0.06, 95% CI -0.044 to 0.001) or ORs (P-value = 0.15, 95% CI -0.25 to 0.04). However, the variability of differences between the HRSD and MADRS largely depends on the number of patients included in the comparison.

Conclusion: No systematic differences between the two scales were found supporting the use of standardized measures in meta-analyses. However, the same trial may give very different results with either scale, especially in small trials. Further research is needed to understand the causes of this variability.