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.