Hamilton and MADRS scales are interchangeable in meta-analyses but can strongly disagree at trial-level

Abstract Introduction Major Depressive Disorder is a multidimensional disease, in which demonstrating the efficacy of treatments is difficult. The Hamilton Depression Rating Scale and the Montgomery-Asberg Depression Scale cover different domains but are used interchangeably as primary measures of outcome in trials and - with standardised measures - in meta-analyses. We aimed at understanding (i) whether the choice of outcome measurement tool can influence the outcome of a trial, and if so, (ii) whether one systematically outperforms the other, and (iii) whether using standardised measures of effect in meta-analysis is justified. Methods Short-term randomised trials in patients with Major Depressive Disorder that employed both scales were systematically searched and results collected. In order to quantify the differences in results – both in terms of Standardised Mean Difference (SMD) and Odds Ratio for response (OR) - and their range, data were analysed and plotted with the Bland-Altman method. Results 161 comparisons from 80 studies were included, involving a total of 18189 patients. Neither of the two scales appears systematically more sensitive to 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, variability of differences between HRSD and MADRS largely depends on the number of subjects included in the comparison. Discussion and Conclusion No systematic differences between the two scales were found supporting the use of standardised 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.