To identify the minimal clinically important difference (MCID) for the Montgomery-Asberg Depression Rating Scale (MADRS) in randomised studies of depression, and to cross-validate the estimated MCID.

Placebo-treated patients from three similarly-designed, 8-week, double-blind, randomised depression trials with a stable health status between baseline and Week 1 (‘no change’ rating on the Clinical Global Impression-Improvement scale) were eligible. To calculate the MCID using the distribution-based approach, the standard deviation was estimated using baseline MADRS data while the reliability parameter was measured as the Intraclass Correlation Coefficient (ICC) between baseline and Week 1. For cross-validation, patients from an observational study were matched to identify the ‘MCID change’ (MADRS change from baseline to endpoint score plus the estimated MCID) and ‘control’ groups. Comparisons of clinical and health-related quality of life (HRQoL) measures were performed.

In total, 177 placebo-treated patients were identified. MCID estimates for MADRS ranged from 1.6 to 1.9. A total of 105 matched pairs were identified for the cross-validation analyses. Mean change from baseline in MADRS scores (10.6 +/- 8.5 vs. 12.5 +/- 7.9, p=0.038) and remission rates (71.6% vs. 57.1%, p<0.05) significantly differed between the ‘MCID change’ and ‘control’ groups at endpoint. Numerically higher response rates and greater improvements in HRQoL scores in the ‘MCID change’ group were also found.

These preliminary findings support the value of the estimated MCID for the MADRS and may aid decision makers in evaluating antidepressant treatment effects and improving long-term patient outcomes.