Estimates of the minimal important difference to evaluate the clinical significance of antidepressants in the acute treatment of moderate-to-severe depression.

The efficacy of antidepressants in the acute treatment of moderate-to-severe depression remains a controversial issue. The minimal important difference (MID) is relevant to judge the clinical significance of treatment effects. In this analysis paper, we discuss estimates of the MID for common depression outcome measures.For the Hamilton Depression Rating Scale 17-item Version (HDRS-17), according to both anchor-based and distribution-based approaches, MID estimates range from 3 to 8 points, and the most accurate values are likely between 3 and 5 points. For the 6-item version (HDRS-6), MID estimates range between 2 and 4 points. For both the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Beck Depression Inventory II (BDI-II), MID estimates range between 3 and 9 points, with estimates of 3-6 points likely being the most accurate. Quality of life appears to be more important to patients than core depression symptoms. We thus also evaluated the Short-Form 36 (SF-36) mental component score, a popular mental-health-related quality of life measure. Its MID estimate is likely about 5 points. By contrast, the average treatment effects of antidepressants on the HDRS-17, HDRS-6, MADRS, BDI-II and SF-36 are 2 points, 1.5 points, 3 points, 2 points and 3-5 points, respectively.In conclusion, the efficacy of antidepressants in the acute treatment of moderate-to-severe depression consistently fails to exceed the lower bound of the MID estimates for common depression outcome measures. The clinical significance of antidepressants thus remains uncertain and we call for more research on quality of life measures, which are the patients' most valued outcome domains.