One (effect) size does not fit at all: Interpreting clinical significance and effect sizes in depression treatment...

The efficacy of antidepressants in major depressive disorder has been continually questioned, mainly on the basis of studies using the sum-score of the Hamilton Depression Rating Scale as a primary outcome parameter. On this measure antidepressants show a standardised mean difference of around 0.3, which some authors suggested is below the cut-off for clinical significance. Prompted by a recent review that, using this argument, concluded antidepressants should not be used for adults with major depressive disorder, we (a) review the evidence in support of the cut-off for clinical significance espoused in that article (a Hamilton Depression Rating Scale standardised mean difference of 0.875); (b) discuss the limitations of average Hamilton Depression Rating Scale sum-score differences between groups as measure of clinical significance; (c) explore alternative measures of clinical importance; and (d) suggest future directions to help overcome disagreements on how to define clinical significance. We conclude that (a) the proposed Hamilton Depression Rating Scale cut-off of 0.875 has no scientific basis and is likely misleading; (b) there is no agreed upon way of delineating clinically significant from clinically insignificant; (c) evidence suggests the Hamilton Depression Rating Scale sum-score underestimates antidepressant efficacy; and (d) future clinical trials should consider including measures directly reflective of functioning and wellbeing, in addition to measures focused on depression psychopathology.