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

Research output: Contribution to journalReview article

Original languageEnglish
JournalJournal of Psychopharmacology
Publication statusPublished - 6 Apr 2020

King's Authors


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

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