The apparently positive effects of antidepressants on depression are even smaller than previously thought and “fall far short” of clinical significance, according to a new analysis of the trial data published in Contemporary Clinical Trials. The study was conducted by Irving Kirsch, author of The Emperor’s New Drugs: Exploding the Antidepressant Myth, and MIA Blogger Joanna Moncrieff.
“Meta-analyses indicate that antidepressants are superior to placebos in statistical terms, but the clinical relevance of the differences has not been established,” began Kirsch and Moncrieff in their paper. They noted that antidepressant trials typically found small effect sizes and mere 3-point differences on the Hamilton rating scale for depression (HAM-D). Such tiny impacts, they suggested, may not even be “clinically significant” or meaningful to people.
In their analysis, Kirsch and Moncrieff then compared scores on the HAM-D with scores from the Clinical Global Impressions-Improvement (CGI-I) scale. They determined that “a HAM-D difference of 3 points is undetectable by clinicians using the CGI-I scale.” Conversely, “A difference of 7 points on the HAM-D, or an effect size of 0.875, is required to correspond to a rating of ‘minimal improvement’ on the CGI-I.”
“By these criteria differences between antidepressants and placebo in randomised controlled trials, including trials conducted with people diagnosed with very severe depression, are not detectable by clinicians and fall far short of levels consistent with clinically observable minimal levels of improvement,” concluded Kirsch and Moncrieff. This insight, they argued, should be considered when physicians and patients weigh the risks of antidepressants. “Clinical significance should be considered alongside statistical significance when making decisions about the approval and use of medications like antidepressants.”
Moncrieff, Joanna, and Irving Kirsch. “Empirically Derived Criteria Cast Doubt on the Clinical Significance of Antidepressant-Placebo Differences.” Contemporary Clinical Trials 43 (July 2015): 60–62. doi:10.1016/j.cct.2015.05.005. (Full text)