Randomized clinical trials underestimate the efficacy of antidepressants in less severe depression

Isacsson G, Adler M. Randomized clinical trials underestimate the efficacy of antidepressants in less severe depression. Objective: Demonstrating the superiority of antidepressants over placebo in randomized clinical trials of antidepressants (RCT-ADs) has been difficult. A recent meta-analysis of six RCT-ADs concluded that the efficacy of antidepressants was non-existent to negligible in mild and moderate depression. The aim of this study was to reanalyze the same data in order to investigate whether the meta-analysis could be biased from the shortcomings of the rating scale used, the Hamilton Depression Rating Scale (HDRS). Method: We got access to the primary data on item and individual level from five of the six meta-analyzed RCT-ADs (597 individuals). We reanalyzed these data by means of item response theory. Results: Each study showed rapidly decreasing reliability of measurement with diminishing depression; 38% of the combined sample at endpoint was measured with less than half the maximal reliability. Conclusion: The HDRS Scale provides unreliable primary data. Low effect sizes can be expected because of the scales low precision and low sensitivity to change, particularly in mild and moderate depression. The conclusion of the meta-analysis by Fournier et al. is therefore unfounded. The clinical value of antidepressants cannot be evaluated from unreliable data. It is urgent that better measurement techniques for depression severity are developed.