The International Journal of Neuropsychopharmacology


Efficacy of antidepressants: a re-analysis and re-interpretation of the Kirsch data

Konstantinos N. Fountoulakisa1 c1 and Hans-Jürgen Möllera2

a1 3rd Department of Psychiatry, School of Medicine, Aristotle University of Thessaloniki, Greece

a2 Department of Psychiatry, Ludwig-Maximilians-University, Munich, Germany


Recently there has been much debate on the true usefulness of antidepressant therapy especially after the publication of a meta-analysis by Kirsch et al. (PLoS Medicine 2008, 5, e45). The aim of the current paper was to recalculate and re-interpret the data of that study. Effect-size and mean-score changes were calculated for each agent separately as well as pooled effect sizes and mean changes on the basis of the data reported by Kirsch et al. The weighted mean improvement was (depending on the method of calculation) 10.04 or 10.16 points on the Hamilton Depression Rating Scale (HAMD) in the drug groups, instead of 9.60, and thus the correct drug–placebo difference is 2.18 or 2.68 instead of 1.80. Kirsch et al. failed to report that that the change in HAMD score was 3.15 or 3.47 points for venlafaxine and 3.12 or 3.22 for paroxetine, which are above the NICE threshold. Still the figures for fluoxetine and nefazodone are low. Thus it seems that the Kirsch et al.'s meta-analysis suffered from important flaws in the calculations; reporting of the results was selective and conclusions unjustified and overemphasized. Overall the results suggest that although a large percentage of the placebo response is due to expectancy this is not true for the active drug and effects are not additive. The drug effect is always present and is unrelated to depression severity, while this is not true for placebo.

(Received May 27 2010)

(Reviewed June 30 2010)

(Revised June 30 2010)

(Accepted July 19 2010)

(Online publication August 27 2010)


c1 Address for correspondence: K. N. Fountoulakis, M.D., 6, Odysseos str (1st Parodos Ampelonon str.), 55535 Pylaia, Thessaloniki, Greece. Tel.: +30 2310 435702 Fax: +30 2310 266570 Email: