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

  • Konstantinos N. Fountoulakis (a1) and Hans-Jürgen Möller (a2)

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.

Corresponding author
Address for correspondence: K. N. Fountoulakis, M.D., 6, Odysseos str (1st Parodos Ampelonon str.), 55535 Pylaia, Thessaloniki, Greece. Tel.: +30 2310 435702Fax: +30 2310 266570Email:
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The International Journal of Neuropsychopharmacology
  • ISSN: 1461-1457
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