It would be misleading to attribute all the innacurate coverage of this paper purely to the media.

The results themselves, and the interpretation given to them by the authors and PLoS editors' summary, set the tone.

It is unfortunate that these results are somewhat less straightforward than they appear because it was a valuable service of Kirsch et al to obtain the details of all these pre-licencing studies, and it remains imperative to secure access to all data of this kind if we are to truly assess the clinical benefits of medical treatments.

In particular, recommendations about the suitability of newer anti-depressants for the APA/NICE categories of 'moderate' and 'severe' depression in this paper are made on the basis of essentially one or two studies and the extrapolation of a regression line, because all other studies included in this analysis were in the 'very severe' range. Rather than make recommendations on such flimsy data it would have been better for Kirsch et al to point out that the FDA did not have strong evidence available at the time of licencing to justify the use of these newer anti-depressants in milder forms of depression.

The use by Kirsch et al of a standardised mean difference (SMD) as the outcome measure for each group (rather than the raw change score) is unusual and the resulting comparison (the drug SMD minus the placebo SMD) is difficult to interpret (in particular with respect to the NICE effect size criterion for 'clinical significance) in comparison to more conventional outcome measures (such as the drug change in HRSD minus the placebo change in HRSD, the more obvious measure for outcome using the same instrument as in this study, or even the SMD of the change, which is more appropriate for studies using different instruments). Carrying out separate regressions for the drug and placebo groups rather than on the overall effect size is also unusual.

Many of the findings in this paper depend on the authors' use of the SMD. In particular their finding that placebo responses decrease while drug responses remain constant with increasing baseline HRSD severity does not hold when the raw HRSD change score is used, in fact the reverse is the case and placebo response remains fairly constant while drug responsiveness increases.

Also, by analysing raw HRSD change scores the NICE criteria for 'clinical significance' are met by paroxetine and venlafaxine, and an overall regression on these scores suggests that the NICE criteria are exceeded at a lower baseline HRSD score than Kirsch et al report.

It is probably also worth noting that Moncrieff & Kirsch have previously noted the arbitrary nature of the NICE 'clinical significance' criteria and that the APA/NICE severity category of 'severe' depression would be considered moderate in clinical practice.