URSULA WERNEKE responds on behalf of the authors:

We are surprised at this letter suggesting that our meta-analyses may be meaningless. Dr Schmidt justifies this opinion raising issues we have actually addressed in the original article.¹ Our meta-analyses showed that St John’s wort might be less effective in the treatment of depression than previously assumed. In our cumulative analysis, we also identified a trend towards reduced effect size with the increase of sample size. We pointed out that with the reduction of cumulative effect size over time St John’s wort might finally be shown to be ineffective if future trials continued to confirm this trend.

We then explored further explanations for our findings. Where available we looked at the hyperforin contents. However, there is only one trial available comparing different hyperforin concentrations.² We also tried to account for this by exploring the impact of the dose of the extracts in toto in our meta-regression, and found this not to be significant. We then concluded that “future trials should test extracts in which the hyperforin content is maximised”. We also analysed further factors which could influence the outcome of individual trials or meta-analyses. Most trials were conducted in heterogeneous patient populations so that the question of whether St John’s wort was effective in patients with mild depression remained unresolved. We acknowledged that, although St John’s wort may be found to be no more effective than placebo, effect sizes for conventional antidepressants were also surprisingly low.

The suggestion that all trials which did not standardise on hyperforin should be discarded is ill-founded. All currently available St John’s wort preparations are standardised on hypericin, and clinical effectiveness studies are about the “real world” rather than an “ideal world” of a hyperforin enriched extract, which to our knowledge currently is not widely or easily available. It is important to discuss these issues with patients in order to avoid unrealistically high expectation without supporting clinical evidence.

References

1. Werneke U, Horn O, Taylor D. How effective is St John’s wort? The evidence revisited. Journal of Clinical Psychiatry 2004;65:611–7.
2. Laakmann G, Schule C, Baghai T et al. St John’s wort in mild to moderate depression: the relevance of hyperforin for the clinical efficacy. Pharmacopsychiatry 1995;31 (1 Suppl):54–59.