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Some studies did not use placebo controls despite the known very high level of placebo effect in such studies For example Woelk et al (2000) compared the effects of St John s wort and imipramine and reported no discernible difference in their ef cacy; this study caused great impact in the UK when it was published but did not include a placebo group Some studies were said to have used inadequate outcome measures Most comparative studies had compared St John s wort with older rst generation antidepressants rather than with modern SSRIs Barnes (2002a) noted that a Cochrane review of 27 randomised controlled trials of St John s wort extracts in patients with neurotic depression and mild to moderate clinical depression lasting from four to twelve weeks had results consistent with the earlier summary of the consensus from these early trials.

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However, Barnes goes on to say that another meta-analysis conducted around the same time using stricter criteria for inclusion had included only six trials of patients who met formal diagnostic criteria for clinical depression Four had compared St John s wort with a placebo and two with a tricyclic antidepressant Although the overall direction of the ndings were similar in the two meta-analyses, the differences in the number of trials meeting the different inclusion criteria suggest that the quality of many of these early trials was low In 1999, three major well-funded clinical trials of St John s wort were started in the USA, one of them funded by the National Institutes of Health (NIH) (Bunk 1999) The NIH-funded study was conducted by the same research group at Duke University Medical Center that published one of the positive meta-analyses of earlier St John s wort trials (Nangia et al.

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2000) but the conclusions were much less positive The Hypericum Depression Trials Study Group (2002) had three groups each with over 100 patients; one was treated with hypericum, one given a placebo and the third group given sertraline an SSRI antidepressant The rst phase of the trial lasted for eight weeks but patients who responded to initial treatment were offered a further 18 weeks of treatment in order that longer term effects of treatment could be monitored Neither the St John s wort nor the SSRI antidepressant produced statistically signi cant differences to the placebo when outcome was assessed using the Hamilton Depression Scale The SSRI did produce a bigger improvement in the Clinical Global Impression Improvements scale than either St John s wort or the placebo.

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