The Pharmaceutical Journal Vol 265 No 7104 p49
July 8, 2000 Letters

St John's wort

More knowledge needed

From Dr D. Wheatley, FRCPsych

SIR,-I write concerning the "Onlooker" feature in a recent issue of The Journal entitled "Tricky wort" (June 17, p896).
I am a practising psychiatrist and have conducted several clinical research studies on St John's wort (hypericum), the subject of the annotation, and a few years ago wrote a review article on the clinical uses of this interesting herbal compound in the treatment of depression.¹ As "Onlooker" remarks, one of its main claims to fame, which dates from antiquity, is as a "healer of wounds". It would seem that this is more than justified by the recent demonstration that hyperforin (a principal constituent of St John's wort) has antibiotic properties against gram-positive infecting organisms of a potency comparable to that of synthetic antibiotics.²
However, my interest is in hypericum's usefulness in psychiatric disorders, particularly depression. One of the main problems facing a psychiatrist in treating depression is the "lag period" of two to four weeks before the therapeutic effect even starts to become established - but side effects occur straight away. It is in the nature of the illness that the patient has given up all hope that treatment can be effective, and side effects are interpreted as the illness becoming worse due to that very treatment. The result? The patient stops the treatment and it is difficult to persuade her or him to resume it. This does not happen with St John's wort, since side effects with this compound are virtually non-existent. Contrary to misinformed belief, it is not a monoamine oxidase inhibitor, but acts in exactly similar manner to synthetic antidepressant drugs as a reuptake inhibitor of serotonin, noradrenaline and dopamine.³ Its effectiveness in mild to moderate depression is not in doubt⁴ as evidenced by well over 50 double-blind clinical trials against both placebo and standard antidepressant drugs. This abundance of authentic clinical research hardly constitutes the designation of being "rather vague", and will be almost certainly confirmed by the current large-scale, US government-sponsored, double-blind trial against placebo and sertraline. Hence hypericum becomes the pragmatic treatment of choice for this type of case and may well provide salvation for the depressed patient who cannot tolerate side effects.
True, it has some drug interactions, but so do most other synthetic compounds, including many selective serotonin reuptake inhibitors and tricyclic antidepressants. That is no reason to stop using them, but simply calls on the doctor to be more discriminating in their prescription.
It would appear that the whole question of drug involvement in the cytochrome P450 enzyme system is far more complex than was originally supposed. At a recent meeting in the US,⁵ it emerged that the same drug can antagonise or stimulate this system, depending on such diverse factors as dose, mode of administration, ethnicity of the individual and whether they may be fast or slow drug metabolisers. Also there are other systems that may be relevant to the problem, which have not as yet been studied. We need to know much more before leaping to definite conclusions. Meanwhile, published clinical evidence coupled with intelligent interpretation of official guidelines, should ensure effective and safe use of St John's wort for its very important medical indications.

David Wheatley
London W1

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