PsychoTropical Research - Dr Ken Gillman, Serotonin Syndrome, Mirtazapine, Dual Action Drugs. St John's Wort - Efficacy.

PsychoTropicalResearch, serotonin and serotonin syndrome research.

St John's Wort - Efficacy

St John's Wort - Efficacy

Date Created: 30/08/1999   Last Modified: 27/05/2001   Last Checked: 17/04/2004

St John's Wort (traditionally pronounced as 'wurt'), botanical name hypericum perforatum, is widely used as an antidepressant, especially in Germany. Issues concerning its use and effectiveness serve as an excellent paradigm for all the views and arguments concerning 'natural' vs 'medical' treatments.

The presence of so many specific receptor (and ion channel) blockers, especially in plants and invertebrates, is remarkable. It may be best explained by a 'Darwinian' perspective (there is now a journal of Darwinian medicine).

It may be worth recalling the days, not so long ago (around 1970), when the supply of 'digitalis' changed from that made by mixing large patches of foxglove plant extract to modern chemical synthesis. Prior to this student doctors had lots of experience of cardiac arrhythmias because patients often came in with digoxin toxicity after changing from one batch of tablets to another: the differences in potency as a result of the imprecision of biological assays (used to standardise the potency) sometimes resulted in toxicity (or ineffectiveness). Such problems almost vanished after the introduction of synthetic digoxin.

Natural substances derived from plants can only cause effects on the body's workings by their chemical actions; in this sense they are 'drugs' and have the same problems and dangers irrespective of whether they come from 'nature' or are synthetic.

Indeed it seems that 'nature' has contrived more harmful, noxious and poisonous substances than yet achieved by humankind. One botanist has estimated that there are twenty-six poisonous plants in a typical Australian garden. Lucrezia Borgia would be envious!

It is interesting to reflect on the biological achievements of the poppy plant and the extent to which its production of narcotics has effected its distribution through its extra-ordinarily successful manipulation of human behaviour; Darwinian principles in action? Perhaps it is arrogant for us to imagine that we know which plants really are safe to eat; do we actually know what long term effects they might have? (Dietary toxins have been posited as a cause of Parkinson's disease).

And so to St John's Wort. It may well have some small anti-depressant action. It is probably in the same ball-park as moclobemide in terms of efficacy, or lack of if, but with less evidence. It probably has rather more undesirable side effects. I would suggest there is a strong tendency to under-report side effects which is likely to be greater for 'natural' remedies, so it is hard to make comparisons. There are clearly some less common, but quite serious, side effects reported including photosensitivity, cataracts and acute neuropathy.

St John's Wort has been reported recently to produce significant increase in plasma growth hormone and a decrease in plasma prolactin which suggests it may increase brain dopamine function in humans. It also appears to inhibit serotonin and norepinephrine reuptake. A reputable Oxford group have shown significantly increased latency to rapid eye movement (REM) sleep which is consistent with its proposed clinical antidepressant effect.

The existing literature may, I suggest, be viewed skeptically. There are vested interests in this area just as much as there are with established pharmaceuticals. The 'Josey' study (click 'view references' to go to the references screen where you can also see the associated notes / abstract summary) identified four controlled studies appearing to demonstrate that St. John's Wort was as effective as other antidepressant medications and more effective than placebo. The side-effect profile 'appears to be superior to any current U.S.- approved antidepressant medication'.

However most of these studies used methodologies significantly poorer than typical antidepressant drug studies, and many of those leave much to be desired. So I would suggest that 'appearances' may be deceptive.

Much better quality evidence is still required (and this is also the case for many antidepressant drugs). More rigorous trial standards and methodologies are required across the board.

5/2001

In the most recent large trial (JAMA 2001), a randomized, double-blind, placebo-controlled trial in 11 academic centers in the United States involving two hundred adult outpatients, the percentage of patients responsing did not differ from placebo.

The number reaching remission of illness was significantly higher with St John's wort than with placebo (P = 0.02), but extremely low, with St John's wort 14.3% vs placebo 4.9%.