IS ST JOHN’S WORT AN EFFECTIVE ANTI-DEPRESSANT?
The only studies of efficacy of St John’s Wort conducted to date have been done in Europe. These studies came to the attention of the US medical community initially when an issue of the Journal of Geriatric Psychiatry and Neurology was devoted to Hypericum in 1994 and later, when the highly regarded British Medical Journal published a meta-analysis of randomized clinical trials of the herbal remedy. In a meta-analysis, several small studies are combined together in order to determine whether certain general conclusions can be derived from the data obtained from them.
In their meta-analysis, Linde and colleagues addressed three simple questions: Is Hypericum more effective than placebo? Is it as effective as standard anti-depressant treatments? And does it have fewer side-effects than standard anti-depressant treatments ? In order to increase their chances of reaching valid conclusions, these researchers included in their meta-analysis only those studies that randomly assigned patients to different treatment conditions, which is generally regarded as a prerequisite for a valid clinical trial. It would not be valid, for example, to assign severely depressed patients one type of treatment and mildly depressed patients another. These researchers also used state-of-the art statistical methods to compare the treatment interventions.
Interestingly, when Linde and colleagues used only conventional computerized searches of the medical literature, they located fewer than a third of those clinical trials that they ultimately chose to include. This reflects the division separating herbal and conventional medicine which has been so prominent until recently and which persists to some extent even at the present time. Almost all studies were published in languages other than English, reflecting the fact that the recent development of herbal medicine has come predominantly from the German-speaking world. Finally, the authors had to go through many revisions before the prestigious mainstream British Medical Journal was willing to publish the review.
Altogether the authors analysed 23 randomized trials involving 1,757 patients suffering from mild to moderate depressions. In 13 trials of Hypericum versus placebo, Linde and colleagues found Hypericum to be clearly superior to placebo, yielding a response rate of 55 per cent as compared with 22 per cent for the control placebo treatment. In three trials of Hypericum versus standard anti-depressants, the two treatments were very similar, possibly favouring Hypericum. But when side-effects were compared, Hypericum emerged as the clear winner, with approximately 20 per cent of the Hypericum group reporting side-effects, as compared with about 53 per cent of those taking standard anti-depressants. Several studies reviewed by the researchers used combinations of St John’s Wort and valerian, an herbal sedative. I have excluded those studies from the present discussion, though their results were consistent with those which used St John’s Wort alone.
Linde and colleagues concluded rather persuasively that Hypericum is superior to placebo in the treatment of mild to moderate depression and that it has a very benign side-effect profile. Evidence is less persuasive when it comes to comparing the relative efficacy of St John’s Wort with other anti-depressants, mostly because adequate studies have not been performed. Studies comparing herbal and synthetic anti-depressants used dosages of the synthetic compounds that were lower than those often used in clinical practice.
Clearly there is room for more research on the efficacy of St John’s Wort, especially into questions of who would best benefit from Hypericum versus conventional anti-depressants, how best to regulate dosage and how to blend Hypericum with conventional anti-depressants. To date, there have been no head-to-head comparisons between St John’s Wort and the SSRIs. Such a comparison is part of the design of the multi-centre US study currently being planned under the aegis of the US National Institute of Mental Health. It is important to compare these two types of anti-depressant, since the SSRIs are the most commonly used anti-depressants at present and, in practice, both doctor and patient may often wish to choose between these and St John’s Wort in deciding how to initiate the treatment of a depression. There have also been no long-term studies of the anti-depressant effects of St John’s Wort but, in this regard, the herbal antidepressant is no different from many of the conventional anti-depressants for which long-term studies are lacking. While these questions have yet to be resolved to the satisfaction of scientists, for the person seeking relief from the painful symptoms of depression they are of much less importance than the fundamental question, ‘Does the herbal anti-depressant work?’ In my view this question has already been answered with a resounding ‘Yes.’
To date there has been only one study that has addressed the question of whether St John’s Wort works for more serious depression. The work of Daniel in the 1930s, mentioned in Chapter
6, suggests that the herbal remedy might be helpful in severe as well as in milder cases. In recent times, Vorbach and colleagues in Germany conducted a multi-centre study of 209 severely depressed patients, of whom 38 were hospitalized at the time of the study. They used a higher dosage of Hypericum than has been used in the studies of mild to moderate depressions (1,800 mg as opposed to 900 mg) and compared this with imipramine, an old standard anti-depressant. While the anti-depressant effects of these two treatments were very similar, far fewer side-effects were reported by those receiving Hypericum than by those receiving imipramine (23 per cent versus 41 per cent). This study suggests that there may indeed be a role for Hypericum in the treatment of severe depression, though more studies in such patients are clearly needed before St John’s Wort can be used with any confidence as a first-line treatment in those suffering from profound depressions.
As I have noted elsewhere, there is one study that suggests that Hypericum may be of value in seasonal affective disorder (SAD), though no one has properly researched how best to combine the herbal remedy with light therapy.
I should mention that most of the research on the St John’s Wort and depression has been conducted with the Kira™ brand of the herb. This preparation is extracted from the leaves and flowers of the plant by a special method and it is unclear whether the research findings with this type of extract can be generalized to other preparations.
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