St John's wort for depression

“The herbal remedy St John’s wort can be as good at lifting depression as drugs like Prozac,” the Daily Express reported. It said that scientists had pooled data from 29 studies that compared the effect of the plant Hypericum perforatum to placebos and anti-depressants in treating people with depression. The_ Daily Mail_ said this was the most thorough study of the plant yet, and found it not only to be just as effective as Prozac, but to also have fewer side effects. However, cautions are made that some St John’s wort products are more effective than others.

This systematic review and meta-analysis is the most reliable evidence of the effects of St. John’s wort for major depression to date. The findings – that it is more effective than placebo and the same as standard antidepressants (albeit safer) - apply mainly to people with mild to moderate depression. The authors say that for severe major depression, the evidence is ‘still insufficient to draw conclusions’. Given the various preparations of St. John’s wort that are available over the counter, and the potentially serious interactions that can occur with other commonly used medications, people who want to take this drug should speak to their doctors.

Where did the story come from?

Doctors Linde, Berner and Kriston carried out this secondary research of studies into the effects of St John’s wort. The authors declare that they did not receive external support for this work. The study was published in the Cochrane Database of Systematic Reviews, a publication of the Cochrane Collaboration.

What kind of scientific study was this?

This was a systematic review of double-blind randomised controlled trials that investigated St. John’s wort (Hypericum perforatum ) in the treatment of major depression.

The researchers used a variety of methods to find as the largest possible amount of double-blind, randomised controlled studies on the use of St John’s wort for major depression. This involved searching publicly available databases of research, hand searching the bibliographies from these, and directly contacting the manufacturers of St John’s wort and the researchers involved. No language restrictions were applied to their search for studies.

From this pool of studies, the researchers included trials that compared the effects of St John’s wort with placebo or with standard antidepressants in people with major depression aged over 16 years. They were particularly interested in the effects St John’s wort had on the symptoms of depression, the number of people who responded to its use, and its safety. From these trials, two independent researchers collected data on age, gender, depression episodes, depression scores at the beginning of the trial, number of participants, number of dropouts, reasons for dropout and adverse effects.

The researchers found that some studies categorised people to be ‘responders’ based on improvements in their depression scores at the end of their treatment. Other studies used the average depression scores before and after treatment. A statistical technique called meta-analysis was then carried out, which took these differences into account. Safety data were also assessed in this way by combining the odds of an adverse event with treatment across trials.

What were the results of the study?

The researchers found 29 studies with 5,489 participants that met their inclusion criteria. Of these, 18 studies compared St. John’s wort with placebo and 17 compared St. John’s wort with standard antidepressants. The majority of the studies (19 of them) described their participants as having mild to moderate depression, with nine describing participants as having moderate to severe depression (one didn’t report severity). The studies were conducted in a variety of countries across the world. The researchers report that most of the studies were ‘of high quality’.

Compared with placebo, people taking St. John’s wort were 28% more likely to ‘respond’ to treatment. This analysis included the highest quality studies. There were no significant differences in depression response rates between St. John’s wort and standard antidepressants (SSRIs or tricyclics). Patients taking St. John’s wort were less likely to drop out of trials due to adverse effects than those taking standard antidepressants.

What interpretations did the researchers draw from these results?

The researchers conclude that the preparations of St. John’s wort tested in these studies are superior to placebo and as effective as standard antidepressants in people with major depression. They also have fewer side effects than standard antidepressants. The researchers conclude that treating mild to moderate major depression with St. John’s wort (of the type used in the studies) is justified, while the evidence for severe major depression is ‘still insufficient to draw conclusions’.

What does the NHS Knowledge Service make of this study?

This comprehensive, well-conducted systematic review and meta-analysis provides the best evidence to date of the effects of St. John’s wort in people with mild to moderate major depression and moderate to severe major depression.

The researchers say that although the review was limited to major depression and did not look at atypical depression, major depression is not the only or best indication for its use. They acknowledge that people with atypical depression may be particularly suited to treatment with St. John’s wort.

While systematic review and meta-analysis is the most robust way to summarise the results from many studies, there are still limitations with these methods. Some researchers question the validity of combining studies that are quite different from each other, i.e. heterogenous, and in this review, the studies comparing St. John’s wort with placebo were statistically heterogenous.

Although there are other potential sources of bias, the researchers have attempted to address these through their systematic methods and in their discussion. For example, they observed that the effect of St. John’s wort compared with placebo was greater in the less precise trials, and this may suggest publication bias (i.e. studies with negative findings are less likely to be published). To counteract this effect, they found unpublished studies (some of which were negative) and therefore doubt that this had a large effect on the overall results.

The researchers also acknowledge that studies from German-speaking countries yielded ‘more favourable’ results and that this is difficult to interpret. This may have been because of slight differences in the characteristics of enrolled patients (e.g. in German-speaking countries this was through private practices, while in other countries academic or hospital centres were more commonly used). However, major biases in this review are unlikely.

In summary, by adding the large studies that have recently been conducted to the existing body of research, the evidence suggests that St. John’s wort is a viable treatment for mild to moderate major depression. Importantly, there is considerable variation in the preparations of St. John’s wort available over the counter. The researchers say that their findings apply only to the extracts that were used in the studies in this review, or possibly to very similar preparations. People who want to take St. John’s wort should speak to their doctors about the best preparation for them, and the risks and benefits compared to standard antidepressants.

It should be noted that St. John’s wort is an unlicensed herbal medication, so would not be prescribed by a general practitioner (as the newspapers suggest). St. John’s wort can have serious interactions with a large number of commonly used medications (e.g. warfarin), by affecting enzymes in the body involved with the metabolic processing of drugs; therefore a discussion with a doctor is important. Additionally, St. John’s wort must not be started while another antidepressant is being taken.