People tend to like good news, and I am not much different. I am constantly searching the recent medical literature for ‘good news’ in my area. Sadly, there is preciously little of it. But when I find some, I rejoice and report on it, provided it is of high quality. The paper I want to write about today certainly does fulfil this criterion.
It is a summary of all clinical trials, or a systematic review, of a herbal remedy, St John’s wort (SJW), for the treatment of depression. Its specific objective was to evaluate the efficacy and safety of SJW in adults with major depressive disorder compared to placebo or conventional anti-depressants.
The authors searched multiple electronic databases and went through several existing reviews to locate all relevant studies. Two independent reviewers screened the citations, abstracted the data, and assessed their methodological quality. They considered all randomised controlled trials (RCTs) examining the effects of at least a four-week administration of St John’s wort on depression.
Thirty-five RCTs with a total of 6,993 patients could eventually be included in the review. The collective findings show that St John’s wort was superior to placebo in alleviating the symptoms of major depressive disorder. It was also just as efficacious as conventional antidepressants and patients were significantly less likely to experience adverse events.
The authors concluded cautiously:
SJW monotherapy for mild and moderate depression is superior to placebo in improving depression symptoms and not significantly different from antidepressant medication. However, evidence of heterogeneity and a lack of research on severe depression reduce the quality of the evidence. Adverse events reported in RCTs were comparable to placebo and fewer compared with antidepressants.
However, assessments were limited due to poor reporting of adverse events and studies were not designed to assess rare events. Consequently, the findings should be interpreted with caution.
An even more recent systematic review of 27 clinical trials with a total of 3,808 patients specifically looked at comparisons of St John’s wort with SSRIs, the most common class of conventional anti-depressants. St John’s wort demonstrated comparable response and remission rates. It also significantly lowered the discontinuation/dropout rates compared to standard SSRIs.
As these are high-quality reviews from reputable and independent teams, we can, I am sure, trust their findings. But that does not mean that we should ignore any potential problems, of which there are several.
The first issue of concern is that St John’s wort is known to interact with a very wide range of prescription drugs. Through two different mechanisms it lowers their blood level. This means that a patient on an anti-coagulant, for instance, who decides to start taking St John’s wort might lose the benefit of the anti-clotting drug and consequently develop a thrombotic event.
Conversely, someone might have been taking both the anti-coagulant and St John’s wort for months with stable readings on the regular blood tests until, one day, he decides to discontinue his St John’s wort. This patient would thereby increase the blood level of the anti-coagulant which could easily lead to a life-threatening bleed.
The simplest solution to the problem is to avoid combining St John’s wort with other drugs. If this is impossible or impractical, the best is to consult a physician who knows about the interactions of the remedy with other medicines and can therefore provide responsible and safe guidance.
The second problem with using St John’s wort is the vexing questions about the optimal type of extract and the most effective dose. At present, there is not enough evidence to provide conclusive answers to either of these. This might be one of the reasons why the enthusiasm of many doctors for prescribing it is limited.
In my view, the best advice is to avoid purchasing St John’s wort products ‘on the cheap’. The internet is rife with rather dubious offers of inexpensive SJW pills and tinctures. My advice is to buy high-quality products (which are not cheap), preferably those that were used in the clinical trials mentioned above.
The third concern is that practically all the studies published so far have been relatively short term. Yet treatment of depression often must be continued for long periods, and we currently cannot be sure that SJW is effective when taken for 12 weeks or longer.
Despite these caveats, St John’s wort deserves careful consideration for patients suffering from depression. I wish there were more alternative therapies that are supported by such strong evidence.
Edzard Ernst, emeritus professor at the University of Exeter, is the author of Homeopathy: The Undiluted Facts and the awardee of the John Maddox Prize 2015 for standing up for science. He blogs at edzardernst.com.