Depression in our society is very prevalent, yet it can be invisible to others. Many struggle alone, and may even be reluctant to seek the advice of health professionals. Some may choose to self-medication. This may explain the persistent popularity of St. John’s wort (SJW) a herbal remedy that can be purchased over-the-counter in pharmacies and in most supplement stores. The effectiveness of SJW for the treatment of depression, and the relative merits of SJW versus prescription drug alternatives, has been the subject of debate for some time.

There is no a priori reason why herbal remedies shouldn’t have medicinal properties. After all, herbs are just unstandardized, unpurified drugs. And a huge number of commercially-produced drug products have botanical sources as their roots. But there are important differences between raw herbal remedies, like SJW, and prescription drugs that need to be considered when considering the merits of either. The key questions are: Does SJW effectively treat depression? And how does SJW compare to other treatment approaches, including prescription antidepressants?

Does St. John’s Wort effectively treat depression?

St. John’s wort (Hypericum perforatum), pictured above, is a flower that has been used as medicine for many hundreds of years for different “nervous” conditions. There are a number of compounds with biological effects that have been identified in SJW. Earlier research suggested that the active ingredient might be hypericin, and many products you’ll find in stores state the standardized amount of hypericin per capsule. However, more recent research suggests the chemical hyperforin may have a larger role in giving SJW its neurological and psychiatric effects. This ingredient may not be reported on the label. Like antidepressant drugs, hyperforin may affect neurotransmitter levels in the brain of compounds like serotonin, norepinephrine, and dopamine. Ultimately, however, the mechanism of action, and the active ingredient(s) of SJW, when used to treat depression, are not known with certainty.

Before looking at the evidence, it’s important to note how the multitude of chemicals in SJW complicate clinical trials. If there was a clinical trial conducted of a particular brand (and lot) of a SJW product, there is no simple way to verify that other lots even of the same brand contain the same combination of ingredients. While standardizing one or more ingredients may be helpful, even this isn’t an assurance of quality, unless it’s absolutely clear that it’s the standardized ingredient(s) that are producing the effect. This puts herbal products at a disadvantage in clinical trials. If we are not certain of the active ingredient, and the product isn’t standardized with verified ingredients, we can’t be certain that a negative trial is negative because it really doesn’t work – or if it didn’t contain the precise combination of chemicals to be effective.

The data on St. John’s Wort is of mixed quality, with the research methods often poorly described. Studies are generally of a short duration and usually funded by manufacturers (which is also the case for many pharmaceutical antidepressants). A recent review identified seven systematic reviews of randomized controlled trials examining effectiveness in moderate depression. It found:

  • A response rate (more than 50% decrease in symptoms) of 56% vs. 35% with placebo, over a median follow-up of six weeks.
  • No difference in remission rates from placebo.
  • No difference in adverse effects from placebo.
  • A clinically detectable and statistically significant improvement, when measured on a depression scale.

There was an interesting observation made in data made by the Cochrane review:

Overall, the St. John’s wort extracts tested in the trials were superior to placebo, similarly effective as standard antidepressants, and had fewer side effects than standard antidepressants. However, findings were more favourable to St. John’s wort extracts in studies from German-speaking countries where these products have a long tradition and are often prescribed by physicians, while in studies from other countries St. John’s wort extracts seemed less effective. This differences could be due to the inclusion of patients with slightly different types of depression, but it cannot be ruled out that some smaller studies from German-speaking countries were flawed and reported overoptimistic results.

Given the inconsistent and regional effects, there is some skepticism about the overall effectiveness of SJW.

SJW appears to be well tolerated when taken alone. The most common side effects are gastrointestinal effects, CNS effects (dizziness/confusion), tiredness/sedation, dry mouth and photosensitivity, albeit at rates similar to placebo in some trials. There is a lack of evidence to suggest that it is safe to use while pregnant or breastfeeding, however.

How does St. John’s wort compare to antidepressants?

Harriet Hall discussed the effectiveness of antidepressants a few weeks ago, and I will not go into that issue in depth today. While antidepressants have little effect on mild depression, they have been shown to be effective for moderate to major depression. There have been comparisons to prescription antidepressants, over about 27 trials, which were noted to be of poor to fair quality. While the quality of the trial data raises questions about the overall validity of the evidence, it appears that, for moderate depression:

  • depression scores, remission rates, and response rates are similar between SJW and antidepressants
  • SJW appears to be better tolerated than antidepressants

The supplement quality con

Supplements like SJW, and ongoing questions of its effectiveness, illustrate how weak and ineffective supplement regulation harms consumers. While regulations will differ between countries, supplements like SJW get a light touch, from a regulatory perspective, from most governments. This means that SJW isn’t subject to the licensing requirements (and evidence standards) that applies to conventional drug products. It will vary somewhat depending on what country you live in, but in countries like the USA and Canada, this is what you’ll find:

  • There are few limits on what can be legally sold as a supplement or natural health product.
  • There are few limits on the health claims that can be made about these products.
  • There are few, if any, requirements to directly test supplements for safety.
  • There are often no requirements to test supplements for actual effectiveness.

The result is a marketplace that is a boon to supplement makers, but puts consumers at a considerable disadvantage. What’s on the label should accurately describe what’s in the bottle. Product quality standards are essential. And when it comes to ensuring the products we buy are of high quality, drugs, supplements, or otherwise, we’re all effectively reliant on others to verify this. While the product manufacturer may be reputable, it’s only a regulator, or possibly independent testing, that can realistically verify and enforce production of complex and sophisticated molecules like pharmaceuticals to strict quality standards. The same cannot be said for products like supplements and herbs which are regulated differently than drugs, and held to different, and in some cases, weaker standards. A weak regulatory framework, which doesn’t hold manufacturers to account, would be expected to result in a product of lower quality. And that’s exactly what we see in the supplement market today. And that could be contributing to the mix evidence we have on SJW.

Interactions with everything

Once we swallow a substance, be it a herb or a drug, our body can’t distinguish the difference in source – whether that source is a steel vat or a plant. Chemicals are absorbed into the bloodstream, circulate in the body, and presumably reach the site of action and then have some sort of biological effect. Like prescription drugs, herbal remedies can interact with other drug products. And SJW is one of the worst offenders, seemingly causing drug interactions with almost every drug product on the market. SJW has an effect on several different metabolic pathways, increasing their effect. This has led to a decreased effectiveness of other drugs, and treatment failures have been noted from concurrent use of SJW with contraceptives, organ transplant drugs, narcotics, treatments for HIV, blood thinners and other therapies. The safest approach is to assume that SJW shouldn’t be taken concurrently with any other medication, without verifying a lack of problem with a pharmacist.

Conclusion

While it may be tempting to consider a “natural” alternative for depression, there are several reasons why few health professionals or mental health organizations recommend St. John’s wort. Given the weak regulation of herbal products like SJW and the potential for multiple drug interactions, prescription antidepressants give more certainty about the drug, the dosing, and the relative safety of the product purchased. And while there is some data that shows that SJW has an antidepressant effect, the evidence is not consistent across different studies, and may reflect the underlying variety in manufacturing processes and products available on the market. But perhaps most importantly, depression is a condition that seems to most effectively respond to a combination of drug therapy and psychotherapy. Working with a health professional who can give an accurate diagnosis and help assess the relative appropriateness of any medical treatment – be it St. John’s wort, or pharmacotherapy, is likely to yield a better approach than self-medication.

Photos from flickr users Bob Peterson and xlibber used under a CC license.

Posted by Scott Gavura