New Hope Network is part of the Informa Markets Division of Informa PLC

This site is operated by a business or businesses owned by Informa PLC and all copyright resides with them. Informa PLC's registered office is 5 Howick Place, London SW1P 1WG. Registered in England and Wales. Number 8860726.

New St. John’s wort Study Misleads Public

Submitted by:

Hyla Cass, M.D.
Contact: (310) 459-9866
e-mail: • website:
Assistant Clinical Professor of Psychiatry, UCLA School of Medicine;
Author of: St John's Wort: Nature's Blues Buster; All About Herbs; Kava:Nature’s Answer to Stress, Anxiety, and Insomnia; and Natural Highs (2002)

A study on the popular herbal remedy St. John’s wort published in the April 10 edition of the Journal of the American Medical Association (JAMA) concluded that neither St. John’s wort nor the widely prescribed antidepressant Zoloft® (sertraline) are more effective overall than placebo in treating severe forms of depression. Unfortunately, it ignores the traditional use of St. John’s wort and recent modern clinical trials that have shown conclusively that St. John’s wort is effective in the treatment of “mild to moderate” depression.

Why all the fanfare from JAMA over the fact that St. John’s wort is not shown to be effective for a condition that it was never intended to treat? The real story here is that if this study is believable, it showed that a blockbuster drug, with sales of over $2 billion and prescribed to millions of Americans for severe forms of depression, may be no more effective than placebo. In fact, the placebo group responded better than both of the other two. Does that make it the superior treatment. Perhaps. More on that below. Here are some relevant Q and A’s:

Shouldn’t the headline read: Zoloft No Better Than Placebo For Depression?

I completely agree, and am puzzled by the fact that the JAMA article chose to focus only on the St. John's wort failure. It seems like a knee-jerk reaction -"herbs don't work" -- when the true news is that "neither works in this population, " as any psychiatrist already knows. The inclusion criteria, of severe major depression, made the conclusion foregone. The study was a waste of both the taxpayers’ $4 million, and the opportunity to make a real contribution to the study of depression treatment. Could it be due to some prejudice on the part of those who set it up, who assumed that they would be able to eliminate St. John's wort as a treatment, while allowing the 'active', Zoloft® to do its usual?

The conclusions also do a great disservice to the public. Speaking as a clinician who regularly prescribes St. John's wort, I have seen negative repercussions with this kind of interpretation of an herbal study. The human mind is complex, and many factors go into the healing process. As we see in all placebo-controlled trials, the placebo effect is actually a very significant aspect of treatment, and as physicians, we do best when we fully support it. Research has shown that this is true for almost all medications. Moreover, there is no way to tell in any one individual how much relief is due to the placebo and how much, the herb or medication.

At this point, many individuals who have been successful in relieving their depression with St. John's wort may question their positive response, lose confidence in the herb, discontinue use, and revert to their depressive state. Or they may turn to medication, with its more severe side effects, not to mention expense. In addition, many who have been considering taking the herb may not now even give it (and themselves) a chance.

We know that even mild to moderate depression can be a debilitating illness, and yet we are in effect 'hexing' the use of a perfectly good herbal medicine that has been prescribed successfully in Europe. Does St. John's wort lose its efficacy when it crosses the Atlantic? The medical profession is bound by the Hippocratic oath to "first do no harm," and to use the simplest most natural least harmful medicines first. Why put so many people as risk?

This study does not simply suggest the equal ineffectiveness of a known antidepressant and an herb in treating severe major depression, but shows us the power of the placebo effect. This will come as no surprise to those of us practicing psychiatry.

Isn't this study, the first from the NIH Center for Alternative and Complementary Medicine, one of the better done studies yet looking at St. John’s wort for depression?

The fact that the Zoloft® was not effective showed that this trial lacked testing sensitivity and should be dismissed as an unsuccessful study. In many studies of antidepressants, perhaps as many as one-third, the tested drug doesn't do any better than placebo. The cause is probably a combination of the high placebo effect often seen in studies testing antidepressants and the relative coarseness and subjectivity of the type of rating scales.

This study does not invalidate the use of St. John's wort in clinical depression. There are still many well-controlled trials supporting the use of St. John’s wort in mild to moderate depression.

The study chose a very difficult population, with a high depression score (HAM-D over 20). These patients are often immobilized by their illness, feeling totally hopeless and helpless, often suicidal. Their treatment requires a great deal of attention, with manipulation of various medications and doses. Often, too, there are underlying undiagnosed medical problems that are not readily apparent (eg hormonal imbalances such as low thyroid, which very often goes undiagnosed, and even allow the individual to be included in a study such as this.).

Did many clinicians dealing with depression embrace St. John’s wort as viable treatment? Do you consider it an effective treatment for any stage of depression?

The U.S. has been behind other countries in embracing herbal medicine, while in Germany alone, an estimated 131 million doses a year are prescribed by physicians for the treatment of depression as a first line treatment for mild to moderate depression. If it doesn’t work, then they can always put the patient on more powerful, pharmaceutical anti-depressants.

More than 22 controlled studies have been published in European medical journals suggesting that the leading St. John’s wort extract (Jarsin in Germany, Kira in the US) is a safe and effective remedy for mild to moderate depression. As a clinician, I have been impressed with the efficacy of St. John's wort, both with my own patients and in the many reports I have received as an author of a book on the subject (St. John's Wort: Nature's Blues Buster, Putnam, 1998).

There are a lot of problems with drug interactions and St. John’s wort. Is that reason enough to hold off recommending use until there is data to support its effectiveness?

It certainly is important to inform people of such interactions (which occur with most drugs, as well). St. John's wort can increase the breakdown of a number of drugs, making them less effective. However, the ones that are problematic can be easily delineated, and many are for very select populations (eg protease inhibitors for HIV patients; Cyclosporin for transplant patients). A less-known and perhaps more significant fact is that grapefruit juice will also enhance breakdown of many drugs, and though people should be warned about this, they are often not, to their detriment.

The truth is, the side effects of the antidepressant medications are far more frequent and severe than those of St. John's wort, seriously affecting the quality of life of those who are already trying hard to overcome a debilitating condition. Why add more problems, such as loss of libido, memory impairment, headaches, nausea, and withdrawal symptoms when discontinuing use? In contrast, St. John's wort side effects are generally mild and transitory, with no withdrawal symptoms upon discontinuation. The risk/benefit ratio is certainly a good one, and better than that of the prescription medications.

RE: Davidson JRT et al. Effect of Hypericum perforatum (St John’s Wort) in major depressive disorder: A randomized controlled trial. JAMA. 2002;287:1807-1814.

For more Information:
Hyla Cass, M.D.
Contact: (310) 459-9866
Assistant Clinical Professor of Psychiatry, UCLA School of Medicine;
Author of St John's Wort: Nature's Blues Buster; All About Herbs; Kava:Nature’s Answer to Stress, Anxiety, and Insomnia; and Natural Highs (2002)
e-mail: • website:

Hide comments


  • Allowed HTML tags: <em> <strong> <blockquote> <br> <p>

Plain text

  • No HTML tags allowed.
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.