St. Johnís Wort: Does it Help Treat Depression?-Part VI

The results of a study of the effectiveness of St. John's wort in treating major depression were published in the Journal of the American Medical Association. This study is the first one that was funded by the National Institute's of Health's National Center for Complementary and Alternative Medicine.

The study showed that after 8 weeks, St. John's wort did not show any statistical significant effect in improving people's overall moods, or in conveying a "full response"-essentially a full lifting of the depression. In the study, 340 people with major depression were randomly assigned to receive either an extract of the plant's active ingredient, called hypericum, or Zoloft, the world's biggest selling antidepressant, or a placebo. There were 340 people with major depression in the study group.

Interestingly enough, 31.9 % of the placebo patients experienced a full response versus only 23.9% of those on St. John's wort. Only 24.8% of Zoloft patients experienced a full response. St. John's wort costs about $8 for a bottle of 90 300-milligram caplets, versus about $80 for a months supply of Zoloft. The Zoloft used in the study was administered at fairly low dosed of 50 to 100 milligrams when in fact it is usually given in its 200-milligram form.

The question does remain however as to the effectiveness of St. John's wort in treating mild to moderate depression. Further studies will evaluate its effectiveness in the mild to moderate depression patients. 

We recently came across two letters to the editor in Trends in Pharmacological Sciences (2001; 22(11)) worth noting. Two Italian researchers discuss the range of action of St Johnís wort in humans. It would seem that the two agree on the merits of treating mild-to-moderate depression with St. Johnís wort and see it as a "valid alternative to fluoxetine". It has a narrower range of side effects and may be more cost-effective. They do not believe it can work with severe depression.

The mechanism of action of the active ingredient, hyperforin, both agree "is complex because extracts contain a wide range of pharmacological active constituents that might in a synergistic (or antagonistic) way contribute to the pharmacological activity." They see St. Johnís wort as possessing a pharmacological profile that is unique among all other antidepressants ". It inhibits the uptake of 5-HT, noradrenaline and dopamine with the same potency, and also inhibits the uptake of glutamate and GABA". It appears to work in a general way, rather than being a specific binder or neurotransmitter transporter. In fact, there is speculation that it may work in the same way as electric convulsive therapy (ECT) in that it upregulates 5-HT 2 receptors.

The problem starts with the fact that the molecular basis of depression is clouded and still under investigation. That leaves the mechanism of action of St. Johnís wort in question.

Before anyone runs out and buys St. Johnís wort, you should know of the wide discrepancy found in a study of the supposed ingredients in some of the commercially available product. See our other articles on St. Johnís wort. Better monitoring of the ingredients in supplements is needed. They are not subject to the same set of phase evaluation that pharmaceutical drugs must undergo. Also not enough is known about potential interactive effects of St. Johnís wort with other drugs.


The email addresses of the two researchers mentioned above are as follows:

Tiziana Mennini:

Angelo A. Izzo:

The controversy continues about the value of St. Johnís wort as a treatment herb for depression. The latest results reported in the JAMA of April 18, 2001, reflect negative findings that are in sharp contrast to previous research.

Dr. Richard C. Shelton, the director of the study, described the results as "remarkably negative". He went on to recommend other active treatments rather than St. Johnís wort to treat depression. He felt that there is no convincing evidence to support the use of St. Johnís wort for any type of depression. For the study the term depression was defined as a condition of feeling sad or in a depressed mood that lasts two weeks or more. At least 4 other symptoms were required before meeting the definition of depressed. They were:

The symptoms could be classified as anywhere from mild to severe. Some advocates of St. Johnís wort continue to feel it works in cases of minor depression. There are at least 20 studies showing that the herb did work for depression.

This study was conducted at 11 teaching hospitals in the United States and involved 200 moderately depressed patients who were in this double blind study for 8 weeks. They either received three tablets each containing 300 milligrams of St. Johnís wort to be taken per day, or a placebo taken the same way. Results indicated that about 27% of patients who took St. Johnís wort showed improvements compared to 19% of the placebo group. This was not statistically significant (It should be noted that antidepressants are considered helpful in 60% to 80% of the treated cases.) The National Institute of Mental Health and Pfizer Inc., which manufactures antidepressants and a St. Johnís wort extract, financed the study.

This research certainly contains some robust evidence that questions the value of St. Johnís wort. We do however question whether 8 weeks was a long enough period of time for the herbal supplement to show optimal effect. We also question whether the dosage was at a therapeutic level, or whether the extract itself contained the parts of St. Johnís wort that are most effective. The latter question relates to a report in the NY Times (April 17, 2001) entitled: "When Pills With Wort Come Up Short". The article indicated that tests done by, "which tests the quality of dietary supplements and nutrition products found that one-third of the St. Johnís wort did not pass muster". Almost 25% contained less of the active ingredient.

The NY Times article stated that "[T]he products most likely to pass the tests were made from the flowers, sometimes mixed with leaves of St. Johnís wort as opposed to those made from aerial parts of the plant, which include all parts that grow above the ground."

According to the Nutrition Business Journal Americans spent about $195 million on St. John's wort in 2000. The Journal estimates that about 1.5 million Americans use it and about 5 million others have tried it in the last 5 years.St. Johnís wort is used extensively in Europe, especially Germany, where the government controls pricing of drugs and may have a vested interest in putting the least expensive drug on the market. In the US, the pharmaceutical industry does not receive governmental support for their marketed drugs. They have a vested interest to provide medications that can recoup the costs of manufacture and provide a profit to their shareholders. Herbals and supplements do not provide them a prolonged exclusivity on the marketing of these products, reducing chances of extensive profits.

Please See: Herbs and Dietary Supplements-St. John's Wort-Part I
St. Johnís Wort -Herbs and Dietary Supplements-Part II-Ephedra
Phytomedicine or Herbalist-What is It?-Part III
Herbal Medicine and Botanical Supplements Caveat-Part IV
Treating Osteoarthritis with Dietary Supplements-Part V
Herbal Products: Use With Caution-Part VII
Kava: Safety Alert-Part VIII
Herbal Usage for Hormone Replacement Therapy-Part IX
Latest Research Questions the Effectiveness of Herbal Supplements-Part X



Harold Rubin, MS, ABD, CRC, Guest Lecturer
Updated April 15, 2002

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