St. Johns Wort: is it effective and harmless?

It is important to be knowledgeable about St. John`s Wort and other popular herbs, their effects, adverse effects, and drug interactions.

It is important to be knowledgeable about St. John`s Wort and other popular herbs, their effects, adverse effects, and drug interactions.

Cynthia R. Biron, RDH

St. John`s Wort, named after St. John the Baptist due to its tendency to bloom during the feast of St. John in Germany, is an extract that comes from a perennial flowering plant ( whose botanical name is Hypericum perforatum L. (LI 160). Within the plant, one of the extracts, hypericin, is thought to be effective for treatment of mild to moderate depression.

St. John`s Wort is not recommended for the treatment of severe depression. Anyone with severe depression (particularly someone who contemplates suicide) should seek professional treatment promptly from a physician. However, the herb may alleviate mild to moderate depression.

Approximately 200 million dollars was spent on St. John`s Wort in this country in 1998. Is this money being wasted or well spent? As with all other herbs, effectiveness and safety are of great concern to consumers as well as health professionals. Most consumers want to know if St. John`s Wort is of any value.

An effective antidepressant?

Only short-term studies (six weeks) have been conducted in demonstrating the effectiveness of St. John`s Wort as an antidepressant. Most of the studies have been conducted in Germany, where the herb is most commonly prescribed by physicians. Even though prescriptions are not necessary to obtain the herb, it is prescribed there four times more often than fluoxetine hydrocholoride (Prozac).

In Munich, an overview and meta-analysis of randomized clinical trials (23 in all) included a total of 1,757 outpatients with mainly mild to moderate depression. Fifteen trials were placebo-controlled, while one compared St. John`s Wort with standardized antidepressants. Results suggest that St. John`s Wort is superior to the placebo (ratio = 2.67; 95% confidence interval 1.78 to 4.01). Also, the results suggested the herb to be as effective as standard antidepressants (single preparations 1.10; 0.93 to 1.31, combinations 1.52; 0.78 to 2.94).

Dropouts for side effects with St. John`s Wort were 0.8%. Three percent of patients taking standard antidepressants dropped out of the study due to side effects. Tolerable side effects occurred in 19.8% of patients taking St. John`s Wort, but 52.8% of patients on the standard antidepressants experienced side effects. Numerous smaller studies produced similar results.

There have not been any long-term studies on the effects of St. John`s Wort. It is not known whether patients will build a tolerance to the herb, if the herb loses its effectiveness entirely, has withdrawal effects, or long-term adverse effects.

More information will be available in approximately three years. The National Institute of Health, Office of Alternative Medicine has funded a three-year, $4.3-million clinical trial comparing St. John`s Wort with a placebo and fluoxetine hydrochloride (Prozac).

Other uses of St. John`s Wort

Some in-vitro studies have shown that hypericum has antiviral activity, but, to date, these effects have not been demonstrated in vivo. Some herbalists have recommended St. John`s Wort for enhancement of wound healing, as well as for anti-inflammatory and analgesic effects. There is no valid research that confirms the effectiveness of St. John`s Wort for these problems.

St. John`s Wort has shown some promise in the treatment of Seasonal Affective Disorder (SAD). A four-week study of patients diagnosed with SAD, who were treated with 900mg. of St. John`s Wort daily, demonstrated a significant reduction in the total score of the Hamilton Depression Rating Score.

Additional studies have been conducted to show St. John`s Wort`s effects on sleep disorders. Twelve older, healthy adults participated in a four-week, double-blind, placebo-controlled study that compared tricyclic antidepressants and MAO inhibitors with St. John`s Wort. Unlike the antidepressants, St. John`s Wort induced an increase of deep sleep during the total sleeping period. In another study, patients taking St. John`s Wort were evaluated for rapid eye movement (REM) during sleep, and the effects were similar to those seen on patients taking conventional antidepressants.

Mechanism of action

The mechanism of action in which St. John`s Wort alleviates depression is not exactly known. Researchers theorize mood elevation is provided by a combination of low-grade monoamine-oxidase inhibition and noradrenaline and serotonin-reuptake blockade. Because St. John`s Wort has so many compounds, other undiscovered mechanisms probably alleviate depression.

It is believed that a combination of individually weak mechanisms serve to produce the total antidepressant effect. In one study conducted on rats, the hypericum extract was shown to cause a 50 percent inhibition of serotonin uptake by synaptosomes at a concentration of 6.2 microglml.

Another study compared blood samples taken from depressed and healthy patients who had taken St. John`s Wort and compared the samples with a similar number of patients taking a placebo. The test results indicated that those patients taking the St. John`s Wort had massive suppression of interleukin-6. This suggests another possible relationship to the antidepressant effects of the hypericum extract, the most active ingredient in St. John`s Wort. It is believed that St. John`s Wort has a component much like that found in other antidepressants - especially the tricyclic antidepressants - that also inhibit 5-HT or norepinephrine reuptake, and monoamine oxidase.

Adverse effects

The World Health Organization (WHO) reports that St. John`s Wort has a high safety profile with adverse effects limited to gastrointestinal symptoms, dizziness, confusion, tiredness, and sedation. The only potentially serious adverse effect has been photosensitivity. Although the incidences of photosensitivity have been rare (less than 1%), those that have occurred were quite serious. Anyone taking St. John`s Wort should wear sunscreen on all areas of the skin that are even remotely exposed to the sun, avoiding sun exposure as much as possible. Because studies conducted on St. John`s Wort to date have been short term, future long-term studies on this product may demonstrate a higher risk for incidences of photosensitivity.

Drug interactions

Few drug interactions with St. John`s Wort have been reported to date. Good pharmacological sense indicates that the actions of St. John`s Wort would contraindicate its use with other drugs exhibiting the same actions. Therefore, even all clinically approved antidepressants of the tricyclic, selective serotonin reuptake inhibitor, monoamine oxidase inhibitor families, are contraindicated for concommitant use with St. John`s Wort.

Whether other types of antidepressants are contraindicated, such as those which elevate dopamine levels, has yet to be determined. At this time, it is recommended that St. John`s Wort not be taken in combination with any other antidepressants, tranquilizers, psychoactive, or mood-altering drugs.

Future research may prove that combining St. John`s Wort with other drugs will potentiate the actions of drugs that may have a narrow safety margin. Such an approach would allow for a reduction in dosage of these drugs while obtaining desired efficacy. Extensive testing in this area could be quite promising for safer treatment of depression.

Recommended dosage

The dosage shown to be effective in clinical trials was reported at 300 mg. three times a day of a 0.3% hypericin content St. John`s Wort preparation.

The extract hyperforin

Some studies showed that the therapeutic effect of St. John`s Wort was dependent on its hypeforin content. A randomized, double-blind, placebo-controlled, multicenter study conducted at the University of Munich compared two different types of St. John`s Wort according to their hyperforin content. The 42-day treatment study involved 147 male and female patients suffering from mild to moderate depression. Two identical Hypericum preparations with different hyperforin content were compared, one contained 0.5% hyperforin and the other contained 5% hyperforin. At the end of the trial, the 5% hyperforin was superior to the placebo in alleviating depression at p=0.004. The 0.5% hyperforin combination and the placebo were descriptively comparable in their effects on depression.

Lack of consistency in extracts

The Consumer Safety Symposium on Dietary Supplements and Herbs reported that a Good Housekeeping Institute study found drastic discrepancy in the amounts of standardized extracts in six different types of St. John`s Wort supplements. One product showed a 17-fold difference between the capsules containing the smallest amount of the extract and those containing the largest amount, according to the manufacturer`s maximum recommended dosage. Another product showed a 13-fold difference in the extract in the capsules. In yet another product, a seven- to eight-fold differential was noted from the highest to the lowest levels of extract in the liquid preparations.

This is of great concern in maintaining consistency of the therapeutic dosages of St. John`s Wort. Unless the companies preparing the products can standardize the amounts of extracts in each pill and/or liquid, therapeutic effects and safety cannot be ascertained.

100-percent natural?

Many people assume that herbs are all natural and harmless. Neither assumption is accurate. Herbs are botanicals like derivatives of opium (poppy seeds) are drugs. Herbs may or may not be safe and should not be taken indiscriminately. Of particular interest, is the fact that all herbs are not natural. Some are recreated in the laboratory just as synthetic vitamins are recreated in the laboratory.

The following statement was released from the Good Housekeeping Institute indicating the ratio of natural herb (Hypercin) and synthetic herb (Pseudohypericin), in brands of St. John`s Wort:

"The relative levels of Hypercin and Pseudohypericin, respectively in various brands of St. John`s Wort extract and supplemental capusules are: Futurebiotics (1:1), to Best Organics (1:2), Herb Pharm (4:4), Natures Herbs (5:6) Schiff (7:8), Herbs Etc. (7:8), Hypericalm (9:6), Natures Fingerprint (12:13), and Natures Way (17:10)."

Lack of long-term research

While there have been numerous valid studies conducted for four to six week periods, there is no data from long-term studies available to evaluate effectiveness and safety of St. John`s Wort. For this reason, taking St. John`s Wort in excess of 900mg. per day and/or for longer than six weeks is not recommended. Many cases of depression last longer than six weeks, and, if depression is relieved for the six weeks, it may return when there is cessation of herb therapy.

When depression is caused by an endogenous source, the individual cannot give reasons for feeling depressed. That is to say, it is unrelated to emotional, personal, or family (exogenous causes). Endogenous causes are more often a chemical imbalance. The chemical imbalance may involve a lack of circulating neurotransmitters, mood elevators, etc., and require the expertise of a medical specialist.

What to tell patients

While we may want to inform patients about St. John`s Wort, recommending herbs to patients, friends, and family members is contraindicated for health professionals in fields outside of general medicine, psychotherapy, and psychiatry. Although we may be tempted to recommend St. John`s Wort to such people, it is not safe practice. It is important to be knowledgeable about such popular herbs, their effects, adverse effects, and drug interactions.

Such knowledge adds significantly to our ability to provide proper risk management to prevent complications with dental treatment. Recommending these products is as inadvisable as dictating treatment for various conditions with which patients present. Always refer patients with mental and/or physical complaints to their primary-care physician. The primary-care physician may determine which specialist could provide the best care for the patient.

References

- Bennett DA Jr, Phun L, Polk JF, Voglino SA, Zlotnik V, Raffa RB. Neuropharmacology of St. John`s Wort. Ann Pharmacother 1998 Nov;32(11):1201-8.

- Bove GM. Acute neuropathy after exposure to sun in a patient treated with St John`s Wort. Lancet 1998 Oct 3;352(9134):1121-2.

- Bowman MA, Nicklin DE. New developments in family medicine. JAMA 1998 May 13;279(18):1437-8.

- Chatterjee SS, Bhattacharya DK, Wonnemann M, singer A, Muller WE. Hyperforin as a possible antidepressant component of hypericum extracts. Life Sci 1998;63(6):499-510.

- Cott JM, Fugh-Berman A. Is St. John`s Wort (Hypericum perforatum) an effective antidepressant? J Nerv Ment Dis 1998 Aug; 186(8):500-1.

- De Smet PAGN, Nolen WA. St. John`s Wort as an antidepressant: Longer-term studies are needed before it can be recommended in major depression. British Medical Journal 313:241-242, 1996.

- Ernst E, Rand JI, Barnes J, Stevinson C. Adverse effects profile of the herbal antidepressant St. John`s Wort. Eur J Clin Pharmacol 1998 Oct;54(8):589-94.

- Hippius H. St. John`s Wort (Hypericum perforatum) - a herbal antidepressant. Curr Med Res Opin 1998;14(3):171-84.

- Kasper S. Treatment of seasonal affective disorder (SAD) with hypericum extract. Pharmacopsychiatry 1997 Sep;30 Suppl 2:89-93.

- Laakmann G, Schule C, Baghai T, Kieser M. St. John`s Wort in mild to moderate depression: the relevance of hyperforin for the clinical efficacy. Pharmacopsychiatry 1998 Jun;31 suppl 1:54-9.

- Linde K et al. St. John`s Wort for depression - an overview and meta-analysis of randomixed clinical trials. British Medical Journal 313:253-258, 1996.

- Miller AL. St. John`s Wort (Hypericum perforatum): clinical effects on depression and other conditions. Altern Med Rev 1998 Feb;3(1):18-26.

- Neary JT, Bu Y. Hypericum LI 160 inhibits uptake of serotonin and norepinephrine in astrocytes. Brain Res 1999 Jan 23;816(2):359-363.

- Schulz H, Jobert M. Effects of hypericum extract on the sleep EEG in older volunteers. J Geriatr Psychiatry Neurol 1994 Oct;7 Suppl 1:S39-43.

- Sharpley AL, McGavin CL, Whale R, Cowen PJ. Antidepressant-like effect of Hypericum perforatum (St John`s Wort) on the sleep polysomnogram. Psychopharmacology (Berl) 1998 Oct;139(3):286-7.

- Thiele B, Brink I, Ploch M. Modulation of cytokine expression by hypericum extract. J Geriatr Psychiatry Neurol 1994 Oct;7 Suppl 1:S60-2.

- www.Quackwatch.com

Cynthia R. Biron, RDH, is chair of the dental hygiene program at the Tallahassee Community College. She is also a certified emergency medical technician.

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