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St. John's Wort

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St. John's Wort is a popular treatment for mild to moderate depression; St John's Wort is also used to treat anxiety, seasonal affective disorder, and sleep disorders.¹ St. John's Wort (Hypericum perforatum) is a long-living, wild-growing herb with yellow flowers that has been used for centuries to treat mental disorders as well as nerve pain. In ancient times, doctors and herbalists (herb specialists) wrote about St John's Wort as a sedative and antimalarial agent as well as a balm for wounds, burns, and insect bites.

The use of St. John's Wort is growing in the United States, and several brands now are available. St John's Wort extracts are sold as a nutritional supplement. St John's Wort is available in capsule, tea, or tincture forms. St. John's Wort was among the top-selling botanical products in the United States in 1997, with industry-estimated sales of $400 million in 1998.⁴

St. John's Wort is widely used in Germany, where doctors prescribed almost 66 million daily doses in 1994 for psychological complaints.² In fact, German doctors prescribe St. John's Wort about 20 times more often than Prozac, one of the most widely prescribed antidepressants in the United States.³

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Treating Depression with St. John's Wort
Depression is a common illness that strikes perhaps 1 in 15 Americans each year. A person's mood, thoughts, physical health, and behavior all may be affected. Symptoms can include a persistent sad, anxious, or "empty" feeling; loss of energy, appetite, or sexual drive; and lack of interest in socializing, work, or hobbies.

Depression can be mild, moderate, or severe. Mild depression is characterized by difficulty in functioning normally, while moderate depression may involve impaired functioning at work or in social activities. Severe depression, which may involve delusions or hallucinations, markedly interferes with a person's ability to work or otherwise function and may lead to suicide. Genetic factors may put a person at risk for developing depression, and alcohol or drug use can make the problem worse.⁸ While the public misperception persists that depression is voluntary or a "character flaw," depression is a real condition that can be treated effectively by qualified professionals.⁹

Specific psychotherapies (such as interpersonal and cognitive-behavioral therapy) and antidepressant medications both have been found to be effective for patients with major depression. Major depression includes mild, moderate, or severe depression that is not characterized by manic-depressive mood swings or induced by a substance such as alcohol. Several antidepressant drugs have become more widely used in the past several years and been found to be effective. However, patients sometimes report unpleasant side effects such as a dry mouth, nausea, headache, diarrhea, or impaired sexual function or sleep.¹⁰

In part because of these types of drug side effects, many patients with depression are turning to herbal treatments such as St. John's Wort. Researchers are studying St John's Wort for possibly having fewer and less severe side effects than antidepressant drugs. St. John's Wort also costs far less than antidepressant medication. In addition, St. John's Wort does not require a prescription.¹¹

St. John's Wort is not completely free of side effects, however. Some users have complained of a dry mouth, dizziness, gastrointestinal symptoms, increased sensitivity to sunlight, and fatigue.¹² In addition, St. John's Wort treatments often are not as potent or as quick to act as conventional treatments. Furthermore, herbal treatments may not produce the desired results and may not be as effective as conventional medicine. Still, some people turn to St John's Wort because they prefer to use "natural" products.

Clinical depression is a serious medical disorder that, in many cases, can be treated. However, St. John's Wort is not a proven therapy for clinical depression. Therefore, there is some risk in taking St. John's Wort to treat clinical depression.⁵

In any case, St. John's Wort should not be mixed with other standard antidepressants because side effects may result. This is one reason why it is important to tell your doctor about all herbs and medications you are taking. Check with your doctor before taking St. John's Wort or any other herb or medication. Your doctor can help you weigh the risks and benefits of a particular treatment so you can make informed health care decisions.

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Drug Interaction Advisory
NIH Clinical Center research shows that St. John's Wort may reduce the effectiveness of several drugs by speeding up activity in a key pathway responsible for their breakdown. The end result is that blood levels of these drugs decrease because the body breaks them down faster. St. John's Wort especially affects Crixivan (indinavir) and other protease inhibitors used to treat HIV infection. It also may affect cyclosporine, a drug used to help prevent organ transplant rejection, and other immunosuppressant drugs; and other medications that work through the same pathway, including birth control pills, cholesterol-lowering medications such as Mevacor (lovastatin), cancer medications, seizure drugs, and blood thinners such as Coumadin (warfarin). Doctors and patients should be aware of these negative drug interactions that could interfere with the proper functioning of these drugs.

For more information, visit NCCAM's Web site http://nccam.nih.gov; or the Food and Drug Administration (FDA) Center for Drug Evaluation and Research's Web site http://www.fda.gov/cder/drug/advisory/stjwort.htm; or call the FDA Center for Food Safety and Applied Nutrition at 201-800-332-4010.

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How St. John's Wort Works
The major components in extracts of St. John's Wort include flavonoids, kaempferol, luteolin, biapigenin, hyperforin, polycyclic phenols, hypericin, and pseudohypericin. Researchers believe the last three substances are the active ingredients of St. John's wort.⁵ New research suggests that hyperforin also may play a large role in St. John's Worts antidepressant effects. Some German manufacturers of St. John's Wort have begun standardizing St. John's Wort, not only to hypericin as most U.S. manufacturers do, but to hyperforin as well.¹³ Standardizing means that the manufacturer ensures that each individual supplement contains a uniform amount of a certain compound, in the case of St. John's Wort — hypericin and hyperforin.

Recent research suggests a possible application of St. John's Wort for alcoholism. Researchers from the University of North Carolina at Chapel Hill found that St. John's Wort reduced alcohol intake in laboratory animals.¹⁴

Several mechanisms of action of St. John's Wort have been proposed, including the following:

• St. John's Wort inhibits monoamine (serotonin, dopamine, and norepinephrine) re-uptake: St. John's Wort appears to reduce the rate at which brain cells reabsorb serotonin (an important neurotransmitter or chemical that aids communication between nerve cells). Low levels of serotonin in the body are associated with depression.^15,16
• St John's Wort modulates interleukin-6 (IL-6) activity: Raised levels of IL-6, a protein involved in the communication between cells in the body's immune (disease-fighting) system, may lead to increases in adrenal regulatory hormones, a hallmark of depression. St. John's Wort may reduce levels of IL-6, and thus help treat depression.¹⁷

More research is needed to determine precisely the active ingredients in St. John's Wort and to learn how the herb works.

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