Even those with mild depression should not use St. John's Wort without consulting a physician. This herbal substance is not regulated and there is no guarantee of quality in any brands currently available.

What is it?

St. John's wort (hypericum perforatum) is a star-shaped, yellow plant that has been used for various medicinal purposes since antiquity. Its use as a salve or balm for burns or wounds is mentioned by physicians in the First Century A.D., and its use for a variety of ailments, including psychological symptoms, is described in the early Middle Ages. Its first successful use for depression (then called melanh2cholia) was reported in the 1600's, and its use for anxiety and depression has been described in the German literature since that time.

The modern use of St. John's wort for depression arose from an incidental finding by a German doctor in the 1930's who was studying its effects on rats exposed to sunlight. Noting that the rats treated with St. John's wort appeared more active, that doctor began to prescribe St. John's wort for persons with depression and found it helpful.

Studies of St. John's wort lay dormant until the 1980's, when the German government commissioned a study of herbs with possibly medicinal effects and concluded that St. John's wort might have antidepressant properties. German pharmaceutical firms then conducted studies that found St. John's wort effective and generally well tolerated for mild to moderate depression. An analysis of those studies published in a British medical journal in 1996 has since led to increasing use of St. John's wort outside of Germany.

Like earlier studies, many studies reported since 1996 have found St. John's wort effective for mild to moderate depression and possibly for premenstrual syndrome, anxiety, and other disorders. However, new questions have arisen about the safety of St. John's wort and about its ability to interact with other medicines. An ongoing multicenter study sponsored by the National Institutes of Health is expected to answer questions about whether St. John's wort is more effective than placebo (a sugar pill) for depression and whether it is as effective and as safe as modern antidepressants. Results are expected next year.

Is it Effective for Depression?

Approximately thirty studies have compared St. John's wort to placebo or standard antidepressants. Nearly all of them found that St. John's wort was more effective than placebo and equivalent to the older generation tricyclic antidepressants. Overall, persons treated with St. John's wort had fewer side effects than did persons treated with older generation antidepressants.

Even so, many of those studies have been criticized because the persons in them had very mild depression, because very high percentages of persons treated with placebo experienced antidepressant effects, and because dosages of standard antidepressants were unusually low. A recent well-designed study by Richard Shelton, of Vanderbilt University, found St. John's wort no more effective than a placebo and less effective than the SSRI antidepressant Zoloft. Definitive answers will likely come from a multicenter study now in progress that is being sponsored by the National Institutes of Health.

How does it work?

Studies have reported that hyperforin, an ingredient of St. John's wort, affects brain chemicals called neurotransmitters in ways similar to those of antidepressants, such as Prozac, Zoloft, Paxil, Luvox, and Celexa. St. John's wort also has been reported to affect other neurotransmitters and the receptors on which they act. The significance of those effects on mood are not yet known.

What dosages have been found effective for depression?

Because St. John's wort is not regulated as a drug, different brands vary in how much of the active ingredient they contain. In general, three capsules per day (containing 300 milligrams of hypericin each) is recommended as a typical antidepressant dosage. Treatment of at least two weeks may be needed for antidepressant effects to occur.

What Precautions and Warnings should I know about?

The safety of St. John's wort in persons with heart, lung, liver, kidney, or other diseases is not known. The safety of St. John's wort in persons with epilepsy or other neurological disorders also is unknown. (Standard antidepressants may make seizures more likely.)

Also unknown is whether St. John's wort is safe to take during pregnancy or breastfeeding. St. John's wort has been reported to reduce blood levels of prolactin (a hormone involved in normal breast feeding) and of growth hormone (a hormone important in normal growth and in regulation of blood sugar).

St. John's wort has been reported to induce hypomania or mania in persons with depression or bipolar disorder, and may cause a variety of side effects and drug interactions (see below).

St. John's wort should not be used by persons with medical illness without consulting their doctors.

Does St. John's wort interact with other medicines?

St. John's wort may cause serious toxicity when taken with other antidepressants, including MAO-inhibitors, SSRI's, and tricyclic antidepressants. Possible reactions include very high blood pressure or "serotonin syndrome," (characterized by shivering, muscle jerking, restlessness, anxiety, and wide swings in blood pressure or heart rate). St. John's wort also may have potential to cause these symptoms when used along with the dietary supplement 5-HTP (5-hydroxytryptophan), the common over-the-counter cough suppressant dextromethorphan, or opiate analgesics such as codeine, meperidine, tramadol, or hydrocodone.

It is not known whether St. John's wort is safe when used in combination with alcohol or abusable drugs.

Regular use of St. John's wort has been reported to "induce" (that is, increase) the breakdown of several other drugs and may diminish their effects.

Specifically, St. John's wort has been reported to reduce or to probably reduce the blood levels of the immune modulator cyclosporine (Sandimmune), the heart drug digoxin, anti-HIV drugs such as indinavir (Viracept), the anticoagulant ("blood thinner") warfarin (Coumadin), and the asthma drug theophylline.

The effects of St. John's wort on liver enzymes have potential to lower the blood levels of oral contraceptives and of many medications used to treat heart disease, high blood pressure, infections of various kinds, and other diseases. Persons who start a medication while taking St. John's wort may have increased blood levels and experience increased effects of that medication after St. John's wort is stopped.

Persons taking medications should consult their doctors before taking St. John's wort.

What are the more common adverse effects of St. John's wort?

Although St. John's wort has been reported to be generally well tolerated when used to treat depression, it may cause allergy, rash, upset stomach, restlessness or jitteriness, sleep difficulty, anxiety, headaches, sweating, dizziness, and other side effects.

Some persons may develop severe sunburn while taking St. John's wort.

Some persons with depression or bipolar disorder have been reported to experience hypomania or mania during treatment with St. John's wort.

The effects of St. John's wort on body weight, blood sugar, or blood fat levels are not known, nor are the effects of St. John's wort on the heart or blood pressure.

It is not known whether St. John's wort may cause sexual dysfunction (as do SSRI's and some other antidepressants).

Some circumstantial reports by clinicians suggest that St. John's wort may cause withdrawal symptoms when abruptly stopped after regular use.

Should I use St. John's wort?

Compared with SSRI antidepressants such as Prozac, Zoloft, Paxil, and others, the main advantages of St. John's wort are convenience and confidentiality. The disadvantages include insufficient information about its effectiveness for more than mild depression, variable purity of various brands, necessity of taking it more than once per day, potential adverse effects in persons with bipolar depression, unknown effects in persons with medical illness or during pregnancy, and potentially severe drug interactions. The well-documented benefits of SSRI antidepressants should be weighed against the uncertain benefits of St. John's wort, and the well-documented safety profile of SSRI antidepressants should be weighed against the less well-documented safety profile of St. John's wort.