St. John's Wort Overview

St. John's wort is a common perennial herb of many branches and bright yellow flowers that grows wild in much of the world. Its name derives from the herb's tendency to flower around the feast of St. John. (A wort simply means plant in Old English.) The species name perforatumderives from the watermarking of translucent dots that can be seen when the leaf is held up to the sun.

St. John's wort has a long history of use in treating emotional disorders. During the Middle Ages, St. John's wort was popular for "casting out demons." In the 1800s, the herb was classified as a nervine, or a treatment for "nervous disorders." When pharmaceutical antidepressants were invented, German researchers began to look for similar properties in St. John's wort.

St. John’s Wort works as a monoamine (MAO) inhibitor, preventing MAOs from breaking down certain neurotransmitters in the brain. Therefore, it increases the amount and time of mood elevating neurotransmitters, norepinephrine and dopamine, existing in between the synapses of the brain. It also works to increase the amount of serotonin in the brain, which helps regulates a person’s mood.

St. Johns Wort also works to activate gamma-aminobutyric (GABA) receptors in the brain, inhibiting reuptake. Increased GABA activity slows down brain processes, which can lead to feelings of relaxation. This may help with depressive symptoms of restlessness, and increase concentration and the ability to fall asleep.

Depression

There have been two main kinds of studies: those that compared St. John's wort to placebo, and others that compared it to prescription antidepressants. A 2008 detailed review of 29 randomized, placebo controlled trials found that St. Johns wort was consistently more effective than placebo and equally effective to standard antidepressants. ¹

St. John's Wort Versus Placebo

Studies of St. John's wort (and other antidepressants) use a set of questions called the Hamilton Depression Index (HAM-D). This scale rates the extent of depression, with higher numbers indicating more serious symptoms.

Double-blind, placebo-controlled trials involving a total of more than 1,500 participants with major depression of mild to moderate severity have generally found that use of St. John's wort can significantly reduce HAM-D scores as compared to placebo. ² In addition, continued treatment with St. Johns Wort over 6 months may be effective at preventing a relapse of moderate depression in patients who recover from an initial acute episode. ³ For example, in a 6-week trial, 375 individuals with average 17-item HAM-D scores of about 22 (indicating major depression of moderate severity) were given either St. John's wort or placebo. ⁴ Individuals taking St. John's wort showed significantly greater improvement than those taking placebo.

Three double-blind, placebo-controlled trials evaluating individuals with a similar level of depression have failed to find St. John’s wort more effective than placebo. ⁵ However, three studies cannot overturn a body of positive research. Keep in mind that 35% of double-blind studies involving pharmaceutical antidepressants have also failed to find the active agent significantly more effective than placebo. ⁶ As if to illustrate this, in two of the three studies in which St. John’s wort failed to prove effective, a conventional drug (Zoloft in one case, Prozac in the other) also failed to prove effective. The reason for these negative outcomes is not that Zoloft or Prozac does not work. Rather, statistical effects can easily hide the benefits of a drug, especially in a condition like depression where there is as a high placebo effect and no really precise method of measuring symptoms. Thus, unless a whole series of studies find St. John’s wort ineffective, especially trials in which a comparison drug treatment does prove effective, St. John’s wort should still be regarded as probably effective for major depression of mild to moderate severity.

St. John's Wort Versus Medications

At least 8 double-blind trials enrolling a total of more than 1,200 people have compared St. John’s wort to fluoxetine (Prozac), citalopram (Celexa), paroxetine (Paxil) or sertraline (Zoloft). ⁷ In all of these studies, the herb proved as effective as the drug and generally caused fewer side effects.

In the largest of these trials, a 6-week study of 388 people with major depression of mild-to-moderate severity, St. John's wort proved equally effective as the drug citalopram (Celexa) and more effective than placebo. ⁸ Additionally, Celexa caused a significantly higher rate of side effects than St. John's wort. There were also significantly more side effects in the placebo group than in the St. John's wort group—presumably because treatment of depression reduces physical symptoms of psychological origin.

St. John’s wort has also been compared to older antidepressants, with generally favorable results. ^{9 10 11 12}

How Does St. John’s Wort Work for Depression?

Like pharmaceutical antidepressants, St. John's wort is thought to raise levels of neurotransmitters in the brain, such as serotonin, norepinephrine, and dopamine. ¹³ The active ingredient of St. John’s wort is not known. Extracts of St. John’s wort are most often standardized to the substance hypericin, which has led to the widespread misconception that hypericin is the active ingredient. However, there is no evidence that hypericin itself is an antidepressant. Another ingredient of St. John's wort named hyperforin has shown considerable promise as the most important ingredient. Hyperforin was first identified as a constituent of Hypericum perforatumin 1971 by Russian researchers, but it was incorrectly believed to be too unstable to play a major role in the herb's action. ¹⁴ However, subsequent evidence corrected this view. It now appears that standard St. John's wort extract contains about 1% to 6% hyperforin. ¹⁵ Evidence from animal and human studies suggests that it is the hyperforin in St. John’s wort that raises the levels of neurotransmitters. ^{16 17} Nonetheless, there may be other active ingredients in St. John's wort also at work. ¹⁸ In fact, 2 double-blind trials using a form of St. John's wort with low hyperforin content found it effective. ¹⁹ The bottom line remains that more research is necessary to discover just how St. John’s wort acts against depression.

Polyneuropathy

A double-blind, placebo-controlled trial of 54 people with diabetic neuropathy or other forms of neuropathy (pain, numbness and/or tingling caused by injury to nerves) did not find St. John's wort effective for this purpose. ²⁰

The typical dosage of St. John's wort is 300 mg 3 times a day of an extract standardized to contain 0.3% hypericin. Some products are standardized to hyperforin content (usually 2% to 3%) instead of hypericin. These are usually taken at the same dosage. Two studies found benefits with a single daily dose of 900 mg. ²¹ Yet another form of St. John's wort has shown effectiveness in double-blind studies. This form contains little hyperforin and is taken at a dose of 250 mg twice daily. ²² There is some evidence that this form of St. John's wort may be less likely to interact with medications. (See Drug Interactions .)

If the herb bothers your stomach, take it with food.

Remember that the full effect takes 4 weeks to develop. Don't give up too soon!

If you are taking a prescription drug for mild to moderate depression, switching to St. John's wort may be a reasonable idea if you would prefer taking an herb. To avoid overlapping treatments, the safest approach is to stop taking the drug and allow it to wash out of your system before starting St. John's wort. Consult with your doctor on how much time is necessary.

However, if you are taking medication for severe depression, switching over to St. John's wort is nota good idea. The herb probably won't work well enough, and you may sink into a dangerous depression.

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