St. Johns Wort

St. Johns 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 herbs tendency to flower around the feast of St. John. (A wort is simply a plant in Old English.) The species name perforatum derives from the watermarking of translucent dots that can be seen when the leaf is held up to the sun. St. Johns 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, conceivably an archaic description of curing mental illness. In the 1800s, the herb was classified as a nervine, or a treatment for nervous disorders. It began to be considered a treatment for depression in the early 1900s, and when pharmaceutical antidepressants were invented, German researchers began to look for similar properties in St. Johns wort. Today, St. Johns wort is one of the best-documented herbal treatments, with a scientific record approaching that of many prescription drugs. Indeed, this herb is a prescription antidepressant in Germany, covered by the national health-care system, and is prescribed more frequently for depression than any synthetic drug. Evidence suggests that for mild to moderate depression, it is at least as effective as standard drugs, with fewer and less severe side effects. The active components in St. Johns wort are found in the buds, flowers, and newest leaves. Extracts are usually 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. Recent attention has focused on another ingredient of St. Johns wort named hyperforin as the potential active ingredient. Hyperforin was first identified as a constituent of Hypericum perforatum in 1971 by Russian researchers, but it was incorrectly believed to be too unstable to play a major role in the herbs action. However, recent evidence has corrected this view. It now appears that standard St. Johns wort extract contains about 1 to 6% hyperforin. We dont really know how St. Johns wort works. Early research suggested that St. Johns wort works like the oldest class of antidepressants, the MAO inhibitors. However, later research essentially discredited this idea. More recent research suggests that St. John's wort may inhibit the reuptake of serotonin, norepinephrine, and dopamine. Evidence from animal and human studies suggests that hyperforin is the ingredient in St. Johns wort that raises the levels of these neurotransmitters. Nonetheless, there may be other active ingredients in St. Johns wort also at work. In fact, two double-blind trials using a form of St. Johns wort with low hyperforin content found it effective. St. Johns wort appears to be reasonably safe when taken alone. However, there is good reason to believe that it may interact harmfully with numerous medications. (See Safety Issues for details).

Studies of St. Johns wort have evaluated individuals with major depression of mild to moderate intensity. (Contrary to widespread misreporting, this is clinical depression.) This contradictory-sounding language indicates that the level of depression is more severe than simply feeling blue. However, it is not as severe as the most intense forms of depression, which usually require hospitalization. Typical symptoms of major depression of mild to moderate severity include depressed mood, lack of energy, sleep problems, anxiety, appetite disturbance, difficulty concentrating, and poor stress tolerance. Irritability can also be a sign of depression.
Taken as a whole, research suggests that St. Johns wort is effective in about 55% of cases. As with other antidepressants, the full effect takes approximately 4 to 6 weeks to develop.
Warning: St. Johns wort should never be relied on for the treatment of very severe depression. If you or a loved one feels suicidal, unable to cope with daily life, paralyzed by anxiety, incapable of getting out of bed, unable to sleep, or uninterested in eating, see a physician at once. Drug therapy may save your life.
Furthermore, various systemic diseases may masquerade as depression, such as hypothyroidism, chronic hepatitis, and anemia. Make sure to find out whether you have an undiagnosed medical illness before treating yourself with St. Johns wort.
Because prescription antidepressants can help you sleep, it has been suggested that the herb St. Johns wort may be useful in the same way. A double-blind trial of 12 non-insomniacs found no sleep-promoting benefit, but this says little about its effectiveness in individuals with sleep problems. Similar reasoning has led physicians to try St. Johns wort for anxiety and seasonal affective disorder (SAD).
While standard antidepressants are often used for polyneuropathy (nerve pain), a double-blind placebo-controlled trial failed to find St. Johns wort effective for this purpose.
Early reports suggested that St. Johns wort or synthetic hypericin might be useful against viruses such as HIV, but these havent panned out. There is some evidence that the presumed active ingredient in St. Johns wort, hyperforin, may be able to fight certain bacteria, including some that are resistant to antibiotics. However, this evidence is far too preliminary to count St. Johns wort as an effective antibiotic.
Highly preliminary evidence suggests that St. Johns wort might be helpful for PMS and menopause.

The results of numerous studies suggest St. Johns wort is effective for mild to moderate depression.
There have been two main kinds of studies: those that compared St. Johns wort to placebo, and others that compared it to prescription antidepressants.
St. Johns Wort Versus Placebo
Studies of St. Johns 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 a thousand participants with major depression of mild to moderate severity have generally found that use of St. Johns wort can significantly reduce HAM-D scores as compared to placebo.
For example, in a 64-week trial, 375 indivdiuals with average 17-item HAM-D scores of about 22 (indicating major depression of moderate severity ) were given either St. Johns wort or placebo. Individuals taking St. Johns wort showed significantly greater improvement than those taking placebo.
Two 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. However, two 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. As if to illustrate this, in the more recent of the two trials in which St. John’s wort failed to prove effective, the drug sertraline (Zoloft) also failed to prove effective. The reason for these negative outcomes is not that Zoloft (or Prozac, or any other drug) 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 mild to moderate depression.
St. Johns Wort Versus Medications
Several studies have found that St. John’s wort is equally as effective as standard antidepressants, but causes fewer side effects.
The largest of these trials was a 6-week, double-blind trial of 240 individuals with mild to moderate depression that compared St. Johns wort (250 mg twice daily of a 4–7:1 alcohol extract) to fluoxetine (Prozac) at the standard dose of 20 mg daily. The results showed that St. Johns wort at least as effective as Prozac, and caused fewer and less severe side effects.
Four other double-blind trials enrolling a total of more than 300 indviduals have compared St. John’s wort to either fluoxetine (Prozac) or sertraline (Zoloft). In all of these studies, the herb proved as effective as the drug, and caused fewer side effects.
St. John’s wort has also been compared to older antidepressants.
An 8-week study of 263 individuals with moderate depression compared the effectiveness of a slightly high dose of St. Johns wort (350 mg 3 times daily of an extract standardized to contain 2 to 3 % hyperforin) against placebo and the somewhat outdated, but nonetheless effective, antidepressant imipramine. The results showed that imipramine and St. Johns wort were equally effective, and both were more effective than placebo.
However, according to a double-blind study of 209 people, St. Johns wort, even in double the usual dose, is not as effective as imipramine for severe depression.
Ten other trials of individuals with mild to moderate depression have compared St. Johns wort against older antidepressants including imipramine, maprotiline, and amitriptyline. However, these studies used very low doses of the standard drug, and therefore proved little.
Depression-Related Symptoms
In many of the studies described above, anxiety and insomnia associated with depression were noted to improve with St. Johns wort treatment.
Seasonal Affective Disorder
One small controlled study found St. Johns wort to be effective in the treatment of seasonal affective disorder (SAD), a form of depression that occurs primarily during the winter.
Polyneuropathy
A double-blind placebo-controlled trial of 54 individuals with polyneuropathy (nerve pain) did not find St. Johns wort effective for this purpose.

The standard dosage of St. John's wort is 300 mg 3 times a day of an extract standardized to contain 0.3% hypericin. A few new products on the market are standardized to hyperforin content (usually 2 to 3%) instead of hypericin. These are taken at the same dosage. Some people take 500 mg twice a day, or 600 mg in the morning and 300 mg in the evening. Yet another form of St. Johns wort has also passed double-blind studies. This form contains little hyperforin, and is taken at a dose of 250 mg twice daily. If the herb bothers your stomach, take it with food. Remember that the full effect takes 4 weeks to develop. Dont give up too soon!

St. Johns wort taken alone usually does not cause immediate side effects. In a study designed to look for side effects, 3,250 people took St. Johns wort for 4 weeks. Overall, about 2.4% reported problems. The most common complaints were mild stomach discomfort (0.6%), allergic reactions—primarily rash—(0.5%), tiredness (0.4%), and restlessness (0.3%). Another study followed 313 individuals treated with St. Johns wort for 1 year. The results showed a similarly low incidence of adverse effects.
In the extensive German experience with St. Johns wort as a treatment for depression, there have been no published reports of serious adverse consequences from taking the herb alone. Animal studies involving enormous doses of St. Johns wort extracts for 26 weeks have not shown any serious effects.
In a study of 101 children under the age of 12 given standardized St. John’s wort extract at a dose ranging from 300–1800 mg, adverse effects were seen Nonetheless, the safety of St. John’s wort for young children cannot be regarded as fully evaluated; similarly, it has not been proven safe for pregnant or nursing women, or individuals with severe liver or kidney disease. Individuals in these high risk groups should use St. John’s wort only under physician’s supervision.
In addition, there are a number of other potential safety risks with St. Johns wort that should be considered. These are outlined in the following sections.
Photosensitivity
Cows and sheep grazing on St. Johns wort have sometimes developed severe and even fatal sensitivity to the sun. In one study, highly sun-sensitive people were given twice the normal dose of the herb. The results showed a mild but measurable increase in reaction to ultraviolet radiation. Another trial found that a one-time dose of St. John’s wort containing 2 or 6 times the normal daily dose did not cause an increased tendency to burn; nor did seven days treatment at the normal dose. However, there is a case report of severe and unexpected burning in an individual who used St. Johns wort and then received ultraviolet therapy for psoriasis. In addition, two individuals using topical St. Johns wort experienced severe reactions to sun exposure.
The morals of the story are as follows: if you are especially sensitive to the sun, dont exceed the recommended dose of St. Johns wort, and continue to take your usual precautions against burning; if you are receiving UV treatment, do not use St. John’s wort at all; and if you apply St. John’s wort to your skin, keep that part of your body away from the sun.
In addition, you might get into problems if you combine St. Johns wort with other medications that cause increased sun sensitivity, such as sulfa drugs and the anti-inflammatory medication Feldene (piroxicam). The medications Prilosec (omeprazole) and Prevacid (lansoprazole) may also increase the tendency of St. Johns wort to cause photosensitivity.
Finally, a recent report suggests that regular use of St. Johns wort might also increase the risk of sun-induced cataracts. While this is preliminary information, it may make sense to wear sunglasses when outdoors if you are taking this herb on a long-term basis.
Drug Interactions
Herbal experts have warned for some time that combining St. Johns wort with drugs in the Prozac family (SSRIs) might raise serotonin too much and cause a number of serious problems. Recently, case reports of such events have begun to trickle in. This is a potentially serious risk. Do not combine St. Johns wort with prescription antidepressants except on the specific advice of a physician. Since some antidepressants, such as Prozac, linger in the blood for quite some time, you also need to exercise caution when switching from a drug to St. Johns wort. (See Transitioning from Medications to St. Johns Wort.)
The antimigraine drug sumatriptan (Imitrex) and the pain-killing drug tramadol also raise serotonin levels and might interact similarly with St. Johns wort.
Perhaps the biggest concern with St. Johns wort is the possibility that it may decrease the effectiveness of various medications, including protease inhibitors (for HIV infection), non-nucleoside reverse transcriptase inhibitors such as nevirapine (NNRTIs – also used for HIV infection), cyclosporine (for organ transplants), digoxin (for heart disease), statin drugs (used for high cholesterol) warfarin (a blood thinner), chemotherapy drugs (such as doxorubicin, etoposide, mitoxantrone, teniposide, and irinotecan), oral contraceptives, tricyclic antidepressants, olanzapine or clozapine (for schizophrenia), and theophylline (for asthma). Furthermore, if you are taking St. Johns wort and one of these medications at the same time and then stop taking the herb, blood levels of the drug may rise. This rise in drug level could be dangerous in certain circumstances.
These interactions could lead to catastrophic consequences. Indeed, St. Johns wort appears to have caused several cases of heart, kidney, and liver transplant rejection by interfering with the action of cyclosporine. Also, many people with HIV take St. Johns wort in the false belief that the herb will fight the AIDS virus. The unintended result may be to reduce the potency of standard AIDS drugs.
In addition, meaningful case reports and scientific studies suggest that the herb decreases the effectiveness of oral contraceptives, and has caused unwanted pregnancies.
The bottom line: We recommend that individuals taking any oral or injected medication that is critical to their health should entirely avoid using St. Johns wort until more is known.
It is probably advisable on general principles to discontinue all herbs and supplements prior to surgery and anesthesia, due to the possibility of unpredictable interactions. However, there does not appear to be any specific foundation to publicized claims that St. Johns wort interacts with anesthetic drugs.
Safety in Special Circumstances
One animal study found no ill effects on the offspring of pregnant mice. However, these findings alone are not sufficient to establish St. Johns wort as safe for use during pregnancy. Furthermore, the St. Johns wort constituent hypericin can accumulate in the nucleus of cells and directly bind to DNA.70 For this reason, pregnant or nursing women should avoid St. Johns wort. Furthermore, safety for use by young children or people with severe liver or kidney disease has not been established.
Like other antidepressants, case reports suggest that St. Johns wort can cause episodes of mania in individuals with bipolar disorder (manic-depressive disease).
There is also one report of St. Johns wort causing temporary psychosis in a person with Alzheimers disease.
Other Concerns
One small study suggests that high doses of St. Johns wort might slightly impair mental function.
One case report associates use of St. Johns wort with hair loss. The authors note that standard antidepressants may also cause hair loss at times.
One study raised questions about possible antifertility effects of St. Johns wort. When high concentrations of St. Johns wort were placed in a test tube with hamster sperm and ova, the sperm were damaged and less able to penetrate the ova. However, since it is unlikely that this much St. Johns wort can actually come in contact with sperm and ova when they are in the body rather than in a test tube, these results may not be meaningful in real life.
Older reports suggested that St. Johns wort works like the class of drugs known as MAO inhibitors. This led to a number of warnings, including avoiding cheese and decongestants while taking St. Johns wort. However, St. Johns wort is no longer believed to act like an MAO inhibitor, and these warnings are now thought to be groundless.

If you are taking a prescription drug for mild to moderate depression, switching to St. Johns 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. Johns wort. Consult with your doctor on how much time is necessary. However, if you are taking medication for severe depression, switching over to St. Johns wort is not a good idea. The herb probably wont work well enough, and you may sink into a dangerous depression.

If you are taking:

• Antidepressant drugs, including MAO inhibitors, SSRIs, and tricyclics; or possibly the drugs tramadol or sumatriptan (Imitrex): Do not take St. Johns wort at the same time. Actually, you need to let the medication flush out of your system for a while (perhaps weeks, depending on the drug) before you start the herb.
   
• Digoxin, cyclosporine, any medications for HIV infection, oral contraceptives, tricyclic antidepressants, Coumadin (warfarin), statin drugs (used for high cholesterol), theophylline, chemotherapy drugs, newer antipsychotic medications (such as olanzapine and clozapine) or any critical medication: St. Johns wort might cause the drug to be less effective. Furthermore, if you are already taking St. Johns wort and your physician adjusts your medication dosage to achieve proper blood levels, suddenly stopping St. Johns wort could cause the level of the drug in your body to rebound to dangerously high levels.
   
• Medications that cause sun sensitivity such as sulfa drugs and the anti-inflammatory medication Feldene (piroxicam), as well as Prilosec (omeprazole) or Prevacid (lansoprazole): Keep in mind that St. Johns wort might have an additive effect.