St. John's Wort

NATURAL PRODUCTS

St. John’s Wort (Hypericum perforatum)

St. John’s Wort has found a niche in being a natural product that has antidepressant effects, but it has also been used to help with anxiety, wounds, inflammatory conditions of the skin, insomnia, and blunt injuries. The antidepressant effects of St. John’s Wort are due to a combination of the extracted compounds, which includes Hypericin, and no single agent is responsible for the effect.

Studies have shown that St. John’s Wort has some monoamine oxidase (MAO) inhibition, from the hyperforin component, and some serotonin (5-HT) reuptake inhibition. The serotonin reuptake inhibition is similar to the actions of the prescription antidepressants Prozac and Paxil. In addition, a recent article in the journal Lancet (February 12, 2000) reported that St. John's Wort has been shown to be an inducer of the cytochrome P450 metabolic pathway, which is responsible for the metabolism of many drugs. Unfortunately, all of these actions lead to several important drug interactions, which are discussed below.

St. John’s Wort is not nearly as potent in its effects as are the prescription medication antidepressant drugs. Some people are taking it with these drugs or are using it alone to replace prescription antidepressants without medical supervision. Caution should be taken, especially with the elderly and when driving or working with machinery.

St. John’s Wort, like other natural products, has quality assurance issues and questionable dosage ranges. Even supposedly controlled clinical studies, of which there are few, of St. John’s Wort in depression have conflicting information. A 1999 study published in the journal Phytomedicine concluded that a standardized hypericin dose of no more than 1 milligram daily resulted in an improvement in depressive symptoms of about 50%. Contradicting this study was one published a year prior that claimed the effective hypericin dose for depression is 300 milligrams three times a day. Likewise, another study suggested a daily dose of 30 milligrams. Besides the questionable dosage range is the fact that there appear to be multiple mechanisms for the effects seen with hypericin and the other compounds found in St. John’s Wort.

St. John's Wort has been shown to have a significant drug interaction with indinavir (Crixivan, MSD), a protease inhibitor used to treat HIV infection. It was shown that St. John's Wort substantially decreased blood concentrations of indinavir leading to a loss of effectiveness. It is postulated that St. John's Wort will decrease the blood concentrations of other protease inhibitors, like saquinavir (Fortovase or Invirase), ritonavir (Norvir), amprenavir (Agenerase), and nelfinavir (Viracept). It also may interact in a similar fashion with non-nucleoside reverse transcriptase inhibitors for HIV therapy, such as Sustiva, Rescriptor, and Viramune. St. John’s Wort should not be taken by anbody on HIV therapy, without first discussing its use with his or her physician and/or pharmacist. There are many drugs commonly used to treat other medical problems, including hypertension, depression, contraception, heart disease, and infection. Some of these drugs may have a similar drug interaction with St. John's Wort.

Sympathomimetics like phenylpropanolamine, ephedrine, and pseudoephedrine, and tyramine containing foods such as red wines and aged cheeses should be avoided with St. John’s Wort, to prevent a hypertensive crisis requiring medical intervention. St. John’s Wort should also be avoided by anybody taking monoamine oxidase inhibitors, such as Parnate, Nardil, and Marplan, for the same reason. Furthermore, it is suggested that at least a two week wash-out period should exist between stopping monoamine oxidase inhibiting drugs and starting St. John’s Wort or between stopping St. John’s Wort and starting monoamine oxidase inhibiting drugs. Since St. John’s Wort also acts as a serotonin reuptake inhibitor, its effects are additive to selective serotonin reuptake inhibitors like Prozac, Paxil, and Zoloft.

Use of St. John’s Wort with serotonin reuptake inhibitors has been reported to lead to a toxic effect of serotonin overdose, known as serotonin syndrome, and it may also increase the sedative effect of these drugs. The symptoms of serotonin syndrome can be quite severe, and include high blood pressure, severe anxiety, sleep disturbances, fever, tremors, rhabdomyolysis (muscle breakdown with painful muscle weakness), diarrhea, and convulsions. It requires emergency medical treatment. A documented prescription drug, non-prescription drug, and natural product history will help the treating physician in diagnosing the condition and starting appropriate treatment. Once again, it is suggested that there should be a two week wash-out period after stopping a prescribed serotonin reuptake inhibitor and starting St. John’s Wort or between stopping St. John’s Wort and starting the prescription medication.

Additional drug interactions with St. John's Wort are being reported as more patients take it with other drugs and researchers investigate potential interactions. A study by Johne, A., Brockmoller, J., et.al., published in Clinical Pharmacology and Therapeutics, in October 1999 reported that St. John's Wort, after 10 days of use, can lower Digoxin levels and the total amount absorbed significantly. Since Digoxin is used to treat heart failure and atrial fibrillation, and has a very narrow therapeutic blood level range between effectiveness and toxicity, it is imperative that anybody taking or contemplating taking digoxin and St. John's Wort talk with their physician. Any digoxin dosage changes made to maintain effectiveness, while taking St. John's Wort, can lead to digoxin toxicity when St. John's Wort is stopped. It is imperative that the prescribing physician and pharmacist be immediately notified that St. John's Wort therapy has been stopped.

Other recent drug interactions found with St. John's Wort include theophylline (for asthma), cyclosporine (immunosuppressant to help prevent organ transplant rejection), and phenprocoumon (a relative of the anticoagulant warfarin [Coumadin]) that is generally not available in the U.S. In each of these drugs, St. John's Wort can decrease their effectiveness and potentially lead to a treatment failure or worse. Once again, adjusting their dosages, while on St. John's Wort, can lead to potential toxicity when St. John's Wort is stopped. It is imperative that the prescribing physician and pharmacist be immediately notified that St. John's Wort therapy has been stopped. Information on these interactions can be found in the January 8, 2000, March 18, 2000, and May 27, 2000 issues of the medical journal Lancet.

A pharmacist or physician, who knows your medical history and current drug history, should be consulted prior to starting St. John's Wort, to prevent potential drug interactions.

Legal Info: Solumedia is not responsible for errors or omissions. The information provided on the natural product pages is only a guideline based on current literature and the pharmacological action of these products. It should not be used as the sole source of information on these products. Many of the drug interactions listed are not found in current literature but are based on likely interactions due to the actions of the interacting drugs. It is recommended that a qualified and licensed healthcare professional be consulted for additional information. Although the information provided is from reliable sources, Solumedia has no liability. This information is provided only as a service.

This page was last updated on 04/29/05.