The herbal remedy or supplement St. John’s wort has been used to lift moods for hundreds of years and has been a staple of homeopathic medicine in the U.S. for decades. The Mayo Clinic notes that a number of studies support the use of the supplement in treating mild-to-moderate depression and it is prescribed for this purpose in Europe. In combination with black cohosh, the herb may also reduce some symptoms of menopause.

The National Institutes of Health, however, caution that St. John’s wort doesn’t always relieve depression and trying it may delay treatment with a more effective medication. The NIH also reports that St. John’s wort may worsen psychotic symptoms in individuals with schizophrenia or bipolar disorder. Pregnant or nursing women should not take it.

Unlike other supplements or drugs, the tricky part about St. John’s wort is what to do when it does work.

The biggest risk occurs when someone takes St. John’s wort with a prescription antidepressant, including most selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and monoamine oxidase inhibitors.

It doesn’t take much for the combination to dangerously elevate serotonin levels. New Zealand’s Medsafe regulatory authority reported a case of serotonin syndrome requiring hospitalization following one cup of St. John’s wort tea and 2 days of citalopram.  

Symptoms of serotonin syndrome may start within minutes or take a few hours to become noticeable. They include headache, shivering, profuse sweating, agitation, dilated pupils, confusion, diarrhea, rapid heart rate, hypertension, muscle rigidity, loss of muscle coordination, and hallucination. Serious cases may experience irregular heartbeat, high fever, seizures, and loss of consciousness. Anyone experiencing these symptoms after taking St. John’s wort with an antidepressant should be advised to seek medical attention immediately.

Outside of antidepressants, St. John’s wort mostly reduces the effectiveness of the drugs with which it interacts. That could be life-threatening for patients taking cancer medications such as docetaxel, irinotecan, or imatinib, or if they need immunosuppressive drugs after transplantation or to manage an autoimmune disease. St. John’s wort diminishes the ability of warfarin to reduce blood clotting and can interfere with medications used to treat HIV infections.

The drug also impairs the effectiveness of several classes of drugs, including barbiturates, contraceptives, narcotics, and triptans. In addition, it reduces the benefit from alprazolam, bupropion, simvastatin, digoxin, ketamine, omeprazole, phenytoin, and voriconazole.

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