St. John’s Wort

St. John’s wort is probably the best known natural antidepressant. It works similarly to conventional antidepressants in that it inhibits the reuptake of serotonin, norepinephrine and dopamine. Most products used in scientific study are standardized to the component hypericin, but antidepressant activity has also been attributed to hyperforin. Standardization is important, as many St. John’s wort products available over the counter have been shown to contain little or none of these active ingredients, making them essentially useless.

St. John’s wort has been the subject of much discussion and controversy in the scientific and medical community. The vast majority of evidence suggests that St. John’s wort is effective for improving mood and reducing insomnia and somatic symptoms of depression in those with mild to moderately severe depression. St. John’s wort appears to be comparable to low-dose tricyclic antidepressants, as well as the SSRIs fluoxetine (Prozac), sertraline (Zoloft) and paroxetine (Paxil). In addition, there are significantly fewer side effects than with antidepressant medications making St. John’s wort much more tolerable over the long-term.

However, St. John’s wort is not without its disadvantages. In particular, St. John’s wort can cause a lot of negative drug interactions. St. John’s wort is a potent inducer of cytochrome P450 3A4 (CYP3A4) enzymes in the liver. These same enzymes are needed by about 50% of the drugs on the market, which means that taking these drugs along with St. John’s wort can significantly reduce the effectiveness of the medications. Therefore, St. John’s wort has the potential to interact with a very long list of drugs, including:

• Clopidogrel (Plavix)
• Cyclosporine (Neoral, Sandimmune)
• Digoxin
• Fexofenadine (Allegra)
• Imatinib (Gleevec)
• Indinavir (Crixivan)
• Irinotecan (Camptosar)
• Nevirapine (Viramune)
• Paroxetine (Paxil)
• Simvastatin (Zocor)
• Tacrolimus (Prograf, Protopic)
• Warfarin (Coumadin)
• Oral contraceptives

If you are taking any medications, you need to consult your health care provider prior to taking St. John’s wort.

If you want to try St. John’s wort, the typical dose used in clinical trials is to take 300 mg (standardized to 0.3% hypericin and 3-5% hyperforin) three times daily.