Using St. John’s Wort With Other Antidepressants

I have used St. John’s wort with patients who were already on antidepressants, including Prozac, Zoloft, Effexor (venlafaxine hydrochloride), and the tricyclics (see Prozac and Beyond-The Synthetic Antidepressants), as well as those taking the amino acids such as tyrosine. Of possible concern in these cases is “serotonin syndrome,” or an excessive serotonin buildup in the brain. There is no record of this occurring, despite thousands of people having taken the combination of St. John’s wort and SSRIs. When asked about this possibility, Dr. Jerry Cott, a psychopharmacologist at the National Institute of Mental Health, asserted that “there have been no deaths or toxic reactions, no adverse interactions related to MAO inhibition, and no incidents of serotonin syndrome reported in the literature. There is no clear evidence that serotonin is even [activated] by St. John’s wort in . . . animal studies or in human trials.” It is clear that more research is needed before we fully understand how this herb works.


One of the most common questions I am asked concerns the best way to switch from an antidepressant to St. John’s wort. There is no research data on this subject, only the experiences of many patients and their physicians. We all look forward to having definitive reports in the future. For now, I can say that the process must be done under a doctor’s supervision, preferably the one who prescribed the antidepressant. If your doctor is reluctant to do this, I would encourage you to share this book with him or her. The doctor can thus become familiar with the clinical use of St. John’s wort. He or she can also look up the research evidence in Chapter 6, including an explanation of why there is so little North American research on this subject. Appendix C will provide your doctor with the appropriate changeover protocol.


It is important to point out that switching from a synthetic antidepressant to St. John’s wort without appropriate supervision can pose serious problems. For example, if me antidepressant is stopped abruptly, a rebound effect could result, leading to renewed anxiety and depression. Or, if St. John’s wort is combined with the wrong drug, there can be negative consequences. This is especially true of MAO-inhibiting antidepressants such as Nardil (phenelzine sulfate) or Parnate (tranylcypromine sulfate). Also, as we have discussed, St. John’s wort is not recommended as the sole treatment in major depression, and its use in bipolar disorder remains a question.


As we’ve seen in this chapter, St. John’s wort is pretty simple to use– just take it with meals. While the side effects are generally minimal, it is essential to speak with your doctor if you have a preexisting medical condition or if you are already taking an antidepressant. Finding a doctor open to natural therapies may be an important consideration. In the next chapter, I’ll discuss the studies that support the use of St. John’s wort.

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Hyla Cass MD Written by Hyla Cass MD

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