Why You Should Avoid the Herbal Supplement St. John’s Wort

St. John’s wort is an herbal dietary supplement that is commonly available in capsules, tablets or teas.[1] It is derived from a yellow flowering plant called hypericum perforatum.

Whereas medieval Europeans claimed the herb could ward off evil spirits, in recent years it has been promoted as a treatment for medical conditions, mainly depression.

Public Citizen’s Health Research Group for years has designated St. John’s wort as Do Not Use for depression and other conditions because the evidence about its effectiveness, appropriate dosage and safety is weak. Because it is a dietary supplement, St. John’s wort has not been evaluated for use by the Food and Drug Administration (FDA). This herb also has potentially dangerous interactions with numerous medications. Our recommendation is consistent with the positions of the American College of Physicians[2] and the American Psychiatric Association.[3]

Limited effectiveness and safety evidence

Two major systematic reviews have analyzed the collective evidence pertaining to St. John’s wort from randomized clinical trials.[4] The first review, published in 2008 by researchers from the Cochrane Collaboration,[5] examined evidence from trials that enrolled subjects with major depression. Although these researchers found that St. John’s wort did slightly better than placebo and was similar to standard antidepressants, this finding was almost exclusively true only in studies conducted in Germany. The researchers acknowledged that all German trials recruited subjects during physician office visits (these patients are more likely to have minor depression). In contrast, trials conducted in other countries included subjects in academic research settings or hospital outpatient units (subjects who are more likely to have severe depression).

The second systematic review, published by researchers from the RAND corporation in 2016, found that St. John’s wort is superior to placebo but no better than standard antidepressants in improving mild and moderate depressive symptoms.[6] However, they downgraded the strength of their findings because of significant heterogeneity (differences) between the trials. The fact that German trials reported a stronger effect of St. John’s wort than other studies still did not explain the heterogeneity between trials. Generally, the trials lasted up to 12 weeks only and did not include subjects with severe depression. This means that the long-term usefulness of St. John’s wort is unknown, particularly for severe depression.

Previous research showed that St. John’s wort is associated with photosensitivity, allergic skin reactions (itching or redness), mania and psychotic episodes.[7] However, the RAND researchers noted that the assessments of adverse effects were limited in clinical trials, which makes it hard to assess the safety of this herb.

Importantly, very few trials compared different dosages and products of St. John’s wort,[8] and there are no proper standards regarding the potency or purity of these products because they are neither approved nor regulated by the FDA.[9]

Interactions with drugs

Another key reason to stay clear of St. John’s wort is that it interacts with more medications than any other herbal or dietary supplement.[10] These interactions occur because one of the main active ingredients of St. John’s wort, hyperforin, activates an enzyme in the liver that speeds up the breakdown of many drugs, including antidepressants, birth-control pills, immunosuppressants, and certain heart and blood pressure medications (see Table, below, for some examples of these oral medications).[11] As a result, the therapeutic effects of the interacting drugs may be reduced or eliminated.

Furthermore, St. John’s wort increases the risk of serotonin syndrome when it is taken with certain medications called selective serotonin reuptake inhibitors (including citalopram [CELEXA], escitalopram [LEXAPRO], fluoxetine [PROZAC], paroxetine [PAXIL, PEXEVA] and sertraline [ZOLOFT]) and selective serotonin and norepinephrine reuptake inhibitors (including desvenlafaxine [PRISTIQ], duloxetine [CYMBALTA, DRIZALMA SPRINKLE], levomilnacipran [FETZIMA], milnacipran [SAVELLA] and venlafaxine [EFFEXOR XR]).[12],[13] Serotonin syndrome is a life-threatening condition that is characterized by high blood pressure, rapid heart rate, elevated body temperature, sweating, confusion, muscle rigidity, tremors and diarrhea.[14]

Oral Drugs Whose Effects Are Decreased by St. John’s Wort[15],[16],[17]

†Brand-name combination products were excluded.
*Designated as Do Not Use by Worst Pills, Best Pills News
**Designated as Limited Use by Worst Pills, Best Pills News
***High-dose simvastatin (80 milligrams) is designated as Do Not Use by Worst Pills, Best Pills News. Lower-dose forms are acceptable.

What You Can Do

If you are struggling with depression, it is best to avoid St. John’s wort and other unproven products. Instead, seek medical help because both cognitive behavioral therapy and second-generation antidepressants are similarly effective for treating major depression.[18] Always inform your doctor about any dietary supplements that you are taking.
 

References

[1] Fujihashi A, Ramesh S, Govindarajulu M, et al. St. John’s wort: A therapeutic herb to be cautioned for its potential neurotoxic effects and major drug interactions. In: Agrawal DC, Dhanasekaran M, eds. Medicinal Herbs and Fungi. Springer; 2021:369-389.

[2] Qaseem A, Barry MJ, Kansagara D, et al. Nonpharmacologic versus pharmacologic treatment of adult patients with major depressive disorder: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2016;164(5):350-359.

[3] American Psychiatric Association. Practice guideline for the treatment of major depressive disorder. 2010. https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf. Accessed October 6, 2021.

[4] Haller H, Anheyer D, Cramer H, Dobos G. Complementary therapies for clinical depression: an overview of systematic reviews. BMJ Open. 2019;9(8):e028527.

[5] Linde K, Berner M, Kriston L. St John’s wort for major depression (review). Cochrane Database Syst Rev. 2008;2008(4):CD000448.

[6] Apaydin EA, Maher AR, Shanman R, et al. A systematic review of St. John’s wort for major depressive disorder. Syst Rev. 2016;5(1):148.

[7] Knüppel L, Linde K. Adverse effects of St. John’s Wort: a systematic review. J Clin Psychiatry. 2004;65(11):1470-1479.

[8] Apaydin EA, Maher AR, Shanman R, et al. A systematic review of St. John’s wort for major depressive disorder. Syst Rev. 2016;5(1):148.

[9] Qaseem A, Barry MJ, Kansagara D, et al. Nonpharmacologic versus pharmacologic treatment of adult patients with major depressive disorder: A clinical practice guideline from the American College of Physicians. Ann Intern Med. 2016;164(5):350-359.

[10] Tsai HH, Lin HW, Simon Pickard A, et al. Evaluation of documented drug interactions and contraindications associated with herbs and dietary supplements: A systematic literature review. Int J Clin Pr. 2012;66(11):1056-1078.

[11] Fujihashi A, Ramesh S, Govindarajulu M, et al. St. John’s Wort: A therapeutic herb to be cautioned for its potential neurotoxic effects and major drug interactions. In: Agrawal DC, Dhanasekaran M, eds. Medicinal Herbs and Fungi. Springer; 2021:369-389.

[12] Borrelli F, Izzo AI. Herb-drug interactions with St John’s wort (Hypericum perforatum): An update on clinical observations. AAPS J. 2009;11(4):710-727.

[13] Eli Lilly and Company. Label: duloxetine delayed release (CYMBALTA). July 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/021427s056lbl.pdf. Accessed October 7, 2021.

[14] National Center for Complementary and Integrative Health. Get the facts: St. John’s wort and depression. December 2017. https://www.nccih.nih.gov/health/st-johns-wort-and-depression-in-depth. Accessed October 7, 2021.

[15] Smith-Stephens SL. Highs, lows, and health hazards of herbology: A review of herbal medications with psychotropic effects. Nurs Clin North Am. 2021;56(1):137-152.

[16] Asher GN, Corbett AH, Hawke RL. Common herbal dietary supplement-drug interactions. Am Fam Physician. 2017;96(2):101-107.

[17] Fujihashi A, Ramesh S, Govindarajulu M, et al. St. John’s Wort: A therapeutic herb to be cautioned for its potential neurotoxic effects and major drug interactions. In: Agrawal DC, Dhanasekaran M, eds. Medicinal Herbs and Fungi. Springer; 2021:369-389.

[18] Qaseem A, Barry MJ, Kansagara D, et al. Nonpharmacologic versus pharmacologic treatment of adult patients with major depressive disorder: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2016;164(5):350-359.