Saint Johns Wort

Updated | 2017-11-29


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Saint Johns Wort


Overview

Botanical Name: Hypericum perforatum


Order: Malpighiales


Family: Hypericaceae


Saint John's Wort is commonly used to treat depression. Although, this plant is widely used, it has a relatively large list of major interactions.



Evidence

Strong:

-

Good:

  • Minor to Mild to Moderate Depression [1-42]
    • Clinical trials have found that Saint John’s wort independently or in combination with valerian may be effective. Some suggest the possibility of a placebo effect or that the effects of Saint John’s wort are dose dependent. It appears that Saint John’s wort may affect the response, remission, recovery, relapse, and recurrence of depression

Promising:

  • Peri-menopausal and Menopausal Complaints, Saint John’s wort in combination with black cohosh or chaste tree [43-48]
  • Somatic Symptom Disorder [49-51]
  • Winter Depression [52-54]

Conflicting (Unclear):

  • Major Depression (Major Depressive Disorder), an NCCAM funded study [Hypericum Depression Trail Study Group 2002] found that Saint John’s wort might not be effective in relieving major depression [55-71]
    • Many have reported that Saint John’s wort is effective for major depression, while others have found it to be ineffective

Limited Evidence:

  • Anti-platelet Agent [72-73]
  • Atopic Dermatitis (Eczema), a cream containing Saint John’s wort [74]
  • C-Section Wound Healing, an ointment containing Saint John’s wort [75-76]
  • Ear Inflammation in Children, drops containing either Saint John’s wort / calendula flowers / mullein in olive oil or Saint John’s wort / garlic / calendula flowers / mullein / lavender / vitamin E in olive oil [77-78]
  • Herpes, a cream containing Saint John’s wort / copper sulfate pentahydrate [79]
  • Irritable Bowel Syndrome [80-81]
  • Non-melanoma Skin Cancer, an ointment containing Saint John’s wort [82]
  • Obsessive Compulsive Disorder (ODC) [83-84]
  • Osteomyelitis in the feet of Diabetics, local injection of a mixture of phenothiazine (2% in water) and Saint John’s wort extract (10% in propylene glycol) [85]
  • Premenstrual Syndrome (PMS) [86]
  • Schizophrenia [87]
  • Venous Ulcers, an ointment containing Saint John’s wort / garlic / calendula [88]

No Evidence:

  • Attention Deficit Hyperactivity Disorder (ADHD) [89]
  • Autism [90]
  • Burning Mouth Syndrome [91]
  • Chronic Pain [92-93]
  • Cognition and Memory [94-96]
  • Hepatitis C [97]
  • Knee Pain, a blend with Saint John’s wort / Arnica montana / Bryonia alba / Ruta graveolens [98]
  • Social Phobia [99]
  • Quit Smoking (Smoking Cessation) [100-103]

No Clinical Research:

All other conditions.


Side Effects
Side effects may include:
  • Allergic Reactions
  • Constipation
  • Diarrhea
  • Dizziness
  • Dry Mouth
  • Fatigue
  • Feeling of Fullness
  • Frequent Urination
  • Gastrointestinal Upset
  • Headache
  • Indigestion
  • Insomnia
  • Itching
  • Sensitivity to Sunlight
  • Restlessness
  • Trouble Sleeping
Precautions and Adverse Events:
  • Avoid or contact a licensed healthcare practitioner, since some people may have allergic reactions (rashes, itching) to Saint John’s wort, and use caution if you have had a history of mania, photosensitivity, psychiatric disorders.
  • There have been rare adverse events such as photosensitivity, phototoxic reaction to a laser treatment, mania (from high doses of Saint John’s wort), severe nosebleed (after nasal insertion of Saint John’s wort), schizophrenia relapse, neuropathy, severe anxiety, sleep disorders, psychosis, serotonin syndrome, impotence (erectile dysfunction), decreased sex drive, anorexia, and changes in blood pressure and pulse. If you have any of these adverse events, consult a licensed healthcare practitioner.
  • A case of scalp and eyebrow hair loss was reported after a schizophrenia patient on olanzapine began taking Saint John’s wort.
  • A rare serious adverse event (and possibly death) from bone marrow necrosis may have been caused by Saint John’s wort.
  • Saint John’s wort has a long list of interactions (not a complete list below). If you are taking any medications, consult a licensed healthcare practitioner before using Saint John’s wort.
[104-117]


Pregnant or Nursing

There is not enough research on the use of supplements containing Saint John’s wort during pregnancy and breast-feeding, so consult a licensed healthcare practitioner before use or avoid use. A small study of infants born to mothers using Saint John’s wort reported an increase in colic, drowsiness, and lethargy. Saint John’s wort may have uterine stimulant properties. [104-117]



Interactions

Major

  • Avoid using Saint John’s wort if you are taking selective serotonin reuptake inhibitors, anti-coagulants (for example, cyclosporine), oral contraceptives, protease inhibitors (for example, HIV/AIDS drugs)
  • Saint John’s wort may interact with anesthetics, so do NOT use Saint John’s wort at least 2 weeks before a surgery
  • Drugs changed by Cytochrome P450s (CYPs) in the liver
  • Warfarin
  • Adrenergic Vasopressors
  • Alprazolam
  • Amiodarone
  • Amitriptyline
  • Amprenavir
  • Amsacrine
  • Anesthetics, general
  • Anti-Coagulants
  • Anti-Depressants; Saint John’s wort may enhance their activity
  • Anti-Diabetic Drugs
  • Atazanavir
  • Atorvastatin
  • Barbiturates
  • Benzodiazepines
  • Bupropion
  • Buspirone
  • Calcium Channel Blockers
  • Chlorzoxazone
  • Cyclosporine (Ciclosporin)
  • Darunavir
  • Digoxin
  • Docetaxel
  • Drugs transported by P-glycoproteins
  • Eletriptan
  • Erlotinib
  • Erythromycin
  • Ethinyl Estradiol
  • Etopside
  • Fenfluramine
  • Fexofenadine
  • Finasteride
  • Fluoxetine
  • Gliclazide
  • Heart Beta-Blockers
  • Hormone-Like Drugs (such as drugs containing estrogen)
  • Imatinib
  • Immunosuppressant Drugs
  • Indinavir
  • Irinotecan
  • Ivabradine
  • Ketodesogestrel
  • Lapatinib
  • Linezolid
  • Loperamide; Saint John’s wort interacts with loperamide and has caused delirium
  • Lopinavir
  • Lovastatin
  • Mephenytoin
  • Methadone
  • Methylphenidate
  • Midazolam
  • Nefazodone
  • Nevirapine
  • Nifedipine
  • Norethindrone
  • Nortriptyline
  • Omeprazole
  • Opioid Painkillers
  • Oral Contraceptives; Saint John’s wort may cause failure of contraceptive and inter-menstrual bleeding
  • Paclitaxel
  • Paroxetine
  • Phenprocoumon
  • Phenytoin
  • Propofol, an anesthetic
  • Protease Inhibitors including HIV/AIDS Drugs
  • Quazepam
  • Rasagiline
  • Reserpine
  • Ritonavir
  • Rosuvastatin
  • Saquinavir
  • Selective Serotonin Reuptake Inhibitors (SSRIs); Saint John’s wort has caused serotonin syndrome (particularly in elderly people) and mania
  • Selegiline
  • Sertraline
  • Sevoflurane, an anesthetic
  • Simvastatin
  • Sirolimus
  • Sunitinib
  • Tacrolimus
  • Talinolol
  • Tamoxifen
  • Theophylline
  • Tibolone; Saint John’s wort interacts with tibolone and may cause liver damage
  • Tramadol
  • Trazodone
  • Tricyclic Antidepressants
  • Tryptophan (which is naturally occurring in many foods, including, diary products, poultry, etc.)
  • Verapamil
  • Venlafaxine
  • Voriconazole
[118-150]

Moderate

  • Herbal Medicines Containing Ginkgo (Ginkgo biloba)
  • Amphetamines
  • Cerivastatin
  • Clozapine
  • Cyclophosphamide
  • Fluvastatin
  • Monoamine Oxidase Inhibitors (MAOIs)
  • Olanzapine
  • Phenelzine
  • Serotonin Agonists
  • Sorafenib
  • Temozolomide, a drug for radio-chemotherapy
  • Tranylcypromine
[118-150]

Potential

  • Iron-Containing Products; since Saint John’s wort contains tannins, take iron and Saint John’s wort at least several hours apart to prevent non-absorption of iron
  • Acitretin
  • Carbamazepine
  • Cimetidine
  • Debrisoquine
  • Caffeine Products (for example, coffee, tea, etc.)
  • Food Containing Tyramine (for example, wine, beer, aged cheese, etc.)
  • Saint John’s wort may NOT interact with Dextromethorphan, Ibuprofen, Mycophenolic Acid, Pravastatin, Prednisone, Tolbutamide (though Saint John’s wort may not interact with tolbutamide, it may cause an increase in hypoglycemia incidences)
[118-150]


Dosage

Saint John’s wort is not a "drug", so the best doses have not been thoroughly established. Make sure to follow the specific product instructions and take as directed on the label, or consult a licensed healthcare practitioner before use.



Compounds
Saint Johns Wort compounds


References

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Eur Arch Psychiatry Clin Neurosci. 2005 Feb;255(1):40-7. 5. Brattström A. Long-term effects of St. John's wort (Hypericum perforatum) treatment: a 1-year safety study in mild to moderate depression. Phytomedicine. 2009 Apr;16(4):277-83. 6. Brenner R, Azbel V, Madhusoodanan S, Pawlowska M. Comparison of an extract of hypericum (LI 160) and sertraline in the treatment of depression: a double-blind, randomized pilot study. Clin Ther. 2000 Apr;22(4):411-9. 7. Dimpfel W, Koch K, Weiss G. Early effect of NEURAPAS® balance on current source density (CSD) of human EEG. BMC Psychiatry. 2011 Aug 2;11:123. doi: 10.1186/1471-244X-11-123. 8. Donovan JL, DeVane CL, Lewis JG, Wang JS, Ruan Y, Chavin KD, Markowitz JS. Effects of St John's wort (Hypericum perforatum L.) extract on plasma androgen concentrations in healthy men and women: a pilot study. Phytother Res. 2005 Oct;19(10):901-6. 9. Friede M, Henneicke von Zepelin HH, Freudenstein J. Differential therapy of mild to moderate depressive episodes (ICD-10 F 32.0; F 32.1) with St. John's wort. Pharmacopsychiatry. 2001 Jul;34 Suppl 1:S38-41. 10. Gastpar M, Singer A, Zeller K. Efficacy and tolerability of hypericum extract STW3 in long-term treatment with a once-daily dosage in comparison with sertraline. Pharmacopsychiatry. 2005 Mar;38(2):78-86. 11. Gastpar M, Singer A, Zeller K. Comparative efficacy and safety of a once-daily dosage of hypericum extract STW3-VI and citalopram in patients with moderate depression: a double-blind, randomised, multicentre, placebo-controlled study. Pharmacopsychiatry. 2006 Mar;39(2):66-75. 12. Harrer G, Hübner WD, Podzuweit H. Effectiveness and tolerance of the hypericum extract LI 160 compared to maprotiline: a multicenter double-blind study. J Geriatr Psychiatry Neurol. 1994 Oct;7 Suppl 1:S24-8. 13. Harrer G, Sommer H. Treatment of mild/moderate depressions with Hypericum. Phytomedicine. 1994 Jun;1(1):3-8. 14. 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Phytomedicine. 2006 Mar;13(4):215-21. 32. Rapaport MH, Nierenberg AA, Howland R, Dording C, Schettler PJ, Mischoulon D. The treatment of minor depression with St. John's Wort or citalopram: failure to show benefit over placebo. J Psychiatr Res. 2011 Jul;45(7):931-41. 33. Schrader E. Equivalence of St John's wort extract (Ze 117) and fluoxetine: a randomized, controlled study in mild-moderate depression. Int Clin Psychopharmacol. 2000 Mar;15(2):61-8. 34. Sharpley AL, McGavin CL, Whale R, Cowen PJ. Antidepressant-like effect of Hypericum perforatum (St John's wort) on the sleep polysomnogram. Psychopharmacology (Berl). 1998 Oct;139(3):286-7. 35. Singer A, Schmidt M, Hauke W, Stade K. Duration of response after treatment of mild to moderate depression with Hypericum extract STW 3-VI, citalopram and placebo: a reanalysis of data from a controlled clinical trial. Phytomedicine. 2011 Jun 15;18(8-9):739-42. 36. Sommer H, Harrer G. Placebo-controlled double-blind study examining the effectiveness of an hypericum preparation in 105 mildly depressed patients. J Geriatr Psychiatry Neurol. 1994 Oct;7 Suppl 1:S9-11. 37. Uebelhack R, Gruenwald J, Graubaum HJ, Busch R. Efficacy and tolerability of Hypericum extract STW 3-VI in patients with moderate depression: a double-blind, randomized, placebo-controlled clinical trial. Adv Ther. 2004 Jul-Aug;21(4):265-75. 38. Vorbach EU, Arnoldt KH, Hübner WD. Efficacy and tolerability of St. John's wort extract LI 160 versus imipramine in patients with severe depressive episodes according to ICD-10. Pharmacopsychiatry. 1997 Sep;30 Suppl 2:81-5. 39. Vorbach EU, Hübner WD, Arnoldt KH. Effectiveness and tolerance of the hypericum extract LI 160 in comparison with imipramine: randomized double-blind study with 135 outpatients. J Geriatr Psychiatry Neurol. 1994 Oct;7 Suppl 1:S19-23. 40. Wheatley D. LI 160, an extract of St. John's wort, versus amitriptyline in mildly to moderately depressed outpatients--a controlled 6-week clinical trial. Pharmacopsychiatry. 1997 Sep;30 Suppl 2:77-80. 41. Woelk H. Comparison of St John's wort and imipramine for treating depression: randomised controlled trial. BMJ. 2000 Sep 2;321(7260):536-9. 42. Woelk H, Burkard G, Grünwald J. Benefits and risks of the hypericum extract LI 160: drug monitoring study with 3250 patients. J Geriatr Psychiatry Neurol. 1994 Oct;7 Suppl 1:S34-8. 43. Abdali K, Khajehei M, Tabatabaee HR. Effect of St John's wort on severity, frequency, and duration of hot flashes in premenopausal, perimenopausal and postmenopausal women: a randomized, double-blind, placebo-controlled study. Menopause. 2010 Mar;17(2):326-31. 44. Al-Akoum M, Maunsell E, Verreault R, Provencher L, Otis H, Dodin S. Effects of Hypericum perforatum (St. John's wort) on hot flashes and quality of life in perimenopausal women: a randomized pilot trial. Menopause. 2009 Mar-Apr;16(2):307-14. 45. Chung DJ, Kim HY, Park KH, Jeong KA, Lee SK, Lee YI, Hur SE, Cho MS, Lee BS, Bai SW, Kim CM, Cho SH, Hwang JY, Park JH. Black cohosh and St. John's wort (GYNO-Plus) for climacteric symptoms. Yonsei Med J. 2007 Apr 30;48(2):289-94. 46. Grube B, Walper A, Wheatley D. St. John's Wort extract: efficacy for menopausal symptoms of psychological origin. Adv Ther. 1999 Jul-Aug;16(4):177-86. 47. van Die MD, Bone KM, Burger HG, Reece JE, Teede HJ. Effects of a combination of Hypericum perforatum and Vitex agnus-castus on PMS-like symptoms in late-perimenopausal women: findings from a subpopulation analysis. J Altern Complement Med. 2009 Sep;15(9):1045-8. 48. van Die MD, Burger HG, Bone KM, Cohen MM, Teede HJ. Hypericum perforatum with Vitex agnus-castus in menopausal symptoms: a randomized, controlled trial. Menopause. 2009 Jan-Feb;16(1):156-63. 49. Hübner WD, Lande S, Podzuweit H. Hypericum treatment of mild depressions with somatic symptoms. 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Comparison of Hypericum extract WS 5570 and paroxetine in ongoing treatment after recovery from an episode of moderate to severe depression: results from a randomized multicenter study. Pharmacopsychiatry. 2006 Nov;39(6):213-9. 56. Chen JA, Papakostas GI, Youn SJ, Baer L, Clain AJ, Fava M, Mischoulon D. Association between patient beliefs regarding assigned treatment and clinical response: reanalysis of data from the Hypericum Depression Trial Study Group. J Clin Psychiatry. 2011 Dec;72(12):1669-76. 57. Farabaugh A, Mischoulon D, Fava M, Wu SL, Mascarini A, Tossani E, Alpert JE. The relationship between early changes in the HAMD-17 anxiety/somatization factor items and treatment outcome among depressed outpatients. Int Clin Psychopharmacol. 2005 Mar;20(2):87-91. 58. Fava M, Alpert J, Nierenberg AA, Mischoulon D, Otto MW, Zajecka J, Murck H, Rosenbaum JF. A Double-blind, randomized trial of St John's wort, fluoxetine, and placebo in major depressive disorder. J Clin Psychopharmacol. 2005 Oct;25(5):441-7. 59. Findling RL, McNamara NK, O'Riordan MA, Reed MD, Demeter CA, Branicky LA, Blumer JL. An open-label pilot study of St. John's wort in juvenile depression. J Am Acad Child Adolesc Psychiatry. 2003 Aug;42(8):908-14. 60. Gelenberg AJ, Shelton RC, Crits-Christoph P, Keller MB, Dunner DL, Hirschfeld RM, Thase ME, Russell JM, Lydiard RB, Gallop RJ, Todd L, Hellerstein DJ, Goodnick PJ, Keitner GI, Stahl SM, Halbreich U, Hopkins HS. The effectiveness of St. John's Wort in major depressive disorder: a naturalistic phase 2 follow-up in which nonresponders were provided alternate medication. J Clin Psychiatry. 2004 Aug;65(8):1114-9. 61. Hänsgen KD, Vesper J, Ploch M. Multicenter double-blind study examining the antidepressant effectiveness of the hypericum extract LI 160. J Geriatr Psychiatry Neurol. 1994 Oct;7 Suppl 1:S15-8. 62. Hypericum Depression Trial Study Group. Effect of Hypericum perforatum (St John's wort) in major depressive disorder: a randomized controlled trial. JAMA. 2002 Apr 10;287(14):1807-14. 63. Kieser M, Szegedi A. Predicting stable treatment response in patients with major depression treated with hypericum extract WS 5570/5572. Pharmacopsychiatry. 2005 Sep;38(5):194-200. 64. Murck H, Fava M, Alpert J, Nierenberg AA, Mischoulon D, Otto MW, Zajecka J, Mannel M, Rosenbaum JF. Hypericum extract in patients with MDD and reversed vegetative signs: re-analysis from data of a double-blind, randomized trial of hypericum extract, fluoxetine, and placebo. Int J Neuropsychopharmacol. 2005 Jun;8(2):215-21. 65. Papakostas GI, Crawford CM, Scalia MJ, Fava M. Timing of clinical improvement and symptom resolution in the treatment of major depressive disorder. A replication of findings with the use of a double-blind, placebo-controlled trial of Hypericum perforatum versus fluoxetine. Neuropsychobiology. 2007;56(2-3):132-7. 66. Sarris J, Fava M, Schweitzer I, Mischoulon D. St John's wort (Hypericum perforatum) versus sertraline and placebo in major depressive disorder: continuation data from a 26-week RCT. Pharmacopsychiatry. 2012 Nov;45(7):275-8. 67. Sarris J, Kavanagh DJ, Deed G, Bone KM. St. John's wort and Kava in treating major depressive disorder with comorbid anxiety: a randomised double-blind placebo-controlled pilot trial. Hum Psychopharmacol. 2009 Jan;24(1):41-8. 68. Shelton RC, Keller MB, Gelenberg A, Dunner DL, Hirschfeld R, Thase ME, Russell J, Lydiard RB, Crits-Cristoph P, Gallop R, Todd L, Hellerstein D, Goodnick P, Keitner G, Stahl SM, Halbreich U. Effectiveness of St John's wort in major depression: a randomized controlled trial. JAMA. 2001 Apr 18;285(15):1978-86. 69. Simeon J, Nixon MK, Milin R, Jovanovic R, Walker S. Open-label pilot study of St. John's wort in adolescent depression. J Child Adolesc Psychopharmacol. 2005 Apr;15(2):293-301. 70. Szegedi A, Kohnen R, Dienel A, Kieser M. 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