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Background

Extracts of Hypericum perforatum L. (St. John's wort) have been recommended traditionally for a wide range of medical conditions. The most common modern-day use of St. John's wort is the treatment of depression. Numerous studies report St. John's wort to be more effective than placebo and equally effective as tricyclic antidepressant drugs in the short-term treatment of mild-to-moderate major depression (1-3 months). It is not clear if St. John's wort is as effective as selective serotonin reuptake inhibitor (SSRI) antidepressants such as sertraline (Zoloft®).

Recently, controversy has been raised by two high-quality trials of St. John's wort for major depression that did not show any benefits. However, due to problems with the designs of these studies, they cannot be considered definitive. Overall, the scientific evidence supports the effectiveness of St. John's wort in mild-to-moderate major depression. The evidence in severe major depression remains unclear.

St. John's wort can cause many serious interactions with prescription drugs, herbs, or supplements. Therefore, people using any medications should consult their healthcare providers including their pharmacist prior to starting therapy.

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Synonyms

Amber touch-and-heal, balm-of-warrior's wound, balsana, bassant, Blutkraut, bossant, Calmigen®, corancillo dendlu, devil's scorge, Eisenblut, flor de Sao Joa, fuga daemonum, goatweed hartheu, heofarigo on, herba de millepertius, herba hyperici, herrgottsblut, hexenkraut, hierba de San Juan, hipericao, hiperico hipericon, HP, isorhamnetin, Jarsin, Johanniskraut, klammath weed, liebeskraut, LI 160, lord God's wonder plant, millepertius pelicao, perforate, pinillo de oro, PM235, pseudohypericin, rosin rose, SJW extract LI 160, St. John's wort WS 5572, STW 3-VI, tenturotou, Teufelsflucht, touch and heal, Walpurgiskraut (Dutch), witcher's herb, WS 5572.

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Evidence

Uses based on scientific evidence	Grade*
Depressive disorder (mild-to-moderate) St. John's wort has been extensively studied in Europe over the last two decades, with more recent research in the United States. Short-term studies (1-3 months) suggest that St. John's wort is more effective than placebo (sugar pill), and equally effective as tricyclic antidepressants (TCAs) in the treatment of mild-to-moderate major depression. Comparisons to the more commonly prescribed selective serotonin reuptake inhibitor (SSRI) antidepressants, such as fluoxetine (Prozac®) or sertraline (Zoloft®), are more limited. However, other data suggest that St. John's wort may be just as effective as SSRIs with fewer side effects. Safety concerns exist as with most conventional and complementary therapies.	A
Anxiety disorder Overall, there is currently not enough evidence to recommend St. John's wort for the primary treatment of anxiety disorders.	C
Atopic dermatitis Early study of hypericum-cream in the topical treatment of mild to moderate atopic dermatitis shows positive results. Further studies are needed before a firm recommendation can be made.	C
Depressive disorder (severe) Studies of St. John's wort for severe depression have not provided clear evidence of effectiveness.	C
Nerve pain Early study shows that St. John's wort may help neuropathic (nerve) pain. Further research is needed to confirm these results.	C
Obsessive-compulsive disorder (OCD) There are a few reported cases of possible benefits of St. John's wort in patients with obsessive-compulsive disorder (OCD). Currently there is not enough scientific evidence to recommend St. John's wort for this condition.	C
Peri-menopausal symptoms There is currently not enough scientific evidence to recommend St. John's wort for this indication.	C
Premenstrual syndrome (PMS) Further studies are needed before a strong recommendation can be made.	C
Seasonal affective disorder (SAD) Despite some promising early data, there is currently not enough evidence to recommend St. John's wort for depressive disorder with seasonal pattern or Seasonal Affective Disorder (SAD).	C
Somatoform disorders Somatoform disorders show physical symptoms that cannot be attributed to organic disease and appear to be of psychic origin. Early evidence shows that St. John's wort may help with somatoform disorders. Further research is needed to confirm these results.	C
Human immunodeficiency virus (HIV) Anti-viral effects of St. John's wort have been observed in laboratory studies, but were not found in one human study. Multiple reports of significant adverse effects and interactions with drugs used for HIV/AIDS, including protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs), suggest that patients being treated for HIV/AIDS should avoid this herb. Therefore, there is evidence to recommend against using St. John's wort in the treatment of patients with HIV/AIDS.	D
Social phobia Results of early study on the efficacy of St. John's wort in social phobia do not show benefit. More study is needed to confirm these findings.	D

Key to grades
A Strong scientific evidence for this use
B Good scientific evidence for this use
C Unclear scientific evidence for this use
D Fair scientific evidence against this use (it may not work)
F Strong scientific evidence against this use (it likely does not work)

Grading rationale

Uses based on tradition or theory

Abdominal discomfort or irritation, alcoholism, allergies, anti-inflammatory, antioxidant, antiviral, asthma, athletic performance enhancement, bacterial skin infections (topical), bedwetting, benzodiazepine withdrawal, bruises (topical), burns (topical), cancer, chronic bowel irritation, chronic ear infections, dental pain, diarrhea, diuretic (increasing urine flow), Epstein-Barr virus infection, fatigue, glioma (brain tumor), heartburn, hemorrhoids, herpes virus infection, influenza, insomnia, joint pain, liver protection from toxins, malaria treatment, menstrual pain, mood disorders (menopause), nicotine withdrawal, pain relief, rheumatism, skin scrapes, sleep, snakebites, sprains, ulcers, weight loss, wound healing (topical).

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Dosing

Adults (18 years and older)

Clinical trials have used a range of doses, including 0.17-2.7 milligrams of hypericin by mouth, and 900-1,800 milligrams of St. John's wort extract daily by mouth.

1.5% hyperforin (verum) has been applied to the skin for the treatment of atopic dermatitis.

Children (younger than 18 years)

There is not enough scientific data to recommend St. John's wort in children.

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Safety

Allergies

Infrequent allergic skin reactions, including rash and itching, are reported in human studies.

Side Effects and Warnings

In published studies, St. John's wort has generally been well tolerated at recommended doses for up to 1-3 months. The most common adverse effects include gastrointestinal upset, skin reactions, fatigue/sedation, restlessness or anxiety, sexual dysfunction (including impotence), dizziness, headache, and dry mouth. Several recent studies suggest that side effects occur in one to three percent of patients taking St. John's wort, and that the number of adverse events may be similar to placebo (and less than standard antidepressant drugs). Animal toxicity studies have found only non-specific symptoms such as weight loss. One small study reported elevated thyroid stimulating hormone (TSH) levels to be associated with taking St. John's wort.

It has been reported that St. John's wort may cause psychiatric symptoms such as suicidal and homicidal thoughts.

Delayed ejaculation has been reported in animal studies.

Pregnancy & Breastfeeding

There is not enough scientific evidence available to recommend use during pregnancy or breastfeeding.

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Methodology

This patient information is based on a professional level monograph edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Monograph methodology

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Selected references

1. Behnke K, Jensen GS, Graubaum HJ, et al. Hypericum perforatum versus fluoxetine in the treatment of mild to moderate depression. Adv Ther 2002;19(1):43-52.
2. Briese V, Stammwitz U, Friede M, et al. Black cohosh with or without St. John's wort for symptom-specific climacteric treatment--results of a large-scale, controlled, observational study. Maturitas 2007 Aug 20;57(4):405-14.
3. Chung DJ, Kim HY, Park KH, et al. Black cohosh and St. John's wort (GYNO-Plus) for climacteric symptoms. Yonsei Med J 2007 Apr 30;48(2):289-94.
4. Fava M, Alpert J, Nierenberg AA, et al. 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.
5. Franklin M, Hafizi S, Reed A, et al. Effect of sub-chronic treatment with Jarsin (extract of St John's wort, Hypericum perforatum) at two dose levels on evening salivary melatonin and cortisol concentrations in healthy male volunteers. Pharmacopsychiatry 2006 Jan;39(1):13-5.
6. Hammerness P, Basch E, Ulbricht C, et al. St John's wort: a systematic review of adverse effects and drug interactions for the consultation psychiatrist. Psychosomatics 2003;44(4):271-282.
7. Muller T, Mannel M, Murck H, et al. Treatment of somatoform disorders with St. John's wort: a randomized, double-blind and placebo-controlled trial. Psychosom.Med. 2004;66(4):538-547.
8. Murphy PA, Kern SE, Stanczyk FZ, et al. Interaction of St. John's Wort with oral contraceptives: effects on the pharmacokinetics of norethindrone and ethinyl estradiol, ovarian activity and breakthrough bleeding. Contraception. 2005 Jun;71(6):402-8.
9. Philipp M, Kohnen R, Hiller KO. Hypericum extract versus imipramine or placebo in patients with moderate depression: randomised multicentre study of treatment for eight weeks. BMJ 12-11-1999;319(7224):1534-1538.
10. Randlov C, Mehlsen J, Thomsen CF, et al. The efficacy of St. John's Wort in patients with minor depressive symptoms or dysthymia--a double-blind placebo-controlled study.Phytomedicine. 2006 Mar;13(4):215-21.
11. Saarto T, Wiffen PJ. Antidepressants for neuropathic pain. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD005454. Update of: Cochrane Database Syst Rev 2005;(3):CD005454.
12. Schempp CM, Windeck T, Hezel S, et al. Topical treatment of atopic dermatitis with St. John's wort cream--a randomized, placebo controlled, double blind half-side comparison. Phytomedicine 2003;10 Suppl 4:31-37.
13. Schulz V. Safety of St. John's Wort extract compared to synthetic antidepressants. Phytomedicine 2006 Feb;13(3):199-204.
14. Shelton RC, Keller MB, Gelenberg A, et al. Effectiveness of St John's wort in major depression: a randomized controlled trial. JAMA 4-18-2001;285(15):1978-1986.
15. Uebelhack R, Blohmer JU, Graubaum HJ, et al. Black cohosh and St. John's wort for climacteric complaints: a randomized trial. Obstet Gynecol 2006 Feb;107(2 Pt 1):247-55.

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