St. John's wort (Hypericum perforatum L.)
  
St. John's wort (Hypericum perforatum L.)
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 provider and pharmacist prior to starting therapy.
Synonyms
Amber touch-and-heal, balm-of-warrior's wound, balsana, bassant, Blutkraut, bossant, 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, Johanniskraut, klammath weed, liebeskraut, LI 160, lord God's wonder plant, millepertius pelicao, perforate, pinillo de oro, rosin rose, tenturotou, Teufelsflucht, touch and heal Walpurgiskraut, witcher's herb, WS 5572.
Evidence
These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.
Uses based on scientific evidenceGrade*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.
A
Depressive disorder (severe)
Studies of St. John's wort for severe depression have not provided clear evidence of effectiveness. A recent study reported that neither St. John's wort nor the SSRI drug sertraline (Zoloft®) provided benefits over placebo for severe depression. Other recent well-designed research has suggested no benefit of St. John's wort for severe depression; although the evidence is still not completely clear in this area.
C
Anxiety disorder
Several studies in patients with depression report that in addition to effects on depression, St. John's wort may also reduce anxiety symptoms. There is one study of St. John's wort (in a combination product with valerian), which specifically treated people with anxiety. It is important to realize that valerian alone is often used to treat anxiety, and therefore any effects of the combination product may be due to valerian and not to St. John's wort. Therefore, there is currently not enough evidence to recommend St. John's wort for the primary treatment of anxiety disorders.
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). However, due to a lack of large, controlled studies comparing St. John's wort to placebo or drugs, there is currently not enough scientific evidence to recommend St. John's wort for this condition.
C
Peri-menopausal symptoms
Several small studies suggest possible benefits of St. John's wort for psychological symptoms experienced around menopause. However, there is currently not enough scientific evidence to recommend St. John's wort for this indication.
C
Premenstrual syndrome (PMS)
One small study suggests that St. John's wort may be effective in reducing symptoms of premenstrual syndrome (PMS). Further studies are need before a 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
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
* 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).
Uses based on tradition or theory
The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.
Abdominal discomfort or irritation, alcoholism, allergies, anti-inflammatory, antiviral, athletic performance enhancement, bacterial skin infections (topical), bedwetting, bruises (topical), benzodiazepine withdrawal, burns (topical), cancer, chronic bowel irritation, chronic ear infections, dental pain, diarrhea, diuretic (increasing urine flow), Epstein-Barr virus infection, fatigue, glioma, heartburn, hemorrhoids, herpes virus infection, influenza, insomnia, joint pain, liver protection from toxins, malaria treatment, menstrual pain, nerve pain, pain relief, rheumatism, snakebites, skin scrapes, sprains, ulcers, wound healing (topical).
Dosing
The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.
Standardization
Standardization involves measuring the amount of certain chemicals in products to try to make different preparations similar to each other. It is not always known if the chemicals being measured are the "active" ingredients. St. John's wort products are often standardized to contain 0.3% of one of the components called hypericin, although there has been a movement within the manufacturing industry to standardize to a different component called hyperforin (usually 2-5%). In one analysis of eight German St. John's wort products, large differences in hypericin and hyperforin content were found, and there was also variability within batches of the same brand.
Adults (18 years and older)
Depression : Starting dose : 300 milligrams of St. John's wort, standardized to 0.3% hypericin extract, taken by mouth three times daily (may be standardized to 2-5% hyperforin as well) has been studied. Maintenance dose : 300-600 milligrams daily may be sufficient for maintenance therapy, although this has not been well studied. A liquid form may be used, taken three times daily and standardized to contain equivalent amounts of hypericin or hyperforin as noted above. (Note: Clinical trials have used a range of doses, including 0.17-2.7 milligrams of hypericin, and 900-1450mg of St. John's wort extract daily.)
Children (younger than 18 years)
There is not enough scientific data to recommend St. John's wort in children. One study of 101 children under the age of 12 years with symptoms of depression used 300-1800 milligrams of St. John's wort extract daily for 4-6 weeks, with good tolerance.
Safety
The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.
Allergies
Infrequent allergic skin reactions, including rash and itching, are reported in human studies. A drug monitoring study of 3,250 patients reported 17 cases of allergic reactions and 10 cases in which St. John's wort was stopped due to the allergy.
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.
Pregnancy & Breastfeeding
There is insufficient data available at this time to recommend use during pregnancy or breastfeeding.
References
1. Albert D, Zundorf I, Dingermann T, et al. Hyperforin is a dual inhibitor of cyclooxygenase-1 and 5-lipoxygenase. Biochem Pharmacol 2002;64 (12) :1767-1775.
2. Andelic S. [Bigeminy--the result of interaction between digoxin and St. John's wort][Article in Croatian] Vojnosanit Pregl 2003;60(3):361-364.
3. Bauer S, Stormer E, Johne A, Kruger H, Budde K, Neumayer HH, Roots I, Mai I. Alterations in cyclosporin A pharmacokinetics and metabolism during treatment with St John's wort in renal transplant patients. Br J Clin Pharmacol 2003;55(2):203-11.
4. 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.
5. Dean AJ, Moses GM, Vernon JM. Suspected withdrawal syndrome after cessation of St. John's wort. Ann Pharmacother 2003;37(1):151.
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;44:271-282.
7. Kalb R, Trautmann-Sponsel RD, Kieser M. Efficacy and tolerability of hypericum extract WS 5572 versus placebo in mildly to moderately depressed patients: a randomized double-blind multicenter clinical trial. Pharmacopsych 2001;34(3):96-103.
8. Kim HL, Streltzer J, Goebert D. St. John's wort for depression: a meta-analysis of well-defined clinical trials. J Nerv Ment Dis 1999;187(9):532-539.
9. Linde K, Mulrow CD. St John's wort for depression. Cochrane Database Syst Rev 2000;(2):CD000448.
10. Linde K, Ramirez G, Mulrow CD, et al. St John's wort for depression: an overview and meta-analysis of randomised clinical trials. BMJ 1996;313(7052):253-258.
11. Miller LG. Drug interactions known or potentially associated with St. John's wort. J Herbal Pharmacother 2001;1(3):51-64.
12. Parker V, Wong AH, Boon HS, et al. Adverse reactions to St John's wort. Can J Psychiatry 2001;46(1):77-79.
13. 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 1999; 319(7224):1534-1538.
14. Shelton RC, Keller MB, Gelenberg A, et al. Effectiveness of St John's wort in major depression: a randomized controlled trial. JAMA 2001;285(15):1978-1986.
15. Wheatley D. Safety of St John's wort (). Lancet 2000; 355(9203):576.
January 01, 2004 
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