Author: Robert B Saper, MD, MPH

Section Editor: Joann G Elmore, MD, MPH

Deputy Editor: Judith A Melin, MA, MD, FACP

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Apr 2018. | This topic last updated: Dec 06, 2017.

INTRODUCTION — St. John's wort (Hypericum perforatum) is a five petal yellow flower (picture 1)
that has been used medicinally since antiquity [1]. It was commonly referred to as "Fuga Demonum"
(the devil's scourge) since it was used to protect against demonic possession and "evil spirits" [2].
One of the earliest references to the name St. John's wort is noted in a Gaelic legend from the sixth
century where the missionary St. Columba carried a piece of St. John's wort because of his high
regard for St. John [1]. It is believed that the name may have been derived from the fact that the
flowers bloom around June 24th, the birthday of St. John the Baptist. Wort represents the old English
term for plant.

St. John's wort has been utilized mainly for its antidepressant activity, but also for its purported
antiinflammatory and wound healing properties [3]. The 2007 National Health Interview Survey found
a large decrease in St. John's wort use by adults in the United States [4]. In 2002, St. John's wort
was the sixth most popular natural product in the United States, used by 2.2 percent of American
adults [5]. In 2007, St. John's wort was not among the 20 most commonly used dietary supplements
[4]. This decrease may reflect the public's response to interim news reports of negative clinical trials
[6-8] and potentially harmful interactions with prescription drugs [9-22].

Patients considering the use of St. John's wort should be counseled and cautioned regarding
evidence of effectiveness and safety, the variability and lack of regulation in St. John's wort products
in the United States, and the potential for herb-drug interactions.

MECHANISM OF ACTION — A number of compounds isolated from St. John's wort possess
pharmacologic activity. Naphthodianthrones (hypericin, pseudohypericin, protohypericin,
protopseudohypericin, and cyclopseudohypericin), flavonoids (quercetin, rutin, and luteolin),
hyperforin, several amino acids, and tannins have been isolated [23].

Neuropsychiatric activity — The majority of in vitro studies of St. John's wort have attempted to
define its neuropharmacology. Hyperforin and hypericin have been studied most extensively.
Hypericin was originally thought to be the major active component for St. John's wort in depression;
however, it is now believed that hyperforin and related compounds are mostly responsible for St.
John's wort's effect on mood.

Hyperforin extracts have been shown to modulate neurotransmitter levels including serotonin,
norepinephrine, and dopamine [24,25]. This may be in part from inhibition of neurotransmitter
uptake. Other studies have found that hypericum extract possesses a weak catechol-O-methyl
transferase activity [26], and the hypericum extract LI 160 causes 50 percent inhibition of serotonin
uptake by rat synaptosomes [27]. The latter occurred only at relatively high concentrations.
St. John's wort standardized extract LI 160 is capable of decreasing cell surface 5-HT receptors. LI
160 also suppresses the release of interleukin-6 (IL-6), which induces the release of corticotropin
releasing hormone (implicated in depression) [28,29]. St. John's wort extracts also have been shown
to inhibit binding at the muscarinic cholinergic receptor (mAchR), 5HT, and norepinephrine uptake
sites, but only at high concentrations [30]. Extracts may have further effects upon melatonin
secretion, biological rhythms, and sexual activity [31]. Others have hypothesized that hypericum
extract increases dopamine turnover resulting in an increased concentration of dopamine [32]. MAO
inhibition was formerly believed to be a mechanism of St. John's wort, but animal studies suggest
that MAO inhibition is minimal and likely not clinically significant [33].

Antiviral and antibacterial activity — In vitro antiviral activity has been reported against murine
cytomegalovirus, parainfluenza 3 virus, Sindbis virus, vesicular stomatitis virus, and equine infectious
anemia virus [34-36]. In addition, hypericin and pseudohypericin inhibit herpes simplex types 1 and 2
[3]. Other studies have indicated immunologic and potential clinical benefits of utilizing hypericin in
vitro for HIV [37-39]. Hypericin and pseudohypericin display activity against retroviruses in mice [40].

Hypericin also has antibacterial activity against gram-positive and gram-negative organisms [3,41].
These effects may explain the use of St. John's wort for wound healing.

Other activity — Other activities associated with St. John's wort extracts include:

● Experimentally induced inflammation and leukocyte infiltration is suppressed in mice using a

topical extract of St. John's wort [42].

● Flavonoid fractions (mainly quercetin) have analgesic activity in mice [43].

● The tannin component of the plant probably exerts an astringent action that may contribute to its
purported effectiveness as a wound healing agent [3].

● Oral and topical administration of hypericin has been utilized for the treatment of vitiligo and as
an antiinflammatory and antiulcerogenic agent, due most likely to the component amentoflavone
[3].

EVIDENCE OF EFFECTIVENESS

Depression — Given the inconsistent evidence for efficacy, and the lack of regulated standardized
herbal products, we suggest not treating depression with St. John's wort. There are also multiple
interactions between St. John's wort and many commonly used medications. (See 'Drug interactions'
below.)

Although a 2008 meta-analysis of 29 trials (23 Europe, 4 US, 1 Canada, 1 Brazil) found standardized
extracts of St. John's wort to be more effective than placebo and comparable in efficacy to standard
antidepressants in the short-term treatment of mild to moderate depression [44], these results were
not observed in the US trials [6-8,45]. Reasons for this discrepancy may include differences in
patients enrolled, lack of concealment of treatment allocation, or the variation in herbal preparations
studied. (See "Unipolar depression in adults and initial treatment: Investigational approaches",
section on 'St. John’s wort'.)

Somatoform disorders — Two placebo-controlled trials, each lasting six weeks, found St. John's
wort (300 mg twice daily) was efficacious for treating somatoform disorders independent of any
existing depression, and was also well tolerated and safe [46,47]. In one study involving 149
patients, more patients improved with St. John's wort than placebo (81 versus 50 percent,
respectively) [46]. Relative responses were similar in another study of 173 patients (45 versus 21
percent, respectively) [47].

Menopausal symptoms — Two randomized placebo-controlled trials suggest St. John's wort may
reduce the frequency and severity of hot flashes [48,49]. In one study involving 100 women
randomized to St. John's wort extract (standardized to 0.2 percent hypericin) or placebo, there were
significant reductions in hot flash frequency, duration, and severity at eight weeks [49]. However,
weaknesses in these trials included small sample size, incomplete characterization of herbal product,
and no assessment of the effectiveness of patient blinding.

Attention deficit/hyperactivity disorder — A randomized trial in 54 children and adolescents with

attention deficit/hyperactivity disorder found no benefits on attention or hyperactivity with St. John's
wort 300 mg (standardized to 0.3 percent hypericin) three times daily for eight weeks, compared with
placebo [50]. Adverse events were also similar with St. John's wort or placebo.

HIV infection — A phase I trial of 30 HIV-infected patients with CD4 counts less than 350 cells/mm3
evaluated the safety and antiretroviral activity of hypericin [51]. Subjects received intravenous
hypericin (0.25 or 0.5 mg/kg body weight twice weekly or 0.25 mg/kg three times weekly) or oral
hypericin (0.5 mg/kg daily). Treatment was discontinued in 16 of 30 (53 percent) before completing
eight weeks because of moderate or severe phototoxicity. Only two patients completed 24 weeks of
therapy. No demonstrable antiretroviral activity at the doses tested was noted. Analyses of HIV p24
antigen levels, culture titers, and RNA levels showed no significant changes. Median CD4 cell counts
decreased during the study. The authors concluded that the hypericin therapy utilized was too toxic
to allow evaluation of any antiretroviral potential.

Smoking cessation — Two randomized trials found no benefit of St. John's wort for smoking
cessation, in comparison to placebo [52,53].

Irritable bowel syndrome — A 12 week randomized trial of St. John's wort (900 mg daily) versus
placebo in 70 patients with irritable bowel syndrome showed greater benefit for placebo compared to
St. John's wort for self-reported bowel symptom score [54].

SAFETY

Adverse effects — A systematic review of the adverse effects of St. John's wort in clinical studies
found that dropout and adverse effects rates in patients receiving St. John's wort were comparable to
placebo, lower than tricyclic antidepressants, and slightly lower than SSRIs [9,55]. The most
common drug reactions included gastrointestinal symptoms, dizziness/confusion, tiredness/sedation,
photosensitivity, dry mouth, urinary frequency, anorgasmia, and swelling [7,9].

Case reports of photosensitivity have been reported in patients taking oral St. John's wort [51,56,57].
These involved a delayed hypersensitivity/photodermatitis following ingestion of herbal tea [56] and
reversible photosensitivity after taking 240 mg of hypericum extract daily for three years [57].
Erythematous lesions in light-exposed areas developed but cleared with discontinuation. Limited
phototoxicity of oral extracts was seen in a randomized placebo-controlled multiple cross-over study
of 13 subjects receiving hypericum extract at various doses who were exposed to solar and UVA light
before and four hours after drug intake [58]. External use of hypericum extracts have been noted in
several anecdotal reports to lead to second degree burns, resulting in scarring, after exposure to
direct sunlight [59].

An in vitro study noted that high concentrations of St. John's wort had adverse effects upon oocytes
and was mutagenic to sperm cells, leading to concerns that use may lead to decreased fertility [60].

Contraindications — Use of St. John's wort should be avoided during pregnancy and lactation
since there are inadequate data to demonstrate its safety. Some in vitro uterotonic effects have been
reported in animal models [61]. No large scale observational studies in humans have been
conducted to evaluate the safety of St. John's wort in pregnancy. One small study, however,
compared birth outcomes between 54 pregnancies exposed to St. John's wort, 54 exposed to
conventional anti-depressants, and 54 healthy non-exposed women [62]. Major fetal malformations
were found in 5.3, 4.3, and 0 percent, respectively (p = 0.26).

The authors of a literature review of herb use in the perioperative period suggested that, because of
the various drug interactions with St. John's wort, it should be discontinued at least five days prior to
a planned surgical procedure [63].

DRUG INTERACTIONS — Interactions between St. John's wort and medications are the most
common source of adverse effects related to St. John's wort [9]. Demonstrated adverse interactions
between St. John's wort and certain medications were among the first herb-drug interactions
reported [10]. These reports contributed to the growing recognition among clinicians of the potential
for adverse herb-drug interactions and the need to ask all patients about nonprescription herb and
supplement use. Specific interactions of St. John's wort with other medications may be determined
using the drug interactions tool (Lexi-Interact Online) included in UpToDate. This tool can be
accessed from the UpToDate online search page or through the individual drug information topics in
the section on Drug interactions.

Treatment failures with a wide variety of agents including anticoagulants, antiretrovirals, antifungals,
immunosuppressive agents, narcotics, digoxin, and hormonal contraceptives have been associated
with the concomitant use of St. John's wort due to significant induction of CYP 1A2, 2C19, 2C9, and
3A4, as well as intestinal P-glycoprotein/MDR-1 drug transporters [12-22,64-69].

Use of St. John's wort should be avoided in combination with other antidepressants until a definitive
mechanism of action is elucidated to avoid the potential for the serotonin syndrome [70]. Several
cases of serotonin excess (agitation, hyperthermia, diaphoresis, tachycardia, and neuromuscular
disturbances including rigidity) also have been reported in elderly individuals taking St. John's wort
and SSRIs together [71]. It is prudent to have a three- to seven-day wash-out period prior to
switching from an SSRI to St. John's wort, and a three-week wash-out period prior to switching from
an MAO inhibitor to St. John's wort. (See "Switching antidepressant medications in adults", section
on 'Between SSRIs' and "Switching antidepressant medications in adults", section on 'Switching to or
from MAOIs'.)

Examples of significant interactions include:

● In a study in healthy volunteers, peak plasma levels of the protease inhibitor indinavir were
 reduced more than 50 percent when St. John's wort was taken concomitantly [10]. A reduction
of this magnitude would be sufficient to cause treatment failure in an HIV-infected patient
receiving antiretroviral therapy.

● There was a report of two cases of acute heart transplant rejection from a reduction in
cyclosporine levels due to concomitant St. John's wort [11].

● There are case reports of breakthrough bleeding and undesired pregnancy in women taking oral
contraceptive pills, presumably due to lowering of ethinylestradiol concentrations [21].

Avoidance of foods containing tyramine while taking St. John's wort is considered unnecessary due
to St. John's wort's limited MAO inhibitory activity [26,72].

ADMINISTRATION — The majority of studies of St. John's wort utilized extracts standardized to
either 0.3 percent hypericin or 5 percent hyperforin in a dosage of 300 to 400 mg three times per day
[6,7,73,74]. Caution should be employed with long-term use of hypericum extracts due to a lack of
studies beyond 8 to 12 weeks.

Good Manufacturing Practices for the dietary supplement industry have been established by the
United States Food and Drug Administration (FDA) and were phased in from 2008 to 2010 [75]. (See
"Overview of herbal medicine and dietary supplements".) However, no studies have been published
after 2010 to assess the impact of these new regulations on standardization and quality. The
resultant uncertainty in the quality of products is another reason arguing against recommending St.
John's wort in the United States.

Patients who choose to use St. John's wort can use brands that have passed specified quality
criteria by independent commercial laboratories (table 1).

SUMMARY AND RECOMMENDATIONS

● Patients considering the use of St. John's wort should be counseled and cautioned regarding
evidence of effectiveness and safety, the variability and lack of regulation in St. John's wort
products in the United States, and the potential for herb-drug interactions. (See 'Introduction'
above.)

● European studies of well-defined standardized extracts of St. John's wort in the short-term
treatment of mild-to-moderate depression suggest it is more effective than placebo and
equivalent to tricyclic antidepressants and SSRIs. However, studies in the US do not support its
efficacy. The reasons for this discrepancy are unclear but may include differences in study
design, such as concealment of treatment allocation, or in the herbal preparations studied. (See
'Depression' above.)

● Given the inconsistent evidence for efficacy, and the lack of regulated standardized products
proven to be efficacious, we suggest not treating depression with St. John's wort (Grade 2B).
(See "Unipolar major depression in adults: Choosing initial treatment" and 'Depression' above.)

● St. John's wort has the potential for multiple herb-drug interactions through induction of the
CYP3A4 and P-glycoprotein systems. Concurrent use of St. John's wort and medications
metabolized by these systems should be avoided. Additionally, there have been reports of
 serotonin syndrome in patients taking St. John's wort concurrently with SSRI antidepressants.
(See 'Drug interactions' above.)

● The variability in St. John’s wort quality and contents is a limitation to their clinical utility. For
patients who choose to use it, they should select products that meet specific quality criteria
according to independent laboratory testing (table 1). (See 'Administration' above.)

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REFERENCES

1. Hobbs C. St. John's wort--ancient herbal protector. Pharm Hist 1990; 32:166.
2. Pratt A. Wild Flowers, Society for Promoting Christian Knowledge, London 1853.
3. St. John's Wort. In: Lawrence Review of Natural Products, Facts and Comparisons, St. Louis 1
997.
4. Barnes PM, Bloom B, Nahin RL. Complementary and alternative medicine use among adults
and children: United States, 2007. Natl Health Stat Report 2008; :1.
5. Barnes PM, Powell-Griner E, McFann K, Nahin RL. Complementary and alternative medicine
use among adults: United States, 2002. Adv Data 2004; :1.
6. Shelton RC, Keller MB, Gelenberg A, et al. Effectiveness of St John's wort in major depression:
a randomized controlled trial. JAMA 2001; 285:1978.
7. Hypericum Depression Trial Study Group. Effect of Hypericum perforatum (St John's wort) in
major depressive disorder: a randomized controlled trial. JAMA 2002; 287:1807.
8. 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; 25:441.
9. Knüppel L, Linde K. Adverse effects of St. John's Wort: a systematic review. J Clin Psychiatry
2004; 65:1470.
10. Piscitelli SC, Burstein AH, Chaitt D, et al. Indinavir concentrations and St John's wort. Lancet
2000; 355:547.
11. Ruschitzka F, Meier PJ, Turina M, et al. Acute heart transplant rejection due to Saint John's
wort. Lancet 2000; 355:548.
12. Johne A, Brockmöller J, Bauer S, et al. Pharmacokinetic interaction of digoxin with an herbal
extract from St John's wort (Hypericum perforatum). Clin Pharmacol Ther 1999; 66:338.
13. Sugimoto K, Ohmori M, Tsuruoka S, et al. Different effects of St John's wort on the
pharmacokinetics of simvastatin and pravastatin. Clin Pharmacol Ther 2001; 70:518.
14. Mathijssen RH, Verweij J, de Bruijn P, et al. Effects of St. John's wort on irinotecan metabolism.
J Natl Cancer Inst 2002; 94:1247.
15. Smith PF, Bullock JM, Booker BM, et al. Induction of imatinib metabolism by hypericum
perforatum. Blood 2004; 104:1229.
16. Mueller SC, Uehleke B, Woehling H, et al. Effect of St John's wort dose and preparations on
the pharmacokinetics of digoxin. Clin Pharmacol Ther 2004; 75:546.
17. Jiang X, Williams KM, Liauw WS, et al. Effect of St John's wort and ginseng on the
pharmacokinetics and pharmacodynamics of warfarin in healthy subjects. Br J Clin Pharmacol
2004; 57:592.
18. Tannergren C, Engman H, Knutson L, et al. St John's wort decreases the bioavailability of R-
and S-verapamil through induction of the first-pass metabolism. Clin Pharmacol Ther 2004;
75:298.
19. Hebert MF, Park JM, Chen YL, et al. Effects of St. John's wort (Hypericum perforatum) on
tacrolimus pharmacokinetics in healthy volunteers. J Clin Pharmacol 2004; 44:89.
20. Eich-Höchli D, Oppliger R, Golay KP, et al. Methadone maintenance treatment and St. John's
Wort - a case report. Pharmacopsychiatry 2003; 36:35.
21. Mills E, Montori VM, Wu P, et al. Interaction of St John's wort with conventional drugs:
systematic review of clinical trials. BMJ 2004; 329:27.
22. Nieminen TH, Hagelberg NM, Saari TI, et al. St John's wort greatly reduces the concentrations
of oral oxycodone. Eur J Pain 2010; 14:854.
23. Bennett DA Jr, Phun L, Polk JF, et al. Neuropharmacology of St. John's Wort (Hypericum). Ann
Pharmacother 1998; 32:1201.
24. Müller WE, Singer A, Wonnemann M, et al. Hyperforin represents the neurotransmitter
reuptake inhibiting constituent of hypericum extract. Pharmacopsychiatry 1998; 31 Suppl 1:16.
25. Singer A, Wonnemann M, Müller WE. Hyperforin, a major antidepressant constituent of St.
John's Wort, inhibits serotonin uptake by elevating free intracellular Na+1. J Pharmacol Exp
Ther 1999; 290:1363.
26. Thiede HM, Walper A. Inhibition of MAO and COMT by hypericum extracts and hypericin. J
Geriatr Psychiatry Neurol 1994; 7 Suppl 1:S54.
27. Perovic S, Müller WE. Pharmacological profile of hypericum extract. Effect on serotonin uptake
by postsynaptic receptors. Arzneimittelforschung 1995; 45:1145.
28. Müller WE, Rossol R. Effects of hypericum extract on the expression of serotonin receptors. J
Geriatr Psychiatry Neurol 1994; 7 Suppl 1:S63.
29. Thiele B, Brink I, Ploch M. Modulation of cytokine expression by hypericum extract. J Geriatr
Psychiatry Neurol 1994; 7 Suppl 1:S60.
30. Muller WE, Schafer C. Johanniskraut: in-vitro Studie uber Hypericum-Extrakt, Hypericin und
Kampferol. Deutsche Apotheker Zeitung 1996; 136:1015.
31. Demisch, L, Nispel, J, Sielaff, T, et al. Influence of subchronic Hyperforat administration on mel
atonin production. Arbeitsgemeinschaft fur Neuro und Psychopharmakologie-symposium Abstr
acts, Nurnberg 1991.
32. Winterhof H, Butterweck V, Nahrstedt A, et al. Phytopharmaka in Forschung unf klinischer Anw
endung, Steinkopff Verlag GmbH and Co, Darmstadt, Germany 1995. p.S39.
33. Negrash AK. Comparative study of chemotherapeutic and pharmacological properties of
antimicrobial preparation from common St. John's Wort. Fitonsidy Mater Soveshch 1969; :198.
34. Lopez-Bazzocchi I, Hudson JB, Towers GH. Antiviral activity of the photoactive plant pigment
hypericin. Photochem Photobiol 1991; 54:95.
35. Wood S, Huffman J, Weber N, et al. Antiviral activity of naturally occurring anthraquinones and
 anthraquinone derivatives. Planta Medica 1990; 56:651.
36. Carpenter S, Kraus GA. Photosensitization is required for inactivation of equine infectious
anemia virus by hypericin. Photochem Photobiol 1991; 53:169.
37. Lavie G, Valentine F, Levin B, et al. Studies of the mechanisms of action of the antiretroviral
agents hypericin and pseudohypericin. Proc Natl Acad Sci U S A 1989; 86:5963.
38. Schinazi RF, Chu CK, Babu JR, et al. Anthraquinones as a new class of antiviral agents
against human immunodeficiency virus. Antiviral Res 1990; 13:265.
39. Hudson JB, Lopez-Bazzocchi I, Towers GH. Antiviral activities of hypericin. Antiviral Res 1991;
15:101.
40. Meruelo D, Lavie G, Lavie D. Therapeutic agents with dramatic antiretroviral activity and little
toxicity at effective doses: aromatic polycyclic diones hypericin and pseudohypericin. Proc Natl
Acad Sci U S A 1988; 85:5230.
41. Gaind KN, Ganjoo TN. Antibacterial principle of Hypericum perforatum Linn. Indian J Pharm
1959; 21:172.
42. Shipochliev T, Dimitrov A, Aleksandrova E. [Anti-inflammatory action of a group of plant
extracts]. Vet Med Nauki 1981; 18:87.
43. Vasilchenko EA. Analgesic action of flavonoids of Rhododendron luteum Sweet, Hypericum
perforatum L., Lespedeza bicolor Turcz, and L. hedysaroids (Pall.). ) Kitag Rastit Resur 1986;
22:12.
44. Linde K, Berner MM, Kriston L. St John's wort for major depression. Cochrane Database Syst
Rev 2008; :CD000448.
45. Rapaport MH, Nierenberg AA, Howland R, et al. The treatment of minor depression with St.
John's Wort or citalopram: failure to show benefit over placebo. J Psychiatr Res 2011; 45:931.
46. Müller T, Mannel M, Murck H, Rahlfs VW. Treatment of somatoform disorders with St. John's
wort: a randomized, double-blind and placebo-controlled trial. Psychosom Med 2004; 66:538.
47. Volz HP, Murck H, Kasper S, Möller HJ. St John's wort extract (LI 160) in somatoform
disorders: results of a placebo-controlled trial. Psychopharmacology (Berl) 2002; 164:294.
48. Al-Akoum M, Maunsell E, Verreault R, et al. Effects of Hypericum perforatum (St. John's wort)
on hot flashes and quality of life in perimenopausal women: a randomized pilot trial.
Menopause 2009; 16:307.
49. 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; 17:326.
50. Weber W, Vander Stoep A, McCarty RL, et al. Hypericum perforatum (St John's wort) for
attention-deficit/hyperactivity disorder in children and adolescents: a randomized controlled
trial. JAMA 2008; 299:2633.
51. Gulick RM, McAuliffe V, Holden-Wiltse J, et al. Phase I studies of hypericin, the active
compound in St. John's Wort, as an antiretroviral agent in HIV-infected adults. AIDS Clinical
Trials Group Protocols 150 and 258. Ann Intern Med 1999; 130:510.
52. Parsons A, Ingram J, Inglis J, et al. A proof of concept randomised placebo controlled factorial
trial to examine the efficacy of St John's wort for smoking cessation and chromium to prevent
weight gain on smoking cessation. Drug Alcohol Depend 2009; 102:116.
53. Sood A, Ebbert JO, Prasad K, et al. A randomized clinical trial of St. John's wort for smoking
cessation. J Altern Complement Med 2010; 16:761.
54. Saito YA, Rey E, Almazar-Elder AE, et al. A randomized, double-blind, placebo-controlled trial
of St John's wort for treating irritable bowel syndrome. Am J Gastroenterol 2010; 105:170.
55. Kasper S, Gastpar M, Möller HJ, et al. Better tolerability of St. John's wort extract WS 5570
compared to treatment with SSRIs: a reanalysis of data from controlled clinical trials in acute
major depression. Int Clin Psychopharmacol 2010; 25:204.
56. Newall CA, Anderson LA, Phillipson JD. Herbal medicines: A guide for health-care professional
s, The Pharmaceutical Press, London 1996.
57. Golsch S, Vocks E, Rakoski J, et al. [Reversible increase in photosensitivity to UV-B caused by
St. John's wort extract]. Hautarzt 1997; 48:249.
58. Brockmöller J, Reum T, Bauer S, et al. Hypericin and pseudohypericin: pharmacokinetics and
effects on photosensitivity in humans. Pharmacopsychiatry 1997; 30 Suppl 2:94.
59. Upton, R (ed). American Herbal Pharmacopoeia and Therapeutic Compendium. St. John's Wor
t Hypericum perforatum 1997.
60. Ondrizek RR, Chan PJ, Patton WC, King A. An alternative medicine study of herbal effects on
the penetration of zona-free hamster oocytes and the integrity of sperm deoxyribonucleic acid.
Fertil Steril 1999; 71:517.
61. Kŭnchev K, Liutskanov D, Arsenov L. [Comparative studies of plans for controlling American
foulbrood in public aviaries]. Vet Med Nauki 1981; 18:94.
62. Moretti ME, Maxson A, Hanna F, Koren G. Evaluating the safety of St. John's Wort in human
pregnancy. Reprod Toxicol 2009; 28:96.
63. Ang-Lee MK, Moss J, Yuan CS. Herbal medicines and perioperative care. JAMA 2001;
286:208.
64. Gordon RY, Becker DJ, Rader DJ. Reduced efficacy of rosuvastatin by St. John's Wort. Am J
Med 2009; 122:e1.
65. Ernst E. Second thoughts about safety of St John's wort. Lancet 1999; 354:2014.
66. Moore LB, Goodwin B, Jones SA, et al. St. John's wort induces hepatic drug metabolism
through activation of the pregnane X receptor. Proc Natl Acad Sci U S A 2000; 97:7500.
67. Markowitz JS, Donovan JL, DeVane CL, et al. Effect of St John's wort on drug metabolism by
induction of cytochrome P450 3A4 enzyme. JAMA 2003; 290:1500.
68. Mannel M. Drug interactions with St John's wort : mechanisms and clinical implications. Drug
Saf 2004; 27:773.
69. Mueller SC, Majcher-Peszynska J, Uehleke B, et al. The extent of induction of CYP3A by St.
John's wort varies among products and is linked to hyperforin dose. Eur J Clin Pharmacol
2006; 62:29.
70. Wong AH, Smith M, Boon HS. Herbal remedies in psychiatric practice. Arch Gen Psychiatry
1998; 55:1033.
71. Lantz MS, Buchalter E, Giambanco V. St. John's wort and antidepressant drug interactions in
the elderly. J Geriatr Psychiatry Neurol 1999; 12:7.
72. Bladt S, Wagner H. Inhibition of MAO by fractions and constituents of hypericum extract. J
 Geriatr Psychiatry Neurol 1994; 7 Suppl 1:S57.
73. 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; 313:253.
74. Treatment of Depression–Newer Pharmacotherapies. Summary, Evidence Report/Technology
Assessment: Number 7, March 1999. Agency for Health Care Policy and Research, Rockville,
MD. Available at: www.ahcpr.gov/clinic/epcsums/deprsumm.htm (Accessed on August 08, 200
5).
75. www.fda.gov/bbs/topics/NEWS/2007/NEW01657.html (Accessed on October 09, 2007).

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