About Herbs, Botanicals & Other Products

Scientific Name
Hypericum perforatum
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Common Name

Saint John's wort, hypericum, goatweed, God's wonder plant, witches herb

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Clinical Summary

Derived from the flowering parts of the plant, St. John's wort generally is used for depression, seasonal affective disorder, and anxiety. Hyperforin, one of the major constituents of St. John's wort demonstrated neuroprotective properties in vitro and in vivo (34). In a study done in rats, St. John's wort ameliorated neuropathic pain (35).

Studies comparing St. John's wort to standard antidepressants suggest it may be as effective as imipramine or selective serotonin reuptake inhibitors (SSRIs) to treat mild to moderate depression (1) (2) (3), and found it's use safe over a period of one year (32). Data also indicate that the effectiveness of St. John's Wort is comparable to paroxetine (4) and other SSRIs (33) in the treatment of moderate to severe depression and is well tolerated. In addition, reductions in depression were sustained with continued use of St. John's wort in those with acute moderate depression (5) (6). However, meta-analyses show that data is inconsistent when all types of depression are analyzed (7) (8); a randomized trial found St. John's wort ineffective in the treatment of minor depression (44).

Studies also show efficacy of St. John's wort in the management of premenstrual syndrome (9) (36), and vasomotor symptoms in peri- and postmenopausal women (37), but failed to show its usefulness for attention-deficit/hyperactivity disorder (ADHD) in children and adolescents (10) and in individuals with stomatodynia (11).

St. John's wort can interact with many medications due to induction of cytochrome p450 (CYP) 3A4, CYP2C9 (12)and other mechanisms (13). Significant interactions include decreased efficacy of, cyclosporin, tacrolimus, irinotecan, and other chemotherapeutic agents. Serotonin syndrome may occur when combined with sympathomimetics, antidepressants, or triptans (14).

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Purported Uses
  • Depression
  • Fatigue
  • Insomnia
  • Pain
  • Pediatric nocturnal incontinence
  • Premenstrual syndrome
  • Seasonal affective disorder (SAD)
  • Wound healing
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Constituents
  • Anthraquinones: Napthodianthrones, including hypericin and pseudohypericin
  • Phloroglucinols: Hyperforin, adhyperforin
  • Flavonoids: Hyperin, hyperoside, quercetin, kaempferol, rutin
  • Bioflavonoids: Amenotoflavone, II8-biapigenin
  • Phenols: Caffeic, chlorogenic, para-coumaric, para-hydroxybenzoic acid, hyperfolin
  • Volatile oils: Methyl-2-octane, trace amounts monoterpenes (limonene), and sesquiterpenes (caryophyllene, humulene)
  • Tannins: Proanthocyanidins
    (15)
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Mechanism of Action

The hypericin component of St. John's wort is thought responsible for antidepressant activity, but conflicting reports exist. It was initially shown to inhibit monoamine oxidase although this effect has not been demonstrated with use of the whole botanical. Hypericin demonstrates modest receptor affinity for muscarinic cholinergic and sigma receptors. In vitro studies with whole plant exact of St. John's wort report weak inhibition of catechol-O-methyl-transferase (COMT) and limited reuptake of norepinephrine. Hyperforin, a phloroglucinol, has been shown to inhibit the reuptake of serotonin, dopamine, norepinephrine, GABA, and L-glutamine in vitro. In addition, hyperforin activates transient receptor potential (TRP) C6 channels, inducing neurite outgrowth and possibly influencing monoamine uptake (16). Analgesic and CNS activity may be due to its bioflavonoid content.(15) Hyperforin is also responsible for CYP 3A4 induction through activation of the pregnane X receptor (17).
St. John's Wort extract and its constituents were shown to modulate P-glycoprotein activity via protein kinase C (PKC) at the Blood-Brain Barrier (38).

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Pharmacokinetics

Hypericin: Oral administration peak concentration at approximately 2 hours, elimination half-life approximately 25 hours. Steady state concentrations with three times daily dosing occurred by day 4. Terminal half-life is 42 hours.

Hyperforin: Oral administration peak concentration occurred at approximately 3.5 hours. Elimination half-life is approximately 9 hours. Steady state concentration with 300 mg St. John's wort (standardized to 14.8 mg hyperforin) equal to 100 ng/ml.

Pseudohypericin: Oral administration peak concentration at approximately 30 minutes. Terminal half-life is approximately 23 hours. (13)

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Warnings
  • May cause photosensitivity.
  • St. John's wort should be discontinued one week before surgery or chemotherapy.
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Contraindications

Pregnant or nursing women should not consume St. John's wort.

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Adverse Reactions

Common: Headache, nausea, abdominal discomfort, constipation, dizziness, confusion, fatigue, dry mouth, sleep disturbances, and sedation.
Infrequent: Photosensitivity or photodermatitis, elevated liver function tests, acute neuropathy, increased prothrombin time (PT) (13) (15).
Case reports:
Mania in 3 patients with underlying bipolar disorder. Resolved promptly in 2 patients following discontinuation while the third experienced persistent agitation for several months (13).
Serotonin syndrome: Hypertension, diaphoresis, agitation, dizziness, and weakness with acute onset following 10 days of St. John's wort. Syndrome resolved following supportive care and discontinuation of St. John's wort (14).
Erythroderma affecting both light-exposed and non light-exposed areas of skin. Developed 4 days after initiation of St. John's wort and resolved after 5 weeks with concomitant oral steroids (18).
Sexual dysfunction: Decreased sexual libido that returned following discontinuation of St. John's wort (19).
Withdrawal syndrome: Nausea, anorexia, dry retching, dizziness, dry mouth, thirst, cold chills, and extreme fatigue in patient within 24 hours of stopping treatment of St. John's wort after 32 days of treatment (20).
Prolonged facial dystonia has been reported in a 58-year-old Caucasian woman following use of bupropion along with St. John's wort (39).

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Herb-Drug Interactions

UGT (Uridine 5'-diphospho-glucuronosyltransferase) substrates: St. John's wort modulates UGT enzymes in vitro and can increase the side effects of drugs metabolized by them (43).


Cytochrome P450 3A4 substrates: St. John's wort has been shown to induce cytochrome isoenzyme 3A4, therefore affecting metabolism of certain medications and reducing serum concentrations. CYP 3A4 levels return to normal 1 week after discontinuing St. John's wort (21). Drugs metabolized by 3A4 include:

  • Theophylline: Blood levels of theophylline may be significantly reduced, resulting in decreased efficacy.
  • HIV protease inhibitors: Blood levels of indinavir, nelfinavir, ritonavir, and saquinavir can be significantly reduced, resulting in increased HIV viral load and development of viral resistance.
  • HIV non-nucleoside reverse transcriptase inhibitors: Blood levels of efavirenz and nevirapine can be significantly reduced, resulting in increased HIV viral load.
  • Cyclosporin / Tacrolimus: Blood levels of cyclosporin or tacrolimus can be significantly reduced, resulting in decreased efficacy.
  • Diltiazem / Nifedipine: Blood levels of diltiazem or nifedipine can be reduced, resulting in decreased efficacy (13).
  • Irinotecan: Due to changes in hepatic metabolism caused by St. John's wort, levels of irinotecan metabolite SN-38 may be lowered by as much as 40% for up to 3 weeks following discontinuation of St. John's wort (22).
  • Warfarin: May increase or decrease activity when administered concomitantly. Internal normalization ratio (INR) should be monitored routinely. S-isomer may have increased metabolism due to CYP 3A4 induction. S-isomer may have decreased metabolism due to CYP 1A2 inhibition (23).
  • Digoxin: Prolonged concurrent administration may result in decreased absorption of digoxin with lowered plasma concentrations (24).
  • Triptans: Increased serotonergic effect and possible serotonin syndrome when combined with sumatriptan, naratriptan, rizatriptan, or zolmitriptan (13).
  • SSRIs: Increased serotonergic effect and possible serotonin syndrome when combined with citalopram, fluoxetine, fluvoxamine, paroxetine, or sertraline.
  • Tricyclic Antidepressants: Increased serotonergic effect and possible serotonin syndrome when combined with nefazodone, amitriptyline, or imipramine. Possible reduction in efficacy of antidepressants due to changes in metabolism (13).
  • Oral Contraceptives: May reduce blood levels resulting in decreased efficacy (i.e., breakthrough bleeding or pregnancy) (40).
  • Alcohol: May result in increased sedation (13).
  • Anesthetics: Case report of cardiovascular collapse (hypotension without anaphylactic symptoms) shortly after induction of general anesthesia with fentanyl, propofol, d-tubocurarine, and succinylcholine followed by nitrous oxide, oxygen, and isoflurane.
  • Chemotherapy: Due to changes in hepatic metabolism caused by St. John's wort, chemotherapy levels may be altered, resulting in increased toxicity or decreased efficacy. Caution should be exercised when administering concomitantly with chemotherapy (i.e., cyclophosphamide, paclitaxel, etoposide, irinotecan).
  • Tamoxifen: Due to changes in hepatic metabolism caused by St. John's wort, levels of tamoxifen may be lowered, resulting in reduced efficacy.
  • Alprazolam: May reduce blood levels, resulting in decreased efficacy (25).
  • Dextromethorphan: May reduce blood levels, resulting in decreased efficacy (25).
  • Sympathomimetics: Concomitant administration may produce increased serotonergic activity and possible serotonin syndrome (26).
  • Imatinib: Increase clearance (27)(28).
  • Simvastatin: Increase clearance, resulting in increased LDL cholesterol (30).
  • Atorvastatin: Increase clearance, resulting in increased LDL cholesterol (31).
  • Rosuvastatin: Reduces efficacy via increased clearance (41).
  • Oxycodone: St. John's wort reduces plasma concentrations of oxycodone significantly reducing its effectiveness (42).
  • Gliclazide: Increased clearance (12).
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Herb Lab Interactions

Elevated liver function tests.

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Literature Summary and Critique

Kasper S, et al. Continuation and long-term maintenance treatment with Hypericum extract WS((R)) 5570 after recovery from an acute episode of moderate depression - A double-blind, randomized, placebo controlled long-term trial. Eur Neuropsychopharmacol. Nov 2008;18(11):803-813.To determine the long-term effects of sustained treatment with hypericum extract WS 5570 in 426 individuals with recurrent, moderate depression (defined as Hamilton Depression Rating Scale [HAMD] total score ¡Ý20 and ¡Ý3 previous episodes in 5 years), this double-blind, randomized, placebo-controlled study was performed. Participants were given WS 5570 (3˟300 mg/day) or placebo for 26 weeks during which relapse rates, time to relapse, HAMD scores, as well as adverse events were assessed. Time until relapse was significantly greater and HAMD scores were lower in the WS 5570-treated group as compared to the placebo group. Also, there was no difference in adverse events reported between the 2 groups. Thus, in individuals treated for recurrent, moderate depression, WS 5570 maintenance therapy reduced relapse; however, further studies are required to determine if WS 5570 maintenance therapy is comparable to conventional maintenance therapies.

Szegedi A, et al. Acute treatment of moderate to severe depression with hypericum extract WS 5570 (St John's Wort): randomised controlled double blind non-inferiority trial versus paroxetine. BMJ 2005;330 (7490):503.
A total of 251 patients with acute major depression were given either 900 mg/day hypericum extract WS 5570 three times a day or 20 mg paroxetine, an SSRI, once a day for six weeks. At two weeks, the doses were increased to 1800 mg/day of hypercium and 40 mg paroxetine for patients who did not respond to the treatments. Researchers found that both the treatment groups showed significant decrease in depression scores. St John's Wort appears to be as effective as paroxitene in the management of severe depression. However, care should be taken while taking St John's Wort as it can interact with other drugs.

Shelton RC, et al. Effectiveness of St. John's Wort in major depression: a randomized controlled trial. JAMA 2001;285:1978-86.
A prospective, randomized, multicenter, placebo-controlled evaluation of 900-1200 mg per day of St. John's wort or placebo for major depression. A total of 167 patients completed the 8-week trial, 87 receiving placebo and 80 receiving St. John's wort. Patients who had previously taken St. John's wort, were refractory to traditional antidepressant, or had a history of concomitant psychological disorder (i.e. panic, schizophrenia, bipolar disorder) were excluded. No significant difference was found between St. John's wort and placebo for measured outcomes including Hamilton depression scale, Hamilton anxiety scale, Beck depression inventory, and global assessment of function. This study indicates that St. John's wort should not be used as monotherapy in patients with severe depression. However, the results of this study do not represent those for patients with minor to moderate depression.

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;15:61-8.
A prospective evaluation of 240 patients randomized to receive 20 mg/day of fluoxetine (n=114) or 500 mg/day of St. John's wort (n=126). Both treatment arms had Hamilton depression scores of approximately 19.5. One patient in the St. John's wort group withdrew from the study immediately following baseline assessment and one patient in the fluoxetine group withdrew due to adverse effects. Following 6 weeks of therapy, St. John's wort and fluoxetine were equally efficacious with respect to change in Hamilton depression scale and clinical global impression. Adverse events associated with St. John's wort were gastrointestinal disturbance, dizziness, and fatigue. Fluoxetine and St. John's wort appear to be equally efficacious for the management of mild to moderate depression.

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References
  1. Brenner R, Azbel V, Madhusoodanan S, et al. Comparison of an extract of hypericum (LI 160) and sertraline in the treatment of depression: a double-blind, randomized pilot study. Clin Ther. Apr 2000;22(4):411-419.
  2. Linde K, Knuppel L. Large-scale observational studies of hypericum extracts in patients with depressive disorders—a systematic review. Phytomedicine. Jan 2005;12(1-2):148-157.
  3. Schrader E. Equivalence of St John's wort extract (Ze 117) and fluoxetine: a randomized, controlled study in mild-moderate depression. Int Clin Psychopharmacol. Mar 2000;15(2):61-68.
  4. Szegedi A, Kohnen R, Dienel A, et al. Acute treatment of moderate to severe depression with hypericum extract WS 5570 (St John's wort): randomised controlled double blind non-inferiority trial versus paroxetine. BMJ. Mar 5 2005;330(7490):503.
  5. Kasper S, Volz HP, Moller HJ, et al. Continuation and long-term maintenance treatment with Hypericum extract WS((R)) 5570 after recovery from an acute episode of moderate depression - A double-blind, randomized, placebo controlled long-term trial. Eur Neuropsychopharmacol. Nov 2008;18(11):803-813.
  6. Kasper S, Anghelescu IG, Szegedi A, et al. Placebo controlled continuation treatment with Hypericum extract WS 5570 after recovery from a mild or moderate depressive episode. Wien Med Wochenschr. 2007;157(13-14):362-366.
  7. Linde K, Mulrow CD, Berner M, et al. St John's wort for depression. Cochrane Database Syst Rev. 2005(2):CD000448.
  8. Linde K, Berner MM, Kriston L. St John's wort for major depression. Cochrane Database Syst Rev. 2008(4):CD000448.
  9. Stevinson C, Ernst E. A pilot study of Hypericum perforatum for the treatment of premenstrual syndrome. BJOG. Jul 2000;107(7):870-876.
  10. 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. Jun 11 2008;299(22):2633-2641.
  11. Sardella A, Lodi G, Demarosi F, et al. Hypericum perforatum extract in burning mouth syndrome: a randomized placebo-controlled study. J Oral Pathol Med. Aug 2008;37(7):395-401.
  12. Xu H, Williams KM, Liauw WS, et al. Effects of St John's wort and CYP2C9 genotype on the pharmacokinetics and pharmacodynamics of gliclazide. Br J Pharmacol. Apr 2008;153(7):1579-1586.
  13. Barnes J, Anderson LA, Phillipson JD. St John's wort (Hypericum perforatum L.): a review of its chemistry, pharmacology and clinical properties. J Pharm Pharmacol. May 2001;53(5):583-600.
  14. Parker V, Wong AH, Boon HS, et al. Adverse reactions to St John's Wort. Can J Psychiatry. Feb 2001;46(1):77-79.
  15. Fetrow CW, Avila JR. Professional's Handbook of Complementary & Alternative Medicine. Springhouse (PA): Springhouse; 1999.
  16. Leuner K, Kazanski V, Muller M, et al. Hyperforin—a key constituent of St. John's wort specifically activates TRPC6 channels. FASEB J. Dec 2007;21(14):4101-4111.
  17. Mueller SC, Majcher-Peszynska J, Mundkowski RG, et al. No clinically relevant CYP3A induction after St. John's wort with low hyperforin content in healthy volunteers. Eur J Clin Pharmacol. Sep 3 2008.
  18. Holme SA, Roberts DL. Erythroderma associated with St John's wort. Br J Dermatol. Nov 2000;143(5):1127-1128.
  19. Bhopal JS. St John's wort-induced sexual dysfunction. Can J Psychiatry. Jun 2001;46(5):456-457.
  20. Dean AJ, Moses GM, Vernon JM. Suspected withdrawal syndrome after cessation of St. John's wort. Ann Pharmacother. Jan 2003;37(1):150.
  21. Imai H, Kotegawa T, Tsutsumi K, et al. The recovery time-course of CYP3A after induction by St John's wort administration. Br J Clin Pharmacol. May 2008;65(5):701-707.
  22. Mathijssen RH, Verweij J, de Bruijn P, et al. Effects of St. John's wort on irinotecan metabolism. J Natl Cancer Inst. Aug 21 2002;94(16):1247-1249.
  23. 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. May 2004;57(5):592-599.
  24. Gurley BJ, Swain A, Williams DK, et al. Gauging the clinical significance of P-glycoprotein-mediated herb-drug interactions: comparative effects of St. John's wort, Echinacea, clarithromycin, and rifampin on digoxin pharmacokinetics. Mol Nutr Food Res. Jul 2008;52(7):772-779.
  25. 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. Sep 17 2003;290(11):1500-1504.
  26. Brinker F. Herb Contraindications and Drug Interactions. 3rd ed. Sandy (OR): Eclectic Medical Publications; 2001.
  27. Frye RF, Fitzgerald SM, Lagattuta TF, et al. Effect of St John's wort on imatinib mesylate pharmacokinetics. Clin Pharmacol Ther. Oct 2004;76(4):323-329.
  28. Smith P, Bullock JM, Booker BM, et al. The influence of St. John's wort on the pharmacokinetics and protein binding of imatinib mesylate. Pharmacotherapy. Nov 2004;24(11):1508-1514.
  29. Schwarz UI, Hanso H, Oertel R, et al. Induction of intestinal P-glycoprotein by St John's wort reduces the oral bioavailability of talinolol. Clin Pharmacol Ther. May 2007;81(5):669-678.
  30. Eggertsen R, Andreasson A, Andren L. Effects of treatment with a commercially available St John's Wort product (Movina) on cholesterol levels in patients with hypercholesterolemia treated with simvastatin. Scand J Prim Health Care. Sep 2007;25(3):154-159.
  31. Andren L, Andreasson A, Eggertsen R. Interaction between a commercially available St. John's wort product (Movina) and atorvastatin in patients with hypercholesterolemia. Eur J Clin Pharmacol. Oct 2007;63(10):913-916.
  32. 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.
  33. Rahimi R, Nikfar S, Abdollahi M. Efficacy and tolerability of Hypericum perforatum in major depressive disorder in comparison with selective serotonin reuptake inhibitors: a meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2009 Feb 1;33(1):118-27.
  34. Griffith TN, Varela-Nallar L, Dinamarca MC, Inestrosa NC. Neurobiological Effects of Hyperforin and its Potential in Alzheimer's disease Therapy. Curr Med Chem. 2010;17(5):391-406.
  35. Galeotti N, Vivoli E, Bilia AR, Vincieri FF, Ghelardini C. St. John's Wort reduces neuropathic pain through a hypericin-mediated inhibition of the protein kinase Cgamma and epsilon activity. Biochem Pharmacol. 2010 May 1;79(9):1327-36.
  36. Canning S, Waterman M, Orsi N, et al. The efficacy of Hypericum perforatum (St John's wort) for the treatment of premenstrual syndrome: a randomized, double-blind, placebo-controlled trial. CNS Drugs. 2010 Mar 1;24(3):207-25.
  37. 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.
  38. Ott M, Huls M, Cornelius MG, Fricker G. St. John's Wort Constituents Modulate P-glycoprotein Transport Activity at the Blood-Brain Barrier. Pharm Res. 2010 Mar 13. [Epub ahead of print]
  39. Milton JC, Abdulla A. Prolonged oro-facial dystonia in a 58 year old female following therapy with bupropion and St John's Wort. Br J Clin Pharmacol. 2007 Nov;64(5):717-8.
  40. Vlachojannis J, Cameron M, Chrubasik S. Drug interactions with St. John's wort products. Pharmacol Res. 2011 Mar;63(3):254-6.
  41. Gordon RY, Becker DJ, Rader DJ. Reduced efficacy of rosuvastatin by St. John's Wort. Am J Med. 2009 Feb;122(2):e1-2.
  42. Nieminen TH, Hagelberg NM, Saari TI, et al. St John's wort greatly reduces the concentrations of oral oxycodone. Eur J Pain. 2010 Sep;14(8):854-9.
  43. Mohamed ME, Frye RF. Effects of herbal supplements on drug glucuronidation. Review of clinical, animal, and in vitro studies. Planta Med. 2011 Mar;77(4):311-21.
  44. 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 Jul;45(7):931-41.
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How It Works


Bottom Line: St. John's wort can help relieve depression. However, this herb can affect the activity of many drugs, including those used in chemotherapy.Several animal and human studies have shown that St. John's wort is effective against depression and is safe and well tolerated; however, some data contradict this. Compounds known as hypericin and hyperforin may interact with chemicals and counteract processes in the brain that are associated with depression and anxiety. St. John's wort was found to have neuroprotective effects in rats. It may also be useful in treating premenstrual syndrome and in reducing vasomotor symptoms in peri- and postmenopausal women. More studies are needed.

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Purported Uses
  • To treat depression
    Several studies in humans support the use of this herb for depression.
  • To treat anxiety
    Although many studies support its use in depression, none have studied it to treat anxiety. No clinical evidence supports this use.
  • To treat chronic fatigue
    Some research supports this use, but more is needed.
  • To treat insomnia
    There is not enough evidence to support this use.
  • To reduce the symptoms of premenstrual syndrome (PMS)
    St. John's wort was shown in randomized trials to reduce symptoms of premenstrual syndrome.
  • To treat seasonal affective disorder (SAD)
    So far, a few studies show that St. John's wort is not effective for this use.
  • Topically, for wound healing
    In laboratory studies, wort acts as an antibiotic and antiviral agent, but there is no proof from clinical trials that it can help wounds heal.
  • To treat HIV
    A small study showed high toxicity and no benefit.
  • To attention-deficit/hyperactivity disorder (ADHD)
    A small study showed that St. John's wort is not effective for this use.
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Research Evidence

Depression:
In a recent trial, 251 patients with acute major depression were given hypericum extract or paroxetine, an SSRI, daily for six weeks. Researchers found that both the treatment groups showed significant decrease in depression scores. St John's Wort appears to be as effective as paroxitene in the management of severe depression. However, care should be taken while taking St John's Wort as it can interact with other drugs.

A clinical trial carried out at multiple hospitals compared 900-1200 mg per day of St. John's wort to placebo in 167 patients with major depression. There were no significant differences in depression, anxiety, or functioning between the two groups, indicating that patients with severe depression should not use St. John's wort alone as a treatment.

In a clinical trial with 28 patients who had mild to moderate depression, 900 mg/day of St. John's wort was just as effective as 75 mg/day of sertraline (Zoloft®, a common antidepressant) in treating depression when given for seven weeks.

In a larger study of 240 patients with mild to moderate depression, 500 mg/day of St. John's wort was just as effective as 20 mg/day of fluoxetine (Prozac® or SarafemTM) in treating depression when given for six weeks.

To study the ability of St. John's wort to prevent depression relapse, 426 patients with recurrent, moderate depression were given a St. John's wort extract (3˟300 mg/day) or placebo for 6 months. Patients taking St. John's wart showed a significant decrease in depression scores. Also, there was no difference in adverse events reported between the 2 groups.

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Patient Warnings
  • This product may cause your skin to be more sensitive to sunlight, leading to sunburn, rash, or redness of the skin.
  • This product is regulated by the FDA as a dietary supplement. Unlike approved drugs, supplements are not required to be manufactured under specific standardized conditions. This product may not contain the labeled amount or may be contaminated. In addition, it may not have been tested for safety or effectiveness.
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Do Not Take If
  • You are pregnant or nursing.
  • You are undergoing treatment with UV light (Since St. John's wort makes the skin more sensitive to light).
  • You have bipolar disorder (This herb caused mania in a few patients with bipolar disorder. Take with caution).
  • You are taking warfarin (Patients should have their bleeding time monitored routinely. St. John's wort may interfere with the action of warfarin).
  • You are taking digoxin (St. John's wort might lessen its effect).
  • You are taking triptans such as sumatriptan, naratriptan, rizatriptan, or zolmitriptan (St. John's wort might have additive effects).
  • You are taking selective serotonin reuptake inhibitors (SSRIs) such as citalopram, fluoxetine, fluvoxamine, paroxetine, or sertraline (St. John's wort might have additive effects).
  • You are taking tricyclic antidepressants such as nefazodone, amitriptyline, or imipramine.
  • You are taking birth control pills (St. John's wort can increase the risk of pregnancy).
  • You regularly consume alcohol (St. John's wort may result in increased sedation. Take with caution).
  • You plan to undergo general anesthesia for surgery (St. John's wort should be discontinued two weeks before surgery).
  • You are undergoing chemotherapy with drugs such as cyclophosphamide, paclitaxel, docetaxel, irinotecan, or etoposide (St. John's wort has been shown to reduce the effectiveness of chemotherapy).
  • You are taking tamoxifen (St. John's wort may lessen its effect).
  • You are taking sympathomimetics (St. John's wort may increase the effect).
  • You are taking HIV protease inhibitors such as indinavir, nelfinavir, ritonavir, saquinavir (St. John's wort has been known to lessen their effects).
  • You are taking any of the following drugs: theophylline, efavirenz, nevirapine, cyclosporin, tacrolimus, diltiazem, nifedipine, alprazolam, dextromethorphan, simvastatin, atorvastatin, rosuvastatin, gliclazide (St. John's wort can lessen their effects).
  • You are taking oxycodone (St. John's wort can decrease its effectiveness).
  • You are taking drugs that are substrates of UGT (Uridine 5'-diphospho-glucuronosyltransferase) enzymes (St. John's wort may increase the risk of side effects of these drugs).
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Side Effects
  • Headache
  • Gastrointestinal upset: nausea, abdominal discomfort, constipation
  • Dizziness, confusion, sedation · Sleep disturbances
  • Fatigue
  • Dry mouth
  • Skin sensitivity to sunlight
  • Contact your doctor if you experience: pain or tingling in the extremities, wounds that will not heal, or yellowing of the eyes or skin.
  • There is one case report of serotonin syndrome, consisting of high blood pressure, profuse perspiration, agitation, dizziness, and weakness.
  • Sexual dysfunction has been reported.
  • A case of prolonged orofacial dystonia (sustained muscle contractions that produces twisting and repetitive movements) has been reported.
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Special Point
  • Do not use St. John's wort if you are undergoing chemotherapy.
  • St. John's wort interferes with the action of many different drugs. Check with your doctor or pharmacist to make sure that other medications you are taking do not interact with St. John's wort.
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Dosage (Inside MSKCC Only)
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Aliases
Hypericum Perforatum
Saint John's Wort
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E-mail your questions and comments to aboutherbs@mskcc.org.
Last updated: June 15, 2011