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Hypericum perforatum (St John's wort)

Derivation: The word hypercum in Greek means over an apparition, derived from its ancient use for protecting against demonic possession. The Greek word perforatum means holes. The leaves of the plant have small holes throughout apparent when held up to the light. The name St John's wort derives from the observation that the flowers bloom around St John's day (June 24). Also, the red pigments observed when buds & flowers are squeezed have been associated with St John, the baptist. Distribution: The herb grows in Europe & the US. It grows particularly well in Northern California. Uses: Traditional use: 1) wound healing 2) burn healing 3) snakebites 4) kidney stones 5) diuretic 6) antidepressant 7) chronic neuropathic pain Current uses: 1) depression: (at least as effective as paroxetine) [15]* 2) anxiety [17] 3) topical wound healing 4) topical anti-inflammatory agent for arthritis 5) antiviral properties a) HIV b) Herpes * appears to be effective for mild-moderate depression Contraindications: Caution: 1) pregnancy: no safety data, not recommended 2) not recommended for children 3) do not use with antidepressants Dosage: 1) pills 300 mg most common 2) common dose 300 mg TID 3) 600 mg TID for severe depression [15] 4) pills have standardized extract to 0.3% hypericin 5) discontinue 5 days before surgery [17] Pharmacokinetics: 1) hypercin 1/2 life: 24-46 hours 2) pseudohypericin 1/2 life 16-36 hours 3) effects are not observed until treatment is continued for several weeks 4) appears to induce cyt P450s CYP2C9 & CYP3A4, but not CYP2D6 [14] Adverse effects: 1) generally well tolerated 2) mild photosensitivity, especially at high doses 3) insomnia, vivid dreams, irritability, restlessness, anxiety 4) GI symptoms: diarrhea, constipation, nausea 5) dizziness 6) dry mouth 7) allergic reaction 8) sexual dysfunction [11] 9) urinary frequency [11] 10) delayed emergence from anesthesia [12] 11) hypomania [17] 12) headache [18] Drug interactions: 1) do not use with antidepressants a) possible interaction with MAO inhibitors b) possible serotonin syndrome when used with selective serotonin reuptake inhibitors (SSRI) 2) possible interaction with sympathomimetic amines 3) do not use with other photosensitizing agents 4) may reduce efficacy of a) oral contraceptives [13] b) antiretroviral protease inhibitors (indinavir 57% [10]) c) non-nucleoside reverse-transcriptase inhibitors, i.e. nevirapine [20] d) cyclosporine 60% [6,10] e) finasteride [17] 5) St John's wort induces CYP1A2, CYP2C9, CYP3A4 & CYP3A5 a) any drug metabolized by cyt P450s CYP1A2, CYP2C9 or CYP3A4/CYP3A5 may show diminished levels when use concurrently with St John's wort [9,16] b) digoxin levels may be reduced 25%, [10] c) warfarin levels decreased 6) irinotecan (Camptosar) levels reduced 50% [1] 7) may reduce efficacy of imatinib [20] Mechanism of action: 1) active ingredients: a) hyperforin (active ingredient [20]) b) hypericin (a napthodianthrone) c) pseudohyperican d) the flowering tops have the greatest concentrations of these substances, followed by upper leaves & stems 2) in vitro MAO-inhibitory properties, not demonstrated in vivo 3) conjecture that it effects serotonin a) serotonin inhibitor b) serotonin re-uptake inhibitor c) down-regulation of serotonin receptors 4) conjecture that it may effect synaptosomal re-uptake of a) dopamine b) norepinephrine 5) no clear consensus on mechanism of action 6) induces cyt P450 1A2, 2C9 & 3A4 [6,9,16] 7) induces P-glycoprotein Clinical trials: 1) Ref 5 sited in ref 4: - may be reasonable 1st line agent in moderately depressed patient - still much variability in different commercial products - as effective & better tolerated than imipramine [7] 2) 900-1200 mg/day no more effective than placebo [8] 3) Neither St John' wort 900-1500 mg/day or sertraline 50-100 mg/day more effective than placebo for moderate to severe depression [10, 11] Notes: - suncreen recommended

Interactions

drug interactions

Related

cytochrome P450 2C9; cytochrome P450 BP-1; cytochrome P450 MP-4; S-mephenytoin-4-hydroxylase; limonene 6-monooxygenase; limonene 7-monooxygenase (CYP2C9, CYP2C10) cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4)

General

pharmaceutical herb; medicinal herb; herbal supplement; botanical

References

  1. Victoria Rand, UCSF Fresno Lecture, 10/7/98
  2. Linde et al, BMJ, 1996
  3. Kaiser Permanente, Northern California Regional Pharmacy & Therapeutics Committee
  4. Journal Watch 20(3):21, 2000
  5. Phillip et al BMJ 319:1534, 1999
  6. Prescriber's Letter 7(10):59 2000
  7. Journal Watch 20(20):162, 2000 Woelk H, BMJ 321:536, 2000
  8. Journal Watch 21(11):85, 2001 Shelton RC et al, JAMA 285:1978, 2001
  9. Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: 220233 (subscription needed) http://www.prescribersletter.com
  10. Prescriber's Letter 9(5):27 2002
  11. Journal Watch 22(10):75, 2002 JAMA 287:1807, 2002 Kupfer DJ & Frank E, JAMA 287:1853, 2002
  12. Prescriber's Letter 10(2):12 2003
  13. Prescriber's Letter 10(7):41 2003
  14. Journal Watch 23(22):179, 2003 Markowitz JS et al, JAMA 290:1500, 2003 PMID: 13129991
  15. Journal Watch 25(9):75, 2005 Szegedi A, Kohnen R, Dienel A, Kieser M. 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 Mar 5;330(7490):503. Epub 2005 Feb 11. Erratum in: BMJ. 2005 Apr 2;330(7494):759. dosage error in text. PMID: 15708844 http://bmj.bmjjournals.com/cgi/content/full/330/7490/503
  16. Prescriber's Letter 13(2): 2006 Cytochrome P450 drug interactions Detail-Document#: 220233 (subscription needed) http://www.prescribersletter.com
  17. Geriatrics at your Fingertips, 13th edition, 2011 Reuben DB et al (eds) American Geriatric Society
  18. Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013
  19. Medical Knowledge Self Assessment Program (MKSAP) 17, 18. American College of Physicians, Philadelphia 2015, 2018
  20. Paauw DS Dangerous and Deadly Drug Combinations Medscape. June 30, 2016 http://www.medscape.com/features/slideshow/dangerous-drug-combinations
  21. Linde K, Berner MM, Kriston L. St John's wort for major depression. Cochrane Database Syst Rev. 2008 Oct 8;(4):CD000448. Review. PMID: 18843608

Component-of

docosahexaenoate/eicosapentaenoate/folic acid/hypericum perforatum