Pharmacology Book

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St. John's Wort

Aka: St. John's Wort, Hypericum perforatum, Hypericin
  1. Indications (evidence-based)
    1. Dysthymia
    2. Mild to moderate Major Depression
    3. Do not use for severe Major Depression
  2. Precautions
    1. Potency and purity not regulated
    2. Discontinue at least 5 days before surgery
    3. Risk of Serotonin Syndrome when used with Selective Serotonin Reuptake Inhibitors
    4. Significant drug interactions (see below)
      1. Counters the activity of Warfarin, cardiac drugs, HIV agents, and Oral Contraceptives
  3. Ingredients
    1. Derived from flowering plant Hypericum perforatum
    2. Contents
      1. Hypericin (Naphthodianthrone) is Active Ingredient
      2. Amount of Hypericin in plant is quite variable
  4. Mechanism: Hypericin
    1. Inhibits Serotonin, Norepinephrine, and Dopamine uptake
    2. Binds to GABA receptors in vitro
    3. Hypericin is a MAO inhibitor at high dose
      1. Not present at standard doses described below
  5. Pharmacokinetics: Hypericin
    1. Half life: 24 to 48 hours
    2. Peaks effect: 5 hours
    3. Excretion mechanism unknown
    4. Induces Cytochrome P450 3A4
  6. Efficacy
    1. Effective in mild-moderate depression in recent trials
      1. Better than Placebo in mild-moderate depression
      2. Similar effect when compared to standard agents
        1. Elavil 75 mg
        2. Imipramine 100-150 mg
        3. Fluoxetine 20 mg
        4. Sertraline 75 mg
      3. References
        1. Kasper (2002) Psychopharmacology 164:301-8
        2. Lawvere (2005) Am Fam Physician 72:2249-54
    2. However trial results are inconsistent (despite above)
      1. Several reviews have shown marginal efficacy
      2. Do not use for severe Major Depression
      3. References
        1. (2002) JAMA 287:1807-14
        2. Werenke (2004) J Clin Psychiatry 65:611-7
    3. Early clinical trials flawed
      1. Placebo response rate low
      2. Trials of very short duration (most 4-8 weeks)
      3. Depression diagnosis not well established
      4. Hypericin dosages varied widely across studies
      5. Compared with too low dose standard Antidepressants
      6. Linde (1996) BMJ 313: 253
  7. Adverse Effects
    1. Transient Photosensitivity (most common side effect)
      1. Elevated, pruritic, red lesions in response to sun
      2. Neuropathic pain
    2. Dry Mouth
    3. Dizziness
    4. Gastrointestinal side effects (e.g. Constipation)
    5. Confusion
    6. Allergic Reaction
    7. Fatigue
    8. Serotonin Syndrome
  8. Drug Interactions: Serotonin Syndrome Risk
    1. May interact with Antidepressants (e.g. SSRIs)
    2. Consider 2 week "washout" when switching to SSRI
  9. Drug Interactions: Cytochrome P450
    1. Effects
      1. St. John's Wort has more cardiac drug interactions than any other supplement
      2. Induces CYP3A4 and therefore decreases CYP3A4 metabolized drug serum levels
      3. More than half of all medications are 3A4 metabolized
      4. Also affects CYP2C9, CYP1A2 and the P-glycoprotein transport protein
    2. Drugs with decreased activity or serum levels when used with St. John's Wort
      1. Cyclosporine
      2. Digoxin
      3. Oral Contraceptives
        1. Hall (2003) Clin Pharmacol Ther 74:525-35
      4. Nevirapine and Indinavir used in HIV Infection management
        1. de Maat (2001) AIDS 15:420-1
      5. Statins
      6. Tegretol
      7. Verapamil
      8. Warfarin
    3. Reference
      1. Markowitz (2003) JAMA 290:1500-4
      2. Zhou (2004) J Psychopharmacol 18:262-76
  10. Dosing
    1. St. John's Wort 300 mg three times daily or
    2. St. John's Wort 450 mg twice daily
  11. Cost
    1. $10 to $25 per month
  12. References
    1. (1997) Med Lett Drugs Ther 39(1014): 107-8
    2. Ang-Lee (2001) JAMA 286:208-16
    3. Cupp (1999) Am Fam Physician 59(5):1239-44
    4. Lawvere (2005) Am Fam Physician 72:2249-54
    5. Woelk (2000) BMJ 321: 536-9

hypericin (C0063220)

Definition (NCI) An anthraquinone derivative that is naturally found in the yellow flower of Hypericum perforatum (St. John's wort) with antidepressant, potential antiviral, antineoplastic and immunostimulating activities. Hypericin appears to inhibit the neuronal uptake of serotonin, norepinephrine, dopamine, gamma-amino butyric acid (GABA) and L-glutamate, which may contribute to its antidepressant effect. Hypericin may also prevent the replication of encapsulated viruses probably due to inhibition of the assembly and shedding of virus particles in infected cells. This agent also exerts potent phototoxic effects by triggering apoptotic signaling that results in formation of reactive oxygen species.
Concepts Organic Chemical (T109) , Pharmacologic Substance (T121)
MSH C004965
SnomedCT 123681008
English 1,3,4,6,8,13-hexahydroxy-10,11-dimethylphenanthro(1,10,9,8-opqra)perylene-7,14-dione, hypericin, HYPERICIN, 4,5,7,4',5',7'-Hexahydroxy-2,2'-dimethyl-mesonapthtodianthron, Hypericin, Hypericin (substance)
Spanish hipericina (sustancia), hipericina
Sources
Derived from the NIH UMLS (Unified Medical Language System)


ST. JOHN'S WORT EXTRACT (C0813171)

Definition (NCI) An herbal extract prepared from the plant Hypericum perforatum (St. John's wort) with photodynamic, antineoplastic, and antidepressant activities. Hypericin, one of the active compounds found in Hypericum perforatum, is a photosensitizer that, when exposed to a particular wavelength and intensity of light, may induce tumor cell apoptosis. Another compound, hyperforin, induces caspase-dependent apoptosis in certain tumor cell lines. Hypericum perforatum preparations may also stimulate the activity of cytochrome P450 enzymes and P-glycoprotein drug transporters, resulting in increased metabolism and decreased efficacy of various chemotherapeutic agents and other drugs.
Definition (NCI) An herbal product sold as an over-the-counter treatment for depression. It is being studied for its ability to lessen certain side effects of cancer treatment.
Definition (PDQ) An herbal preparation isolated from the plant St. John's Wort with photodynamic, antineoplastic, and antidepressant properties. Hypericin, one of the active compounds found in hypericum perforatum, is a photosensitizer that, when exposed to a particular wavelength and intensity of light, may induce tumor cell apoptosis. Another compound, hyperforin, induces caspase-dependent apoptosis in certain tumor cell lines. Hypericum perforatum preparations may also stimulate the activity of cytochrome P450 enzymes and P-glycoprotein drug transporters, resulting in increased metabolism and decreased efficacy of various chemotherapeutic agents and other drugs. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=37989&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=37989&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C2589" NCI Thesaurus)
Concepts Organic Chemical (T109) , Pharmacologic Substance (T121)
SnomedCT 412515006
English St. John's wort, St. John's Wort Extract, hypericum perforatum, St. John's Wort, ST. JOHN'S WORT, Hypericum Perforatum Extract, St. John's wort (medication), HYPERICUM PERFORATUM, ST. JOHN'S WORT EXTRACT, st john's wort, st. john's wort, Hypericum perforatum, Klamath weed, St John's Wort, HyP, Hypericum perforatum extract (substance), Hypericum perforatum extract, Saint Johns wort extract, St Johns wort extract, St. John's wort extract, Saint John's Wort, Hypericum Perforatum
Spanish extracto de Hypericum perforatum (sustancia), extracto de Hypericum perforatum
Sources
Derived from the NIH UMLS (Unified Medical Language System)


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