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St. John's Wort

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St. John's Wort, St John's Wort, Hypericum perforatum, Hypericin

  • Indications (evidence-based)
  1. Dysthymia
  2. Mild to moderate Major Depression
  3. Do not use for severe Major Depression
  • 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
  • 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
  • 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
  • Pharmacokinetics
  • Hypericin
  1. Half life: 24 to 48 hours
  2. Peaks effect: 5 hours
  3. Excretion mechanism unknown
  4. Induces Cytochrome P450 3A4
  • 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 [PubMed]
      2. Lawvere (2005) Am Fam Physician 72:2249-54 [PubMed]
  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 [PubMed]
      2. Werenke (2004) J Clin Psychiatry 65:611-7 [PubMed]
  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 [PubMed]
  • 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
  • Drug Interactions
  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 increased effects
    1. SSRI and other serotinergic agents (Serotonin Syndrome Risk)
      1. May interact with Antidepressants (e.g. SSRIs), Tramadol or other causative agents
      2. Consider 2 week "washout" when switching to SSRI
    2. Clopidogrel (Plavix)
      1. Increased bleeding risk
  3. Drugs with decreased activity or serum levels when used with St. John's Wort (esp. Cytochrome P450)
    1. Cyclosporine
    2. Digoxin
    3. Oral Contraceptives
      1. Hall (2003) Clin Pharmacol Ther 74:525-35 [PubMed]
    4. Nevirapine and Indinavir used in HIV Infection management
      1. de Maat (2001) AIDS 15:420-1 [PubMed]
    5. Statins
    6. Tegretol
    7. Verapamil
    8. Factor Xa Inhibitors (Rivaroxaban, Apixaban)
    9. Warfarin
  4. Reference
    1. Markowitz (2003) JAMA 290:1500-4 [PubMed]
    2. Zhou (2004) J Psychopharmacol 18:262-76 [PubMed]
  • Dosing
  1. St. John's Wort 300 mg three times daily or
  2. St. John's Wort 450 mg twice daily
  • Cost
  1. $10 to $25 per month