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