II. Indications (evidence-based)
- Dysthymia
- Mild to moderate Major Depression
- Do not use for severe Major Depression
III. Precautions
- Potency and purity not regulated
- Studies showing benefit used standardized extracts containing 0.3% Hypericin
- 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
IV. Ingredients
- Derived from flowering plant Hypericum perforatum
- Named St. John's Wort for its flowering time that occurs around the time of St. John the Baptist's feast
- Contents
- Hypericin (Naphthodianthrone) is Active Ingredient
- Amount of Hypericin in plant is quite variable
V. 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
VI. Pharmacokinetics: Hypericin
- Half life: 24 to 48 hours
- Peaks effect: 5 hours
- Excretion mechanism unknown
- Induces Cytochrome P450 3A4
VII. Efficacy
- Effective in mild-moderate depression in recent trials
- Better than Placebo in mild-moderate depression
- Similar effect when compared to standard agents at low dose
- Elavil 75 mg
- Imipramine 100-150 mg
- Fluoxetine 20 mg
- Sertraline 75 mg
- References
- However trial results are inconsistent (despite above)
- Several reviews have shown marginal efficacy
- Do not use for severe Major Depression
- References
- 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]
VIII. 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 or Psychosis (rare)
- Suicidality (rare)
- Allergic Reaction
- Fatigue
- Sedation
- Serotonin Syndrome (see Drug Interactions below)
- Antidepressant Withdrawal (on stopping St Johns Wort)
IX. Safety
- Avoid in pregnancy
- Associated with birth defects
- Avoid in Lactation
- Associated with infant sedation and colic
X. 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 CYP3A4 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
- SSRI and other serotinergic agents (Serotonin Syndrome Risk)
- Drugs with decreased activity or serum levels when used with St. John's Wort (esp. Cytochrome P450)
- Reference
XI. Dosing
- Studies showing benefit used extracts containing 0.3% Hypericin
- St. John's Wort 300 mg three times daily or
- St. John's Wort 450 mg twice daily
XII. Cost
- $10 to $25 per month