St. John's Wort

Primer

St. John's Wort (SJW) (Hypericum perforatum) is a plant used as a herbal medicine for many centuries in the treatment of mood disorders. The active ingredient is thought to be from hypericin/hyperforin and other flavonoids.

Pharmacokinetics

Pharmacokinetics of St. John's Wort

Absorption
Distribution
Metabolism
Elimination
Half-life

St. John's Wort: Cytochrome P450 Metabolism

Substrate of (Metabolized by)
Induces 3A4 (potent!)[1]
Inhibits

Pharmacodynamics

Mechanism of Action

  • St. John's wort's is thought to have a direct effect on serotonin receptors, monoamine oxidase inhibition, and neuroendocrine and ion channel modulation.

Toxicity

Indications

Dosing

Dosing for St. John's Wort

Starting 300 mg TID (or 450 mg BID)
Titration Plasma levels gradually rise over several weeks
Maximum 1800 mg
Taper
  • The typical treatment duration in major depressive disorder is between 4 to 12 weeks.[3][4]

Formulations

  • St. John's Wort comes in oral tablets typically.

Monitoring

Contraindications

Absolute

Relative

Drug-Drug Interactions

  • One of the main concerns with the use of St. John's wort is it is an inducer of cytochrome (CYP) P450 3A4 activity (a substantial number of medications are metabolized via this pathway).
  • High potency extracts can interfere with the metabolism of various medications.

Side Effects

  • St. John's wort is typically better tolerated than many first-line antidepressants.
  • Side effects include headaches, gastrointestinal upset, skin irritation, photosensitivity, and dry mouth.
  • Transient photosensitivity is the most common side effect and occurs more commonly at higher dosages

Adverse Events

Clinical Pearls

Special Populations

Geriatric

Pediatric

Obstetric and Fetal

Medically Ill

Resources

References

1) Markowitz, J. S., Donovan, J. L., DeVane, C. L., Taylor, R. M., Ruan, Y., Wang, J. S., & Chavin, K. D. (2003). Effect of St John's wort on drug metabolism by induction of cytochrome P450 3A4 enzyme. Jama, 290(11), 1500-1504.
2) Ravindran, A. V., Balneaves, L. G., Faulkner, G., Ortiz, A., McIntosh, D., Morehouse, R. L., ... & CANMAT Depression Work Group. (2016). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 5. Complementary and alternative medicine treatments. The Canadian Journal of Psychiatry, 61(9), 576-587.
3) Ravindran, A. V., Balneaves, L. G., Faulkner, G., Ortiz, A., McIntosh, D., Morehouse, R. L., ... & CANMAT Depression Work Group. (2016). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 5. Complementary and alternative medicine treatments. The Canadian Journal of Psychiatry, 61(9), 576-587.
4) Sarris, J., Panossian, A., Schweitzer, I., Stough, C., & Scholey, A. (2011). Herbal medicine for depression, anxiety and insomnia: a review of psychopharmacology and clinical evidence. European neuropsychopharmacology, 21(12), 841-860.