Hypericum perforatum

Hypericum Perforatum (St. John's Wort) is an anti-depressant herb that is commonly used for its neurological effects. While it appears effective, it is well known to adversely interact with a variety of pharmaceuticals due to inducing a particular enzyme (CYP3A4).

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St. John's Wort (Hypericum Perforatum) is a herb which, through the active component Hypericin, works as a dopamine-related anti-depressant and is effective at doing so. This is also the prototypical 'adverse drug-interaction' herb

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Also Known As

St. John's Wort

Things to Note

  • St. John's Wort is a relevant CYP3A4 inhibitor, and should not be used by pharmaceuticals that are metabolized by this enzyme

Caution Notice

St. John's Wort is a relevant CYP3A4 inhibitor, and should not be used with pharmaceuticals that are metabolized by this enzyme. If using any of these pharmaceuticals, consult a medical professional before supplementation of St. John's Wort with other CYP3A4 inhibitors (like Berberine)

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Table of Contents:

Edit1. Sources and Composition

The plant Hypericum perforatum, commonly referred to as 'St. John's Wort',

Edit2. Pharmacology

2.1. Enzymatic Interactions

Edit3. Neurology

3.1. Depression

A 2008 Cochrane Meta-Analysis[1] of 29 trials (5489 patients) that were blinded and randomized in patients with major depression (DSM-IV criteria) noted that in the trials against placebo that St. John's Wort was associated with less depressive symptoms with an Odds Ratio of 1.28 (95% CI of 1.10-1.49) in larger trials and 1.87 (95% CI of 1.22 to 2.87) in the smaller trials.[1] The studies in this meta-analysis were quite heterogeneous, lasting between 4-12 weeks but was comprised of high quality studies (assessed by Jadad; 5/5 median value); this meta-analysis restricted studies to those in Major Depression, rather than the previous Meta-Analysis looking at all depressive studies.[2]

When St. John's Wort was compared to Tricyclic Antidepressants (TCAs) and SSRIs, the respective Odds ratio benefitting St. John's Wort were 1.02 and 1.00 respectively; suggesting that the was no practical difference between the pharmaceuticals and St. John's Wort.[1] Additionally, dropouts associated with St. Johns wort were significantly less than both TCAs (OR of 0.24) and SSRIs (OR of 0.53) suggesting that St. John's wort has less side-effects.[1]

The studies included in this meta-analysis that were against placebo are cited here,[3][4][5][6][7][8][9][10][11][12][13][14][15] with those comparative in nature (against pharmaceuticals) cited here against SSRIs[16][17][18][19][5][20][21][22][23][24][6][25][26][27][28] or TCAs.[29]][29][30][31][32]

Non-response to St. John's Wort has been noted in some persons.[3]

St. John's Wort, overall, appears to reduce depressive symptoms with a potency not significantly different than SSRIs and TCAs (Pharmaceutical anti-depressants); some non-responders to St. John's Wort have been noted, who then respond to regular therapy


  1. Linde K, Berner MM, Kriston L. St John's wort for major depression. Cochrane Database Syst Rev. (2008)
  2. Linde K, et al. St John's wort for depression: meta-analysis of randomised controlled trials. Br J Psychiatry. (2005)
  3. Gelenberg AJ, et al. The effectiveness of St. John's Wort in major depressive disorder: a naturalistic phase 2 follow-up in which nonresponders were provided alternate medication. J Clin Psychiatry. (2004)
  4. Brenner R, Madhusoodanan S, Pawlowska M. Efficacy of continuation treatment with hypericum perforatum in depression. J Clin Psychiatry. (2002)
  5. Fava M, et al. A Double-blind, randomized trial of St John's wort, fluoxetine, and placebo in major depressive disorder. J Clin Psychopharmacol. (2005)
  6. Hypericum Depression Trial Study Group. Effect of Hypericum perforatum (St John's wort) in major depressive disorder: a randomized controlled trial. JAMA. (2002)
  7. Kasper S, et al. Superior efficacy of St John's wort extract WS 5570 compared to placebo in patients with major depression: a randomized, double-blind, placebo-controlled, multi-center trial {ISRCTN77277298}. BMC Med. (2006)
  8. Hypericum treatment of mild–moderate depression in a placebo–controlled study. A prospective, double–blind, randomized, placebo–controlled, multicentre study
  9. Laakmann G, et al. St. John's wort in mild to moderate depression: the relevance of hyperforin for the clinical efficacy. Pharmacopsychiatry. (1998)
  10. Effectiveness of St John's Wort in Major Depression
  11. Kalb R, Trautmann-Sponsel RD, Kieser M. Efficacy and tolerability of hypericum extract WS 5572 versus placebo in mildly to moderately depressed patients. A randomized double-blind multicenter clinical trial. Pharmacopsychiatry. (2001)
  12. Multicenter Double-Blind Study Examining the Antidepressant Effectiveness of the Hypericum Extract LI 160
  13. The Ham D6 is more homogenous and as sensitive as the Ham D17
  14. Lecrubier Y, et al. Efficacy of St. John's wort extract WS 5570 in major depression: a double-blind, placebo-controlled trial. Am J Psychiatry. (2002)
  15. Uebelhack R, et al. Efficacy and tolerability of Hypericum extract STW 3-VI in patients with moderate depression: a double-blind, randomized, placebo-controlled clinical trial. Adv Ther. (2004)
  16. Schrader E. Equivalence of St John's wort extract (Ze 117) and fluoxetine: a randomized, controlled study in mild-moderate depression. Int Clin Psychopharmacol. (2000)
  17. Behnke K, et al. Hypericum perforatum versus fluoxetine in the treatment of mild to moderate depression. Adv Ther. (2002)
  18. Bjerkenstedt L, et al. Hypericum extract LI 160 and fluoxetine in mild to moderate depression: a randomized, placebo-controlled multi-center study in outpatients. Eur Arch Psychiatry Clin Neurosci. (2005)
  19. Brenner R, et al. Comparison of an extract of hypericum (LI 160) and sertraline in the treatment of depression: a double-blind, randomized pilot study. Clin Ther. (2000)
  20. Gastpar M, Singer A, Zeller K. Efficacy and tolerability of hypericum extract STW3 in long-term treatment with a once-daily dosage in comparison with sertraline. Pharmacopsychiatry. (2005)
  21. Gastpar M, Singer A, Zeller K. Comparative efficacy and safety of a once-daily dosage of hypericum extract STW3-VI and citalopram in patients with moderate depression: a double-blind, randomised, multicentre, placebo-controlled study. Pharmacopsychiatry. (2006)
  22. St John's wort or sertraline? Randomized controlled trial in primary care
  23. Harrer G, Hübner WD, Podzuweit H. Effectiveness and tolerance of the hypericum extract LI 160 compared to maprotiline: a multicenter double-blind study. J Geriatr Psychiatry Neurol. (1994)
  24. Harrer G, et al. Comparison of equivalence between the St. John's wort extract LoHyp-57 and fluoxetine. Arzneimittelforschung. (1999)
  25. Vitiello B, et al. Hyperforin plasma level as a marker of treatment adherence in the National Institutes of Health Hypericum Depression Trial. J Clin Psychopharmacol. (2005)
  26. Efficacy and tolerability of Hypericum perforatum in major depressive disorder in comparison with selective serotonin reuptake inhibitors: A meta-analysis
  27. Moreno RA, et al. Hypericum perforatum versus fluoxetine in the treatment of mild to moderate depression: a randomized double-blind trial in a Brazilian sample. Rev Bras Psiquiatr. (2006)
  28. Anghelescu IG, et al. Comparison of Hypericum extract WS 5570 and paroxetine in ongoing treatment after recovery from an episode of moderate to severe depression: results from a randomized multicenter study. Pharmacopsychiatry. (2006)
  29. Philipp M, Kohnen R, Hiller KO. Hypericum extract versus imipramine or placebo in patients with moderate depression: randomised multicentre study of treatment for eight weeks. BMJ. (1999)
  30. Comparison of St John's wort and imipramine for treating depression: randomised controlled trial
  31. Vorbach EU, Arnoldt KH, Hübner WD. Efficacy and tolerability of St. John's wort extract LI 160 versus imipramine in patients with severe depressive episodes according to ICD-10. Pharmacopsychiatry. (1997)
  32. Wheatley D. LI 160, an extract of St. John's wort, versus amitriptyline in mildly to moderately depressed outpatients--a controlled 6-week clinical trial. Pharmacopsychiatry. (1997)

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