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           St. John's Wort

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St. John's Wort

St. John's Wort (Hypericum perforatum) has been used since ancient times to treat a variety of ailments, and has been shown to be effective in comparison to placebo, imipramine or desipramine (tricyclic antidepressants) and fluoxetine (a SSRI) in the treatment of depression, only better tolerated (19.8% vs 52.8% reported side effects on imipramine, 8% vs 23% on fluoxetine in one study). Its efficacy appears to be related to its content of hyperforin (a derivative present in variable strength, depending upon the producer). It is effective in three major biochemical systems relevant for antidepressant activity, namely the inhibition of the synaptic re-uptake system for serotonin (5-HT), noradrenalin (NA) and dopamine (DA). It is the only antidepressant capable of inhibiting the re-uptake of 5-HT, NA and DA with similar potencies. There is one study that suggests it may be effective in the treatment of obsessive-compulsive disorder and seasonal affective disorder, as well.

It is metabolized at least in part in the liver, and has been shown to affect certain drugs, such as digoxin and estrogens, perhaps via induction of the p-glycoprotein drug transporter or cytochrome p-450 system. Therefore the potential for herb-drug interactions must be kept in mind. The long-term safety of administration has not yet been studied.


Ernst, E. St. John's Wort as antidepressive therapy. Fortschr Med 1995 Sep 10;113(25):354-5.

Linde, K et al. St. John's wort for depression-an overview and meta-analysis of randomized clinical trials. BMJ 1996 Aug 3;313(7052_:253-8.

Vorbach EU et al. Efficacy and tolerability of St. John's wort extract LI 160 versus imiprimine in patients with severe depressive episodes according to ICD-10. Pharmacopsychiatry 1997 Sep;30 Suppl 2:81-5.

Miller AL. St. John's wort (Hypericum perforatum): clinical effects on depression and other conditions.Alter Med Rev 1998 Feb;3(1):18-26.

Laakmann, G et al. St. John's wort in mild to moderate depression: the relevance of hyperforin for clinical efficacy. Pharmacopsychiatry 1998 Jun;31 Suppl 1:54-9.

Nathan P. The experimental and clinical pharmacology of St. John's wort

Mol Psychiatry 1999 Jul;4(4):333-8.

Wagner PJ et al. Taking the edge off: why patients choose St. John's wort. J Fam Pract 1999 Aug;48(8):615-9.

Johne, A et al. Pharmacokinetic interaction of digoxin with an herbal extract from St. John's wort. Clin Pharmacol Ther 1999 Ocr;66(4):338-45.

Gaster B et al. St. John's wort for depression: a systematic review. Arch Intern Med 2000 Jan 24;160(2):152-6.

Linde, K et al. St John's wort for depression. Cochrane Database Syst Rev 2000;(2);cd000448.

Schrader E. Equivalence of St. John's wort extract (Ze117) and fluoxetine: a randomized, controlled study in mild-moderate depression. Int Clin Psychpharmacol 2000 Mar;15(2):61-8.

Williams JW. A systematic review of newer pharmacotherapies for depression in adults: evidence report summary. Ann Intern Med 2000 May @;132(9):743-56.

Wentworth, JM et al. St. John's wort, a herbal antidepressant, activates the steroid X receptor. J Endocrinol 2000 Sep;166(3):R11-16.

Woelk H. Comparison of St. John's wort and imipramine for treating depression: a randomized contolrred trial. BMJ 2000 Sep 2;321(7260):536-9.

Taylor LH et al. An open-label trial of St. John's wort in obsessive-compulsive disorder. J Clin Psychiatry 2000 Aug;61(8):575-8.



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Last modified: June 04, 2005