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St. John’s Wort

By Melissa G. Marko, PhD, Ara DerMarderosian, PhD

The flowers of St. John’s wort ( Hypericum perforatum) (SJW) contain its biologically active ingredients, hypericin and hyperforin. SJW may increase CNS serotonin and, in very high doses, acts like a monoamine oxidase inhibitor (MAOI).


Study findings are variable, but SJW may benefit patients with mild-to-moderate depression who have no suicidal ideation. Well-designed studies have been done on SJW treating major depression.

Recommended doses are 300 to 900 mg po once/day of a preparation standardized to 0.2 to 0.3% hypericin, to 1 to 4% hyperforin, or to both (usually). St. John’s wort is also said to be useful for treating HIV infection because hypericin inhibits a variety of encapsulated viruses, including HIV, but has proven adverse interactions with protease inhibitors and non-nucleoside reverse transcriptase inhibitors (NNRTIs) and should therefore be avoided (1-2). SJW has also been claimed to treat skin disorders, including psoriasis, and attention-deficit/hyperactivity disorder (ADHD) in children.


Numerous randomized, placebo-controlled studies have evaluated safety and efficacy of SJW in treating mild-to-moderate depression and, recently, major depressive disorders (3-8). SJW has also been compared with tricyclic antidepressants (amitryptilline, imipramine) and more recently with the SSRIs fluoxetine and sertraline (4-7). Most placebo-controlled studies have shown that standardized extracts of SJW in the dose range of 300 mg to 900 mg once daily are moderately effective in the treatment of mild-to-moderate depressive symptoms. Some studies have shown equivalence of 900 mg of SJW to low-dose imipramine and low-dose fluoxetine. A study of patients with major depression failed to show significant improvement over either placebo or standard doses of sertraline over a short period of time (7). However, the authors state that both SJW and sertraline were equally effective over long periods of time, indicating the potential alternative economic value of SJW as a therapeutic treatment of depression when taken at low doses and when drug interactions are not of concern (7).

Overall, some studies show efficacy of SJW in treating mild depression, whereas in major depression most studies do not show efficacy. Differences in study design (lack of active control and placebo), study populations (major vs mild/moderate depression), length of time, and dosing of SJW or comparator agents are likely responsible for some variance in results.

Two very small pilot studies show potential topical application relief from skin disorders, including psoriasis (9-10). A small trial showed SJW (standardized to hypericin but not hyperforin) did not relieve symptoms of ADHD in children (11).

Adverse effects

Photosensitivity, dry mouth, constipation, dizziness, confusion, and mania (in patients with bipolar disorder) may occur. SJW is contraindicated in pregnant women.

Drug interactions

Potential adverse interactions occur with cyclosporine, digoxin, iron supplements, MAOIs, NNRTIs, oral contraceptives, protease inhibitors, SSRIs, tricyclic antidepressants, and warfarin (12-14).

St. John’s wort references

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