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St. John’s Wort


Laura Shane-McWhorter

, PharmD, University of Utah College of Pharmacy

Last full review/revision Jul 2020| Content last modified Jul 2020
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The flowers of St. John’s wort (Hypericum perforatum) (SJW) contain its biologically active ingredients, hypericin and hyperforin. SJW may increase central nervous system 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 orally 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 (amitryptiline, imipramine) and more recently with the selective serotonin reuptake inhibitors (SSRIs) fluoxetine, sertraline, and paroxetine (4-8). Most placebo-controlled studies have shown that standardized extracts of SJW in the dose range of 300 mg to 900 mg once/day 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.

However, there are 2 recent reviews of SJW for depression (9,10). A 2016 systematic review of 35 studies (6993 subjects) compared SJW to placebo or conventional antidepressants. SJW was superior to placebo but not different than conventional antidepressants for mild-to-moderate depression. However studies were heterogenous and severe depression was not studied (9). A 2017 meta-analysis of 27 studies (3808 subjects) compared SJW to SSRIs. SJW was comparable to SSRIs in response and remission for mild-to-moderate depression but had lower discontinuation rates (10).

Two very small pilot studies show potential topical application relief from skin disorders, including psoriasis (11-12). A small trial showed SJW (standardized to hypericin but not hyperforin) did not relieve symptoms of attention-deficit/hyperactivity disorder (ADHD) in children (13).

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, monoamine oxidase inhibitors (MAOIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), oral contraceptives, protease inhibitors, SSRIs, tricyclic antidepressants, and warfarin (14-16).

St. John’s wort references

  • Maury W, Price JP, Brindley MA, et al: Identification of light-independent inhibition of human immunodeficiency virus-1 infection through bioguided fractionation of Hypericum perforatum. Virol J6:101-113, 2009. doi:10.1186/1743-422X-6-101.

  • Kakuda TN, Schöller-Gyüre M, Hoetelmans RM: Pharmacokinetic interactions between etravirine and non-antiretroviral drugs. Clin Pharmacokinet 50(1):25-39, 2011. doi: 10.2165/11534740-000000000-00000.

  • Solomon D, Adams J, Graves N: Economic evaluation of St. John's wort (Hypericum perforatum) for the treatment of mild to moderate depression. J Affect Disord 148(2-3):228-234, 2013. doi: 10.1016/j.jad.2012.11.064.

  • van Gurp G, Meterissian GB, Haiek LN, et al: St John's wort or sertraline? Randomized controlled trial in primary care. Can Fam Physician 48:905-912, 2002.

  • Woelk H: Comparison of St John's wort and imipramine for treating depression: randomised controlled trial. BMJ 321(7260):536-539, 2000. doi: 10.1136/bmj.321.7260.536.

  • Fava M, Alpert J, Nierenberg AA, et al: A double-blind, randomized trial of St John's wort, fluoxetine, and placebo in major depressive disorder. J Clin Psychopharmacol 25(5):441-447, 2005.

  • Sarris J, Fava M, Schweitzer I, et al: St John's wort (Hypericum perforatum) versus sertraline and placebo in major depressive disorder: continuation data from a 26-week RCT. Pharmacopsychiatry 45(7):275-278, 2012. doi: 10.1055/s-0032-1306348.

  • Seifritz E, Hatzinger M, Holsboer-Trachsler E: Efficacy of Hypericum extract WS(R) 5570 compared with paroxetine in patients with a moderate major depressive episode - a subgroup analysis. Int J Psychiatry Clin Pract 20(3):126-32, 2016. doi: 10.1080/13651501.2016.1179765.

  • Apaydin EA, Maher AR, Shanman R, et al: A systematic review of St. John's wort for major depressive disorder. Systematic Reviews 5:148, 2016. doi: 10.1186/s13643-016-0325-2.

  •  Ng QX, Venkatanarayanan N, Ho CY: Clinical use of Hypericum perforatum (St John's wort) in depression: a meta-analysis. J Affect Disord 210:211-221, 2017. doi: 10.1016/j.jad.2016.12.048.

  • Najafizadeh P, Hashemian F, Mansouri P, et al: The evaluation of the clinical effect of topical St Johns wort (Hypericum perforatum L.) in plaque type psoriasis vulgaris: a pilot study. Australas J Dermatol 53(2):131-135, 2012. doi: 10.1111/j.1440-0960.2012.00877.x.

  • Rook AH, Wood GS, Duvic M, et al: A phase II placebo-controlled study of photodynamic therapy with topical hypericin and visible light irradiation in the treatment of cutaneous T-cell lymphoma and psoriasis. J Am Acad Dermatol 63(6):984-990, 2010. doi: 10.1016/j.jaad.2010.02.039.

  • Weber W, Vander Stoep A, McCarty RL, et al: Hypericum perforatum (St John's wort) for attention-deficit/hyperactivity disorder in children and adolescents: a randomized controlled trial. JAMA 299(22):633-2641, 2008. doi: 10.1001/jama.299.22.2633.

  • Borrelli F, Izzo AA: Herb-drug interactions with St John's wort (Hypericum perforatum): an update on clinical observations. AAPS J11(4):710-727, 2009. doi: 10.1208/s12248-009-9146-8. 

  • Nadkarni A, Oldham MA, Howard M, et al: Drug-drug interactions between warfarin and psychotropics: updated review of the literature. Pharmacotherapy 32(10):932-942. 2012. doi: 10.1002/j.1875-9114.2012.01119.

  • Tsai HH, Lin HW, Simon Pickard A, et al: Evaluation of documented drug interactions and contraindications associated with herbs and dietary supplements: a systematic literature review. Int J Clin Pract 66(11):1056-1078, 2012. doi: 10.1111/j.1742-1241.2012.03008.x.

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