St. John's wort
(Hypericum perforatum) Monograph

This section is compiled by Frank M. Painter, D.C.
Send all comments or additions to:    Frankp@chiro.org

FROM:   Alternative Medicine Review 2004 (Sep); 9 (3): 318–325 ~ FULL TEXT

Clinical Indications

Depression A meta-analysis published in 1996 of 23 studies involving over 1,500 individuals found significantly positive responses to St. John’s wort based on analysis of the Hamilton Depression Scale (HAMD) before and after treatment. [19] This was supported by a more recent meta-analysis covering clinical trials published through 2000. [20] In 2000, the Annals of Internal Medicine featured a two-part overview and critique of newer drug therapies for depression and dysthymia (a chronic but milder form of depression), and included St. John’s wort as a potential treatment for both conditions. [21, 22] Both reviews conclude St. John’s wort is more effective than placebo for the treatment of mild-to-moderate depression and less likely to cause side effects than commonly prescribed antidepressants. The 2000 meta-analysis of St. John’s wort clinical trials lists 16 placebo-controlled trials on persons with mild-to-moderate depression. [20] These studies lasted from four to 12 weeks, with doses varying between 500–900 mg per day. Many of these trials were completed using 300 mg of the LI 160 extract (standardized to 0.3% hypericin) three times daily. [22–25] A significant decrease in HAMD scores compared to placebo was found in all trials. Similar results have been noted for an extract designated ZE 117, [26] as well as standardized Hypericum extracts with the designations WS 5570 and WS 5572. [27, 28] A phase III clinical trial utilizing the WS 5570 extract included 375 patients with major depression, and demonstrated efficacy and safety superior to placebo when the extract was dosed at 900 mg daily for six weeks. This contradicts the results of an earlier well known study published in JAMA that demonstrated 900–1200 mg St. John’s wort daily was ineffective in treating severe depression. [29]

At least 12 clinical trials have compared St. John’s wort directly to prescription antidepressants, including imipramine, amitriptyline, and fluoxetine, in persons with mild-to-moderate depression. [20] Earlier clinical trials comparing 900 mg St. John’s wort daily with imipramine (75 mg daily) or amitriptyline (75 mg daily) in patients with mild-to-moderate depression found St. John’s wort extract (LI 160) to be equally effective in lowering HAMD scores, with fewer side effects. [30, 31] However, these trials have been criticized due to the low dose of the standard antidepressant and lack of a placebo group. One trial comparing 1,050 mg St. John’s wort daily with 100 mg imipramine daily or placebo did find St. John’s wort was safe and effective in treating mild-to-moderate depression. [32] More recently, in a six-week clinical trial (no placebo arm), 500 mg of the ZE 117 extract was as effective as 150 mg of imipramine. [33] Two double-blind, randomized trials (with no placebo arm) suggest 500 mg [34] or 800 mg [35] St. John’s wort daily is as effective as 20 mg/day of fluoxetine (Prozac®). Both trials lasted six weeks and found patients taking St. John’s wort reported fewer side effects. More recently, two similar trials demonstrated Hypericum extract to be 83–percent as effective as fluoxetine therapy in one study [36] and equally effective (100%) as fluoxetine therapy in the other. [37] Dosages of Hypericum extract ranged from 300–500 mg daily; fluoxetine dosage in both studies was 20 mg daily. In these two studies adverse effects in the St. John’s wort group were significantly fewer or equal to fluoxetine adverse effects.[36, 37]

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