St John’s wort: Clinical Use

Up until recently, most trials conducted with St John’s wort used a 0.3% hypericin water and alcohol extract known as LI 150. Subsequently, studies using different preparations, such as WS 5573 (standardised to hyperforin) or ZE 117 (a low concentration hyperforin preparation), have been tested.


Clinical note — The Hamilton Depression Scale

The Hamilton Depression Scale is an observer-rated scale that focuses mainly on somatic symptoms of depression. Although the original version included 21 items, a similar version using 17 items is more commonly used in clinical trials. Most studies using the Hamilton Depression Scale report the number of ‘treatment responders’ (patients achieving a score less than 10 and/or less than 50% of the baseline score).

Mild to moderate depression

St John’s wort has shown efficacy as a successful treatment for mild to moderate depression in numerous double-blind placebo-controlled trials, confirmed by several meta-analyses.

The most recent Cochrane review released in 2005 analysed data from 37 double-blind, randomised studies (n = 4925) that used monopreparations of St John’s wort over a treatment period of at least 4 weeks. It concluded that hypericum extracts improved symptoms more than placebo and produced effects similar to synthetic antidepressants (tricyclics and SSRIs) in adults with mild to moderate depression. This confirms the results obtained in two earlier meta-analyses.

Subsequently, a double-blind study of 388 patients with moderate depression has found St John’s wort extract (900 mg daily of extract STW3-VI) to be as effective as citalopram (20 mg daily) (P < 0.0001). The HDS scores were reduced to 10.3 ± 6.4 for St John’s wort extract, 10.3 ± 6.4 for citalopram and 13.0 ± 6.9 for placebo and both antidepressants were significantly more effective than placebo. At the end of treatment 54.2% of the St John’s wort group and 55.9% of the citalopram group were assessed as responders compared with 39.2% for placebo. In regards to safety, significantly more adverse events were documented in the citalopram group (53.2%) than for St John’s wort (17.2%) or placebo (30%).

Low hyperforin extracts effective?

Considering that hyperforin demonstrates significant antidepressant activity, it is important to evaluate whether low-hyperforin containing St John’s wort preparations remain effective. Three randomised, double-blind studies that have compared low hyperforin extracts (ZE 117) to fluoxetine or imipramine suggest the absence of hyperforin does not hinder the antidepressant effect.

Paediatric use

Results from a post-marketing surveillance study of 101 children under 12 years with mild to moderate depression has suggested that St John’s wort may be an effective and well tolerated treatment in this population. The number of physicians rating effectiveness of treatment with St John’s wort as ‘good’ or ‘excellent’ was 72% after 2 weeks, 97% after 4 weeks and 100% after 6 weeks, and ratings by parents were similar. Although encouraging, it is difficult to interpret the clinical significance of the results, as there was no placebo group and the final evaluation included only 76% of the initial sample.

More recently, an 8-week open pilot study was conducted with St John’s wort (300 mg three times daily) in 26 adolescents with major depressive disorders. The subjects were aged 12-17 years (mean, 14.8 years). Only 11 patients completed the study of which 9 (82%) showed significant clinical improvement based on Clinical Global Improvement change scores. Once again, interpretation of these results is hampered by a large drop-out rate.

Major depression

Although a 2005 Cochrane review stated that St John’s wort shows only minimal benefits over placebo in major depression, two subsequent randomised, double-blind trials found St John’s wort to be as effective as treatment doses of fluoxetine and paroxetine.

Fava et al compared St John’s wort (LI 160 900 mg/day) to fluoxetine 20 mg/day or placebo in 135 patients with major depression in a 12-week study. Mean Hamilton Depression Scale scores reduced to 10.2 with St John’s wort compared with 13.3 for fluoxetine and 12.6 for placebo. There was also a trend toward higher rates of remission (HDS <8) in the St John’s wort group (38%) compared with fluoxetine (30%) or placebo (21 %). According to another randomised, double-blind study, St John’s wort (WS 5570 900 mg/day) was as effective as paroxetine 20 mg/day in 251 outpatients with acute moderate to severe depression. The Hamilton Depression Scale scores decreased by a mean 14.4 (SD8.8) with St John’s wort compared with a decrease of 11.4 (SD8.6) with paroxetine and herbal treatment was better tolerated. The study took place at 21 centres in Germany.

Commission E approves the use of St John’s wort for psychovegetative disturbances, depressive moods, anxiety and nervous unrest.

Clinical note — Relative safety of St John’s wort compared with pharmaceutical antidepressants

Much has been made of the known or suspected risks associated with the use of St John’s wort, with far too little discussion focusing on the decisive question of its relative safety compared with pharmaceutical antidepressants. It has been estimated that approximately 1 in 30,000 people using St John’s wort will experience an adverse reaction, including those attributed to drug interactions. An overview of 16 post-marketing surveillance studies involving different St John’s wort preparations and 34,804 patients found that side-effect incidence varied from 0 to 2.8% in short-term studies (4-6 weeks) and 3.4-5.7% in long-term studies (52 weeks). Gastrointestinal symptoms, sensitivity to light and other skin conditions, and agitation were the most commonly reported side-effects and were generally described as mild. The review found that serious side-effects or interactions were not reported by any study. Taking this into account, the incidence of side-effects to St John’s wort is approximately 10-fold lower than for conventional antidepressants (SSRIs). The most common adverse event among spontaneous reports is photosensitivity, which is estimated to occur in 1 in 300,000 treated cases. This can occur with a dose of 5-10 mg/day hypericin, which is 2-4-fold higher than the recommended dose. St John’s wort has no significant effect on blood pressure or heart rate, making it a safer choice than tricyclic antidepressants in patients with cardiovascular disease. It also lacks atropinic activity, so side-effects such as dry mouth, urinary retention and blurred vision do not occur. In addition, the common side-effects reported for SSRIs, such as anorexia, insomnia, sexual dysfunction, excessive sweating and visual disturbance, have not been reported for St John’s wort. Similar to all standard antidepressants, St John’s wort can interact with other medicines and needs to be judiciously prescribed.


Treatment with a fixed dose of 450 mg of St John’s wort containing 0.3% hypericin twice daily over 12 weeks improved the condition in 5 of 12 patients, according to an open study.


Although St John’s wort is sometimes used for nerve pain, a randomised, double-blind, crossover study of 54 patients identified a trend toward lower total pain score with St John’s wort treatment, although none of the individual pain ratings were significantly changed. The dose of St John’s wort used provided 2.7 mg/day total hypericin and was taken over 5 weeks.


In at least one trial, St John’s wort has been investigated as sole therapy in menopausal and premenopausal women with psychological and psychosomatic symptoms. After 12 weeks’ treatment with 900 mg hypericum (Kira 300 mg three times daily) symptoms diminished or disappeared completely in the majority of women (76.4% by patient evaluation and 79.2% by physician evaluation). Interestingly, sexual wellbeing also improved in 80% of cases.

Another study investigated a fixed combination of isopropanolic black cohosh (Remifemin; standardised to 1 mg triterpene glycosides) and ethanolic St John’s wort (standardised to 0.25 mg total hypericin) in 301 women with menopausal symptoms with pronounced psychological symptoms. The double-blind, randomised study found that 16 weeks of herbal treatment produced a significant 50% reduction in the Menopause Rating Scale score compared to 20% with placebo and a significant 42% reduction in the Hamilton Depression Scale score compared to only 13% in the placebo group.


Wheatley found that people with mild to moderate SAD experienced significant improvements with anxiety, loss of libido and insomnia after 8 weeks’ treatment with St John’s wort. The test group receiving St John’s wort extract (Kira 300 mg) three times daily plus light therapy experienced superior sleep compared with the group receiving St John’s wort as stand-alone treatment.


An open study in patients with PMS found that a low dose of 300 mg St John’s wort daily produced significant reductions in all outcome measures. The degree of improvement in overall PMS scores between baseline and the end of the trial was 51 %, with over two-thirds experiencing at least a 50% decrease in symptom severity.


Based on its antiviral activity, St John’s wort is also used clinically in the treatment of herpes virus infections. One study of unknown design found that oral extract LI 160 (over a period of 3 months) reduced the frequency and severity of episodes of recurrent herpes labialis and herpes.


Preliminary evidence from experimental models suggests that St John’s wort may be of use in reducing nicotine withdrawal signs. In the study, St John’s wort significantly and dose-dependently reduced the total nicotine abstinence score. Further studies are required to determine its usefulness for smoking cessation treatment in humans.


Atopic dermatitis

A cream containing St John’s wort extract (standardised to 1.5% hyperforin) was shown to reduce the intensity of eczematous lesions when used twice daily in a prospective double-blind study. Beneficial effects were already observed at the first review, which was on day 7.

Treatment of acute and contused injuries

No controlled studies are available, but anti-inflammatory, analgesic and bactericidal activities provide a theoretical basis for its use.

Commission E approves the topical use of oily St John’s wort preparations for this indication.


Although no controlled studies are available, anti-inflammatory and analgesic activity provide a theoretical basis for its use in this condition.

Commission E approved the topical use of oily St John’s wort preparations for this indication.

First-degree burns

Although no controlled studies are available, anti-inflammatory, analgesic and bactericidal activity provide a theoretical basis for its use in this condition.

Commission E approves the topical use of oily St John’s wort preparations for this indication.

St John’s wort: Other Uses

In practice, St John’s wort is also used to treat fibrositis, nervous exhaustion, sciatica and gastrointestinal conditions, such as oesophagitis and peptic ulcers. Traditionally, St John’s wort has been used for wound healing, diuretic, melancholy, pain relief, treatment for snake bites, bedwetting in children, malaria and psychosis.