St. John's wort - an effective alternative

St. John’s wort, Hypericum perforatum, a plant widely distributed in Europe, North America, and Western Asia, has become a commonly used herbal antidepressant in recent years, and its efficacy in mild to moderate major depression has been documented with numerous clinical trials.

The plant and its ingredients

St. John’s wort is a frugal plant with a characteristic flower that blooms around “St. John’s Day” (June 24), hence its name. The oil glands present in the leaves make them appear as perforated (Fig. 1), which is expressed in the Latin name: Hypericum perforatum.

Previously, the antidepressant effect was attributed to the anthraquinone derivative hypericin, which occurs in the leaves at a concentration of 0.2-0.3% (including pseudohypericin). It is now known that hypericin-free extracts also have an antidepressant effect and that various ingredients together are responsible for this effect. Therefore, hypericin is used today only for standardization of the extract. The importance of the ingredient, hyperforin, is considered either efficacy-determining or unimportant to efficacy, depending.

Pharmacology

Pharmacological studies using cultured astrocytoma cells from rat cortex showed that a Hypericum extract, like the tricyclic antidepressants and SSRIs, inhibits the reuptake of norepinephrine and serotonin. A clearly recognizable reuptake inhibition of dopamine in St. John’s wort is only rudimentarily present in tricyclics and SSRIs. St. John’s wort also inhibits GABA and L-glutamate reuptake [1–3] and thus has a very broad inhibition profile.

Study data on clinical efficacy

There are dozens of clinical studies conducted with various St. John’s wort extracts that have documented the clinical efficacy of Hypericum perforatum for mild to moderate major depression [4–12]. These studies were either placebo-controlled, comparing St. John’s wort with an established synthetic antidepressant, or designed as a three-arm study (St. John’s wort vs. placebo and St. John’s wort vs. synthetic antidepressants). The St. John’s wort preparations showed equally good efficacy as synthetic antidepressants in the range of mild to moderate depression. Certain trial data even suggest efficacy in major depression [7].

Indications

In Switzerland, there are various St. John’s wort preparations on the market that are covered by basic health insurance (Table 1). Despite the positive study situation, most St. John’s wort preparations in Switzerland did not receive approval for mild to moderate depression, but only for indications such as mood states, listlessness, mood swings, restlessness, irritability, nervousness, or sleep disorders. Recently, however, two preparations, Hyperiplant® and Deprivita®, were also approved for the indication “mild and moderate depression”.

Due to its better tolerability compared to synthetic antidepressants, as proven in studies, St. John’s wort has established itself as an antidepressant that is also used by physicians who are otherwise skeptical of herbal medicines.

Dosage

The concentration of Hypericum preparations vary from 250 to 900 mg of extract per tablet (film-coated tablet). The daily dosage is 500 to 900 mg. However, experienced physicians sometimes increase the daily dose up to 1800 mg as an off-label dose for persistent cases. A St. John’s wort preparation should be taken for at least 14 days because of the latency of its effectiveness, and therapy lasts four to six weeks.

Safety and compatibility

St. John’s wort preparations have better tolerability compared to synthetic antidepressants. They have neither the anticholinergic side effects of tricyclics nor those of SSRIs, such as weight gain.

However, reports of interactions with certain drug groups (anti-HIV drugs, certain immunosuppressants, certain cytostatics, oral coagulants) occurred. However, this primarily concerns patients who are under strict medical supervision due to the severity of their disease. Furthermore, increased interstitial bleeding has been observed in women taking hormonal contraceptives and St. John’s wort preparations at the same time, which is why hormonal contraception is listed under contraindication for St. John’s wort preparations.

Literature:

Kientsch U, et al: St. John’s Wort Extract Ze 117 (Hypericum perforatum) inhibits Norepinephrine and Serotonin Uptake into Rat Brain Slices and Reduces Beta-Adrenoreceptor Number on Cultured Rat Brain Cells. Pharmacopsychiatry 2001(Suppl 1); 34: 556-560.
Honegger UE: St. John’s wort: one step closer to the mechanism of action; St. John’s wort A potent medicinal plant challenges science. Symposium Kursaal Bern, 16.11.2006.
Muller WE: Current St.John’s wort research from mode of action to clinical efficacy. Pharmacologicall Research 2003; 47: 101-109.
Laakmann, et al: Clinical significance of hyperforin for the efficacy of Hypericum extracts on depressive disorders of different severities. Phytomedicine 1998; 5: 435-442.
Kalb R: Efficacy and tolerability of hypericum extract WS 5572 versus placebo in mildly to moderately depressed patients. A randomised double-blind multicentric clinical trial, Pharmacopsychiatry 2001; 34: 96-103.
Linde K, Knüppel L: Large-scale observational studies of hypericum extracts in patients with depressive disorders – a systematic review. Phytomedicine 2005; 12: 148-157.
Szegedi A, et al: Acute treatment of moderate to severe depression with hypericum extract WS 5570 (St John’s wort): randomised controlled double blind non-inferiority trial versus paroxetine. Br Med J 2005; 330: 503-506.
Gastpar M, et al: Comparative efficacy and safety of a once-daily dosage of Hypericum extract STW3-VI and citalopram in patients with moderate depression: a double-blind, randomised, multicentre, placebocontrolled study. Pharmacopsychiatry 2006; 39, 66-75.
Singer A, et al: Duration of response after treatment of mild to moderate depression with Hypericum extract STW 3-VI, citalopram and placebo: A reanalysis of data from a controlled clinical trial. Phytomedicine 2011; 18: 739-742.
Kresimon J, et al: Care of patients with moderate depression treated with Hypericum extract STW3-VI compared with selective serotonin reuptake inhibitors (SSRIs) in everyday practice, Gesundh ökon Qual manag 2012; 17: 198-206.
Kasper S, et al: Efficacy and tolerability of Hypericum extract for the treatment of mild to moderate depression.Eur Neuropsychopharmacol 2010 Nov; 20(11): 747-765.
Brattström A: Long-term effects of St. John’s wort (Hypericum perforatum) treatment: a 1-year safety study in mild to moderate depression. Phytomedicine 2009(4); 16: 277-283.