Hypericum & Depression

Scientific Description of Hypericum Perforatum

Edited version of the ESCOP (European Scientific Corporation of Phototherapy) Proposal of Product Characteristics

Definition

The drug St. John's wort consists of the dried above-ground part of Hypericum perforatum L collected shortly before or during the flowering period. It contains not less than 0.04% naphthodianthrones of the hypericin group (so-called total hypericin). Lower parts of the stem contain few active ingredients (2,3,4).

Components (4-21)

• Hypericum extracts contain at least ten components or groups of components that may contribute to the pharmacological effects. It is not yet possible to correlate the antidepressive mode of action with specific components; therefore, the pharmaceutical quality of the extracts was characterized on the basis of typical leading substances, especially the hypericins. The substances most involved in the antidepressant action are thought to be the hypericins and the flavonoids.
• The red-colored hypericins have been found in very few other plants while most of hypericum's other ingredients are common in the plant kingdom.
• The hypericins also have a photodynamic effect; sometimes they do not occur until the crude drug has been processed and exposed to light. The amount of total hypericin should be measured after light exposition, which transforms the biological precursors, protohypericin and protopseudo-hypericin, into hypericin and pseudohypericin (5-8).
• The concentration of hypericins (mainly hypericin and pseudohypericin) in buds and flowers can vary between 0.06% and 0.75%. The usual concentration is 0.1-0.15%, but lower concentrations (less than 0.1%) might result from harvesting of lower parts of the herb (4). A minimum content of 0.04% total hypericin is required for commercial use.
• Other possible active ingredients are polymerization products of hypericin, the flavonoids quercetin, hyperoside, quercitrin, isoquercitrin, rutin, campherol, luteolin, and 13-118-biapigenin, the total concentration of which can amount to 2% to 4%.
• The 1,3,6,7-tetra-hydroxyxanthone, the aglycone of the mangiferin found in other species of Hypericum, is only present in concentrations of 0.0004%.
• The procyanidines, which are related to the flavonoids, account for about 8%.
• Hyperforin, with a structure related to the hop bitters humulon and lupulon, contributes to about 2.8%.

Pharmaceutical form

Hypericum is available in tablets, capsules, drops and teas. It is also available as an oil for external use.

The oil cannot be recommended for internal use as an antidepressant.

Therapeutic indications

The official German commission monograph lists mild to moderate depressive states (22-51), fear, and nervous disturbances, and somatoform disturbances as clinical indications for hypericum.

Most of the scientific documentation on hypericum has been performed on mild to moderate depressions. Treatment of severe depressions (with suicidal, psychotic or severe melancholic features) with hypericum preparations is not yet recommended.

Clinical effect (22-51,109-110)

Besides numerous case reports and drug monitoring studies (with more than 5,000 patients) on the efficacy and safety of standardized St. John's wort preparations, 25 controlled double-blind studies (with more than 2,000 patients) have been conducted. The major indication was mild to moderate depressive disorders.

Sixteen of the studies compared hypericum with placebo (sugar-pills) and 9 with reference treatments (Imipramine-2 (34, 44), Amitryptilin-2 (32, 48), Maprotiline-1 (46), Desipramine-1(30), Diazepam-2 (27,29), and Light-therapy (47).

In most of the studies, both depressive symptoms (depressed mood, anxiety, loss of interest, feelings of worthlessness, decreased activity) and secondary symptoms (sleep disturbance, lack of concentration, somatic complaints) improved significantly (see Figure 1) (25).

Results are summarized in Table 1. Some facts:

• The response rate has generally been between 50 and 80%, comparable to that of low- to medium dose treatment with "classic" synthetic antidepressants.
• In three of the trials (39,45,109) there was -- were no statistically significant difference between hypericum and placebo. In a criteria-based clinical review by Ernst (110) two of these studies also were judged as questionable because of methodological weaknesses. The third one is a yet unpublished study. They were all made with low dose hypericum test medications.
• Hypericum leads to an increase in deep sleep and does not impair cognitive functions or the ability to work or drive a car (83, 85).
• Hypericum has been shown to have a long-term effect on anxiety comparable to Bromazepam and Diazepam (29, 35).
• A Russian study (102) showed good results combining hypericum with psychotherapy to treat alcoholics with peptic ulcers.
• A preliminary study by Martinez et al. also showed an effect comparable to light therapy in the treatment of seasonal affective disorder (47).
• Anti-inflammatory and antibacterial effects of externally applied St. John's wort preparations have been reported and attributed to the presence of hyperforin. (1).

Hypericin has also been proven to possess promising anticancer properties and has been shown to inhibit growth of gliomas (brain tumors) (103), lung cancer (104) and skin cancer (68) in vitro (in the laboratory). Its photodynamic properties might lead to the use of hypericin in combination with lasers in the photodynamic treatment of cancer (68).

Copyright © 1996 by Harold H. Bloomfield, M.D. and Peter McWilliams

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