Hypercium perforatum, popularly known as St. John’s Wort, is a buzz word in the Herbal Drug industry. H. perforatum is known as herbal Prozac (Prozac is trade name of selective serotonin reuptake inhibitor, fluoxetine); miracle antidepressant remedy. The use of the plant for the treatment of mental illness is documented in the history of herbal medicine.

Hypercium perforatum in traditional medicine

Hypericum perforatum is a member of the family Guttiferae (Clausiaceae) or Hypercinaceae. Hypericum perforatum Linn. is a familiar name as far as herbal medicine is concerned. It is one of the few medicinal plants, which has been thoroughly investigated for its pharmacological activities. The medicinal herb has been used by ancient physicians like Hippocrates, Dioscorides, Galen, Pliny, Paracelsus Hahnermann, Sebastian, Gerard and Culpeper. The plant was extolled as a healing agent in skin diseases and oil of hypericum was official in European Herbal Medicine. The plant has been used in Traditional Chinese System of Medicine (TCM) and Indian System of Medicine (ISM).

Hypercium perforatum in modern era medicine

Traditional and folk medicine prescribes Hypericum perforatum for variety of ailments. Today Hypericum perforatum is widely used in the treatment of mild to moderate depression and anxiety neurosis. Preclinical and clinical studies have justified the use of the plant in treating depressive illness. Mild to moderate depression, seasonal affective disorder (SAD), obsessive compulsive disorder (OCD) and attention deficit disorder (ADD) are major indications. Pharmaceutical companies are marketing quality products of Hypericum perforatum, which includes standardised preparations.

Although the antidepressant constituent of Hypericum perforatum is still to be traced, hypericin and hyperforin have been shown as possible constituents. Although hypericin has shown weak antidepressant action in animal experiments, hyperforin has been shown to interact with all principle neurotransmitter including serotonin, dopamine and catecholamine. Some authors have shown that xanthones and flavonoids (amentoflavone) also contribute to antidepressant activity of Hypericum perforatum. Amentoflavone has been shown to cross blood-brain barrier.

The standardized preparations of Hypericum perforatum are based on hypericin and hyperforin contents. Hypericin, a chemical present in the plant has shown antiviral activity and another constituent, hyperforin has been investigated as an antibiotic. Although the constituent responsible for antidepressant activity of Hypercium perforatum is still to be identified, the plant has a definite role to offer in depression.

What is Depression?

Aetiology: Clinical-depression can strike anybody at any juncture of the life. Depression has impact on the physical and mental abilities of the human body. Several factors contribute to incidence of depression and the clinical treatment requires expert supervision.

Some important factors leading to depression includes chronic diseases like arthritis or cancer, history of depression, drug-addiction, social phobia, and chronic stress, unemployment and family problems.

Exact cause behind depression is still unknown but according to experts, it occurs when a group of chemicals present in the brain, called neurotransmitters are deficient in functioning.

Types: Depression is placed under mood disorder. Depending upon the distribution of the signs symptoms, depression can be mild, moderate, or severe. Severe depression is also known as major depression.

In bipolar disorder, both depression and mania are met. Depression sometimes is apparent when there is a change of season. This condition is medically known as seasonal affective disorder (SAD).

Signs and symptoms: A patient having history of severe depression witnesses major shifts in appetite and sleep. The patient usually complains of loss of appetite or excess of appetite. Weight loss or weight-gain are encountered. Similarly, shift in sleep patterns like insomnia or hypersomina are seen. Loss of memory, social phobia and above all, isolation from the surroundings is routine.

Clinical trials in depression

  • Hypericum extract vs maprotiline

A randomised double-blind study compared the effect of extract of Hypericum perforatum with maprotiline in 24 healthy volunteers. In resting EEGs, both Hypericum perforatum and maprotiline revealed oppositely directed changes in the theta frequencies, and mainly similarly directed changes in alpha and beta frequencies. Measurements of evoked potentials in the theta and beta frequencies supported these results.

In a multicenter double-blind study, comparative anti-depressant effect and tolerance of the extract of Hypericum perforatum (LI 160) was compared to maprotiline. The study included 102 patients with depression. The patients received, over a period of 4 weeks, either 3 x 300 mg of the the extract of Hypericum perforatum or 3 x 25 mg maprotiline tablets of identical appearance. Effectiveness was determined using the Hamilton Depression Scale (HAMD), the Depression Scale according to von Zerssen (D-S), and the Clinical Global Impression Scale (CGI).

  • Hypericum extract vs imipramine

A double-blind study involving 135 depressed patients investigated comparative effect of Hypericum perforatum and imipramine. In both treatment groups, a parallel reduction of the Hamilton score from 20.2 to 8.8 (LI 160, n = 67) or from 19.4 to 10.7 (imipramine, n = 68), and the transformed D-S point values from 39.6 to 27.2 (LI 160) and 39.0 to 29.2 (imipramine) were found. The analysis of Clinical Global Impressions (CGI) revealed comparable results in both treatment groups. In the group receiving extract of Hypericum perforatum (LI 160) fewer side effects were found as compared to imipramine.

  • Hypericum vs. fluoxetine

A randomized, double-blind, investigated comparative antidepressant effect of Hypericum perforatum extracts tablets and the selective serotonin reuptake inhibitor fluoxetine in patients with mild-moderate depression. The age group included 16-24 and number of patients was 240 (fluoxetine: 114 (48%) and hypericum: 126 (52%). Hypericum perforatum safety was substantially superior to fluoxetine, with the incidence of adverse events being 23% on fluoxetine and 8% on hypericum. Several side-effects were recorded in fluoxetine group. The group receiving Hypericum perforatum recorded gastrointestinal disturbances as major side effect.

  • Hypericum and seasonal affective disorder (SAD)

A study explored the efficacy of Hypericum perforatum in seasonal affective disorder (SAD). The study, which lasted for 4 weeks, recorded a significant reduction in the total score of the Hamilton Depression Rating Scale using 900 mg of hypericum. No significant difference when bright light therapy was combined with hypericum, compared to the situation without bright light therapy. Overall, hypericum was well tolerated well.


Comparative studies of Hypericum perforatum with maprotiline, imipramine, sertraline, amitryptline and fluoxetine have suggested equal efficacy as far as antidepressant action is concerned.

 Additional Reading:

St. John’s Wort – An Overview

What is Depression?

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Sumenta with St. John’s Wort