Historically, St. John’s wort has been used as an herbal remedy for depression, anxiety, diuresis, gastritis and insomnia. Recent studies demonstrate that the extract, primarily hypericin, is a strong, and nearly irreversible, inhibitor of monoamine oxidase types A and B.
Patient Presentation and History
JS is a 37-year-old female who comes to the pharmacy intending to purchase St. John’s wort. She has heard that it can relieve depression, and she firmly believes in “natural” treatments. She reports that, for the past three weeks, she has been feeling depressed, has had a decreased appetite with a 15-pound weight loss, has had little energy, no longer enjoys the many recreational activities that pleased her in the past, and finds herself waking up each morning three hours earlier than expected with an inability to fall back to sleep. She is unable to identify any significant, recent stressors in her life, but says that it is becoming increasingly difficult to perform adequately at work and home. She had her annual, routine physical exam one month ago, and all physical and laboratory findings were within normal limits. Aside from her current complaints, she has been in good physical health with no medical problems, alcohol or substance abuse, allergies, or regular use of prescription or nonprescription drugs.
St. John’s Wort
Botanical and Chemical Properties: St. John’s wort (Hypericum perforatum L.), belonging to the family Hypericaceae and also known as klamath weed, amber touch-and-heal, goatweed and rosin rose, is an aromatic shrubby perennial plant with numerous bright yellow flowers that bloom from June to September. The blooms are said to be at their brightest and most abundant around the day traditionally celebrated as the birthday of John the Baptist (June 24).
The plant is native to Europe and can be found as well in the United States and Canada. It is an aggressive weed found in the dry ground of roadsides, meadows, woods and hedges, where it generally grows to a height of one to two feet. Historically, St. John’s wort has been used as an herbal remedy, not only for depression, but also to treat anxiety, diuresis, gastritis and insomnia. In addition, it has been investigated as a treatment for cancer and AIDS.
Low concentrations of hypericin and pseudohypericin are found in the leaves and flowers of St. John’s wort. Other active ingredients are flavonoids, xanthones, phenolic carboxylic acids, essential oils, carotenoids, alkanes, phloroglucinol derivatives, phytosterols, and medium-chain fatty acid alcohols. Tannin, in a concentration of approximately 10%, is most likely responsible for St. John’s wort’s astringent and protein-precipitating effects, contributing to the plant’s traditional, topical use as a wound-healing agent.
Pharmacology
Historically, people thought that the tranquilizing effects of St. John’s wort were secondary to increased capillary blood flow. More recent studies demonstrate that the extract, primarily hypericin, is a strong, and nearly irreversible, inhibitor of monoamine oxidase types A and B. In addition, the extract enhances sleep, extends narcotic-induced sleeping time in a dose-dependent manner, antagonizes the effects of reserpine and decreases aggressive behavior in socially isolated male mice. The Food and Drug Administration has designated hypericin as an investigational new drug. In Germany, it has been approved by the regulatory authorities for the treatment of depression.
Clinical Trials
Hypericum has been tested in over 3,000 patients against placebo and various active medications.2 Linde et al. conducted a meta-analysis of 23 randomized trials (15 in which hypericum was compared with placebo and 8 in which it was compared with another drug treatment); 1,757 outpatients with mainly mild or moderately severe depressive disorders were included. Overall, results of this analysis indicated that extracts of hypericum are more effective than placebo and equal in efficacy compared to standard antidepressants for the treatment of mild to moderately severe depressive disorders. In addition, fewer side effects were seen in patients treated with hypericum (19.8%) than in those treated with standard antidepressants (52.8%).
In a four-week, double-blind trial of 105 outpatients with mild depression of short duration, 67% of patients taking hypericum extract (300 mg three times daily) improved, compared with 28% of patients taking placebo. No significant side effects were noted.
In two studies, hypericum was compared with a standard heterocyclic antidepressant. In one, lasting six weeks, the dose of hypericum extract was 300 mg three times daily and that of imipramine was 25 mg three times daily. Hamilton Depression Rating Scale scores decreased from 20.2 to 8.8 in the hypericum group and from 19.4 to 10.7 in the imipramine group. In addition, fewer and milder side effects were noted in the patients treated with hypericum than in those treated with imipramine. In the other study, lasting four weeks, hypericum extract was compared with maprotiline in 102 depressed patients. The dose of hypericum extract was 300 mg three times daily and that of maprotiline was 25 mg three times daily. At the end of the study, no significant differences in either group were noticed. Overall, the relatively low doses of imipramine and maprotiline and short treatment periods make the results of these studies difficult to interpret.
No trials have been published comparing hypericum with any of the selective serotonin reuptake inhibitors (e.g., fluoxetine, sertraline, paroxetine), nor has there been systematic investigation of its efficacy over the long-term (i.e., six or more months) treatment period required for a major depressive episode. In addition, it has not been studied in patients with severe depression.
Adverse Effects and Toxicity
No adverse effects (e.g., changes in EEG, ECG, or laboratory test parameters) have been reported following treatment for up to six weeks with a standardized hypericum extract in controlled human studies. However, St. John’s wort has been associated with severe photosensitivity in animals grazing extensively on the plant. Photosensitization in humans is characterized by inflammation of the skin and mucous membranes following exposure to light. Toxicity in humans seems unlikely if the agent is used at recommended medicinal doses. Although not reported, orthostatic hypotension is theoretically possible in light of the drug’s monoamine oxidase-inhibiting properties.
Drug Interactions
Although no systematic studies of drug interactions have been conducted, patients taking St. John’s wort should observe the same precautions followed by those taking monoamine oxidase inhibitors (e.g., phenelzine and tranylcypromine). Foods containing large amounts of tyramine (e.g., aged meats and cheeses) and sympathomimetic amines (e.g., amphetamine, phenylpropanolamine, and pseudoephedrine) should be avoided in order to minimize any risk of a hypertensive crisis. In addition, serotonergic agents (e.g., selective serotonin reuptake inhibi-tors, such as venlafaxine, nefazodone, mirtazapine and buspirone, as well as trazodone, some tricyclic antidepressants, lithium, meperidine and possibly dextromethorphan) should be avoided to minimize the risk of a serotonin syndrome, a potentially life-threatening excess in serotonergic activity characterized by confusion, agitation, shivering, fever, diaphoresis, diarrhea, myoclonus, hyperreflexia and tremor.
Dosage
When used for its antidepressant action, St. John’s wort has generally been used as an extract, standardized to contain 0.3% hypericin, taken in a dosage of 300 mg three times daily. Significant effectiveness may not be seen for several weeks, and two or three months of continuous use may be needed to achieve a full effect.
Conclusion
St. John’s wort, in the form of an extract, seems to offer an intriguing option for the treatment of depression, especially in patients with mild to moderately severe depression who insist upon “natural” treatments. In short-term trials, it appears to be effective and, at the same time, relatively safe and well tolerated. However, the potential risks associated with its monoamine oxidase inhibiting activity and ability to induce photosensitivity require a degree of caution. Further studies are needed to assess the role of St. John’s wort in the treatment of severe depression, its long-term efficacy and side effects, as well as to compare it with full therapeutic doses of heterocyclic and newer antidepressants.
Pharmacist Intervention
The symptoms described by JS are classic for a major depression; there does not appear to be a medical or psychosocial etiology. Her preference for a “natural” remedy and her moderate depression make her a good candidate for St. John’s wort. However, the pharmacist must inform the patient of the limitations in our current knowledge regarding this treatment, as well as the significant morbidity and mortality associated with inadequately treated depression. The relative risks and benefits of both standard antidepressants and St. John’s wort should be reviewed. Since JS is of child-bearing age, she must be informed of our lack of information regarding possible teratogenic effects of St. John’s wort.
If JS still wishes to try this “natural” alternative, the pharmacist should become involved in monitoring the therapeutic response and any emergent side effects, as well as advising her to avoid certain foods and drugs and to protect herself against photosensitivity while using St. John’s wort. Finally, the patient should be referred back to her primary care provider or to a local institution or clinic that specializes in the evaluation and treatment of depressive disorders, especially if she does not show a positive response within a few weeks of use. Patient counseling and monitoring, of course, should also be provided to all other patients who wish to try this and other herbal medicines.
Related posts:
- Homeopathic Treatment for Depression Question. Have there been any studies or support in the treatment of depression with homeopathic remedies? Answer. There is a good deal of interest in the use of herbal remedies for the treatment of depression, as well as in the use of naturally-occurring precursors...
- Vestra: Drug for the Treatment of Depression Brand Name: Vestra Active Ingredient: reboxetine mesylate Indication: Treatment of depression Company Name: Pharmacia & Upjohn Vestra: Introduction As a selective norepinephrine reuptake inhibitor (SNRI), Vestra is the first of a new class of antidepressant drugs. This new mechanism of action appears to produce...
- Panic Symptoms Predict Poor Response to Depression Treatment Evidence indicates that patients with major depression and co-occurring anxiety features are at risk for more severe symptoms and less favorable outcome than patients with major depression alone. In particular, the existence of co-occurring panic symptoms has been linked to more severe depressive episodes,...
- Management of treatment-resistant depression: strategies for treatment Common strategies for treatment resistance. Electroconvulsive therapy An important and effective treatment for depression, electroconvulsive therapy (ECT) is effective in about 90% of cases of major depression. The success rate drops when it is used for drug-refractory cases. Using ECT depends on patient-related factors:...
- Management of Resistant Depression. Factors. Treatment Adequate. Are there underlying physical factors? Many physical diseases present with depressive symptoms or complicate depressive illness (Table 2). Some of these illnesses remain undetected for years and account for an apparent treatment-resistant depression (TRD). Normal thyroid function is particularly important; even mild or subclinical...
Hello, everybody, who is interested to be healthy. My name is Kelly. I learnt about depression by my own experience. Now I am ok. Here I want to share my thoughts and ideas how to treat depression symptoms.