The experimental and clinical pharmacology of St John's Wort (Hypericum perforatum L.).

Hypericum (St John's Wort) is a plant that has been used for centuries as a medicinal herb. Pre-clinical animals studies suggest that hypericum is effective in three major biochemical systems relevant for antidepressant activity, namely the inhibition of the synaptic re-uptake system for serotonin (5-HT), noradrenaline (NA) and dopamine (DA). It is the only antidepressant capable of inhibiting the re-uptake of 5-HT, NA and DA with similar potencies. The potencies for monoamine re-inhibition and chronic changes in receptors are also consistent with changes seen with known antidepressants. Behavioral studies suggest that hypericum is active in pre-clinical animal models of depression with comparable effects to known antidepressants. Supporting the pre-clinical pharmacology and efficacy, many clinical studies have shown that hypericum has superior efficacy compared to placebo and comparable efficacy to standard antidepressants in the treatment of mild-to-moderate depression. The advantage of hypericum over other antidepressants may result from its favorable side-effect profile. Although pre-clinical and short-term clinical studies demonstrate antidepressant activity, the lack of long-term use and efficacy, and the heterogeneity of patients, interventions, extract preparations from previous clinical studies suggests that more careful and controlled studies are needed to determine the long-term efficacy of hypericum in mild-to-moderate depression.

St. John's wort for depression: a meta-analysis of well-defined clinical trials.

Studies concluding that St. John's wort (Hypericum perforatum) is an effective antidepressant can be challenged due to questionable methodology. We attempt to correct this by a meta-analysis utilizing only well-defined clinical trials. Controlled, double-blind studies using strictly defined depression criteria were analyzed by the rate of change of depression and by the number of "treatment responders." Rates of side effects and dropouts were also analyzed. Hypericum was 1.5 times more likely to result in an antidepressant response than placebo and was equivalent to tricyclic antidepressants (TCAs). The meta-analysis also showed that there was a higher dropout rate in the TCA group and that the TCAs were nearly twice as likely to cause side effects, including those more severe than hypericum. Hypericum perforatum was more effective than placebo and similar in effectiveness to low-dose TCAs in the short-term treatment of mild to moderately severe depression. However, design problems in existing studies prevent definitively concluding that St. John's wort is an effective antidepressant.

Taking the edge off: why patients choose St. John's Wort.

BACKGROUND: The number of visits to alternative medicine practitioners in this country is estimated at 425 million, which is more than the number of visits to allopathic primary care physicians in 1990. Patients' use of St. John's Wort (SJW) has followed this sweeping trend. The purpose of our study was to examine the reasons people choose to self-medicate with SJW instead of seeking care from a conventional health care provider. METHODS: We used open-ended interviews with key questions to elicit information. Twenty-two current users of SJW (21 women; 20 white; mean age = 45 years) in a Southern city participated. All interviews were transcribed, and descriptive participant quotes were extracted by a research assistant. Quotes were reviewed for each key question for similarities and contextual themes. RESULTS: Four dominant decision-making themes were consistently noted. These were: (1) Personal Health Care Values: subjects had a history of alternative medicine use and a belief in the need for personal control of health; (2) Mood: all SJW users reported a depressed mood and occasionally irritability, cognitive difficulties, social isolation, and hormonal mood changes; (3) Perceptions of Seriousness of Disease and Risks of Treatment: SJW users reported the self-diagnosis of "minor" depression, high risks of prescription drugs, and a perception of safety with herbal remedies; and (4) Accessibility Issues: subjects had barriers to and lack of knowledge of traditional health care providers and awareness of the ease of use and popularity of SJW. Also of note was the fact that some SJW users did not inform their primary care providers that they were taking the herb (6 of 22). Users reported moderate effectiveness and few side effects of SJW. CONCLUSIONS: SJW users report depression, ease of access to alternative medicines, and a history of exposure to and belief in the safety of herbal remedies. Users saw little benefit to providing information about SJW to primary care physicians.

The clinical applications of Ginkgo biloba, St. John's wort, saw palmetto, and soy.

The use of herbal or alternative therapies continues to increase each year. This article extensively reviews four of the more commonly used herbs and dietary supplements: ginkgo biloba, St. John's wort, saw palmetto, and soy. The pharmacology, precautions, therapeutic uses, and adverse effects for each of these therapies are discussed.

Medicinal herbs: a primer for primary care.

Used for centuries as folk remedies, herbs are enjoying a surge of public interest. Some empiric findings have been supported by formal research results. In order to advise patients about such preparations, physicians need to be aware of the indications, contraindications, drug interactions, and potential side effects. Eight popular herbs are reviewed.

Combining different phases in the development of medical treatments within a single trial.

In the development of medical treatments, identification of promising therapies and inference on selected treatments are usually performed in subsequent separate trials. An adaptive two-stage design is proposed for the situation of multiple treatments to be compared with a control, allowing integration of both steps within a single confirmatory trial controlling the multiple level alpha. After the interim analysis, the trial may be terminated early or is continued with a second stage, where the set of treatments may be reduced due to lack of efficacy or to safety problems. The procedure is highly flexible with respect to the distributional assumptions, stopping rules and selection criteria and allows a completely free recalculation of the sample size for the second stage. Simulations show that the method may be substantially more powerful than classical one-stage multiple treatment designs with the same total sample size. As in conventional strategies with a series of separate experiments, a reasonable selection strategy has to be applied in order to prevent proceeding with non-optimal treatments.

Hypericum perforatum extracts as potential antidepressants.

Extracts of Hypericum perforatum have been used in the treatment of mild to moderate depression for many years in Europe. More recently, these extracts have become available in the USA as dietary supplements and have been popularly used to improve mood. In support of this practice, data from several controlled clinical studies suggest that Hypericum perforatum is better than placebo and as effective as established antidepressant drugs. These data have, however, several limitations that should temper our enthusiasm and argue for more research before accepting Hypericum perforatum extracts into our pharmacopoeia of established antidepressants. Extant data on the possible effects of Hypericum perforatum extracts in depression are here critically reviewed and plans for further research presented.

Traditional Chinese medicine, acupuncture, and other alternative medicines for prostate cancer: an introduction and the need for more research.

There are several other alternative medicines apart from vitamins and minerals that the clinician should be aware of because they have grown in popularity in other fields of medicine. In time, these therapies should impact the arena of urologic oncology. Traditional Chinese Medicine, which includes acupuncture, is an area that has received some attention. The theory behind it can be quite daunting because it is so different from the theory behind Western Medical Science. In addition, exactly how acupuncture can be applied to a patient and its potential use in prostate cancer need to be addressed. Other herbal therapies for the patient experiencing symptoms related to a localized cancer diagnosis also need to be evaluated. St John's Wort for depression and Kava for anxiety are two examples of herbal alternatives that some prostate patients are inquiring about. Finally, Ginkgo biloba has received a great deal of attention in the media for erectile dysfunction, but there is a dearth of evidence in this area and the information that already exists can be misleading until further studies are conducted. Also, it is imperative that additional studies be performed in all of the above subjects as they relate to prostate cancer, but a general survey on alternative medicine use in urologic diseases is needed first before an adequate review of the most popular therapies can be published.

St. John's wort: a new alternative for depression?

OBJECTIVE: The primary purpose of this article is to review the existing literature concerning the therapeutic uses, adverse effects, and possible drug interactions of St. John's wort (Hypericum perforatum) as compared to other antidepressant medications. METHODS: Reference material was obtained through database searches with time restrictions of 1985 to the present. Studies selected were those written in the English language which compared the role of St. John's wort, tricyclic antidepressants, monoamine oxidase inhibitors, and serotonin-selective reuptake inhibitors in the treatment of depression. Other studies were selected based on their evaluation of the safety and efficacy of St. John's wort as an antidepressant for a minimum of four weeks. RESULTS: A review of existing literature recognized nine clinical trials that reported the efficacy of St. John's wort as compared to placebo and to other antidepressant medications. Of these nine, four controlled studies were chosen based upon their large patient populations and their consistency in brand and dosage of St. John's wort used. These four studies demonstrated that St. John's wort was as effective as other antidepressant medications and more effective than placebo, as the clinical symptoms of depression greatly decreased upon administration of H. perforatum. The side-effect profile of H. perforatum at this time appears to be superior to any current U.S.-approved antidepressant medication. CONCLUSIONS: From the existing literature, St. John's wort appears to be a safe and effective alternative in the treatment of depression. Tricylic antidepressants and monoamine oxidase inhibitors can produce serious cardiac side-effects, such as tachycardia and postural hypotension, and many unwanted anticholinergic side-effects, including dry mouth and constipation. St. John's wort has proven to be free of any cardiac, as well as anticholinergic, side-effects normally seen with antidepressant medications. Based upon limited studies, St. John's wort appears to be an acceptable alternative to traditional antidepressant therapy, although trials on a larger scale are warranted in this area. Hypericum is available to the lay public as an over-the-counter preparation and may be misused if not fully understood.

Hypericum in seasonal affective disorder (SAD).

Volunteers from the membership of the SAD Association took part in a postal survey, before and after eight weeks' treatment with Hypericum (Kira), using an 11-item rating scale. The maximum score is 44 and the mean score in 168 patients using Kira alone was 21.3. This fell to 13 at endpoint (p < 0.001). The corresponding figures for 133 patients using Kira + light therapy were 20.6 and 11.8, respectively (p < 0.001). In both groups, there was significant improvement in anxiety, loss of libido and insomnia. There were no significant between-group differences on any measure except that improvement in sleep was greater in the Kira + light group (p < 0.01). On the results of this survey, Hypericum would appear to be an effective treatment for SAD.

The effects of nutritional supplements on the treatment of depression, diabetes, and hypercholesterolemia in the renal patient.

The independent use of nutritional supplements has increased dramatically over the past several years. St. John's Wort for the treatment of depression, chromium for improvement of abnormal glucose and insulin regulation, and garlic for hypercholesterolemia, are among the more popular nutritional supplements being used by the population at large for their respective conditions. Depression, diabetes, and hypercholesterolemia are common to the renal patient. However, the efficacy of St. John's Wort, chromium, and garlic for these problems in the patient with impaired renal function is not known. This article reviews the pharmacology, efficacy, safety, and pharmokinetics of these three food supplements in the nonrenal patient. There are encouraging data suggesting successful treatment in the otherwise normal individual. However, clinical studies examining the safety of these three supplements for the treatment of depression, diabetes, and hypercholesterolemia in the patient with renal disease are lacking and preclude recommendation of their use.

Herbal remedies in psychiatric practice.

Patients' use of alternative and complementary health services has created a need for physicians to become informed about the current literature regarding these treatments. Herbal remedies may be encountered in psychiatric practice when they are used to treat psychiatric symptoms; produce changes in mood, thinking, or behavior as a side effect; or interact with psychiatric medications. English-language articles and translated abstracts or articles (where available) found on MEDLINE and sources from the alternative/complementary health field were reviewed. Each herb was assessed for its safety, side effects, drug interactions, and efficacy in treating target symptoms or diagnoses. A synopsis of the information available for each herb is presented. In many cases the quantity and quality of data were insufficient to make definitive conclusions about efficacy or safety. However, there was good evidence for the efficacy of St John's wort for the treatment of depression and for ginkgo in the treatment of memory impairment caused by dementia. More research is required for most of the herbs reviewed, but the information published to date is still of clinical interest in diagnosing, counseling, and treating patients who may be taking botanical remedies.

Neuropharmacology of St. John's Wort (Hypericum).

OBJECTIVE: To review preclinical information related to possible antidepressant mechanism(s) of action of St. John's wort in order to address the issue of whether its purported clinical effectiveness has a rational pharmacologic basis. DATA SOURCES: Primary and review articles were identified by a MEDLINE search (1966-January 1998) and through secondary sources. Many of the original German articles had English abstracts, but where necessary, German articles were translated into English. The results of a new screen of hypericin activity at receptor and uptake sites are summarized. STUDY SELECTION AND DATA EXTRACTION: All of the articles identified from the data sources were evaluated and all information deemed relevant was included in this review. DATA SYNTHESIS: The neuropharmacology of St. John's wort has been examined in only a few studies. A mechanism similar to that of the synthetic antidepressants, such as the selective serotonin-reuptake inhibitors or monoamine oxidase (MAO) inhibitors, might play a role, but other mechanisms are possible. CONCLUSIONS: Hypericum extracts have only weak activity in assays related to mechanisms of the synthetic antidepressants, that is, inhibition of MAO, catechol O-methyltransferase, or serotonin reuptake. It has been postulated that the clinical efficacy of St. John's wort could be attributable to the combined contribution of several mechanisms, each one too weak by itself to account for the overall effect. The recent demonstration of a significant affinity of hypericin for sigma receptors presents new possibilities for consideration.

St John's Wort (Hypericum perforatum)--a herbal antidepressant.

A number of clinical studies conducted over the past few years have indicated that whole extract of St John's wort (Hypericum perforatum L.) has antidepressant effects. The herbal antidepressant St John's wort offers promising results in the treatment of patients with mild and moderate depression (response rate of 60-70% estimated by analysis of pooled data). St John's wort preparations are well tolerated. Their use rarely leads to adverse drug reactions which, when they do occur, are mainly subjective symptoms (e.g. gastrointestinal, dizziness). The generally good tolerability of St John's wort preparations and the resulting high patient compliance in taking the prescribed medication, in conjunction with their efficacy in mild and moderate depression, make these preparations particularly suitable for use in outpatient practice. Tolerability is also very good in elderly patients. If a sufficiently high-dose course of treatment with St John's wort preparations (900 mg daily) does not lead to a clear improvement in depression after four to six weeks, therapy should be continued with an established ('classical') antidepressant.