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The influence of St. John's wort on the pharmacokinetics and protein binding of imatinib mesylate.

STUDY OBJECTIVE: To determine the effect of St. John's wort on the pharmacokinetics of imatinib mesylate. DESIGN: Open-label, complete crossover, fixed-sequence, pharmacokinetic study. SETTING: Clinical research center. SUBJECTS: Ten healthy adult volunteers. INTERVENTION: Single 400-mg oral doses of imatinib were administered before and after 2 weeks of treatment with St. John's wort 300 mg 3 times/day. MEASUREMENTS AND MAIN RESULTS: The pharmacokinetics of imatinib were significantly altered by St. John's wort, with reductions of 32% in the median area under the concentration-time curve from time zero to infinity (p=0.0001), 29% in maximum observed concentration (p=0.005), and 21% in half-life (p=0.0001). Protein binding ranged from 97.7-90.3% (mean 94.9%), was concentration independent, and was not altered by St. John's wort. Therapeutic outcomes of imatinib have been shown to correlate with both dose and drug concentrations. CONCLUSION: Coadministration of imatinib with St. John's wort may compromise imatinib's clinical efficacy.

Administration, Oral↗

Clinical assessment of effects of botanical supplementation on cytochrome P450 phenotypes in the elderly: St John's wort, garlic oil, Panax ginseng and Ginkgo biloba.

OBJECTIVES: Elderly patients are more likely to ingest prescription medications concurrently with botanical supplements, and may therefore be vulnerable to herb-drug interactions. Phytochemical-mediated modulation of cytochrome P450 (CYP) activity may underlie many herb-drug interactions. Some evidence suggests that CYP activity may decrease in the elderly. If so, herb-mediated changes in CYP activity may take on greater clinical relevance in this population. In this study, single timepoint, phenotypic metabolic ratios were used to determine whether long-term supplementation of St John's wort, garlic oil, Panax ginseng, and Ginkgo biloba affected CYP1A2, CYP2D6, CYP2E1 or CYP3A4 activity in elderly subjects. METHODS: Twelve healthy volunteers between the ages of 60 and 76 years (mean age 67 years) were randomly assigned to receive each botanical supplement for 28 days followed by a 30-day washout period. Probe drug cocktails of midazolam, caffeine, chlorzoxazone and debrisoquine were administered before and at the end of supplementation. Pre- and post-supplementation phenotypic ratios were determined for CYP3A4, CYP1A2, CYP2E1 and CYP2D6 using 1-hydroxymidazolam/midazolam serum ratios (1-hour), paraxanthine/caffeine serum ratios (6-hour), 6-hydroxychlorzoxazone/chlorzoxazone serum ratios (2-hour) and debrisoquine urinary recovery ratios (8-hour), respectively. The content of purported 'active' phytochemicals was determined for each supplement. RESULTS: Comparisons of pre- and post-St John's wort phenotypic ratios revealed significant induction of CYP3A4 (approximately 140%) and CYP2E1 activity (approximately 28%). Garlic oil inhibited CYP2E1 activity by approximately 22%. P. ginseng inhibition of CYP2D6 was statistically significant, but the magnitude of the effect (approximately 7%) did not appear to be clinically relevant. None of the supplements tested in this study appeared to affect CYP1A2 activity. CONCLUSIONS: Elderly subjects, like their younger counterparts, are susceptible to herb-mediated changes in CYP activity, especially those involving St John's wort. Pharmacokinetic herb-drug interactions stemming from alterations in CYP activity may adversely affect drug efficacy and/or toxicity. When compared with earlier studies that employed young subjects, the data suggest that some age-related changes in CYP responsivity to botanical supplementation may exist. Concomitant ingestion of botanical supplements with prescription medications, therefore, should be strongly discouraged in the elderly.

Administration, Oral↗

St. John's Wort.

OBJECTIVE: The objective of this article is to review the current knowledge of the pharmacology, sites of action, and therapeutic effectiveness of St. John's Wort. METHOD: The method used was a review of the available literature, using keywords to search the medline database. Bibliographies of the papers, thus obtained, were searched for further documents not referenced by medline. We reviewed papers from this collection. RESULTS: This review reveals that most of the available data on efficacy and safety of St. John's Wort involve its use in mild to moderate depression. Much, but not all of the prevailing opinion is positive. Nevertheless, the quality of therapeutic trials vary so greatly that definitive conclusions are not possible. Both the source and mode of St. John's Wort's therapeutic effect are unclear. We need further controlled studies of effectiveness, safety, and mode of action. In addition to its use in depression, there are reports suggesting possible therapeutic effects in other conditions such as certain malignancies and infections, but these are far too preliminary to permit any conclusions.

Antidepressive Agents↗

Serotonin syndrome and the use of SSRIs.

Nurses need to become more aware of serotonin syndrome to avoid its development and to ensure a therapeutic response when early symptoms emerge. While polypharmacy tends to put individuals at greatest risk for the syndrome, use of a single serotonergic agent may also provoke an adverse response. Because the onset and progression of serotonin syndrome are rapid, prompt action may be needed to avoid potentially life-threatening consequences.

Adult↗

Talking to patients about St. John's wort.

St. John's wort, an unregulated herbal supplement widely used as a self-treatment for depression, can cause side effects and drug interactions. Physicians should ask their patients about use of over-the-counter products such as St. John's wort and discuss their use in a frank but nonjudgmental manner.

Depression↗

Adverse neuropsychiatric reactions to herbal and over-the-counter "antidepressants".

BACKGROUND: Many unregulated over-the-counter agents for the treatment of depression are now available to patients and consumers. The potential for adverse neuropsychiatric effects with these agents has not been systematically studied in most cases. DATA SOURCES: The author performed a MEDLINE search on a variety of herbal and nonherbal over-the-counter agents said to be useful in the treatment of depression. The Physicians' Desk Reference for Herbal Medicines was also consulted. DATA SYNTHESIS: Although many of the herbal agents said to have benefits in depression appear to be safe, serious neuropsychiatric side effects and interactions have been reported for several over-the-counter "antidepressants." There is reason to suspect underreporting of those adverse events. Moreover, there is very little evidence from systematic studies regarding the potential for drug-drug or herb-drug interactions with these over-the-counter agents. Vitamins and amino acids touted for the treatment of depression are also not without risk. CONCLUSION: Although some over-the-counter remedies for depression are probably safe and effective for as-yet unidentified subgroups of depressed individuals, more research is required before these agents can be recommended for routine use. Stricter U.S. Food and Drug Administration oversight of these agents is indicated.

Adverse Drug Reaction Reporting Systems↗

Alternative treatments for depression: empirical support and relevance to women.

BACKGROUND: This article is a critical review of the efficacy of selected alternative treatments for unipolar depression including exercise, stress management techniques, acupuncture, St. John's wort, bright light, and sleep deprivation. Issues related to women across the life span, including pregnancy and lactation, are highlighted. DATA SOURCES: Evidence of efficacy is based on randomized controlled trials. A distinction is made between studies that address depressive symptoms and studies that address depressive disorders. The review emphasizes issues related to effectiveness, such as treatment availability, acceptability, safety, and cost and issues relevant to women. DATA SYNTHESIS: Exercise, stress reduction methods, bright light exposure, and sleep deprivation hold greater promise as adjuncts to conventional treatment than as monotherapies for major depression. The evidence to date is not sufficiently compelling to suggest the use of St. John's wort in favor of or as an alternative to existing U.S. Food and Drug Administration-regulated compounds. Initial evidence suggests that acupuncture might be an effective alternative monotherapy for major depression, single episode. CONCLUSION: This review indicates that some unconventional treatments hold promise as alternative or complementary treatments for unipolar depression in women and have the potential to contribute to its long-term management. Additional research is needed before further recommendations can be made, and there is an urgent need to carefully document and report the frequency of minor and major side effects.

Acupuncture↗

Can St. John's wort trigger psychoses?

BACKGROUND: St. John's wort (SJW) is a popular herbal remedy often self-prescribed for depressed mood. It has recently been associated with psychotic events. AIM: To systematically review the clinical evidence associating SJW with psychotic events. METHODS: Five electronic databases were searched for all relevant reports. Data were extracted according to predefined criteria. RESULTS: Seventeen case reports associated the use of SJW with psychotic events. In 12 instances, the diagnosis was mania or hypomania. Causality is in most cases possible. In no case was a positive rechallenge reported. CONCLUSION: These case reports raise the possibility that SJW may trigger episodes of mania in vulnerable patients. Clinicians should be aware of this possibility and researchers should attempt to ascertain whether the association is causal.

Antidepressive Agents↗

The risk-benefit profile of commonly used herbal therapies: Ginkgo, St. John's Wort, Ginseng, Echinacea, Saw Palmetto, and Kava.

Because use of herbal remedies is increasing, a risk-benefit profile of commonly used herbs is needed. This article provides a clinically oriented overview of the efficacy and safety of ginkgo, St. John's wort, ginseng, echinacea, saw palmetto, and kava. Wherever possible, assessments are based on systematic reviews of randomized clinical trials. Encouraging data support the efficacy of some of these popular herbal medicinal products, and the potential for doing good seems greater than that for doing harm. The published evidence suggests that ginkgo is of questionable use for memory loss and tinnitus but has some effect on dementia and intermittent claudication. St. John's wort is efficacious for mild to moderate depression, but serious concerns exist about its interactions with several conventional drugs. Well-conducted clinical trials do not support the efficacy of ginseng to treat any condition. Echinacea may be helpful in the treatment or prevention of upper respiratory tract infections, but trial data are not fully convincing. Saw palmetto has been shown in short-term trials to be efficacious in reducing the symptoms of benign prostatic hyperplasia. Kava is an efficacious short-term treatment for anxiety. None of these herbal medicines is free of adverse effects. Because the evidence is incomplete, risk-benefit assessments are not completely reliable, and much knowledge is still lacking.

Anxiety↗

Herbal products and supplemental nutrients used in the management of diabetes.

As companies, including large pharmaceutical houses, try to market supplemental nutrients and herbal products to ever-increasing numbers of consumers, diabetics will start to approach their physicians about these alternative remedies. A whole new industry know as "neutraceuticals" has evolved. This new industry is a combination of the vitamin supplement and herbal industries trying to work with regulatory agents to develop good manufacturing processes to ensure that consumers obtain good products. In fact, some diabetics may be taking herbal or nutritional supplements without their physician's knowledge. Therefore, it is important to query diabetic patients at least once a year as to whether they are using any herbal or nutritional products. Once it is determined that a patient is using these products, physicians must decide if they or someone else should address the issue of taking these products. Physicians who have a good comfort level with herbal products by all means should recommend them to their patients. If such a comfort level is lacking or low, patients can be referred for a consultation on the use of supplements or told that information will be forwarded to them after contact is made with someone who has knowledge of diabetes and use of appropriate supplements. This article reviews nine nutrient and herbal remedies commonly used for diabetes to facilitate such patient education.

Depression↗