Herbal remedies,dietary supplements,and seizures

The use of herbal remedies and dietary supplements is widespread throughout the world, and use may be increasing. These are taken for a wide range of perceived benefits, such as energy and memory enhancement and treatment of specific conditions. Individuals with and without epilepsy may use these substances and may not inform their treating physician unless specifically asked. Inquiry about herbal medicine and dietary supplement intake should now be part of routine clinical history taking. Anecdotal accounts suggest that some herbal substances may have anticonvulsant effect, but randomised double-blind controlled trails are lacking. Alternatively many herbals and dietary supplements may predispose to seizures in individuals without epilepsy and worsen seizure control in those with epilepsy. In this article, we review the potential anticonvulsant and proconvulsant effects of herbal remedies and dietary supplements and discuss the potential interaction between these herbal substances and conventional anticonvulsant medications.     

Implications of herbal alternative medicine for electroconvulsive therapy

OBJECTIVES: To clarify the implications of herbal alternative medicine use during electroconvulsive therapy (ECT). BACKGROUND: A substantial proportion of patients with mental disorders report frequent use of herbal alternative medicines. Our current understanding of the biology of such remedies suggests that they may have implications for ECT practice. METHODS: We conducted electronic literature searches using Medline (via PubMed), Cochrane Database of Systematic Reviews, ACP Journal Club, PsychINFO, Database of Abstracts of Reviews of Effects, and Cochrane Central Register of Controlled Trials from their inception to April 2003. The search items were five selected herbal alternative medicines (Ginkgo biloba, ginseng, St. John's wort, valerian, kava-kava) in combination with the terms "drug interaction," "adverse effects," "side effects," "adverse drug reactions," "safety," and "toxicity." All data were included regardless of whether they were case reports, case series, clinical trials, or reviews. RESULTS: Our literature review revealed several potential effects of herbal alternative medicines upon ECT outcome. CONCLUSIONS: The growing use of herbal alternative medicine by patients with psychiatric illness may have implications for ECT practice. Our current knowledge is sparse and incomplete, however, indicating the need for more research.     

Botanicals and herbs: A traditional approach to treating epilepsy

Botanicals and herbs have a centuries-old tradition of use by persons with epilepsy, in many cultures around the world. At present, herbal therapies are tried by patients in developing as well as developed countries for control of seizures or adverse effects from antiepileptic drugs (AEDs), or for general health maintenance, usually without the knowledge of physicians who prescribe their AEDs. Well-designed clinical trials of herbal therapies in patients with epilepsy are scarce, and methodological issues prevent any conclusions of their efficacy or safety in this population. Furthermore, some botanicals and herbs may be proconvulsant or may alter AED metabolism. In spite of these limitations, further preclinical evaluation of botanicals and herbs and their constituent compounds using validated scientific methods is warranted based on numerous anecdotal observations of clinical benefit in patients with epilepsy and published reports showing mechanisms of action relevant to epilepsy or anticonvulsant effects in animal models of epilepsy. This review highlights the use of herbal therapies for epilepsy, outlines the role of the U.S. Food and Drug Administration in regulating herbal products, and presents the author’s approach to the scientific assessment of herbal therapies as potential therapies for patients with epilepsy.     

Herbal Medicines and Epilepsy: The Potential for Benefit and Adverse Effects

The widespread availability and use of herbal medicines raise the potential for adverse effects in the epilepsy population. Herbal sedatives (kava, valerian, chamomile, passionflower) may potentiate the effects of antiepileptic medications, increasing their sedative and cognitive effects. Despite some antiseizure effects in animal models, they should not be used in place of standard seizure medications because efficacy has not been established. Anecdotal, uncontrolled observations suggest that herbal stimulants containing ephedrine (ephedra or ma huang) and caffeine (cocoa, coffee, tea, maté, guarana, cola or kola) can exacerbate seizures in people with epilepsy, especially when taken in combination. Ginkgo and ginseng may also exacerbate seizures although the evidence for this is similarly anecdotal and uncertain. St. John's wort has the potential to alter medication pharmacokinetics and the seizure threshold. The essential oils of many plants contain epileptogenic compounds. There is mixed evidence for evening primrose and borage lowering the seizure threshold. Education of both health care providers and patients is the best way to avoid unintentional and unnecessary adverse reactions to herbal medicines.     

Can herbs provide a new generation of drugs for treating Alzheimer''s disease?

The overall aim of this review is to discuss cellular mechanisms at work in the progression of AD and current therapeutic strategies for treating AD, with a focus on the potential efficacy of herbal treatments. Recent advances in molecular, cellular, and animal model studies have revealed that formation of the 4-kDa amyloid beta peptide is a key factor in the development and progression of AD. Several cellular changes have been identified that are related to amyloid beta plaques and neurofibrillary tangles found in the autopsied brains of AD patients and in AD animal models. Several therapeutic strategies have been developed to treat AD, including anti-inflammatory, anti-oxidant, and anti-amyloid approaches. Recently, herbal treatments have been tested in animal and cellular models of AD and in clinical trials with AD subjects. In AD animal models and cell models, herbal extracts appear to have fewer adverse effects than beneficial effects on Aβ and cognitive functions. These extracts have multi-functional properties (pro-cholinergic, anti-oxidant, anti-amyloid, and anti-inflammatory), and their use in the treatment of AD patients looks promising. The chemical compositions of herbs and their potential for alleviating or reducing symptoms of AD or for affecting the disease mechanism need to be further studied.     

Efficacy and safety of herbal stimulants and sedatives in sleep disorders

World-wide use of herbal medicines is increasing, following regulatory and manufacturing developments. Herbs are attractive alternative medications to many patients with sleep disorders, who may be averse to using conventional drugs. We review here the most common herbal stimulants and sedatives. Caffeine, in herbal teas, black tea, coffee, soft drinks and pharmaceuticals, is used widely to control sleepiness, but more research is needed on its use in sleep disorders. Ephedra, and its constituent ephedrine, are used in both stimulant and weight loss preparations, sometimes with caffeine; safety concerns have arisen with this practice. Yohimbe is another herb used in stimulant and body-building preparations which has safety concerns. Asian and Siberian ginseng have been traditionally used for fatigue, and have some supportive experimental evidence for this use. Herbal sedatives also have some evidence for efficacy; the observations that certain plant flavonoid compounds bind to benzodiazepine receptors adds interest to their use. Valerian and kava have received the most research attention; both have decreased sleep onset time and promoted deeper sleep in small studies, and kava also shows anxiolytic effects. German chamomile, lavender, hops, lemon balm and passionflower are reputed to be mild sedatives but need much more experimental examination.     

Serious psychiatric and neurological adverse effects of herbal medicines -- a systematic review

OBJECTIVE: Psychiatric and neurological patients frequently try herbal medicines often under the assumption that they are safe. The aim of this systematic review was to provide a summary of recent data on severe psychiatric and neurological adverse effects of herbal remedies. METHOD: Computerized literature searches were carried out to identify all reports of psychiatric and neurological adverse effects associated with herbal medicines. These data were subsequently extracted, validated and summarized in narrative and tabular form. RESULTS: Numerous case reports comprise a diverse array of adverse events including cerebral arteritis, cerebral oedema, delirium, coma, confusion, encephalopathy, hallucinations, intracerebral haemorrhage, and other types of cerebrovascular accidents, movement disorders, mood disturbances, muscle weakness, paresthesiae and seizures. Several fatalities are on record. They are caused by improper use, toxicity of herbal ingredients, contamination and adulteration of preparations and herb/drug interactions. CONCLUSION: Herbal medicines can cause serious psychiatric and neurological adverse effects.     

Herbal products and other supplements: use by elderly veterans with depression and dementia and their caregivers

The use of herbal products and other "natural" supplements among the US population is on the rise. Limited data suggest that such use among the elderly may correlate with higher education levels as well as psychiatric symptoms. The authors examined herbal/supplement use among elderly veterans with depression and/or dementia (n = 82) and their primarily elderly caregivers (n = 56). Eighteen percent of subjects and 16% of caregivers used herbals/supplements. Seventy-five percent of subjects who used these products during the study period were also taking potentially interacting medications. Given the prior association of herbal/supplement use with higher education levels, a surprising number of elderly veterans with depression and/or dementia (the majority of whom had high school or less education) used these products. As evidenced by missing documentation in many physician notes, subjects may not have discussed their usage of herbals/supplements with their physicians. In light of the possibility of potentially harmful drug interactions, physicians who treat elderly patients should regularly inquire about the use of these products.     

Herbal products and serious side effects: a case of ginseng-induced manic episode

OBJECTIVE: Ginseng root extract is a widely used herbal product not devoid of side effects. This report describes the development of manic symptoms after ginseng consumption in a patient with affective disorder. Other potentially harmful side effects of ginseng are also reviewed. METHOD: A single case report. RESULTS: A 56-year-old woman with previous affective disorder presented a manic episode during ginseng intake. Symptoms disappeared rapidly with low doses of neuroleptics and benzodiazepines after ginseng suppression. CONCLUSION: Ginseng may produce manic symptoms. A special risk situation seems to be affective patients under antidepressant medication. The case emphasizes the lack of harmlessness of herbal products. Patients should be routinely asked about the use of herbal products and diet supplements.     

What the general psychiatrist should know about herbal medicine

The use of complementary and alternative medicine (CAM) has increased tremendously over the past 10 years. As a result of the increase physicians must understand both the factual information about CAM practices and the psychologic reasons patients seek out such treatments. A particular concern is the use of CAM by patients without the knowledge of their physicians, which may lead to complications resulting from interactions, or adverse effects from treatments of which the physician is unaware. This paper reviews research concerning the use of CAM by patients, explores some of the psychodynamic factors in CAM use, and suggests means of integrating that use into the patient’s therapy. Specific information about herbal and other alternative products is provided.     

Use of herbal medications among 200 psychiatric outpatients: prevalence,patterns of use,and potential dangers

We documented the use rates of herbal medication among a population of psychiatric outpatients to identify patients at risk for drug-herb interactions. Data were collected on 200 patients who, as part of their routine evaluation, provided information regarding their use of herbs. Fifteen percent of patients were currently taking herbs, the majority for treatment of psychiatric symptoms. There were no significant differences in use patterns across gender or between age groups. None of the current users charts, including the "high risk" patients, indicated that treating physicians were aware of potentially dangerous drug-herb combinations. Use of herbal medication was common among this sample of psychiatric outpatients. These data are consistent with reports from other patient populations. It is important for psychiatrists to ask all patients about their use of herbs and provide education about potentially dangerous drug-herb interactions.     

The Rise of a New Psychoactive Agent: Salvia divinorum

Since the 1990s, there has been a rise in the availability and recreational use of a herbal plant called Salvia divinorum. Numerous internet websites have advertised it for sale as a legal herbal alternative to illegal hallucinogens. Initial data surveying use has indicated many young adults are obtaining and using this herb for its psychoactive properties. Reported methods of ingestion for the plant include chewing, and smoking leaves or fortified extracts. Subjective effects of the plant include, affect changes, psychedelic-like changes in perception, and even loss of consciousness. Although the pharmacological properties and possible antidepressant effects have been studied in recent years, little information is known about potential negative impact resulting from recreational use, and scant information about Salvia divinorum currently exists in the psychological and substance abuse literature. While Salvia divinorum appears to be a substance with some therapeutic potential, it also poses some significant dangers as a substance of varying legal status with a potential for abuse.     

Insights from molecular investigations of traditional Chinese herbal stroke medicines: implications for neuroprotective epilepsy therapy

Traditional Chinese herbal medicine is the most widely practiced form of herbalism worldwide. It is based on a sophisticated system of medical theory and practice that is distinctly different from orthodox Western scientific medicine. Most traditional therapeutic formulations consist of a combination of several drugs. The combination of multiple drugs is thought to maximize therapeutic efficacy by facilitating synergistic actions and ameliorating or preventing potential adverse effects while at the same time aiming at multiple targets. Orthodox drug therapy has been subject to critical analysis by the "evidence-based medicine" movement, and demands have been made that herbal medicine should be subject to the same kind of scrutiny. However, evaluation of the effectiveness of herbal medicines can be challenging, as their active components are often not known. Accordingly, it may be difficult to ensure that an herbal preparation used in clinical trials contains the components underlying its purported therapeutic effect. We reasoned that the identification of actions of herbal medicines at well-defined molecular targets and subsequent identification of chemical compounds underlying these molecular effects might serve as surrogate markers in the hypothesis-guided evaluation of their therapeutic efficacy. A research program was initiated to characterize in vitro molecular actions of a collection of 58 traditional Chinese drugs that are often used for the treatment of stroke. The results indicate that these drugs possess activity at disparate molecular targets in the signaling pathways involved in N-methyl-d-aspartate (NMDA) receptor-mediated neuronal injury and death. Each herbal drug contains diverse families of chemical compounds, where each family comprises structurally related members that act with low affinity at multiple molecular targets. The data appear to support the multicomponent, multitarget approach of traditional Chinese medicine. Glutamate release and excessive stimulation of NMDA receptors cause status epilepticus-induced neuronal death and are involved in epileptogenesis. Therefore, these results are also relevant to the development of antiepileptogenic and neuroprotective therapy for seizures. The combination of principles of modern molecular medicine with certain ideas of traditional empirical Chinese medicine may be beneficial in translational medicine in general.     

Over-the-counter sleeping pills: a survey of use in Hong Kong and a review of their constituents

This study examined the composition of over-the-counter (OTC) sleeping pills in Hong Kong and reviewed the current knowledge about the hypnotic efficacy and safety of their major herbal and dietary supplement constituents. We conducted a cross-sectional survey of OTC sleep aids at drug stores in a residential district of 0.3 million population and literature search using MEDLINE, EMBASE, PsycINFO, China Journal Net, China Biomedical Database and relevant English and Chinese literature. We identified 17 brands of OTC sleeping pill: eleven of them were composed of mixtures of Chinese and Western herbal agents and six brands contained 3 mg of melatonin. The Chinese herbal mixture suanzaorentang, comprising zizyphi spinosi semen, poria cocos, ligusticum wallichii, anemarrhenae rhizoma and glycyrrhizae radix in ratio of 7:5:2:1:1, was the most common OTC sleeping pill available in the survey. Our literature review showed that kava, valerian and melatonin were the better-researched herbs and dietary supplements, however, the data on hypnotic efficacy and safety was inadequate to support their clinical use. More rigorous investigations of the risk-benefit relationship of herbal agents and dietary supplements used for insomnia are needed.     

The use of complementary medicines and alternative practitioners in a cohort of patients with epilepsy

Complementary and alternative medicines (CAMs) are increasingly used by patients in the Western world. Some of the most popular herbal remedies are known to act on the cytochrome P450 system, with potential effects on antiepileptic drug (AED) levels. Few studies have explored their use in people with epilepsy. We surveyed 400 patients attending epilepsy clinics in Greater Manchester. Thirty-four percent of our patients had used or were using CAMs; the majority had not told their doctor. Use of CAMs was not predicted by age, sex, seizure frequency, number of AEDs, or dissatisfaction with conventional medicine. Patients who had gone onto higher education were significantly (P < 0.05) more likely to have used or be using CAMs. The majority of patients did not use CAMs for their epilepsy but for general health purposes. Most patients stated that CAMs had little or no effect on seizure frequency or severity.     

Adjuvant use of nutritional and herbal medicines with antidepressants, mood stabilizers and benzodiazepines

Adjuvant use of nutritional and herbal medicines has potential to increase the efficacy of synthetic pharmaceuticals, and perhaps also decrease their side-effects by allowing lower doses to be prescribed. We evaluated current evidence for adjuvant use of nutritional and herbal medicines with antidepressants, mood stabilizers and benzodiazepines; and explored novel future areas of research. The paper also critiques current evidence for co-administration of St. John’s wort with synthetic antidepressants. We performed a systematic search of MEDLINE, CINAHL, PsycINFO, The Cochrane database, China National Knowledge Infrastructure and the Chinese Science Citation Database. Search results were supplemented by a review of reference lists and a forward search using the Web of Science. Where possible we calculated effect sizes. Encouraging evidence exists for the use of omega-3 fatty acids, SAMe, folic acid and l-tryptophan adjuvantly with antidepressants to enhance response and improve efficacy. Various nutrients also have emerging evidence as effective adjuncts with antipsychotics and mood stabilizers. While some evidence supports nutritional adjuvancy with various psychopharmacotherapies, adjuvant use of herbal therapies has not been sufficiently studied to warrant standard clinical application. This remains a promising area of research via robust, safety-conscious studies.     

Systematic Review of Clinical Trials Assessing Pharmacological Properties of Salvia Species on Memory,Cognitive Impairment and Alzheimer's Disease

Salvia officinalis L. and Salvia lavandulaefolia L. have a longstanding use as traditional herbal remedies that can enhance memory and improve cognitive functions. Pharmacological actions of S. officinalis and S. lavandulaefolia on healthy subjects and on patients suffering of cognitive decline have been investigated. Aim of this review was to summarize published clinical trials assessing effectiveness and safety of S. officinalis and S. lavandulaefolia in the enhancement of cognitive performance in healthy subjects and neurodegenerative illnesses. Furthermore, to purchase a more complete view on safety of S. officinalis and S. lavandulaefolia, we collected and discussed articles regarding toxicity and adverse reactions. Eight clinical studies investigating on acute effects of S. officinalis on healthy subjects were included in the review. Six studies investigated on the effects of S. officinalis and S. lavandaeluaefolia on cognitive performance in healthy subjects. The two remaining were carried out to study the effects of sage on Azheimer's disease. Our review shows that S. officinalis and S. lavandulaefolia exert beneficial effects by enhancing cognitive performance both in healthy subjects and patients with dementia or cognitive impairment and is safe for this indication. Unfortunately, promising beneficial effects are debased by methodological issues, use of different herbal preparations (extracts, essential oil, use of raw material), lack of details on herbal products used. We believe that sage promising effects need further higher methodological standard clinical trials.     

Medicinal plants used in Iranian traditional medicine to treat epilepsy

Antiepileptic drugs used to treat epilepsy can cause severe, life threatening side effects. In Iranian traditional medicine, herbal remedies have been used for centuries to treat seizures. In this study, the five most important herbals in Iranian traditional medicine, namely Canon, al-Hawi, al-Abniah ‘an Haqaeq al Adwia, Tuhfat al-Mu’minin, and Makhzan ul-Adwia, were searched for the term “sar-e”, which means epilepsy, to identify the herbs used for treatment in ancient times. We also searched scientific literature for pharmacological evidence of their effectiveness.Twenty-five plants were identified as herbal remedies to treat epilepsy. Pharmacological data related to the antiepileptic activity of eleven of these plants exists. A large number of these plants which have not been investigated pharmacologically for antiepileptic activity would be good candidates for study in exploring new herbal anticonvulsant remedies.     

Functional screening of traditional antidepressants with primary cortical neuronal networks grown on multielectrode neurochips

We optimized the novel technique of multielectrode neurochip recordings for the rapid and efficient screening of neuroactivity. Changes in the spontaneous activity of cultured networks of primary cortical neurons were quantified to evaluate the action of drugs on the firing dynamics of complex network activity. The multiparametric assessment of electrical activity changes caused by psychoactive herbal extracts from Hypericum, Passiflora and Valeriana, and various combinations thereof revealed a receptor-specific and concentration-dependent inhibition of the firing patterns. The spike and burst rates showed significant substance-dependent effects and significant differences in potency. The effects of specific receptor blockades on the inhibitory responses provided evidence that the herbal extracts act on gamma-amino butyric acid (GABA) and serotonin (5-HT) receptors, which are recognized targets of pharmacological antidepressant treatment. A biphasic effect, serotonergic stimulation of activity at low concentrations that is overridden by GABAergic inhibition at higher concentrations, is apparent with Hypericum alone and the triple combination of the extracts. The more potent neuroactivity of the triple combination compared to Hypericum alone and the additive effect of Passiflora and Valeriana suggest a synergy between constituent herbal extracts. The extracts and their combinations affected the set of derived activity parameters in a concomitant manner suggesting that all three constituent extracts and their combinations have largely similar modes of action. This study also demonstrates the sensitivity, selectivity and robustness of neurochip recordings for high content screening of complex mixtures of neuroactive substances and for providing multiparametric information on neuronal activity changes to assess the therapeutic potential of psychoactive substances.     

Oriental medicine as therapy for resistant depression: use of some herbal drugs in the far east (Japan).

1. The advantage of oriental medicine are described. 2. For those whose anxious-depressive state are prolonged, despite several changes in combining drugs, five herbal medicines were introduced. Although their mechanism of action were still unknown, some effects were explained by modern pharmacological techniques.