[1] 10w Understanding herb and dietary supplement use in patients with epilepsy

[1] 29w Objective: To determine the prevalence of herb and dietary supplement use and to provide a comprehensive analysis of factors influencing the use of these products in patients with epilepsy.

[1] 34w One hundred eighty-seven patients completed the survey. Among these, 104 patients (56%) reported the current use of herbs or dietary supplements. Demographic and clinical characteristics of the study population are summarized in Table 1.

[2] 43w Of the herb or dietary supplement users, 34% used one product, 32% used two products, and 34% used three or more products. The most commonly used dietary supplements were multivitamins and minerals (83 patients). The dietary supplements used are summarized in Table 2.

[3] 87w When asked to state their reason(s) for herb and supplement use, most patients listed more than one reason. The most common reason was for general health purposes (35 patients). Other common reasons were physician's recommendation (13 patients), improve bone density (13 patients), increase energy (10 patients), boost immune system (10 patients), and improve memory (seven patients). Only six patients used herbs or supplements for the explicit purpose of benefiting their epilepsy condition. These patients used kava, skullcap, valerian, folic acid, vitamin B6, vitamin E, multivitamins, and minerals.

[4] 130w When asked where they obtained information about herbs and dietary supplements, most patients listed a variety of sources. Fifty patients stated that the primary source of information was their primary physicians. Other common sources of information were friends and family members. Forty-nine percent of the patients reported the use of herbs or supplements for more than 5 years; 26% used herbs and supplements between 1 and 5 years; and 26% used these products for less than one year. Seventy-one percent of the patients disclosed the use of herbs and supplements to their physicians and 32% disclosed this information to their pharmacists. Nine patients reported the occurrence of adverse effects that they attributed to herbs or supplements. No patient reported the occurrence of seizures attributable to their use of these products.

[5] 142w In addition to patient data collection, we performed a comprehensive literature search using MEDLINE for each of the herb and dietary products used by our patients to determine the effect of these products/ingredients on seizures and on their potential for interactions with other drugs metabolized by the liver. We found that five herb and supplement products used by our patients had been reported to alter drug metabolism through inhibition of the cytochrome P450 system. These include St. John's wort, garlic, grapefruit juice, folic acid, and Echinacea; in total, 20 patients were using products containing these ingredients (19% of all users). Seven products contained ingredients reported to potentially increase the occurrence of seizures. These were ginkgo, ginseng, black cohosh, evening primrose, ephedra, dehydroepiandrosterone (DHEA), and caffeine. Products containing one or more of these ingredients were used by 17 patients (16% of all users).

[6] 45w When we examined at the amount of money that our patients spent on herbs and dietary supplements, we found that 88% of patients spent less than $US50 per month, 7% spent between $US50 and $US100 per month, and 5% spent more than $US100 per month.

[7] 49w Logistic regression models were constructed for each predictor to test for independent associations between the demographic variables and herb or dietary supplement use (Table 3). We found that the most powerful independent predictors of herb or supplement use in our patients were partial epilepsy and Caucasian race (Table 4).

[1] 126w The prevalence of herb and dietary supplement use in this study (56%) is higher than that previously reported in patients with epilepsy (Danesi & Adetunji, 1994;Peebles et al., 2000;Tandon et al., 2002;Sirven et al., 2003;Easterford et al., 2005;Kim et al., 2006;Liow et al., 2007). It has been shown that the western and southern United States have a higher prevalence of CAM use than in other areas of the country (Eisenberg et al., 1993;Rawsthorne et al., 1999;Barnes et al., 2004). In addition, the type of dietary supplement included in questionnaires varies between studies due to the lack of standard definition (Yetley, 2007). The definition of dietary supplement used in this study is broad and includes vitamins, minerals, herbs, amino acids, and all substances used as dietary supplements.

[2] 251w Interestingly, we found that a considerable portion (71%) of the patients report their use of dietary supplements to their physician. Moreover, a large number of patients relied on the physicians as their primary source of information. Our findings differ from those of earlier studies in similar setting (Peebles et al., 2000;Sirven et al., 2003;Easterford et al., 2005;Liow et al., 2007), but they are within the range of reports in other chronically ill patients who use CAM (Fairfield et al., 1998;Kemper & O'Connor, 2004;Sawni & Thomas, 2007). Other surveys of epilepsy patients regarding the use of CAM have included other nonproduct therapies, such as prayer/ spirituality, stress reduction, and acupuncture. It is possible that patients may be less likely to share information about these practices than they are about their use of dietary supplements. Eisenberg et al. (1993) demonstrated that physicians were most likely to be informed about the use of homeopathy, megavitamin therapy, and self-help groups, but that they were least likely to be informed about folk remedies, religious, or spiritual healing by others, or imagery. A recent national survey of pediatricians found that the majority of respondents have been asked by their patients and families about complementary therapies (Kemper & O'Connor, 2004;Sawni & Thomas, 2007). It is also possible that physicians in the San Francisco Bay Area are more aware of the unconventional therapies used by their patients given that a substantial number of alternative medicine practitioners and numerous schools of alternative medicine and workshops are located in this area.

[3] 184w Our results suggest that most patients used dietary supplements for health promotion rather than their epilepsy condition. We found no correlation between the use of dietary supplements and epilepsy severity or dissatisfaction with conventional treatment, as measured by seizure frequency, duration of epilepsy, medication adverse effects, and number of antiepileptic drugs. Nevertheless, we observed that some of the reasons for dietary supplement use appeared to be related to epilepsy or common adverse effects caused by antiepileptic medications. For example, 13 patients reported the use of dietary supplements to improve bone health and seven patients used products in order to improve their memory. A comprehensive analysis of factors influencing the decision to use various forms of alternative therapies showed no evidence to support dissatisfaction with conventional treatment as an explanation for the use of alternative therapies (Astin, 1998). However, studies in patients with cancer found that ineffectiveness of conventional treatment or inadequate therapeutic response was among the dominant characteristics of patients who used alternative therapies (Verhoef et al., 1999(Verhoef et al., , 2005)). Therefore, the reason for use of alternative therapy could be disease specific.

[4] 119w Contrary to a number of previous reports (Easterford et al., 2005;Kim et al., 2006;Liow et al., 2007), we did not find that education or income levels predicted the use of dietary supplement in patients with epilepsy. A national telephone survey showed that third-party billing was most common payment method for the services of herbal therapists, providers of biofeedback, chiropractors, and providers of megavitamins (Eisenberg et al., 1993). On average, the respondents spent $US431 per person each year out of pocket for commercial dietary supplements and over-the-counter megavitamins (Eisenberg et al., 1993). This is comparable to the findings in our study. We found that most of the patients (88%) spent less than $US50 per month-or $US600 per year-on dietary supplements.

[5] 77w We found that dietary supplement users tend to be non-Hispanic whites and have partial epilepsy. It has been shown that non-Hispanic whites were more likely to use herbal medicine, relaxation techniques, and chiropractic more frequently than Hispanics and non-Hispanic blacks (Graham et al., 2005). A comprehensive analysis of 1999-2000 National Health and Nutrition Examination Survey (NHANES) showed that non-Hispanic whites tended to use dietary supplements more often than Mexican Americans and non-Hispanic blacks (Radimer et al., 2004).

[6] 68w It is unclear why patients with partial epilepsy tend to use dietary supplement more than patients with generalized epilepsy. Given a high prevalence of comorbid conditions in patients with epilepsy, it is possible that the increased use of dietary supplements among persons with partial epilepsy represents a correlation with comorbid conditions that were not included in the survey, rather than a correlation to the type of epilepsy itself.

[7] 236w This study, as with other studies of CAM use, has limitations. The use of questionnaire subjects our study to selection and recall biases. In addition, survey data were collected at only two clinics, both of which were located in the San Francisco Bay area. Therefore, our results may not be generalizable to other regions. However, other investigators have noted geographic differences in the use of CAM therapies by persons with epilepsy (Sirven et al., 2003;Liow et al., 2007), and our study reinforces this observation. Moreover, there are several complex human behaviors involved in the decision to use dietary supplement or alternative therapies (Astin, 1998). A significant number of potentially relevant variables may not have been included in the regression equation. In addition, epilepsy itself is a complex disorder that is commonly associated with substantial psychiatric and medical comorbidities. Previous studies demonstrated that men and women with epilepsy have a 2-to 5-fold increase in the occurrence of comorbid conditions (Gaitatzis et al., 2004;Wiebe & Hesdorffer, 2007). It may be that some of these other conditions were as relevant to the use of dietary supplements by our patients as was their epilepsy condition. Finally, our sample size is small. The small number of users of certain types of dietary supplement makes it difficult to draw conclusions for a specific product. conduct of the study, the analysis of study results, or in the preparation or approval of the manuscript.

[1] 61w All patients who were visiting the Epilepsy Clinic at the University of California San Francisco (UCSF) Medical Center and San Francisco General Hospital during a oneyear period were recruited. Each patient and/or his or her caregiver were asked to complete the structured questionnaire before leaving the clinic. The questionnaire and study protocol were approved by the UCSF Committee on Human Research.

[2] 207w All patients were asked about the description and frequency of their seizures and the duration of their epilepsy. Epilepsy was then classified as either partial or generalized epilepsy. Partial epilepsy consisted of simple and complex partial seizures with or without secondarily generalization. Generalized epilepsy consisted of tonicclonic, absence, atonic, and myoclonic seizures. The patients were also asked about their current antiepileptic medications including the name and whether or not they experienced any adverse effects. We then asked, ''Do you take any herbal products or dietary supplements including vitamins and other hormonal supplements purchased without a prescription?'' If the answer was yes, they were asked about the name of herbs and supplements, the duration of use, whether they experienced any apparent adverse effects from the product(s), the source of the product(s), and cost per month. In addition, we asked the patients where they learned about herbs and dietary supplements, whether they desired more information regarding the herbs and dietary supplements they were using, if they had informed their physicians or pharmacist about herb and supplement use, and whether or not their health insurance coverage included medications that did not require a prescription. Additional demographic questions including gender, age, race, level of education, and annual income were also collected.

[3] 87w Data were analyzed using Stata statistical software version 10.0 (StataCorp, College Station, TX, U.S.A.). We performed logistic regression analysis to estimate odds ratio (OR) and 95% confidence interval (CI) for each exposure. To assess for possible confounding, predictors with p < 0.2 were selected to enter multiple logistic regression analysis. Only predictors with p < 0.05 from multivariate analysis were selected and defined in the lockterm for backward selection. To assess overall fit of a logistic regression, the Hosmer-Lemershow goodness-offit test was performed. All p-values were two-sided.

[1] 307w Methods: We performed a cross-sectional study using self-administered questionnaires in a selected group of patients who were receiving care at a tertiary epilepsy center. Logistic regression was used to measure the association between the demographic variables and herb and dietary supplement use. In addition, we performed a MEDLINE search for each of the herb and dietary products used by our patients to determine the effect of these products on seizures and on their potential for interactions with other drugs metabolized by the liver. Results: One hundred eighty-seven patients completed the survey. Fifty-six percent of this group of patients with epilepsy used herbs and dietary supplements at the time of the survey. A considerable portion (71%) of these patients reported the use of these products to their physician, and most of them relied on their physicians as the primary source of information. Most of the patients used dietary supplement for health promotion rather than to specifically benefit their epilepsy condition. Approximately one-third of patients used herb or dietary supplements that had the potential to increase seizures (16%) or to interact with hepatically metabolized drugs (19%). The most powerful independent predictors of herb and dietary supplement use were partial epilepsy [odds ratio (OR) 3.36; 95% confidence interval (CI) 1.27-8.88] and Caucasian race (OR 3.55;). Conclusion: Patients with epilepsy commonly used dietary supplements along with their antiepileptic medications. The majority of these patients used herb and dietary supplements for health promotion rather than because of dissatisfaction with conventional treatment. It is important that physicians involved in the care of patients with epilepsy routinely inquire about the use of dietary supplements and that they make use of reliable resources to assess the safety of these products with regard to modification of seizure risk and the potential for interactions with antiepileptic drugs. KEY WORDS: Complementary and alternative medicine, Questionnaire, Multivariate analysis, Prevalence.

[2] 78w The use of complementary and alternative medicine (CAM) has increased dramatically in recent years (Eisenberg et al., 1998). Surveys in the United Kingdom and the United States showed that approximately 24-44% of adults with epilepsy used some forms of CAM therapy (Peebles et al., 2000;Sirven et al., 2003;Easterford et al., 2005;Liow et al., 2007). Studies in children with epilepsy found that 14% of these patients were using CAM while they were being treated conventionally (Gross-Tsur et al., 2003).

[3] 132w Among all forms of CAM, herbs and dietary supplements are probably the most popular (Angell & Kassirer, 1998;Samuels et al., 2008). Although many herbal remedies are harmless, numerous products have effects on the central nervous system and could potentially cause or increase the risk of seizures (Spinella, 2001;Tyagi & Delanty, 2003). A recent review of adverse event reports submitted to the U.S. Food and Drug Administration (FDA) described an association between the use of dietary supplements and seizures (Haller et al., 2005). In addition, many herbs and dietary supplements have the potential to interact with antiepileptic medications via effects on cytochrome P450 enzymes (Spinella, 2001;Samuels et al., 2008). Given the potential proconvulsant effects and drug-herb interactions, it is important to understand the pattern of herb and supplement use in patients with epilepsy.

[4] 115w Currently, there is no comprehensive theoretical model to account for the rationale of CAM use. Previous studies suggested that people who used CAM were different from nonusers in sociodemographic and health characteristics, including gender, age, race, education level, and income (Astin, 1998;Gross-Tsur et al., 2003;Barnes et al., 2004;Easterford et al., 2005;Kim et al., 2006;Wilson et al., 2006). Moreover, dissatisfaction with the cost and effectiveness of conventional therapy (Murray & Rubel, 1992;Gross-Tsur et al., 2003;Jean & Cyr, 2007), the need for personal control over their healthcare decisions (Duggan, 1995), and the compatibility of CAM with individual values, or spiritual or religious philosophy or beliefs (Astin, 1998) play important roles in decisions to seek out alternative therapies.

[5] 87w We hypothesized that the primary reasons for herb and dietary supplement use in patients with epilepsy were perceived ineffectiveness or adverse effects of conventional epilepsy treatments. To test this hypothesis, we performed a cross-sectional study using self-administered questionnaires in a sample of patients who were receiving care at a tertiary epilepsy center. The goal of this study was to determine the prevalence of herb and supplement use and to provide a comprehensive analysis of factors influencing the use of herbs and dietary supplements in patients with epilepsy.

[6] 75w In this study, we used the term ''dietary supplement'' as defined in the Dietary Supplement Health and Education Act (DSHEA) of 1994. ''A dietary supplement is a product taken by mouth that contains a ''dietary ingredient'' intended to supplement the diet. The ''dietary ingredients'' in these products may include: vitamins, minerals, herbs or other botanicals, amino acids, and substances such as enzymes, organ tissues, glandulars, and metabolites'' (Center for Food Safety & Applied Nutrition, 2001).