Knowledge of epilepsy, quality of life, and psychiatric comorbidities in Lebanese adults with epilepsy.

INTRODUCTION: People with epilepsy (PWE) face a variety of psychosocial challenges. A lack of knowledge of epilepsy, a high level of depression and anxiety and a low quality of life (QoL) are among the major problems that affect most PWE. The objective of this study was to examine the association of sociodemographic characteristics, clinical factors and knowledge of epilepsy with the level of QoL, and the presence of psychiatric comorbidities. METHOD: A cross-sectional study was conducted in Lebanon. The PWE were recruited from neurologists' clinics in Beirut and its suburbs. A questionnaire translated into Arabic was used and composed of four parts: sociodemographic factors, clinical characteristics, psychosocial characteristics (QoL, psychiatric disorders), and knowledge epilepsy scale. Backward logistic regression models were developed, the associations were estimated by odds ratio (OR), and the level of significance was set at p ≤ 0.05. RESULTS: Four hundred and four PWE were recruited in this study. About a half of PWE had controlled epilepsy (46.3 %) and 40.3 % had epilepsy for less than 5 years. The QoL was low for 38.6 % of PWE and 30.2 % had psychiatric comorbidities. More than half of PWE had a good level of knowledge (71.5 %). Controlled epilepsy (OR = 1.8; 95 %CI: 1.2-2.9), and good knowledge about epilepsy (OR = 5.5; 95 %CI: 3.4-9.1) were associated with better QoL. Patients on polytherapy with anti-seizure drugs (OR = 0.6; 95 %CI: 0.4-0.9), experienced side effects of anti-seizure drugs (OR = 0.6; 95 %CI: 0.4-0.9) and with psychiatric comorbidities (OR = 0.6; 95 %CI: 0.3-0.9) had a lower QoL. A high number of nonpsychiatric comorbidities (OR = 2.5; 95 %CI: 2.0-3.1) and a polytherapy increased the risk of having psychiatric comorbidities (OR = 1.8; 95 %CI: 1.1-2.8). CONCLUSIONS: Good knowledge of epilepsy and the absence of psychiatric comorbidities are important predictors of good QoL in Lebanese PWE. Educational programs are needed to reduce misconceptions about epilepsy and improve mental health of PWE.

Management of epilepsy in Lebanon: Medication reviews and drug-related problems.

PURPOSE: The goal of epilepsy treatment is to control seizures without drug related problems (DRPs). The evaluation of anti-seizure drugs (ASD) strategies and identification of DRPs are rarely studied. This study aimed primarily to evaluate the choice of ASD according to international guidelines and secondarily to identify and describe anti-seizure drug-related problems. METHODS: A cross-sectional study was conducted during 1 year among Lebanese adults with epilepsy attending neurology clinics. The choice of ASD was compared to National Institute for Health and Care Excellence guidelines. Drug-drug interactions were evaluated by the Lexicomp database, and the DRP classification was performed using the Pharmaceutical Care Network Europe classification. RESULTS: A total of 404 patients with epilepsy were included. The prescription for an ASD was in accordance with the indication set in guidelines in 75.0% of population, and 1078 DRPs were identified. The main DRPs detected were adverse drug reactions (51.0%), inappropriate combinations of drugs (50.0%), and suboptimal drug regimens (46.3%). Single and divorced patients, who living in Mount Lebanon, and who took the old with the new generation had a less risk to have an inadequate prescription to guidelines. However, female gender, controlled epilepsy, multiple ASDs, and living in a rural region increased DRPs. CONCLUSIONS: This study showed that quarter of the population used ASDs contraindicated according to international guidelines. Since DRPs were related to the number and type of ASD prescribed, it is important to assess the case of each patient by a clinical pharmacist to prevent drug-drug interactions and iatrogenic issues.

Differences in knowledge about epilepsy and antiepileptic drugs among pharmacy-dispensing workers in Cambodia and in Lao PDR.

Epilepsy is the most common neurological disorder encountered in primary care in Southeast Asia. People with epilepsy require long-term therapy management. Nonadherence to antiepileptic drugs (AEDs) has been identified as a major factor in suboptimal control of epilepsy. Pharmacies offer patients a first-line point of contact with the healthcare system. Many pharmacies operate with limited or nonqualified human resources that can lead to insufficient knowledge, inappropriate supply of medicines, and insufficient counseling. OBJECTIVE: The aim of this study was to evaluate the qualification and knowledge concerning epilepsy and AEDs among pharmacy-dispensing workers who sell drugs to people with epilepsy. METHOD: A cross-sectional qualitative study was conducted in public and private pharmacies, in both urban and rural areas of Cambodia and Lao People's Democratic Republic (Lao PDR). The knowledge was collected through a questionnaire. RESULTS: A total of 180 respondents from 123 outlets in the two countries were included in this study. A proportion of 40.8% (31) of respondents in Cambodia and 38.5% (40) in Lao PDR were pharmacists, followed by sellers who did not received any healthcare training with a proportion of 18.4% (14) in Cambodia compared to 20.2% (21) in Lao PDR. Head trauma was cited as the main cause of epilepsy by 72.4% (55) in Cambodia and 27.2% (28) in Lao PDR (p < 0.001). Epilepsy was considered as a contagious disease by 6.6% (5) of respondents in Cambodia compared to 18.4% (19) in Lao PDR (p = 0.03). Eighty-seven percent (66) of respondents in Cambodia knew at least one long-term AED versus 67.3% (70) in Lao PDR (p = 0.003). Phenobarbital was mentioned in more than 90.0% of cases in both countries. In overall, 15.4% (21) thought that if seizures are controlled for some months, people with epilepsy could stop taking their AEDs. Only one respondent from Lao PDR was aware of drug-drug interaction between AEDs and oral contraception. CONCLUSION: An educational intervention should be implemented to improve the knowledge of epilepsy and AEDs for pharmacy-dispensing workers. This could include advice for all pharmacy-dispensing workers in order to improve AED management and follow-up of therapeutic adherence.

Self-reported attitudes about medication in Lebanese people with epilepsy.

BACKGROUND: Epilepsy is a common worldwide neurological disorder. For people with epilepsy (PWE), adherence and attitudes towards medication is a crucial step to improve efficacy of prescribed treatment and to prevent seizures. OBJECTIVES: The first aim of this study was to evaluate attitudes towards antiepileptic medications in Lebanese population. Secondary aims were to assess factors affecting attitudes and associated with epilepsy control. MATERIAL AND METHODS: A cross-sectional study was conducted in outpatient neurology clinics located in Beirut-Lebanon. Data were collected using a structured questionnaire. Self-report of medication taking behaviors were assessed using the abbreviated (4 items) Morisky Medication Adherence Scale (MMAS-4). Epilepsy was considered as controlled if the patient had no seizures in the last 6 months. RESULTS: Among 250 PWE recruited in this study, male-to-female ratio was 0.87 (116/134), and 50.8% were married. Mean duration of epilepsy was 13.7 ±â€¯12.8 years. Valproate was the most common antiepileptic drug (AED) used followed by levetiracetam and carbamazepine. About 60.8% of the population presented partial epilepsy. Uncontrolled epilepsy was present in more than half of participants (55.2%), with only 32.4% had positive attitudes to their medication. Positive attitudes towards antiepileptic increased in people who found that their treatment was efficacious (odds ratio (OR) = 4.9; 95% confidence interval (CI): 1.2-20.0; p = 0.03), who had controlled epilepsy (OR = 3.4; 95%CI 1.6-7.1; p = 0.001), and who were diagnosed as PWE between the age of 12-20 years (OR = 3.1; 95%CI 1.1-8.4; p = 0.03). Oppositely, these attitudes decreased in participants who felt their treatment as an economic burden (OR = 0.2; 95%CI 0.1-0.4; p ≪ 0.001), and in people with depression (OR = 0.4; 95%CI 0.2-0.9; p = 0.04). Controlled epilepsy was higher in people who contacted a neurologist if seizure occurred, in people with positive attitudes, and after a long duration of disease, but it decreased if patient did not follow neurologist's instructions in fasting period. CONCLUSIONS: Lebanese PWE were less likely to have positive attitudes towards medication, which may lead to poor epilepsy control. Depression and economic burden were the major factors that decreased these attitudes. Identifying factors affecting attitudes to medication and leading to controlled epilepsy may help clinicians to elaborate educational programs to optimize medication adherence.

Quality of antiepileptic drugs in sub-Saharan Africa: A study in Gabon, Kenya, and Madagascar.

OBJECTIVE: Epilepsy is a major public health issue in low- and middle-income countries, where the availability and accessibility of quality treatment remain important issues, the severity of which may be aggravated by poor quality antiepileptic drugs (AEDs). The primary objective of this study was to measure the quality of AEDs in rural and urban areas in 3 African countries. METHODS: This cross-sectional study was carried out in Gabon, Kenya, and Madagascar. Both official and unofficial supply chains in urban and rural areas were investigated. Samples of oral AEDs were collected in areas where a patient could buy or obtain them. Pharmacological analytical procedures and Medicine Quality Assessment Reporting Guidelines were used to assess quality. RESULTS: In total, 102 batches, representing 3782 units of AEDs, were sampled. Overall, 32.3% of the tablets were of poor quality, but no significant difference was observed across sites: 26.5% in Gabon, 37.0% in Kenya, and 34.1% in Madagascar (P = .7). The highest proportions of substandard medications were found in the carbamazepine (38.7%; 95% confidence interval [CI] 21.8-57.8) and phenytoin (83.3%; 95% CI 35.8-99.5) batches, which were mainly flawed by their failure to dissolve. Sodium valproate was the AED with the poorest quality (32.1%; 95% CI 15.8-42.3). The phenobarbital (94.1%; 95% CI 80.3-99.2) and diazepam (100.0%) batches were of better quality. The prevalence of substandard quality medications increased in samples supplied by public facilities (odds ratio [OR] 9.9; 95% CI 1.2-84.1; P < .04) and manufacturers located in China (OR 119.8; 95% CI 8.7-1651.9; P < .001). The prevalence of AEDs of bad quality increased when they were stored improperly (OR 5.4; 95% CI 1.2-24.1; P < .03). SIGNIFICANCE: No counterfeiting was observed. However, inadequate AED storage conditions are likely to lead to ineffective and possibly dangerous AEDs, even when good-quality AEDs are initially imported.

Interventional programs to improve therapeutic management of people with epilepsy in low- and middle-income countries.

OBJECTIVE: To assess the current status of initiatives carried out in developing countries to improve therapeutic management of people with epilepsy. METHODS: A literature review was performed in 2015 to identify and analyze interventional programs carried out in countries with low- and middle-income economies. Electronic databases were reviewed with no time restriction. Each intervention was categorized according to the level of evidence achieved (A: blind randomized controlled trial, B: randomized controlled trial, C1: randomized trial, C2: controlled trial, D: prospective cohort, E: retrospective evaluation). RESULTS: A total of 46 intervention projects were identified, 13 with no quantitative assessment. The 31 remaining projects were carried out in 18 countries, 52% (16) in Africa, 42% (13) in Asia, and 6% (2) in Latin America. Among those, 13% (4) were level B, 3% (1) C1, 6% (2) C2, 74% (23) D, and 3% (1) were level E. The effectiveness of the intervention, assessed by the efficacy of antiepileptic drugs, was the primary objective in 81% (25). People with epilepsy were on average seizure-free in 44.6%±14.4% of cases at one year, ranging from 25.0% to 78.4%. At two years, on average 50.9%±29.7% are seizure-free, ranging from 4.6 to 92.7%. The median compliance was 79.3% with a minimum of 21.6% and a maximum of 100.0%. DISCUSSION: No blind randomized controlled trial has been used to assess the efficacy of a program to improve access to antiepileptic drugs (AEDs) in developing countries, and the level of evidence was globally low. Phenobarbital remains the AED predominantly used in programs. Adherence to treatment management has been pointed out to be a key element in the success of a program, sometimes not sufficiently considered. Monthly supply of AEDs, at specific and community level, reducing the costs and time spent traveling, appeared to be the most effective strategies. Homogenization and standardization of evaluation practices of programs to improve the management of epilepsy in resource-limited settings would lead to comparison and meta-analysis which would ultimately improve strategies of support for not only epilepsy but also other noncommunicable diseases in developing countries.

Epilepsy-associated levels of perceived stigma, their associations with treatment, and related factors: A cross-sectional study in urban and rural areas in Ecuador.

BACKGROUND: Epilepsy is felt to be a stigmatizing condition. Stigma has been considered one of the major factors contributing to the burden of epilepsy and to the treatment gap. Stigma has a negative effect on the management of people with epilepsy (PWE). Furthermore, lack of information and inappropriate beliefs are still the factors that most contribute to stigma and discrimination. In this study, we assessed the level of perceived stigma in urban and rural areas and we report their association with in antiepileptic drug (AED) use, effects on seeking medical care, and stigma-associated factors. METHODS: A cross-sectional study in urban and rural areas in Ecuador from January 2015 until May 2016. People with a confirmed diagnosis of epilepsy were included using three sources of information. The survey was implemented through a questionnaire to determine perceived stigma and evaluate the factors associated. The perceived stigma was measured using the revised Jacoby's stigma scale to detect differences in levels of stigmatization. Access to treatment was evaluated through self-report of AED use, and attainment of medical care and stigma-associated factors were assessed. Furthermore, a multivariate analysis adjusted for possible confounders was performed using stigma as the outcome variable. RESULTS: A total of 243 PWE were interviewed, 65.8% reported feeling stigmatized and 39.1% reported a high stigmatized level. We found a significant difference in high stigma perception in the urban area compared to the rural area. However, the lack of use of AEDs was significantly higher in the rural areas. No significant correlation was found between use of AEDs and the levels of perceived stigma. PWE who did not talk about their condition and those who did not feel well informed about their epilepsy had significantly higher perceived stigma levels. Additionally, the multivariate analysis demonstrated that area, educational level, type of seizure, talk about epilepsy, and information were associated with perceived stigma. CONCLUSION: The stigma perception was relevant in all PWE. We found a higher stigma level perception in the urban compared to rural area. Moreover, the lack of treatment was a serious problem mainly in rural areas. Even though we did not find that perceived stigma was associated with AED use, our study pointed out the influence of educational level and information related to stigmatization. Consequently, a coordinated effort to reduce stigma should include strategies focused on PWE education and information about their condition.

Effectiveness of topical sodium thiosulfate for ectopic calcifications and ossifications. Results of the CATSS-O study.

INTRODUCTION: Ectopic calcifications (ECs) and heterotopic ossifications (HOs) form in non-mineralized tissues, most often in subcutaneous and muscular areas. Local and systemic complications can cause severe disability. Systemic administration of sodium thiosulfate (STS) gives promising results but is difficult to use in clinical practice. OBJECTIVE: Evaluation of the efficacy and safety of topical STS in ECs and HOs. METHODS: Retrospective analysis of the CATSS-O registry that included patients receiving topical STS 25 % prepared by the pharmacy of Limoges hospital during 2014-2020. The efficacy of STS was assessed by imaging (radiography or CT) after at least 6 months' treatment. RESULTS: Among 126 patients who received STS 25 %, 35 had complete clinical and radiographic data for analysis (28 with ECs and 7 with HOs; 18 children [mean age 8.9 years, range 1.5-16], 17 adults [mean age 52.4 years, range 24-90]). Calcifications or ossifications were due to dermatomyositis (8 children, 6 adults), systemic scleroderma (6 adults) or pseudo-hypoparathyroidism 1A (7 children). They were single (37.1 %) or multiple (62.9 %). Treated regions were in the lower limbs (31.4 %), upper limbs (37.1 %) or both (28.6 %) and the axial region (2.9 %). Topical STS was clinically effective in 9/28 (32.1 %) patients with ECs and 2/7 (28.6 %) children with HOs. Three patients experienced complete disappearance of their calcifications. Response for ECs was better in children than adults (54.5% vs 17.6 %, p = 0.035). Topical STS was well tolerated. CONCLUSION: Local STS seems effective for ossifications, particularly pediatric calcifications or ossifications. Randomized and experimental studies are needed to confirm this observation and to identify the underlying mechanisms.

Do clinical pharmacy activities have an impact on the rehospitalisation rate of elderly patients admitted to a MUPA unit for a fall?

OBJECTIVE: to evaluate the effect of clinical pharmacy interventions on the unplanned rehospitalisation rates of elderly people admitted following a fall to the emergency medical treatment for the elderly unit (médecine d'urgence de la personne âgée [MUPA]) in a teaching hospital. DESIGN AND MEASURES: this was a longitudinal, comparative pilot study. Patients aged at least 75 who were admitted to the MUPA unit following a fall, who had at least two chronic diseases, and who were being treated with two or more medications were included between 1 February 2018 and 30 June 2018 and were followed for 90 days. The main outcomes were the unplanned rehospitalisation rate at Limoges Teaching Hospital within the 90 days (primary outcome), 30 days and 72 h. The estimated cost-saving was also assessed. RESULTS: 252 patients were included. The mean age was 88.4 ± 5.8 years and the average baseline number of medications was 8.3 ± 3.4. In total, 158 pharmaceutical interventions were performed, reflecting an acceptance rate of 94.9%. We found a significant reduction in the rate of unplanned rehospitalisations at 90 days (OR = 0.45 (0.26-0.79) P = 0.005). These results were also consistent at 30 days (P = 0.035) and 72 h (P = 0.041). We found a cost-saving of €37770 related to 21 avoided rehospitalisations. CONCLUSIONS: our results strongly emphasise the positive effects of clinical pharmacy services on the prevention of unplanned rehospitalisations of elderly patients admitted following a fall.

[Do clinical pharmacy activities have an impact on the re-hospitalization rate of elderly patients admitted in an Elderly Emergency Medicine (EMM) unit for fall?] / Les activités de pharmacie clinique ont-elles un impact sur le taux de ré-hospitalisation des patients âgés admis pour chute en unité de médecine d'urgences des personnes âgées (MUPA) ?

To evaluate the effect of clinical pharmacy interventions on the unplanned rehospitalizations rates of elderly people admitted for fall to the elderly emergency medicine (EEM) unit in a teaching hospital. DESIGN AND MEASURES: This was a longitudinal, comparative pilot study. Patients aged at least 75 who were admitted to the EEM unit for a fall and who had at least two chronic diseases and who were being treated with two or more medications were included from February 1, 2018 to June 30, 2018 and followed by 90 days. The main outcomes were the unplanned rehospitalizations rate at Limoges Teaching Hospital within the 90 days (primary outcome), 30 days and 72 hrs. The estimated cost-saving was also assessed. RESULTS: We included 252 patients. The mean age was 88.4 ± 5.8 years and the average baseline number of medications was 8.3 ± 3.4. In total, 158 pharmaceutical interventions were performed, reflecting an acceptance rate of 94.9%. We found a significant reduction of the rate of unplanned rehospitalizations at 90-day (OR = 0.45 (0.26-0.79) p = 0.005). These results were still consistent at 30-day (p = 0.035) and 72 hours (p = 0.041). We found a cost-saving of 37,770 euros related to 21 avoided rehospitalizations. CONCLUSIONS: Our results highly emphasize the positive effects of clinical pharmacy services on the prevention of unplanned rehospitalizations of old adults admitted for fall.

Availability, affordability, and quality of essential anti-seizure medication in Cambodia.

OBJECTIVE: Epilepsy is a major neurological disorder that requires long-term medical treatment. Once epilepsy is diagnosed, people with epilepsy face many difficulties in accessing treatment (treatment gap). Our objective was to assess the situation regarding the availability, price, affordability, and quality of anti-seizure medication (ASM), which are major determinants of access to treatment. METHOD: A cross-sectional study was performed in provincial/district hospitals and private pharmacies in urban and rural areas in Cambodia. Data on ASM availability and price were obtained through drug suppliers. Affordability was estimated as the number of day wages the lowest-paid government employee must work to purchase a monthly treatment. Samples of ASM were collected, and the quality of ASM was assessed through Medicine Quality Assessment Reporting Guidelines. RESULTS: Out of 138 outlets visited, only 72 outlets (52.2% [95% CI 43.5-60.7]) had at least one ASM available. Phenobarbital 100 mg was the most available (35.5%), followed by carbamazepine 200 mg (21.7%), phenobarbital 50 mg (11.6%), sodium valproate 500 mg (9.4%), and phenytoin 100 mg (9.4%). In provincial/district hospitals, ASM was provided free of charge. In private pharmacies, affordability for phenobarbital 50 mg and 100 mg was the best, with 0.6 and 0.5 days, respectively, compared to phenytoin 100 mg (1.8 days), and other ASM. No counterfeit ASM was found in this study. Phenytoin sample presented the worst quality (33.0%) compared to carbamazepine (27.8%), and other ASM. SIGNIFICANCE: A lack of access to affordable and effective ASM due to low availability and poor quality of ASM was identified. Our research highlights the need for future policy efforts to ensure the quality of ASM and improve their availability. This can be achieved by involving the calculation of their annual needs for these drugs and increasing the national production of ASM.

Quality of life and stigma in Lebanese people with epilepsy taking medication.

BACKGROUND: Epilepsy is among the more stigmatising diseases, leading to a negative impact on the quality of life (QoL) of people with epilepsy (PWE). Assessment of the QoL and stigma in PWE reflects the outcome of their disease, and the findings can be used to improve the management of epilepsy. To fill a gap in the literature, our primary aim is to evaluate the QoL and stigma in Lebanese PWE, and our secondary aim is to identify factors affecting these parameters. MATERIAL AND METHODS: A cross-sectional study was conducted for 1 year in Greater Beirut. PWE were interviewed by using a standardised questionnaire. QoL was evaluated by the QoL in Epilepsy Inventory-10 (QOLIE-10), and the stigma was evaluated by the Jacoby scale. Multivariate analyses were used to identify the factors associated with QoL and stigma. RESULTS: The sample was 404 PWE. More than half of the PWE (61.4 %) had a better QoL than the other PWE (mean QOLIE-10 score of 26.9 ± 11.3), and 47.8 % of PWE felt stigmatised. Linear regression showed that presence of psychiatric comorbidities (p = 0.03), stigma (p < 0.001), experiencing side effects (p = 0.001), polytherapy (p = 0.002), living in a northern area (p = 0.003), and older age (p = 0.004) were the major factors associated with a poor QoL. Logistic regression showed that a low level of QoL (p = 0.005) and experiencing side effects (p = 0.045) were associated with a high level of stigma. CONCLUSIONS: An appropriate treatment based on a monotherapy can reduce the risk of side effects, improving QoL of PWE, and decreasing stigma. Furthermore, the management of depression by specialists is an essential step to improve the QoL of Lebanese PWE. Education programmes and information on epilepsy and treatment also play a major role in reducing stigma.

Availability, affordability, and quality of essential antiepileptic drugs in Lao PDR.

OBJECTIVE: Epilepsy is a chronic condition treatable by cost-effective antiepileptic drugs (AEDs), but limited access to treatment was documented. The availability and affordability of good quality of AEDs play a significant role in access to good health care. This study aimed to assess the availability, affordability, and quality of long-term AEDs in Lao PDR. METHOD: A cross-sectional study was performed in both public and private drug supply chains in urban and rural areas in Lao PDR. Data on AEDs availability and price were obtained through drug suppliers. Affordability was estimated as the number of day wages the lowest-paid government employee must work to purchase a monthly treatment. Samples of AEDs were collected, and the quality of AEDs was assessed through Medicine Quality Assessment Reporting Guidelines. RESULTS: Out of 237 outlets visited, only 50 outlets (21.1% [95% CI 16.1-26.8]) had at least one AED available. The availability was significantly different between urban (24.9%) and rural areas (10.0%), P = .017. Phenobarbital 100 mg was the most available (14.3%); followed by sodium valproate 200 mg (9.7%), phenytoin 100 mg (9.7%), and carbamazepine 200 mg (8.9%). In provincial/district hospitals and health centers, AEDs were provided free of charge. In other healthcare facilities, phenytoin 100 mg and phenobarbital 100 mg showed the best affordability (1.0 and 1.2 day wages, respectively) compared to carbamazepine 200 mg (2.3 days) and other AEDs. No sample was identified as counterfeit, but 15.0% [95% CI 7.1-26.6] of samples were classified as of poor quality. SIGNIFICANCE: We quantified and qualified the various factors contributing to the high treatment gap in Lao PDR, adding to diagnostic issues (not assessed here). Availability remains very low and phenobarbital which is the most available and affordable AED was the worst in terms of quality. A drug policy addressing epilepsy treatment gap would reduce these barriers.

Herbal medicine for epilepsy seizures in Asia, Africa and Latin America: A systematic review.

RELEVANCE: More than 70 million people suffer epilepsy worldwide. Low availability of anti-epileptic drugs, side-effects and drug-resistant epilepsy affect the quality of life of persons with epilepsy in countries with a poorly developed health system. Herbal medicine is frequently used for this neurological condition. OBJECTIVES: The main objective was to provide a detailed analysis of Herbal Medicine used for neurological conditions related with epilepsy in Asia, Africa and Latin America. More broadly, this study aims to highlight species with assessed efficacy (cross-cultural use, pharmacological effects on models of epileptic seizures) and safety (toxicological data in laboratory) information, in order to point out species of interest for further studies. A critical assessment of models used in pharmacological evaluations was done. MATERIALS AND METHODS: The systematic search for Herbal Medicine treatments for epilepsy was performed considering all the articles published until February 2017 through three scientific databases. It was made with MeSH terms and free text defining the epilepsy seizures and plant species. We included studies carried out in Asia, Africa and Latin America. All articles reporting the use of Herbal Medicine to treat epilepsy seizures and/or their pharmacological evaluation were retained for further analysis. RESULTS: The search yielded 1886 articles, from 30 countries. Hundred and six articles published between 1982 and 2017 were included, corresponding to a total of 497 use reports for 351 plant species belonging to 106 families. Three hundred and seventy seven use reports corresponding to 264 species in ethnopharmacological surveys and 120 evaluation reports corresponding to 107 species were noted. Twenty-nine reports, for 29 species, combined both ethnopharmacological and pharmacological evaluation. Fifty eight studies originated from Africa, 35 studies from Asia and 18 from Latin America. Highest use report was noted for rhizomes of Acorus calamus L. (12 use report in 1 country) and leaves of Bacopa monnieri (L.) Wettst. (8 use report in 2 countries). Therefore these species display the highest use convergence. Regarding pharmacological evaluation most studied species were: Leonotis leonurus (L.) R.Br. (4 evaluation reports in 1 country), Uncaria rhynchophylla (Miq.) Miq. ex Havil. (3 evaluation reports in 2 countries) and Calotropis gigantea (L.) Dryand. (3 evaluation reports in 1 country). In vivo models of chronic epilepsy were more relevant than in vitro models or chemical models inducing acute seizures for pharmacological assessment. CONCLUSION: Species with the highest use report were not those with pharmacological evaluation. It will be pertinent to assess the pharmacological effects and safety of medicinal plants used mostly by traditional healers on predictive models of seizures.

Quality of antiepileptic drugs in Vietnam.

The purpose of this research was to evaluate the quality of anti-epileptic drugs (AEDs) in a central city of South Vietnam. A cross-sectional study was conducted in all the outlets for AEDs. Out of 33 pharmacies 54% had AEDs. Where the drugs were available, 89% of the pharmacies, 10 units were purchased, choosing the cheapest ones. The information on the packaging, the galenic form and the aspect of the drug were studied. Each sample's tablet was weighted and was considered satisfactory if it was within +/-10% of the average. A HPLC method was used for dosing the active ingredient (AI), which was considered satisfactory within +/-10% of the theoretical value. Eight samples were based on carbamazepin and eight on phenytoin. None of the 16 samples collected were past their expiring date. Tablets were homogeneous in shape, dimension and color. The uniformity of weight was satisfactory but the AI results were alarming for Carbamazepin and more often for Phenytoin. Only 35% of the tablets were correctly dosed. Because of differences of sensitivities of AEDs to storage conditions, environmental factors (heat, light and humidity) could be responsible for this result. Best results were achieved in structures where storage seemed to be better. The influence of storage conditions must be further studied to confirm this conclusion.

Herbal medicine uses to treat people with epilepsy: A survey in rural communities of northern Peru.

ETHNOPHARMACOLOGICAL RELEVANCE: Epilepsy affects 150,000 people in Peru, with a prevalence of 16.6/1000 and a treatment gap of 75%. Herbal medicine (HM) is widely used in this country. AIM OF THE STUDY: We aimed to assess the use of plants in a rural community in northern Peru as part of therapeutic strategies for people with epilepsy (PWE). MATERIALS AND METHODS: The study was a cross-sectional observational and descriptive study. The inclusion criteria for people with epilepsy were 2 years of age and over, having lived in the study area for at least 3 months and a confirmed diagnosis of epilepsy by a neurologist. The information was gathered through structured interviews using a survey questionnaire. Botanical species used by people with epilepsy or traditional healers were collected and identified. RESULTS: Out of the 228 people with epilepsy included, 60.0% had used herbal remedies and 54.8% both herbal medicine and anti-epileptic drugs. The traditional healer was the first practitioner consulted by 45.2% of people with epilepsy. Sixty-six species have been mentioned by the people with epilepsy and traditional healers on the treatment of epilepsy. Carbamazepine was the most prescribed anti-epileptic drug with 33.2% of prescriptions. CONCLUSIONS: This study was the first to measure a percentage of use of herbal medicine for epilepsy in Peru. It would be interesting to conduct a pharmacological evaluation of the most commonly used species on epileptic models to validate and secure their use.

Availability and costs of antiepileptic drugs and quality of phenobarbital in Vientiane municipality, Lao PDR.

PURPOSE: In developing countries, availability and quality of drugs are critical factors for effective management and control of epilepsy. This study investigated the availability and costs of antiepileptic drugs (AEDs), and the quality of phenobarbital in Vientiane Municipality, Lao PDR. METHODS: In March 2004, we enrolled all pharmacies (categories I and II) of four central districts of Vientiane eligible to sell AEDs. Two hundred and eight pharmacies of category III (75.1% of all registered pharmacies) were excluded as the sale of AEDs was not authorized. All pharmacists were interviewed with a standard questionnaire. Whenever phenobarbital was available, a sample was purchased and assayed by liquid chromatography. Phenobarbital was defined as being of correct quality if the active substance average content corresponded to +/-15% of the indicated amount. RESULTS: 66 pharmacies were enrolled (13 and 45 of categories I and II, respectively, and 8 hospital pharmacies). Six generics of AEDs were found (phenobarbital, phenytoin, valproic acid, clonazepam, carbamazepine, diazepam) and all pharmacies sold at least 1 AED. The 2 most widely available drugs were diazepam (5 mg) and phenobarbital (100 mg), present in 87.9 and 53.0% of the pharmacies, respectively. All 34 phenobarbital samples examined showed a correct concentration of the active compound. However, the concentration of phenobarbital 100 mg tablets produced in Lao PDR (mean concentration 94.7 mg) was significantly lower (p = 0.005) than the imported equivalent (mean concentration 99.7 mg). The direct drug costs of a yearly treatment with phenobarbital were estimated to be at least 25.2 USD. CONCLUSIONS: A variety of AEDs are present. Their availability, particularly of phenobarbital, is restricted to higher-category pharmacies and within those it is rather limited. To meet the costs of AEDs in this setting is a major challenge for people with epilepsy. However, the quality of the available phenobarbital was rather satisfactory.

How to reduce the treatment gap for people with epilepsy in resource-limited settings by innovative galenic formulations: A review of the current situation, overview of potential techniques, interests and limits.

Epilepsy is a chronic neurological disease affecting more than 69 million people worldwide, nearly 90% of them in low and middle-income countries (LMICs). In those countries, only four major antiepileptic drugs are commonly used: phenobarbital, carbamazepine, sodium valproate and phenytoin. There are also problems with the accessibility, availability and quality of drugs. The main objective was to review the literature concerning "long" sustained-release formulations of AEDs that have the potential to reduce the number of administrations and help overcome problems of compliance, accessibility and the treatment gap. The main endpoint was a releasing of the active ingredient over more than 24h. We also assessed the feasibility and acceptability in resource-limited settings. Two drugs were found in unconventional release formulations: carbamazepine and sodium valproate; but they were not "long" sustained release because they required administration once a day. Several techniques were available, including: esterification, transdermal devices, liposomes and polymeric devices preformed or formed in situ. In situ methods for the preparation of injectable biodegradable microparticles or implants for controlled delivery seemed best suited to the objective. Furthermore, they appear to fulfil the requirements of feasibility and cost. Sodium valproate appeared as well to be a relevant candidate for a "long" sustained release formulation that would improve access to medicines for people with epilepsy in resource-limited settings. .

Availability and cost of major and first-line antiepileptic drugs: a comprehensive evaluation in the capital of Madagascar.

BACKGROUND: The prevalence of epilepsy is high in Madagascar (23.5/1000), as is the treatment gap (estimated at 92 %). The health system of the country is underfunded; some AEDs are used, and the national drug policy does not encourage price regulation or the administration of generic agents. We conducted a cross-sectional study to assess the availability and cost of solid oral AED formulations in Antananarivo, capital of Madagascar. Data were gathered from all officially registered pharmacies (according to the drug agency list, updated in 2015) by means of telephone interviews lasting no more than 10 min and conducted by a native Malagasy speaker. With regard to other sources (hospitals, illicit sales) data were obtained at specific visits. The study received ethical approval from the Madagascar Ministry of Health. FINDINGS: A total of 91 of 100 pharmacies (the nine not included were because of an inoperative phone number), two of three public hospitals, and two illegal outlets were investigated. Sodium valproate was available in 84.6 % of the pharmacies, while carbamazepine and phenobarbital were available in 68.1 % and 36.3 % of the pharmacies, respectively, but phenytoin was not available in any supply chain. There were more originator brands than generic formulations, with a higher cost (range 20.3-81.1 %, median 40.7 %) compared to the equivalent generic. The public system had only a very limited choice of AED, but offered the lowest costs. Illicit sources were more expensive by 54.3 % for carbamazepine and 62.5 % for phenobarbital. Concerning the annual cost of treatment, the average percentage of the gross national income per capita based on the purchasing power parity was 29.8 %/19.0 % (brand/generic) for sodium valproate, 16.4 %/7.3 % (brand/generic) for carbamazepine, 8.9 %/5.1 % (brand/generic) for phenobarbital. CONCLUSIONS: The main sources of AEDs were private pharmacies, but the stocks held were low. The financial burden was still important in the capital of Madagascar, mainly the consequence of a highly developed private sector at the expense of the public sector. Although sodium valproate remains the most expensive solution, it still remains the most available instead of phenobarbital. The most striking feature of this study concerns the cost of AEDs in the informal sector, mostly used because they are deemed to provide less costly drugs, the opposite was observed there. The assessment of the cost and availability of medicines was easily and quickly implemented. It provided a relevant focus of the situation in areas difficult to investigate, in terms of road network and geographical situation.