L’épilepsie reste un problème mondial de santé publique. Au Liban, un manque de données épidémiologiques sur cette maladie reste le problème majeur contre la mise en oeuvre des interventions.L’objectif de cette étude était d’améliorer les connaissances sur les déterminants de l’épilepsie, la prise en charge médicamenteuse et la qualité de vie des personnes vivant avec l’épilepsie au Liban. Les objectifs de recherche étaient d’identifier les facteurs associésà l’épilepsie dans la population Libanaise, d’évaluer l’adéquation des molécules prescrites avec les recommandations internationales, d’identifier et de décrire les problèmes liés aux médicaments antiépileptiques, d’évaluer les attitudes face au traitement antiépileptique,d’identifier les facteurs associés aux mauvaises attitudes et au mauvais contrôle de l’épilepsie, d’évaluer la qualité de vie et le stigma des personnes épileptiques et d’identifier les facteurs associés à ces deux paramètres.Une étude cas-témoins a été réalisée pour l’identification des facteurs associés à l’épilepsie. Pour les questions d’évaluation du traitement, d’attitudes, de la qualité de vie et du stigma, des études transversales ont été réalisées, au niveau de Beyrouth et ses banlieues. Unquestionnaire standardisé a été utilisé pour la collecte des données de toutes les personnes vivant avec l’épilepsie recrutées, à partir des différents types de structures de santé où les neurologues pouvaient être présents.Les tumeurs cérébrales (OR=4,8; 95%IC:1,9-11,7; p=0,001), les accidents vasculaires cérébraux (OR=4,4; 95%IC:2,4-8,1; p<0,001), la méningite (OR=2,7; 95%IC:1,1-6,6; p=0,03), les traumatismes crâniens (OR=2,3; 95%IC:1,6-3,2; p<0,001), l’accouchement par césarienne (OR=2,0; 95%IC:1,3-3,1; p=0,002), la consanguinité (OR=1,6; 95%IC:1,1-2,3; p=0,008) et la dépression (OR=1,51; 95%IC:1,05-2,19; p=0,03) étaient parmi les facteurs associés à l’épilepsie. Au total, 5,9% des prescriptions des antiépileptiques n’étaient pas conformes aux recommandations, 50% de la population présentaient des interactions médicamenteuses et 51% présentaient des effets indésirables liés aux antiépileptiques. Près de 32,4% des personnes épileptiques avaient des attitudes favorables face à la prise des antiépileptiques. La dépression (OR=0,4; 95%IC 0,2-0,9; p=0,04) et le lourd fardeau économique (OR=0,2; 95%IC 0,1-0,4; p<0,001) étaient les principaux facteurs limitant ces attitudes favorables. Les personnes vivant avec l’épilepsie présentaient globalement une bonne qualité de vie, mais étaient assez stigmatisées (47,8%). La dépression, l’apparition des effets indésirables, la polymédication et la stigmatisation étaient associés à une mauvaise qualité de vie des personnes épileptiques.Des comportements préventifs devraient être pratiqués auprès des facteurs évitables associés à l’épilepsie. La prescription des médicaments génériques à bas prix, l’adaptation des schémas thérapeutiques simples, la prise en compte les différentes maladies présentes et l’explication aux patients la posologie du traitement ainsi que les effets indésirables possibles, sont des démarches à adopter qui visent à améliorer les attitudes et la qualité de vie des patients. Des formations éducatives pour les personnes épileptiques constitueraient une amélioration de leurs connaissances sur la maladie et le traitement. / Epilepsy remains a global public health problem. In Lebanon, a lack of epidemiological data on this disease remains the major problem against the implementation of interventions.The objective of this study was to improve knowledge on the determinants of epilepsy, drug management and quality of life for people living with epilepsy in Lebanon. The research objectives were to identify the factors associated with epilepsy in the Lebanese population, to assess the adequacy of the prescribed molecules with international recommendations, to identify and describe the problems related to antiepileptic drugs and, to evaluate attitudes towards antiepileptic treatment by identifying factors associated with poor attitudes and poor control of epilepsy, assessing the quality of life and stigma of epileptic persons and identifying the factors associated with these two parameters.A case-control study was conducted to identify factors associated with epilepsy at the level of Beirut and its suburbs. For questions of evaluation of treatment choice, attitudes, quality of life and stigma, cross-sectional studies were conducted with people of epilepsy recruited for a case-control study. A standardized questionnaire was used to collect data from all persons living with epilepsy recruited, from the different types of health structures where neurologists could be present.Brain tumors (OR = 4.8, 95% CI: 1.9-11.7, p = 0.001), strokes (OR = 4.4, 95% CI: 2.4-8.1; p <0.001), meningitis (OR = 2.7, 95% CI: 1.1-6.6, p = 0.03), head trauma (OR = 2.3, 95% CI 1.6 -3.2, p <0.001), cesarean delivery (OR = 2.0, 95% CI: 1.3-3.1, p = 0.002), inbreeding (OR = 1.6, 95% CI: 1.1-2.3, p = 0.008) and depression (OR = 1.51, 95% CI: 1.05-2.19, p = 0.03) were among the factors associated with epilepsy. About 5.9% of prescriptions for antiepileptics were not compliant with the recommendations, 50% of the population presented drug interactions and 51% had side effects related to antiepileptic drugs. Nearly 32.4% of people with epilepsy had favorable attitudes about taking antiepileptic drugs. Depression (OR = 0.4, 95% CI 0.2-0.9, p = 0.04), and the heavy economic burden (OR = 0.2, 95% CI 0.1-0.4; <0.001) were the main factors limiting these favorable attitudes. In general, people living with epilepsy had a good quality of life, but were highly stigmatized (47.8%). Depression, onset of adverse effects, polypharmacy and stigma were associated with a low quality of life of people with epilepsy.Preventive behaviors should be practiced for avoidable factors associated with epilepsy. Prescription of generic drugs at low prices, adaptation of simple treatment regimens, considering comorbidities and explanation to the patients of the dosage of the treatment as well as the possible undesirable effects, are steps to adopt in order to improve the attitudes and quality of life of patients. Educational training for people with epilepsy could improve their knowledge of the disease and treatment.

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Dans le cadre du programme commun d’études pharmaco-épidémiologiques de la caisse nationale de l'assurance maladie et de l’agence nationale de sécurité du médicament, visant à évaluer l'impact sanitaire en France de l'exposition in utero à l’acide valproïque à partir des bases de données médico-administratives (BDMA) françaises, l’objectif de cette thèse était d’étudier l’utilisation des antiépileptiques pendant la grossesse et les risques de malformations congénitales et de troubles neuro-développementaux associés chez l’enfant. Le premier volet de cette thèse a consisté à formaliser et publier un algorithme d’identification des grossesses spécifiquement adapté aux BDMA françaises. L’application de cet algorithme à la description de l’utilisation des antiépileptiques pendant la grossesse a permis d’estimer à 6,7‰ la prévalence de l’utilisation des antiépileptiques pendant la grossesse et de montrer une baisse de l’utilisation des antiépileptiques de première génération, en particulier de l’acide valproïque, au bénéfice des antiépileptiques de deuxième génération entre 2007 et 2014. Dans le deuxième volet de cette thèse, l’exposition in utero à l’acide valproïque a été retrouvée associée à une augmentation du risque d’un grand nombre des malformations congénitales majeures (MCM) étudiées, avec une relation dose-effet pour les MCM les plus fréquentes, et l’exposition in utero au topiramate à une augmentation du risque de fentes oro-faciales. Des signaux relatifs à la prégabaline, au clonazépam et au phénobarbital ont aussi été identifiés. Dans le troisième volet de cette thèse, l’exposition in utero à l’acide valproïque a été retrouvée associée à une augmentation du risque de chacun des événements neuro-développementaux précoces étudiés versus lamotrigine, avec une relation dose-effet, à l’inverse des autres antiépileptiques. La réalisation d’études pharmaco-épidémiologiques à partir des BDMA françaises a permis aux autorités sanitaires de fournir rapidement des données sur l’utilisation des antiépileptiques pendant la grossesse en France. La réalisation de ces études a aussi permis de participer à l’enrichissement de la littérature observationnelle internationale sur les conséquences de l’exposition in utero aux antiépileptiques pour l’enfant à naitre. / The works of this thesis have been carried out within a programme of pharmacoepidemiological studies initiated by the National Agency of Medicine and Health Product Safety (ANSM) and the National Health Insurance fund (Cnam) in order to evaluate the public health situation in relation to prenatal exposure to valproic acid in France on the basis of the French health care databases. The objective of this thesis was to study antiepileptic drug (AED) use during pregnancy and the risks of congenital malformations and neurodevelopmental disorders associated with prenatal exposure to these drugs. In a first study, we developed an algorithm to identify pregnancy episodes and related outcomes using the French health care claims databases and applied it to study AED use during pregnancy between 2007 and 2014. Over the study period, 6.7 per 1000 pregnancies were exposed to an AED. The use of newer AEDs increased concomitantly with the decreased use of valproic acid and the other older AEDs. In a second study, prenatal exposure to valproic acid was found to be associated with a wide range of malformations among those investigated, with a dose-response relationship for half of them, and prenatal exposure to topiramate with an increased risk of cleft lip with or without cleft palate. Signals concerning pregabalin, clonazepam and phenobarbital have also been identified. In a third study, prenatal exposure to valproic acid was found to be associated with increased risks of all early neurodevelopmental outcomes investigated compared with lamotrigine, with a dose-response relationship. Prenatal exposure to the other AEDs was not associated with an increased risk of any of these neurodevelopmental outcomes versus lamotrigine. Conducting pharmacoepidemiological studies based on the French health care databases enabled the health authorities to rapidly provide data on the use of AED during pregnancy in France. It also brought additional evidence to the international observational literature on the consequences of prenatal exposure to AEDs for the unborn child.

The prevalence of epilepsy in society is general knowledge; however the impact on social activity as well as other daily factors are not always fully recognised. Epilepsy frequently poses a problem with regard to work–related activities (Heaney, 1999:44). Moran et al. (2004:425) indicated that the major impacts of epilepsy on life were work and school difficulties, driving prohibition, psychological and social life of which restriction of work or schooling has the greatest impact on epileptic’s life. In all cases the type, severity, and frequency of the seizures as well as the age would be relevant. Davis et al. (2008:451) established that 39% of all epileptics were not adherent to their therapy and in patients over 65 this was even higher at 43 %. Non–adherence with antiepileptic medicine appears to be related to increased health care utilisation and costs and may also lead to an increased probable accidents or injuries The general objective was to investigate anti–epileptic medicine prescribing patterns and treatment cost in a section of the private health care sector by using a medicine claims database. A retrospective drug utilisation study was done on the data claims from a pharmacy benefit management company for the study period 1 January 2005 to 31 December 2008. Firstly epilepsy was investigated in order to understand the disease and to determine the prevalence and treatment thereof. It was found that epilepsy is still one of the most common neurological conditions and according to the findings, 2 out of every hundred patients were using anti–epileptic medicine in this section of the private health care sector. To make this condition socially more acceptable and understandable, public education for special target groups concerning the disorder must be conducted as well as employment training programmes for people with epilepsy themselves. The utilisation patterns of anti–epileptic drugs were reviewed, analysed and interpreted. It was determined that anti–epileptic medicine items are relatively expensive with regards to other medicine items on the total database. With regard to gender, more females are using anti–epileptic medicine than males on the database. The largest age group of patients using anti–epileptic medicine, is between > 40 years and <= 64 years of age. It was also clear that prevalence increase as age increase. With regard to the different prescribers, the number of items prescribed by a general practitioner was almost double that of the other prescribers. It was further established that newer anti–epileptic medicines are more expensive than older anti–epileptic medicine according to the cost per tablet in this section of the private health care sector. Carbamazepine and valproate were the two active ingredients that were most frequently prescribed as a single item on a prescription. After a cost–minimisation analysis was done, R134 685.66 could have been saved when generic substitution was implemented. The refill–adherence rate decreased as age increased. Only 30.46% of the trade names was refilled according to acceptable refill–adherence rates. The refill–adherence rate according to active ingredient showed that medicine items containing, phenobarbitone/vit B or gabapentin had the lowest unacceptable refill–adherence rate. The limitations for this study was stipulated and recommendations for further research regarding anti–epileptic medicine were also made. / Thesis (M.Pharm (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2011.

The prevalence of epilepsy in society is general knowledge; however the impact on social activity as well as other daily factors are not always fully recognised. Epilepsy frequently poses a problem with regard to work–related activities (Heaney, 1999:44). Moran et al. (2004:425) indicated that the major impacts of epilepsy on life were work and school difficulties, driving prohibition, psychological and social life of which restriction of work or schooling has the greatest impact on epileptic’s life. In all cases the type, severity, and frequency of the seizures as well as the age would be relevant. Davis et al. (2008:451) established that 39% of all epileptics were not adherent to their therapy and in patients over 65 this was even higher at 43 %. Non–adherence with antiepileptic medicine appears to be related to increased health care utilisation and costs and may also lead to an increased probable accidents or injuries The general objective was to investigate anti–epileptic medicine prescribing patterns and treatment cost in a section of the private health care sector by using a medicine claims database. A retrospective drug utilisation study was done on the data claims from a pharmacy benefit management company for the study period 1 January 2005 to 31 December 2008. Firstly epilepsy was investigated in order to understand the disease and to determine the prevalence and treatment thereof. It was found that epilepsy is still one of the most common neurological conditions and according to the findings, 2 out of every hundred patients were using anti–epileptic medicine in this section of the private health care sector. To make this condition socially more acceptable and understandable, public education for special target groups concerning the disorder must be conducted as well as employment training programmes for people with epilepsy themselves. The utilisation patterns of anti–epileptic drugs were reviewed, analysed and interpreted. It was determined that anti–epileptic medicine items are relatively expensive with regards to other medicine items on the total database. With regard to gender, more females are using anti–epileptic medicine than males on the database. The largest age group of patients using anti–epileptic medicine, is between > 40 years and <= 64 years of age. It was also clear that prevalence increase as age increase. With regard to the different prescribers, the number of items prescribed by a general practitioner was almost double that of the other prescribers. It was further established that newer anti–epileptic medicines are more expensive than older anti–epileptic medicine according to the cost per tablet in this section of the private health care sector. Carbamazepine and valproate were the two active ingredients that were most frequently prescribed as a single item on a prescription. After a cost–minimisation analysis was done, R134 685.66 could have been saved when generic substitution was implemented. The refill–adherence rate decreased as age increased. Only 30.46% of the trade names was refilled according to acceptable refill–adherence rates. The refill–adherence rate according to active ingredient showed that medicine items containing, phenobarbitone/vit B or gabapentin had the lowest unacceptable refill–adherence rate. The limitations for this study was stipulated and recommendations for further research regarding anti–epileptic medicine were also made. / Thesis (M.Pharm (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2011.