Certains médicaments agissant sur le système nerveux central ont comme particularité d'entraîner parfois des troubles de l'abus et de la dépendance. Ces effets indésirables sont étudiés avant la mise sur le marché du médicament, lors des essais cliniques et non cliniques. Cependant, l'abus est un phénomène plurifactoriel, influencé par des facteurs liés à la substance, individuels et environnementaux. Ces déterminants ne peuvent pas être pris en compte avant la mise sur le marché du médicament et rendent essentielle la surveillance de l'abus de médicaments après la mise sur le marché, par l'intermédiaire notamment d'études pharmacoépidémiologiques. Une surveillance efficace de l'abus de médicament implique de comprendre les déterminants de l'abus et ses mécanismes sous-jacents. L'objectif de ce travail de thèse est donc d'analyser des déterminants de l'abus en utilisant des approches pharmacoépidémiologiques. Le premier travail a été d'établir un état des lieux des systèmes de surveillance de l'abus de médicaments en France et à l'étranger (publication n°1). Nous avons par la suite utilisé une enquête en population auprès des patients fréquentant des centres de soins spécialisés pour les usagers de drogues, afin d'étudier l'impact de la mise sur le marché de génériques de la Buprénorphine Haut Dosage (BHD) sur l'abus de BHD (publication n°2). Cette étude nous a permis d'analyser l'influence de la formulation sur l'abus de médicaments. L'exploration de la localisation géographique comme déterminant de l'abus n'a jamais été réalisée en France. / Some central nervous system medications sometimes lead to abuse or dependence. These adverse effects are assessed using premarketing studies such as clinical trials and non clinical studies. However, abuse is influenced by many factors, substance-related, individual and environmental. These factors could not be taken into account in premarketing studies. Thus, postmarketing surveillance of prescription drug abuse, using in particular pharmacoepidemiologic studies is essential. An efficient postmarketing surveillance requires the comprehension of abuse-related factors and underlying mechanisms. The purpose of this work was to analyse prescription drug abuse factors using pharmacoepidemiological approaches. The first part of this work was an overview of postmarketing surveillance systems dedicated to prescription drug abuse in France and in foreign countries (publication n°1). Then, we used a survey in population of patients seen in care centres dedicated to drug users in order to assess the impact of buprenorphine maintenance generic introduction on buprenorphine maintenance abuse (publication n°2). This study allows to observe the influence of the formulation on prescription drug abuse. The factors related to geographic area have never been explored in France, at our knowledge. Therefore, we studied geographic variations of prescription opioid abuse in three regions of southern France, Provence-Alpes-Côte d'Azur-Corse, Rhône-Alpes and Midi-Pyrénées using a pharmacoepidemiologic approach based on prescription drug reimbursement database, the doctor shopping method (publication n°3).

Background: In paediatrics, the limited documentation to guide medication, the lack of suitable dosage forms, and the continuous development in childhood present a scenario where safety of medication is a particular challenge. Aim: To explore reported adverse drug reactions (ADRs) and the challenges in prescribing and administering medicines in paediatrics, in order to identify and suggest areas needing international surveillance within medication safety and improvement in the clinical setting. Methods: Four exploratory studies were conducted. Worldwide reporting of suspected ADRs (individual case safety reports, ICSR) with ages 0-17 years were examined overall. Twenty published case reports and ICSRs for adolescents, who developed a rare and incompletely documented ADR (rhabdomyolysis) during antipsychotic medicine use, were analysed in-depth. Prescribed doses of anti-inflammatory medicines were studied in a UK electronic health record database. Transcribed focus group interviews with 20 registered nurses from four paediatric wards in Sweden were analysed for factors that may promote or hinder safe medication practices. Descriptive statistics, multiple regression, and content analyses were used. Results: Although, skin reactions and anti-infective medicines were most frequently reported, and more reported in paediatric patients than in adults, medication errors and adverse reactions related to psychostimulant medicines were reported with increased frequency during 2005 to February 2010. The in-depth case analysis emphasised the need for increased vigilance following changes in patients’ medicine regimens, and indicated that ICSRs could contribute with clinically valuable information. Prescribed dose variations were associated with type of dosage form. Tablets and capsules were prescribed with a higher dose than liquid dosage forms. Six themes emerged from the interviews: preparation and administration was complex; medication errors caused considerable psychological burden; support from nurse colleagues was highly valued; unfamiliar medication was challenging; clear dose instructions were important; nurses handling medications needed to be accorded higher priority. Conclusions: Age-specific screening of ICSRs and the use of ICSRs to enhance knowledge of ADRs and medication errors need to be developed. Access to age-appropriate dosage forms is important when prescribing medicines to children. To improve medication safety practices in paediatric care, interdisciplinary collaborations across hospitals on national or even global levels are needed.