L’émergence de l’utilisation du méthylphénidate (MPH; Ritalin) par des étudiants universitaires afin d’améliorer leur concentration et leurs performances universitaires suscite l’intérêt du public et soulève d’importants débats éthiques auprès des spécialistes. Les différentes perspectives sur l’amélioration des performances cognitives représentent une dimension importante des défis sociaux et éthiques autour d’un tel phénomène et méritent d’être élucidées. Ce mémoire vise à examiner les discours présents dans les reportages internationaux de presse populaire, les discours en bioéthique et en en santé publique sur le thème de l’utilisation non médicale du méthylphénidate. Cette recherche a permis d’identifier et d’analyser des « lacunes » dans les perspectives éthiques, sociales et scientifiques de l’utilisation non médicale du méthylphénidate pour accroître la performance cognitive d’individus en santé. Une analyse systématique du contenu des discours sur l’utilisation non médicale du méthylphénidate pour accroître la performance cognitive a identifié des paradigmes divergents employés pour décrire l’utilisation non médicale du méthylphénidate et discuter ses conséquences éthiques. Les paradigmes « choix de mode de vie », « abus de médicament » et « amélioration de la cognition » sont présents dans les discours de la presse populaire, de la bioéthique et de la santé publique respectivement. Parmi les principales différences entre ces paradigmes, on retrouve : la description de l’utilisation non médicale d’agents neuropharmacologiques pour l’amélioration des performances, les risques et bénéfices qui y sont associés, la discussion d’enjeux éthiques et sociaux et des stratégies de prévention et les défis associés à l’augmentation de la prévalence de ce phénomène. La divergence de ces paradigmes reflète le pluralisme des perceptions de l’utilisation non médicale d’agents neuropharmacologiques Nos résultats suggèrent la nécessité de débats autour de l’amélioration neuropharmacologique afin de poursuivre l’identification des enjeux et de développer des approches de santé publique cohérentes. / The non-medical use of neuropharmaceuticals has sparked ethical debates. For example, there is mounting evidence that methylphenidate (MPH; Ritalin) is being used by healthy university students to improve concentration, alertness, and academic performance, a phenomenon known as cognitive enhancement. The different perspectives on the ethics of cognitive enhancement represent an important dimension of the social and ethical challenges related to such practices but have yet to be examined thoroughly. This thesis aimed to assess existing positive and negative reports in international print media, bioethics literature, and public health literature on the use of MPH to identify and analyze gaps in the ethical, social, and scientific perspectives about the non-medical use of MPH for cognitive enhancement in healthy individuals. A systematic content analysis of discourses on the non-medical use of methylphenidate for cognitive enhancement identified divergent frameworks employed to describe the non-medical use of methylphenidate and discuss its ethical implications: The frameworks of “lifestyle choice”, “prescription drug abuse” and “cognitive enhancement” are present in print media, bioethics, and public health discourses respectively. Important differences between frameworks include the description of the non-medical use of neuropharmaceuticals for cognitive enhancement, associated risks and benefits, discussion of ethical and social issues surrounding the phenomenon and the prevention strategies and challenges to the widespread use of neuropharmaceuticals for cognitive enhancement. Diverging frameworks reflect pluralism in perceptions if the non-medical use of neuropharmaceuticals for cognitive enhancement. At this time, unacknowledged pluralism and implicit assumptions about cognitive enhancement may impede public health interventions and ethics discussions.

Introdução. Desde 2006 a Assistência Farmacêutica da Coordenação de Atenção Básica da Secretaria Municipal da Saúde de São Paulo (SMS-SP) recebeu, por ano, em média, cerca de 125 solicitações de medicamentos não constantes da Relação Municipal de Medicamentos Essenciais - Remume-SP, antes de 2011, e a partir deste ano 250 solicitações, demanda que ainda não foi objeto de estudo para se conhecer de forma sistemática sua natureza e as implicações quanto à regulação sob o marco do acesso racional a fármacos.Objeto do estudo. Avaliou-se as solicitações de produtos farmacêuticos não constantes da Remume-SP, de 2008 a 2013. Método. Análise de documentos, segundo a prática médica com base em provas científicas, de solicitação de medicamentos não disponíveis na Remume-SP decorrente de prescrição médica por meio de Formulário de Justificação para aquisição de medicamentos não constantes da Remume-SP, e oriunda de serviços da SMS-SP no período do estudo. Resultado. Analisou-se os processos advindos de 1.174 solicitações, de 2008 a 2013, que levou à não autorização de aquisição de 58,9 por cento (N=692), pelos seguintes motivos: 1- não há prova suficiente na literatura, 15 (17 por cento ); 2- consta da Remume-SP, 11 (1 por cento ); 3- disponível na SES-SP, 56 (8 por cento ); 4- informação clínica insuficiente, 151 (22 por cento ); 5- fornecimento CACON, 10 (1 por cento ); 6- fármaco desnecessário, 18 (3 por cento ); 7- indicação de outro fármaco, ou outra concentração do fármaco solicitado, ou outro acessório, ou ainda outro tratamento (cirúrgico, por exemplo), 169 (24 por cento ); 8- solicitação de parecer de área técnica relacionada, 62 (9 por cento ); 9- paciente não acompanhado em serviço municipal de saúde, 12 (2 por cento ); 10- erro de prescrição, 39 (6 por cento ); 11- não há prova suficiente na literatura e informação clínica insuficiente, 49 (7 por cento ). As razões do não acolhimento do pedido do médico estão apresentadas em exemplos, das principais categorias farmacêuticas, considerando-se a variedade das solicitações, todos documentados pela literatura e extraídos dos processos de solicitações. Faz-se recomendações para a melhoria da regulação da prescrição farmacológica e possíveis ajustes na relação entre os formuladores e executores de políticas do município e os conjuntos dos prescritores, tendo como centro das preocupações a segurança do usuário do SUS e a melhoria do acesso a fármacos com a melhor relação benefício-risco. / Introduction. Since 2006, the Assistência Farmacêutica da Coordenação de Atenção Básica da Secretaria Municipal da Saúde de São Paulo (SMS-SP) (Coordination on Pharmaceutical Care of the Municipal Health Secretariat of São Paulo) received about 125 requests yearly, on average,before2011, and after this year, 250 requests yearly for drugs not listed in the Relação Municipal de Medicamentos Essenciais (Municipal Register of Essential Medicines) REMUME-SP, demand whose object of study was not known in a systematic nature and whose implications regarding regulation were not studied under the framework of rational access to drugs. Object of the study. Evaluate requests for pharmaceuticals not listed in REMUME-SP, from 2008 to 2013. Method. Analysis of documents, according to medical practice based on scientific evidence, of request for products not available in REMUMESP, prescribed via Form Justification for the purchase of drugs not listed in REMUME - SP, and generated from SMS-SP, during the studied period. Results. Analysis of processes arising from 1.174 requests, 2008 to 2013, has brought to the non-permit of acquisition of 58,9 per cent (N=692), due to the following reasons: 1- there is not enough evidence in the literature, 15 (17 per cent ); 2- listed in Remume-SP, 11 (1 per cent ); 3- available in SES-SP, 56 (8 per cent ); 4- insufficient clinical information, 151 (22 per cent ); 5- supplied by CACON, 10 (1 per cent ); 6- unnecessary drug, 18 (3 per cent ); 7- indication of other drug, or other concentration of the requested drug, or other device, or still other treatment (surgical, for example), 169 (24 per cent ); 8- solicitation of report from related technical area, 62 (9 per cent ); patient not cared by the municipal health service, 12 (2 per cent ); 10- prescription mistakes, 39 (6 per cent ); 11- there is not enough evidence in the literature and not sufficient clinical information, 49 (7 per cent ). The reasons of the non-acceptance of the medical requests are presented in examples, from the main pharmaceutical categories which were requested, considering its variety, all documented in the literature and extracted from the processes of solicitation. Recommendations on the improvement of medical prescription are done and possible arrangements of prescription in the relationship among policy makers and executors in the municipality and the sets of prescribers, whose main concern is the safety of users of SUS and improving access to drugs with the best benefit-risk relation.

Introdução. Desde 2006 a Assistência Farmacêutica da Coordenação de Atenção Básica da Secretaria Municipal da Saúde de São Paulo (SMS-SP) recebeu, por ano, em média, cerca de 125 solicitações de medicamentos não constantes da Relação Municipal de Medicamentos Essenciais - Remume-SP, antes de 2011, e a partir deste ano 250 solicitações, demanda que ainda não foi objeto de estudo para se conhecer de forma sistemática sua natureza e as implicações quanto à regulação sob o marco do acesso racional a fármacos.Objeto do estudo. Avaliou-se as solicitações de produtos farmacêuticos não constantes da Remume-SP, de 2008 a 2013. Método. Análise de documentos, segundo a prática médica com base em provas científicas, de solicitação de medicamentos não disponíveis na Remume-SP decorrente de prescrição médica por meio de Formulário de Justificação para aquisição de medicamentos não constantes da Remume-SP, e oriunda de serviços da SMS-SP no período do estudo. Resultado. Analisou-se os processos advindos de 1.174 solicitações, de 2008 a 2013, que levou à não autorização de aquisição de 58,9 por cento (N=692), pelos seguintes motivos: 1- não há prova suficiente na literatura, 15 (17 por cento ); 2- consta da Remume-SP, 11 (1 por cento ); 3- disponível na SES-SP, 56 (8 por cento ); 4- informação clínica insuficiente, 151 (22 por cento ); 5- fornecimento CACON, 10 (1 por cento ); 6- fármaco desnecessário, 18 (3 por cento ); 7- indicação de outro fármaco, ou outra concentração do fármaco solicitado, ou outro acessório, ou ainda outro tratamento (cirúrgico, por exemplo), 169 (24 por cento ); 8- solicitação de parecer de área técnica relacionada, 62 (9 por cento ); 9- paciente não acompanhado em serviço municipal de saúde, 12 (2 por cento ); 10- erro de prescrição, 39 (6 por cento ); 11- não há prova suficiente na literatura e informação clínica insuficiente, 49 (7 por cento ). As razões do não acolhimento do pedido do médico estão apresentadas em exemplos, das principais categorias farmacêuticas, considerando-se a variedade das solicitações, todos documentados pela literatura e extraídos dos processos de solicitações. Faz-se recomendações para a melhoria da regulação da prescrição farmacológica e possíveis ajustes na relação entre os formuladores e executores de políticas do município e os conjuntos dos prescritores, tendo como centro das preocupações a segurança do usuário do SUS e a melhoria do acesso a fármacos com a melhor relação benefício-risco. / Introduction. Since 2006, the Assistência Farmacêutica da Coordenação de Atenção Básica da Secretaria Municipal da Saúde de São Paulo (SMS-SP) (Coordination on Pharmaceutical Care of the Municipal Health Secretariat of São Paulo) received about 125 requests yearly, on average,before2011, and after this year, 250 requests yearly for drugs not listed in the Relação Municipal de Medicamentos Essenciais (Municipal Register of Essential Medicines) REMUME-SP, demand whose object of study was not known in a systematic nature and whose implications regarding regulation were not studied under the framework of rational access to drugs. Object of the study. Evaluate requests for pharmaceuticals not listed in REMUME-SP, from 2008 to 2013. Method. Analysis of documents, according to medical practice based on scientific evidence, of request for products not available in REMUMESP, prescribed via Form Justification for the purchase of drugs not listed in REMUME - SP, and generated from SMS-SP, during the studied period. Results. Analysis of processes arising from 1.174 requests, 2008 to 2013, has brought to the non-permit of acquisition of 58,9 per cent (N=692), due to the following reasons: 1- there is not enough evidence in the literature, 15 (17 per cent ); 2- listed in Remume-SP, 11 (1 per cent ); 3- available in SES-SP, 56 (8 per cent ); 4- insufficient clinical information, 151 (22 per cent ); 5- supplied by CACON, 10 (1 per cent ); 6- unnecessary drug, 18 (3 per cent ); 7- indication of other drug, or other concentration of the requested drug, or other device, or still other treatment (surgical, for example), 169 (24 per cent ); 8- solicitation of report from related technical area, 62 (9 per cent ); patient not cared by the municipal health service, 12 (2 per cent ); 10- prescription mistakes, 39 (6 per cent ); 11- there is not enough evidence in the literature and not sufficient clinical information, 49 (7 per cent ). The reasons of the non-acceptance of the medical requests are presented in examples, from the main pharmaceutical categories which were requested, considering its variety, all documented in the literature and extracted from the processes of solicitation. Recommendations on the improvement of medical prescription are done and possible arrangements of prescription in the relationship among policy makers and executors in the municipality and the sets of prescribers, whose main concern is the safety of users of SUS and improving access to drugs with the best benefit-risk relation.

The overall aim of this thesis was to explore aspects of the subjective views and experiences of doctors as prescribers, focusing on responsibility for and factors of importance in achieving appropriate prescribing. To provide insights into the prescriber’s perspective the study designs were qualitative. In the first studies secondary care doctors’ perceptions of appropriate prescribing and influences in prescribing were investigated in interviews. The doctors perceived that appropriate prescribing needed continuous revision. From the perspective of the prescribers the definition of prescribing could be rephrased as: “the outcome of the recurring processes of decision making that maximises net individual health gains within society’s available resources”. Among the influences in prescribing were guidelines, colleagues and therapeutic traditions. In the subsequent studies the experiences of exchanging information regarding a patient’s drugs in an electronic patient medical record (e-PMR) shared between primary and secondary care and views of responsibility was explored, using focus groups with both primary and secondary care doctors. Considering the gap between health care levels, doctors’ views of responsibility in prescribing and exchange of information are of concern. The doctors expressed how they assume information to be in the e-PMR and active information transfer has decreased. On the other hand, they experienced an information overload in the e-PMR system. There is a need for improved and structured communication between health-care givers. Taking responsibility to review all the patient’s medications was perceived as important, but described as still not done. Lack of responsibility taken was often due to acts of omission, i.e. that doctors did not make needed changes to the list of medications due to different barriers. The barriers rested both with individual doctors and the system, but to ensure solutions that are realisable in practise, perspectives of the doctors need to be taken into consideration when overcoming those barriers.

L’émergence de l’utilisation du méthylphénidate (MPH; Ritalin) par des étudiants universitaires afin d’améliorer leur concentration et leurs performances universitaires suscite l’intérêt du public et soulève d’importants débats éthiques auprès des spécialistes. Les différentes perspectives sur l’amélioration des performances cognitives représentent une dimension importante des défis sociaux et éthiques autour d’un tel phénomène et méritent d’être élucidées. Ce mémoire vise à examiner les discours présents dans les reportages internationaux de presse populaire, les discours en bioéthique et en en santé publique sur le thème de l’utilisation non médicale du méthylphénidate. Cette recherche a permis d’identifier et d’analyser des « lacunes » dans les perspectives éthiques, sociales et scientifiques de l’utilisation non médicale du méthylphénidate pour accroître la performance cognitive d’individus en santé. Une analyse systématique du contenu des discours sur l’utilisation non médicale du méthylphénidate pour accroître la performance cognitive a identifié des paradigmes divergents employés pour décrire l’utilisation non médicale du méthylphénidate et discuter ses conséquences éthiques. Les paradigmes « choix de mode de vie », « abus de médicament » et « amélioration de la cognition » sont présents dans les discours de la presse populaire, de la bioéthique et de la santé publique respectivement. Parmi les principales différences entre ces paradigmes, on retrouve : la description de l’utilisation non médicale d’agents neuropharmacologiques pour l’amélioration des performances, les risques et bénéfices qui y sont associés, la discussion d’enjeux éthiques et sociaux et des stratégies de prévention et les défis associés à l’augmentation de la prévalence de ce phénomène. La divergence de ces paradigmes reflète le pluralisme des perceptions de l’utilisation non médicale d’agents neuropharmacologiques Nos résultats suggèrent la nécessité de débats autour de l’amélioration neuropharmacologique afin de poursuivre l’identification des enjeux et de développer des approches de santé publique cohérentes. / The non-medical use of neuropharmaceuticals has sparked ethical debates. For example, there is mounting evidence that methylphenidate (MPH; Ritalin) is being used by healthy university students to improve concentration, alertness, and academic performance, a phenomenon known as cognitive enhancement. The different perspectives on the ethics of cognitive enhancement represent an important dimension of the social and ethical challenges related to such practices but have yet to be examined thoroughly. This thesis aimed to assess existing positive and negative reports in international print media, bioethics literature, and public health literature on the use of MPH to identify and analyze gaps in the ethical, social, and scientific perspectives about the non-medical use of MPH for cognitive enhancement in healthy individuals. A systematic content analysis of discourses on the non-medical use of methylphenidate for cognitive enhancement identified divergent frameworks employed to describe the non-medical use of methylphenidate and discuss its ethical implications: The frameworks of “lifestyle choice”, “prescription drug abuse” and “cognitive enhancement” are present in print media, bioethics, and public health discourses respectively. Important differences between frameworks include the description of the non-medical use of neuropharmaceuticals for cognitive enhancement, associated risks and benefits, discussion of ethical and social issues surrounding the phenomenon and the prevention strategies and challenges to the widespread use of neuropharmaceuticals for cognitive enhancement. Diverging frameworks reflect pluralism in perceptions if the non-medical use of neuropharmaceuticals for cognitive enhancement. At this time, unacknowledged pluralism and implicit assumptions about cognitive enhancement may impede public health interventions and ethics discussions.

Background: There is a widespread and increasing use of psychoactive prescription drugs, such as opioid analgesics, anxiolytics, hypnotics and anti-epileptics, but their use is associated with a risk of drug use disorder, misuse and abuse. Today, these are globally recognized and emerging public health concerns. Aim: The aim of this thesis is to estimate the prevalence of psychoactive prescription drug (PPD) use disorders, misuse and abuse, and to investigate the association with some potential risk factors. Methods: A study using register data from forensic cause of death investigations investigated and described cases of fatal unintentional intoxication with tramadol (Study I). Based on register data on spontaneously reported adverse drug reactions (ADRs) reported cases of tramadol dependence were investigated and summarised (Study II). In a study in suspected drug-impaired drivers with a toxicology analysis confirming the intake of one out of five pre-specified PPDs, the prevalence of non-prescribed use was assessed and associated factors were investigated (Study III). From a cohort of patients initiating prescribed treatment with pregabalin, using data on prescription fills, a study investigated longitudinal utilisation patterns during five years with regards to use of the drug above the maximum approved daily dose (MAD), and factors associated with the utilisation patterns (Study IV). Results: In the first study, 17 cases of unintentional intoxications were identified, of which more concerned men, the median age was 44 years and the majority used multiple psychoactive substances (alcohol, illicit drugs and prescription drugs). The second study identified 104 spontaneously reported cases of tramadol dependence, in which more concerned women, the median age was 45 years, and a third reported a history of substance abuse and 40% of past psychoactive medication use. In the third study, more than half of the individuals suspected of drug-impaired driving used the drug without a recent prescription. Non prescribed use was most frequent in users of benzodiazepines and tramadol, and was more likely in younger individuals and in multiple-substance users. In the last paper five longitudinal utilisation patterns were found in pregabalin users, with two patterns associated with a particularly high risk of doses above the maximum approved dosing recommendation. This pattern of use was associated with male sex, younger age, non-urban residency and a recent prescribed treatment with an antiepileptic or opioid analgesic drug. Conclusions: This thesis shows that psychoactive prescription drug use disorders, misuse and abuse occur and may have serious and even fatal consequences. The prevalence varies between different drugs and populations. Abuse and misuse seem to be more common in young people. Fatal intoxications and misuse of prescribed drugs may be more common in men, while drug use disorders following prescribed treatment may be more common in women and non-prescribed use equally distributed between women and men. Individuals with a history of mental illness, substance use disorder or abuse, or of past use of psychoactive medications are likely important risk groups. In summary, the findings suggest a potential for improvements in the utilisation of psychoactive prescription drugs. The results may be useful in the planning of clinical and regulatory preventive interventions to promote the rational, individualised and safe use of such drugs.

Syftet med detta projekt var att identifiera om en implementering av en standardisering för receptbelagda läkemedelsförpackningar, skulle kunna bidra till en minskad risk gällande feldosering eller felmedicinering av patient. Resultatet av studien konstaterar att en standardisering för ordinationer har större effekt. / The purpose of this project was to identify if an implementation of a standardization for prescription drugs packaging, could contribute to a reduced risk of error when medicating a patient with prescription drugs and dosage. The outcome of the study states that a standardization for prescriptions has a bigger impact.

Il 40 per cento degli intervistati afferma che non ha trovato informazioni esaustive sui rischi e benefici dei farmaci trovati, mentre il 52 per cento afferma che le informazioni trovate hanno aiutato a seguire le indicazioni e i consigli del medico. Tra i rispondenti che si sono sottoposti a visita medica e che hanno discusso le informazioni trovate online con il proprio medico di fiducia, l'84 per cento ha ricevuto la prescrizione di farmaci. Di questi, solo il 17 per cento riporta che il farmaco prescritto era lo stesso trovato online, il 74 per cento è stato inviato da uno specialista e l'80 per cento ha ricevuto una prescrizione per test diagnostici. Più della metà dei rispondenti ha anche riportato azioni intraprese dal medico diverse dalla prescrizione del farmaco trovato online. Il 20 per cento degli intervistati afferma che le informazioni trovate sul farmaco da prescrizione in Internet hanno ridotto il suo / la sua fiducia nel medico, mentre il 41 per cento afferma che lo ha aiutato ad avere una comunicazione migliore con il proprio medico di fiducia. Nonostante le preoccupazioni sulle conseguenze negative della comunicazione di salute online, non abbiamo riscontrato differenze in termini di effetti sulla salute tra i pazienti che hanno assunto i farmaci “menzionati” online e coloro che hanno preso altri farmaci da prescrizione. / We conducted a national online survey about health care experiences associated with digital communication of prescription drugs. 46 percent of the sample (265 adults) found information about prescription drugs during their online search in the last 12 months. 40 percent of respondents agreed they didn’t find exhaustive information about risks and benefits while 52 percent agreed it helped in following their physician’s indications and advise. Among the respondents who had a physician visit during which health information found online was discussed, 84 percent received a drug prescription with only 17 percent being the same drug found on internet, 74 percent was sent to a specialist and 80 percent received a diagnostic test prescription. More than half also reported actions taken by their physician other than prescribing the drug brand found online. 20 percent respondents states that info found on the prescription drug in Internet reduced his/her trust in the physician while 41 percent states it helped in his/her communication with physician. Despite concerns about online health communication’s negative consequences, we found no differences in health effects between patients who took “advocated”/”mentioned” drugs and those who took other prescription drugs.