A estimulacao transcraniana por corrente continua (ETCC) e uma tecnica nao-invasiva de estimulacao cerebral que consiste na aplicacao de uma corrente eletrica de baixa intensidade atraves de eletrodos colocados sobre a cabeca, levando a efeitos neuromodulatorios e de neuroplasticidade. Avaliamos o papel da ETCC no transtorno depressivo maior (TDM), uma condicao prevalente e cronica, atraves de um ensaio clinico duplo-cego, 2 x 2 (fatorial), com uma intervencao farmacologica (sertralina 50mg/dia) e uma nao-farmacologica (ETCC), comparando, portanto a eficacia e seguranca da ETCC ativa vs. simulada, vs. sertralina e da combinacao ETCC/sertralina vs. demais. Dos 850 voluntarios iniciais, incluimos aqueles com depressao moderada/grave, baixa ideacao suicida, ausencia de outras co-morbidades psiquiatricas e clinicas e que nao usavam (ou aceitaram retirar) medicacoes antidepressivas. Nao incluimos aqueles usando sertralina. Randomizamos os 120 participantes em 4 grupos: ETCC simulada/placebo (placebo), ETCC simulada/sertralina (sertralina), ETCC ativa/placebo (ETCC), ETCC ativa/sertralina (tratamento combinado). A ETCC foi aplicada em 2mA/25cm2, sendo o anodo e o catodo posicionados sobre as areas correspondentes ao cortex dorsolateral pre-frontal esquerdo e direito, respectivamente, por 30 minutos diarios, por dez dias consecutivos, excluindo finais de semana. Apos este periodo, duas outras estimulacoes, em semanas alternadas, foram realizadas ate o fim do estudo (6a semana). A ETCC simulada foi realizada da mesma maneira que a ETCC ativa, mas o aparelho era desligado apos 30 segundos iniciais. 103 participantes terminaram o estudo, sendo a analise estatistica por intencao de tratamento. A escala de depressao de Montgomery-Asberg (MADRS) foi o desfecho primario. No inicio, os quatro grupos eram semelhantes. Na 6a semana, o grupo tratamento combinado foi estatisticamente superior (p0,01 para todas as comparacoes) aos grupos placebo (diferenca de 11,5 pontos, Intervalo de Confianca [IC] 95%= 6-17), sertralina (8,5 pontos, IC 95%= 2,9-14) e ETCC (5,9 pontos, IC 95%= 0,36-11,43). ETCC e sertralina nao foram diferentes entre si (2,6 pontos, IC 95%=-2,9 a 8,1, p=0,35). Os resultados medidos por outras escalas foram semelhantes. Apenas vermelhidao na pele na regiao da estimulacao foi um efeito adverso mais observado na ETCC ativa. Os grupos tiveram desempenho semelhante nos testes cognitivos realizados, porem, de sete episodios de hipomania/mania, cinco foram no tratamento combinado. Nos estudos auxiliares, a ETCC nao levou a alteracoes na variabilidade da frequencia cardiaca (medida no inicio e ao fim do tratamento), tambem sugerindo seguranca da tecnica. Alem disso, observamos uma interacao entre o gene transportador da serotonina e a resposta a ETCC, sendo que o alelo curto (s) associou-se a uma pior resposta. Nao observamos interacoes com o polimorfismo Val66Met do BDNF. Finalmente, no estudo de seguimento, dos 42 pacientes que receberam ETCC quinzenal, por 3 meses, seguida de mensal, por 3 meses, a recaida foi de 47%. Em conjunto, os resultados demonstram que, na depressao aguda, a ETCC ativa e superior a simulada, comparavel a sertralina, e o tratamento combinado, superior aos demais. Clinicamente, a ETCC poderia substituir antidepressivos nos pacientes que nao toleram, nao podem ou nao desejam toma-los, ou combinada a estes, por exemplo, no tratamento de episodios graves / Transcranial direct current stimulation (tDCS) is a non-invasive technique of brain stimulation that applies a weak, direct electric current over ones scalp through electrodes, leading to neuromodulatory and neuroplastic effects. We evaluated the role of tDCS as a treatment for major depressive disorder (MDD), a chronic, prevalent condition, through a double-blind, 2x2 (factorial) trial, with one pharmacological (sertraline 50mg/day) and one non-pharmacological (tDCS) intervention; therefore comparing the efficacy and safety of active vs. sham tDCS, vs. sertraline and the combination active tDCS/sertraline vs. other interventions. Of 850 volunteers, we included only those with moderate-tosevere depression, low suicidal ideation, absence of other psychiatric and medical comorbidities and also those either not currently on antidepressants or using and agreeing to discontinue their use. We did not enrol patients on sertraline. The 120 patients were randomized into 4 groups: tDCS sham/placebo (placebo), tDCS sham/sertraline (sertraline), active tDCS/placebo (tDCS) and active tDCS/sertraline (combined treatment). TDCS was applied at 2mA/25cm2, with the anode and the cathode over the left and right dorsolateral prefrontal cortex, respectively, per 30 minutes daily, per 10 weekdays. Thereafter, tDCS was applied every other week, until the endpoint at 6 weeks (i.e., two extra sessions). For sham tDCS, the device was turned off after 30 seconds of stimulation. We performed an intention-to-treat analysis in the 103 patients who finished the study. The Montgomery- Asberg depression rating scale (MADRS) was the primary outcome. The four groups were similar at baseline. At week 6, the combined treatment group was significantly more effective (p0.01 for all comparisons) than placebo (mean difference of 11.5 points, 95% Confidence Interval [CI] =6-17), sertraline (8.5 points, 95% CI=2.9-14) and tDCS (5.9 points, 95% CI=0.36-11.43). TDCS and sertraline presented similar efficacy (2.6 points, 95% CI=-2.9 to 8.1, p=0.35). Other depression scales yielded similar results. The only adverse effect significantly more observed in the active tDCS was skin redness on the stimulated scalp region. The groups had similar performance in the cognitive assessments; although 5 of 7 (hypo)manic episodes were in the combined treatment group. The ancillary studies showed that tDCS treatment did not change heart rate variability (measured at baseline and endpoint), further suggesting that the intervention is safe. Moreover, there was an interaction between the short allele (s) of the serotonin transporter gene (5-HTTLPR) and lower tDCS antidepressant response; no association was observed with the Val66Met BDNF genotypes and tDCS response. Finally, we followed 42 patients for up to 24 weeks, performing tDCS sessions every other week for 3 months and then each month per 3 months, with a relapse rate of 47%. Taken together, these results showed that, for the acute depressive episode, active tDCS is more effective than sham, as effective than sertraline, and less effective than the combined treatment, which is the most effective. In clinical settings, tDCS could be either a substitutive treatment for antidepressants in patients that cannot or would not use them, or as an augmentative treatment that, combined with antidepressants, could boost clinical response in severe cases

Esta pesquisa retrata uma experiência etnográfica sobre o consumo de medicamentos antidepressivos e ansiolíticos fornecidos por uma farmácia pública aos moradores de uma área formada por três bairros da cidade de Ribeirão Preto-SP. Esta área era formada por casas populares, casas luxuosas e por uma favela, sendo coberta pela Estratégia de Saúde da Família, com a exceção de uma parte das casas populares, a qual era formado pelas casas COHAB (Companhia Habitacional). O bairro com as casas luxuosas foi incluído somente na observação participante e na fotografia. Os motivos do consumo destes medicamentos, investigados com entrevistas abertas, observação participante, diário de campo e fotografia, são justificados através de uma remodelação e reorganização de espaços entre os moradores destes bairros, marcados por desigualdades sociais, de gênero e pela busca de diferenciação, numa hierarquia classificada entre o ideal e o indesejado através do curso de vida dos moradores. A seleção dos entrevistados foi realizada a partir dos dados da dispensação dos medicamentos psicoativos pela farmácia pública fornecedora, a qual também estava incluída na experiência etnográfica, tendo sido a dispensação dos medicamentos incluída na observação participante. O consumo de medicamentos psicoativos foi analisado a partir da ótica de seus consumidores, revelando que estariam contribuindo para perpetuar os papéis sociais frente à dinâmica social, como os relacionados ao gênero e à classe social. A pesquisa revela uma associação entre vida cotidiana e consumo de medicamentos psicoativos, destoante de um produzir saúde, esperado da relação entre serviços de saúde e população, e de uma associação entre doença e uso de medicamentos. Aprofundar questões sociais sobre o consumo de medicamentos em grupos populares poderá evitar seu uso abusivo com a função de produzir um corpo explorado quimicamente por se estender seus limites de produção, aprofundando e silenciando desigualdades sociais. O consumo de medicamentos psicoativos deve ser analisado com cautela, devendo seu consumo ser problematizado. / This research shows an ethnographic experience on the use of antidepressant and anxiolytic medicines provided by a public pharmacy to the residents of an area formed by three sectors of the city of Ribeirão Preto-SP. This area was formed by popular houses, luxury houses and a shantytown, and covered by the Family Health Strategy, with the exception of part of the popular houses, wich was formed by COHAB houses (Housing Company). The neighborhood with luxury houses was included only in a participant observation and in the photograph. The reasons for the use of the medecines, investigated with open interview, participant oservation, a field diary and photograph, are justified through a remodeling and recognization of space between the residents of these neigborhoods, marked by social inequality, gender and the search for differentiation, in a classified hierarchy between the ideal and unwanted y the life´s course of residents. The selection of interviewees was made from the data of the dispensing of psychoactive medicines by the provider public pharmacy, wich was also included in the etnographic experience, having been dispensing of medicines included in participant observation. The use of psychoactive medicines has been examined from the perspective of their consumers, revealing that they were helping to perpetuate social roles in the social dynamicsrelated to gender and social class. The research shows an association between daily life and use of psychoactive medicines, diverging from the production of health, which is waited in the relashionship between health services and population, and diverging from assocition between illness and medication use. Deepening social issues on the consumption of medecines in popular groups may prevent their abuse with the function of producing a body explored chemically because it has extended their limits of production, deepening and keeping quiet the social inequalities. The consumption of psychoactive medecines should be examined with caution, their consumption should be problematized

Um método cromatográfico foi desenvolvido para determinação dos antidepressivos mais prescritos no Brasil e seus produtos de biotransfomação (amitriptilina, imipramina, clomipramina, desmetilclomipramina, desipramina, nortriptilina, fluoxetina, norfluoxetina e sertralina) em sangue total por cromatografia em fase gasosa com detector de nitrogênio e fósforo. A extração em fase sólida (EFS) com o cartucho abselutTM NEXUS foi empregada de forma inovadora. O procedimento de extração consistiu na diluição de 0,5mL de sangue total em tampão (pH 9,5), aplicação da amostra no cartucho, remoção de interferentes usando tampão (pH 9,5) e eluição dos analitos com diclorometano/ isopropanol (17/3 v/v); a etidocaína foi adotada como padrão interno. Os limites de detecção (LD) e quantificação (LIQ) encontrados foram de 0,1mg/L a 0,4mg/L e de 0,4mg/L a 1,6mg/L, respectivamente. O método foi preciso, específico e linear na faixa de concentração estudada (do LIQ até 12mg/L). A recuperação média de todos os analitos foi 65,5%. O método foi aplicado em amostras de âmbito forense e de emergência clínica. / A gas chromatographic method was developed to determine antidepressants most prescribed in Brazil and their metabolites (amitriptyline, imipramine, clomipramine, desmethylclomipramine, desipramine, nortriptyline, fluoxetine, norfluoxetine, and sertralina) in whole blood, using solid phase extraction and gas chromatography with nitrogen-phosphorus detection. The solid-phase extraction (SPE) with abselutTM NEXUS was applied in an innovative manner. The extraction procedure consists of the dilution of 0.5mL of whole blood in buffer (pH 9.5), application of the sample in the cartridge, washing with buffer (pH 9.5) and elution of the analytes with dichloromethane/isopropanol (17/3, v/v). The limit of detection (LOD) and quantification (LLOQ) were from 0.1mg/L to 0.4mg/L and from 0.4mg/L to 1.6mg/L, respectively. Etidocaine was used as internal standard. The method was precise, specific and linear in the studied concentration (range from LLOQ to 12mg/L). The average recovery of all analytes was 65,5%. Forensic and clinical emergency samples were submitted to the validated method.

The development of new solid forms of active pharmaceutical ingredients (API) is relevant both from fundamental as well as industrial perspectives. To this end, Crystal Engineering plays an ever-increasing important role in pharmaceutical sciences. Among the crystal engineering strategy, salt formation is the most important and implemented approach. The salt forms of API could be used to modulate and tuned the solubility and stability of API to provide optimal practical uses. Herein, we report pharmaceutical salts of two Selective Serotonin Reuptake Inhibitor antidepressants used in the treatment of depression and anxiety disorders, Paroxetine (PRX) and Fluoxetine (FLX). For this purpose, salt formers, supramolecular synthesis and crystallization protocols have been driven by the systematization of structural and supramolecular data of molecules and analogues from the Cambridge Structural Database. Paroxetine bromide hemihydrate ((PRXBr)0.5H2O), Paroxetine Nitrate hydrate (PRXNO3H2O) and two polymorphs of Fluoxetine Nitrate (FLXNO3) have obtained. All were characterized by a combination of techniques including Single Crystal X-ray Diffraction, Differential Scanning Calorimetry (DSC), Thermogravimetry analysis (TGA), Hot Stage Microscopy, Fourier transform infrared spectroscopy (IR) and solubility measurements. Since the hydration/dehydration process in APIs induces phase transitions that compromise its efficiency, the structural characterization of (PRXBr)0.5H2O help to understand its reversible dehydration process. Also, this study has implication in the understating of dehydration of isostructural PRX hydrochloride salt. Additionally, the (PRXNO3)H2O have shown the conformational flexibility and supramolecular diversity of PRX. On the other hand, the chirality of FLX is related to two nitrate salt polymorphs. A racemate and a non-centrosymmetric structure with independent enantiomers in the asymmetric unit were obtained for FLXNO3. Their packing have shown the existence of different racemic motifs, resulting in different enantiomer orientations The rare occurrence of racemic systems in non-centrosymmetric space groups becomes this event a noteworthy case. By their physicochemical properties, the polymorphs were monotropically related. The scientific contributions of this thesis show the diversity of the solid forms and define candidates to new antidepressants APIs solid formulations. / O desenvolvimento de novas formas sólidas de ingredientes farmacêuticos ativos (API) é relevante tanto numa perspectiva fundamental como industrial. Para tal, a Engenharia de cristais tem desempenhado um papel importante nas ciências farmacêuticas. Dentre as estratégias, a formação de sais é a abordagem mais importante e implementada. Os sais de APIs são capazes de modular e ajustar a solubilidade e a estabilidade, a fim de proporcionar uso prático. Nesta tese, são reportados sais de dois fármacos Inibidores Seletivos de Recaptação de Serotonina, consolidados no tratamento da depressão e distúrbios de ansiedade, a Paroxetina (PRX) e a Fluoxetina (FLX). Brometo de Paroxetina hemiidratado ((PRXBr)0.5H2O), Nitrato de Paroxetina hidratado (PRXNO3H2O) e polimorfos de Nitrato de Fluoxetina (FLXNO3), síntese e protocolos de cristalização foram cuidadosamente delineados, com base na sistematização de dados estruturais e supramoleculares das moléculas e seus análogos, depositados no Cambridge Structural Database. Todos os sais foram caracterizados por Difração de Raios-X por Monocristal, Calorimetria Explanatória Diferencial (DSC), Análise termogravimétrica (TGA), Termomicroscopia, Espectroscopia vibracional na região do infravermelho (IR) e solubilidade. Considerando que a hidratação/desidratação induz mudanças de fases que comprometem a eficiência do API, a caracterização do (PRXBr)0.5H2O auxiliou no entendimento do processo de desidratação reversível que ocorre para esse fármaco. Estas mudanças de fase resultam também em implicações sobre a compreensão do processo de desidratação do sal isoestrutural de cloreto de PRX hemiidratado. Além disso, por meio da elucidação estrutural do (PRXNO3)H2O, foi possível analisar a diversidade conformacional e supramolecular da PRX. Quanto à FLX, verificou-se que sua quiralidade está relacionada com seu polimorfismo. Um racemato e uma estrutura não centrossimétrica com dois enatiômeros independentes na unidade assimétrica foram obtidos para o FLXNO3. A comparação destas estruturas permitiu mostrar a existência de arranjos supramoleculares racêmicos, constituídos por diferentes orientações de enatiômeros. A rara ocorrência de sistemas racêmicos em grupos espaciais não-centrossimétricos tornou este evento um caso notável. A partir das propriedades físico-químicas, os polimorfos puderam ser monotropicamente relacionados. Os resultados desta tese trazem importantes contribuições científicas para diversidade de formas sólidas e também define novas formulações sólidas para utilização como antidepressivos.

Au vu de la croissance considérable de la consommation des antidépresseurs au cours des dernières décennies et de la part non négligeable de patients qui restent non traités ou mal traités, la question du bon usage ou du mésusage de ces médicaments s’impose. Les trois études présentées dans ce rapport se sont intéressées à décrire l’augmentation de la consommation des antidépresseurs et à en comprendre les mécanismes sous-jacents. L’analyse des données de vente indique que la croissance des antidépresseurs diffère entre les pays étudiés, mais qu’elle suit un schéma classique d’augmentation suivie d’une stabilisation à un certain seuil, et que les politiques de limitation des dépenses de santé ont un impact, différent selon la maturité du marché. Les travaux sur données de remboursement montrent que si l‘on peut parler de mésusage dans l’utilisation des antidépresseurs, il semble lié non pas à une prescription hors indication mais plutôt inappropriée : traitement sans diagnostic précis, prescription unique suggérant un traitement injustifié, traitement trop court en regard des recommandations internationales qui préconisent au moins 6 mois pour éviter rechutes et récidives. Les travaux que nous avons menés montrent que les bases de données peuvent constituer un outil fiable d’évaluation de la consommation (données de vente) ou d’utilisation des antidépresseurs (bases de remboursement) : utilisation simple et rapide de données de vente afin d’avoir un panorama des pratiques et utilisation plus complexe des bases de remboursement afin de mieux comprendre les pratiques. Utilisés en pratique courante, des tableaux de bord de suivi de consommation pourraient alerter les pouvoirs publics sur les dérives des consommations et permettre de mettre en place des analyses plus poussées afin de caractériser les pratiques et mieux comprendre les vecteurs de la consommation. / Considering the large increase in antidepressant use observed in the last decades, the question of good or poor usage of antidepressants is of importance. The three studies presented in this report consisted into a descriptive analysis of the increase in the use of antidepressants in different countries, and thereafter analyse the underlying mechanisms. Our analysis of sales database indicates that the increase in antidepressants volume differ from country to country, but follows a classical scheme with rapid increase until stabilisation to a certain threshold and that national policies to ensure expenditure limitations has a different impact on the volume depending on the maturity of the market. The analyses performed afterwards on US claims databases, and show that if improper use of antidepressants is a reality, it does not seem to correspond to a massive off-label use but rather to an incorrect use of antidepressants: treatment without precise diagnosis, isolated prescription which suggest undue treatment, treatment for too short periods of time with regards to international guidelines which recommend at least 6 month to avoid relapse or recurrence of the disease. The analyses we have conducted on databases can serve as a basis for the development of a reliable tool to evaluate drug consumption (sales databases) or drug use (claims databases) : simple and rapid use of sales databases to get a mapping of consumption in their environment, and more complex and time consuming use of claims database to gain an understanding of practice. Used in routine, the sales monitoring tools could play a role to alert public health services on abnormal evolution of drug consumption and allow the initiation of more refined analyses either on large claims databases or through prospective cohort of patients in order to characterise the practice and gain an understanding on the drivers of drug use.

Les bases de données des plans d’assurance maladie permettent de reconstruire l’évolution des patients dans le système de soins sans influencer le comportement du prescripteur ou du patient. Les troubles dépressifs sont largement étudiés en population générale, ils ont cependant fait l’objet d’une attention tardive chez le sujet âgé. Malgré les singularités de la dépression chez les sujets âgés, les traitements demeurent efficaces dans cette population. L’objectif de ce travail était d’utiliser une base de données de remboursements afin de comparer la prise en charge de la dépression chez les sujets âgés de 65 ans et plus et les adultes plus jeunes. Nous avons comparé 6 316 sujets dépressifs âgés à 25 264 sujets dépressifs adultes plus jeunes, en termes d’initiation et de durée de traitement antidépresseur. Comparé à l’échantillon plus jeune, notre échantillon de sujets âgés est apparu sous-traité alors que les sujets âgés initiant un traitement semblaient mieux y adhérer. La présence de comorbidités favorisait l’initiation d’un traitement sans être associé à une durée de traitement différente. De plus, une amélioration du remboursement des médicaments dans notre population fut concomitante d’un allongement de la durée de traitement chez les sujets âgés. Ces résultats, supportés par d’autres études plus classiques, suggèrent que la déviation ? de données collectées à des fins autres que la recherche épidémiologique est une approche permettant d’étudier des cohortes de patients en conditions réelles de prescription, de décrire des groupes spécifiques de patients et de mesurer des expositions médicamenteuses ainsi que de potentiels impacts de politiques de santé. / Healthcare databases allow exhaustive and strictly observational follow-up of patients in the healthcare system. Mood disorders are well described in the literature, but depressed elderly raised less concern. In this work, we have developed methods and strategies allowing the comparison of the management of depression between elderly people and their younger adult counterpart. Aging was associated with lower treatment rates and higher comorbidities. Conversely, in both age groups, the presence of comorbid condition mitigated the risk of being untreated. Besides, in any age group, having comorbid condition was not found associated with difference in persistence rate to antidepressants. Implementation of Medicare Part D was associated with substantial improvement in treatment of older adults with depression. Supported by other field studies, our results show that valuable data can be derived from healthcare databases. The full potential of this rich computerized database has yet to come.

Background and aims: This interdisciplinary thesis was designed to deepen understanding of the co-morbidity of anxiety and depression with chronic diseases of the digestive tract, and inflammatory bowel disease (IBD) in particular. The first part of the thesis aimed to explore the prevalence of psychological problems in IBD compared to irritable bowel syndrome (IBS) and chronic hepatitis C (HCV) groups. It also explored the relationship between the number of co-morbid functional gastrointestinal disorders and the severity of psychological problems in IBD and IBS. It also aimed to determine whether there is a relationship between psychological problems and the response to standard medical treatment/physical outcomes in patients with IBD, IBS and HCV. Furthermore, it aimed to explore whether disclosure of the psychological status of depressed and/or anxious IBD patients to their gastroenterologists influences doctors’ behaviour and affects patients’ responses to treatment/physical outcomes. The second part of the thesis aimed to investigate the potential role of antidepressants in IBD and to determine the feasibility of future randomised controlled trials on the role of antidepressants in IBD. Methods: Overall, a cohort of 139 outpatients (64 IBD, 41 HCV, and 34 IBS) and 18 gastroenterologists participated in the six studies comprising this thesis. A mixed methods design was applied. Two cross-sectional studies, an observational cohort prospective management study, a randomised controlled trial, a systematic review and an exploratory interview study were conducted. Differences between the groups for continuous variables were assesed with one way analysis of variance (ANOVA) and independent samples ttests. Differences in categorical variables were assessed with contingency tables with the Chi-Square test and the Fisher’s Exact Test. Propsective analyses were conducted with repeated measures ANOVA, logistic regression and Poisson regression. Qualitative data were analysed using content analysis. Results: Overall, 42% of participants were anxious and 19% were depressed. Participants with HCV had higher levels of psychological impairment compared with the IBS, the IBD group and the general population (p<0.05). Those IBD participants with fewer co-morbid functional disorders had better physical quality of life than participants with a greater number of these disorders (p=0.025). Moreover, depression/anxiety at baseline did not explain medical outcomes after 12 months in this cohort of patients with chronic diseases of the digestive tract. Doctors’ knowledge of patients’ psychological status was found to have no impact on IBD patients’ outcomes after 12 months. However, interestingly, the level of anxiety in IBD participants significantly dropped between the baseline and nine months indicating a possible benefit from participating in the study. In the literature review, insufficient evidence was found to conclude that antidepressants are efficacious for treatment of psychological co-morbidities or somatic complaints in IBD. However, the qualitative interview study indicated a potential positive impact of treatment with antidepressants on coping with disease symptoms and general wellbeing in patients with IBD. Conclusion: The thesis confirms that there is a significant burden of psychological co-morbidity in patients with chronic gastroenterological diseases. Interdisciplinary approaches to the management of these diseases are therefore warranted in Australian gastroenterology clinics. Anxiety targeted interventions and research in this setting are urgently needed, especially with respect to patients with HCV. Larger studies exploring the gastroenterologists’ role in treatment of co-morbid psychological problems in their patients are recommended. Longer prospective studies on homogenous samples of patients are also needed to clarify the nature of the relationship between psychological problems and relapse of somatic symptoms. Finally, randomised controlled trials exploring the efficacy of antidepressants in IBD are warranted. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1321006 / Thesis (Ph.D.) -- University of Adelaide, School of Population Health and Clinical Practice, 2008

Thesis (M. Pharm.)--North-West University, Potchefstroom Campus, 2008.

Increasing health care costs is an international problem from which South Africa is not excluded. Prescription medication contributes most to these high health care costs, and methods to reduce their costs to society are implemented worldwide. In South Africa, such a method is a managed care reference medicine price list, as introduced by a PBM (pharmacy benefit management) company. This step had some cost implications in the private health sector in South Africa, and these implications were investigated in this study. Central nervous system (CNS) medicine items are among the top ten medicine items claimed and represent a substantial amount of the costs of all medicine items claimed during the study period. Antidepressants, a subdivision of the CNS agents, comprise the largest share of CNS agents claimed and CNS costs, and were therefore investigated more closely. The objective of this study was to analyse the usage patterns and costs of central nervous system medicine items, and more specifically, the antidepressants, against the background of the implementation of a managed care reference medicine price list in the private sector of South Africa. This study was conducted as a retrospective, non-experimental quantitative research project. The study population consisted of all medicine items claimed as observed on the database over the two-year study period of May 2001 to April 2002 (pre-MPL) and May 2002 to April 2003 (post-MPL). Data were provided by MedschemeTM/lnterpharm, and the Statistical Analysis System® SAS 8.2® was used to extract the data from the database. The central nervous system agents had a prevalence of 8.10% (N=49098736) and a total cost of R757576976.72 over the two-year study period. The cost per CNS item increased by 5.98% or R11.50 per CNS item in the year after MPL implementation, and the cost per prescription containing CNS medicine items increased by 4.09% or R9.07 per prescription. CNS agents are classified into ten sub-pharmacological groups, according to the MIMSC3 (Snyman, 2003:13a). One of these sub-pharmacological groups, antidepressants, comprised 33.97% of all CNS medicine items claimed (N=3978364) and 45.53% of all costs associated with CNS medicine items (N=R757576976.72) over the study period. The number one antidepressant claimed was amitriptyline, a tricyclic antidepressant. Of the antidepressants with generic substitutes, all with the exception of clomipramine, were prescribed at generic substitution rates of more than 50%. After the MPL implementation, generic antidepressant products were more frequently prescribed (16.48% increase, N=617190), although patient co-payments did not decrease immediately. Some innovator products had price reductions after the implementation of the MPL. This study indicates that cost minimisation analyses and retrospective drug utilisation reviews are valuable tools in the evaluation of managed care medicine price lists. / Thesis (M. Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2005.

Increasing health care costs is an international problem from which South Africa is not excluded. Prescription medication contributes most to these high health care costs, and methods to reduce their costs to society are implemented worldwide. In South Africa, such a method is a managed care reference medicine price list, as introduced by a PBM (pharmacy benefit management) company. This step had some cost implications in the private health sector in South Africa, and these implications were investigated in this study. Central nervous system (CNS) medicine items are among the top ten medicine items claimed and represent a substantial amount of the costs of all medicine items claimed during the study period. Antidepressants, a subdivision of the CNS agents, comprise the largest share of CNS agents claimed and CNS costs, and were therefore investigated more closely. The objective of this study was to analyse the usage patterns and costs of central nervous system medicine items, and more specifically, the antidepressants, against the background of the implementation of a managed care reference medicine price list in the private sector of South Africa. This study was conducted as a retrospective, non-experimental quantitative research project. The study population consisted of all medicine items claimed as observed on the database over the two-year study period of May 2001 to April 2002 (pre-MPL) and May 2002 to April 2003 (post-MPL). Data were provided by MedschemeTM/lnterpharm, and the Statistical Analysis System® SAS 8.2® was used to extract the data from the database. The central nervous system agents had a prevalence of 8.10% (N=49098736) and a total cost of R757576976.72 over the two-year study period. The cost per CNS item increased by 5.98% or R11.50 per CNS item in the year after MPL implementation, and the cost per prescription containing CNS medicine items increased by 4.09% or R9.07 per prescription. CNS agents are classified into ten sub-pharmacological groups, according to the MIMSC3 (Snyman, 2003:13a). One of these sub-pharmacological groups, antidepressants, comprised 33.97% of all CNS medicine items claimed (N=3978364) and 45.53% of all costs associated with CNS medicine items (N=R757576976.72) over the study period. The number one antidepressant claimed was amitriptyline, a tricyclic antidepressant. Of the antidepressants with generic substitutes, all with the exception of clomipramine, were prescribed at generic substitution rates of more than 50%. After the MPL implementation, generic antidepressant products were more frequently prescribed (16.48% increase, N=617190), although patient co-payments did not decrease immediately. Some innovator products had price reductions after the implementation of the MPL. This study indicates that cost minimisation analyses and retrospective drug utilisation reviews are valuable tools in the evaluation of managed care medicine price lists. / Thesis (M. Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2005.