Psychostimulant dependence is a major public health issue in many parts of the world associated with a wide range of psychological, medical and social problems. Psychosocial interventions are the mainstay of treatment for psychostimulant problems, although their effectiveness is compromised by poor uptake and compliance. Despite increasing knowledge of the neurobiological consequences of psychostimulant use, no medications to date have been any more successful than placebo in reducing psychostimulant use in dependent patients. Modafinil is a non-amphetamine type psychostimulant that may have potential as an agonist pharmacotherapy for psychostimulant dependence. The aim of this thesis was to examine the safety, efficacy and cost-effectiveness of modafinil 200 mg/day over ten weeks plus a four session brief CBT intervention for methamphetamine and cocaine dependence through two concurrent randomised placebo controlled trials. There were no statistically significant differences between modafinil and placebo in treatment retention, medication adherence, psychostimulant abstinence, psychostimulant craving or severity of psychostimulant dependence. Methamphetamine-dependent subjects tended to provide more illicit psychostimulant negative urine samples while in treatment than those who received placebo. There appeared to be a reduction in self-reported days of psychostimulant use among methamphetamine-dependent subjects who received modafinil compared to placebo, but the effect size was too small to be statistically significant in this sample. The reduction in self-reported psychostimulant use did reach statistical significance in methamphetamine-dependent subjects with no other substance dependence. Uptake of counselling was the most significant predictor of reduced psychostimulant use post treatment, and the addition of counselling improved the cost-effectiveness of modafinil relative to placebo. Modafinil appeared to be safe, well-tolerated, and non-reinforcing in this treatment population. Compared to placebo, there was a significant increase in weight in subjects who completed the 10-week course of treatment, and a significant decrease in systolic blood pressure in methamphetamine-dependent subjects who received modafinil. The results support further trials of modafinil in methamphetamine-dependent patients, although future trials in cocaine-dependent patients from this treatment population were not likely to be viable. Modafinil appeared to be modestly effective in reducing, but not stopping, methamphetamine use in selected patients. Multi-centre trials with larger sample sizes, and measures sensitive enough to detect quantitative changes in psychostimulant use would be needed to confirm the findings. Blood pressure and weight may be important indicators of clinical outcome, and warrant particular attention in future trials, particularly given the cardio-toxicity of both methamphetamine and cocaine. Strategies to enhance medication adherence including a higher dose and counselling adherence are recommended to improve outcomes. Given the predominance of behavioural and psychosocial factors in psychostimulant dependence, it is likely that the role of medications such as modafinil will be as an adjunct to psychosocial therapy.

Psychostimulant dependence is a major public health issue in many parts of the world associated with a wide range of psychological, medical and social problems. Psychosocial interventions are the mainstay of treatment for psychostimulant problems, although their effectiveness is compromised by poor uptake and compliance. Despite increasing knowledge of the neurobiological consequences of psychostimulant use, no medications to date have been any more successful than placebo in reducing psychostimulant use in dependent patients. Modafinil is a non-amphetamine type psychostimulant that may have potential as an agonist pharmacotherapy for psychostimulant dependence. The aim of this thesis was to examine the safety, efficacy and cost-effectiveness of modafinil 200 mg/day over ten weeks plus a four session brief CBT intervention for methamphetamine and cocaine dependence through two concurrent randomised placebo controlled trials. There were no statistically significant differences between modafinil and placebo in treatment retention, medication adherence, psychostimulant abstinence, psychostimulant craving or severity of psychostimulant dependence. Methamphetamine-dependent subjects tended to provide more illicit psychostimulant negative urine samples while in treatment than those who received placebo. There appeared to be a reduction in self-reported days of psychostimulant use among methamphetamine-dependent subjects who received modafinil compared to placebo, but the effect size was too small to be statistically significant in this sample. The reduction in self-reported psychostimulant use did reach statistical significance in methamphetamine-dependent subjects with no other substance dependence. Uptake of counselling was the most significant predictor of reduced psychostimulant use post treatment, and the addition of counselling improved the cost-effectiveness of modafinil relative to placebo. Modafinil appeared to be safe, well-tolerated, and non-reinforcing in this treatment population. Compared to placebo, there was a significant increase in weight in subjects who completed the 10-week course of treatment, and a significant decrease in systolic blood pressure in methamphetamine-dependent subjects who received modafinil. The results support further trials of modafinil in methamphetamine-dependent patients, although future trials in cocaine-dependent patients from this treatment population were not likely to be viable. Modafinil appeared to be modestly effective in reducing, but not stopping, methamphetamine use in selected patients. Multi-centre trials with larger sample sizes, and measures sensitive enough to detect quantitative changes in psychostimulant use would be needed to confirm the findings. Blood pressure and weight may be important indicators of clinical outcome, and warrant particular attention in future trials, particularly given the cardio-toxicity of both methamphetamine and cocaine. Strategies to enhance medication adherence including a higher dose and counselling adherence are recommended to improve outcomes. Given the predominance of behavioural and psychosocial factors in psychostimulant dependence, it is likely that the role of medications such as modafinil will be as an adjunct to psychosocial therapy.

Introdução: nas quatro últimas décadas, os medicamentos psicotrópicos assumiram uma significativa importância na vida de milhões de pessoas. Os custos diretos e indiretos associados aos psicotrópicos são frequentemente desconhecidos. Aspectos econômicos dos psicotrópicos foram estudados em outros países, mas essas informações ainda são escassas no Brasil. Uma fonte de dados para estudos sobre despesas familiares e gastos em saúde é a Pesquisa de Orçamentos Familiares. Objetivos: desenhar o perfil de brasileiros que adquirem medicamentos psicotrópicos, bem como, avaliar o gasto com esses medicamentos e o seu impacto no orçamento familiar brasileiro nos últimos anos. Métodos: estudo transversal, onde os dados utilizados são provenientes da Pesquisa de Orçamentos Familiares de 2002-2003 e de 2008-2009, envolvendo entrevistas de uma amostra complexa, composta por 48.470 domicílios pesquisados em 2003, 128.300 pessoas e 55.970 domicílios visitados em 2009. Modelos de regressão multivariáveis de Poisson com variância robusta foram construídos através do SAS/SUDAAN 10.0.1. Todos os rendimentos e despesas foram convertidos para valores mensais e corrigidos para a inflação do período. Resultados: a prevalência de aquisição de psicotrópicos pela população brasileira em 2008-2009 foi de 5,2% (IC95%=5,0-5,5), resultando em um gasto anual de R$507 milhões. Essa aquisição foi mais frequente em mulheres, indivíduos brancos, de idades mais avançadas, que não vivem com o cônjuge, com grau mais 9 elevado de instrução e de maior renda. Indivíduos que gastaram com psicotrópicos apresentaram despesas maiores com plano de saúde (RP=1,40, IC95%: 1,30-1,50) e consultas médicas (RP=2,51, IC95%: 2,32-2,72). A média mensal de despesas com psicotrópicos, por domicílio, aumentou de R$ 54,38 em 2003 para R$ 78,73 em 2009, com os valores já corrigidos pela inflação. Entre os domicílios que não gastaram com psicotrópicos, a renda média mensal per capita foi de R$1.026,73 e os gastos mensais per capita foram de, em média, R$73,92 com saúde, R$130,17 com alimentação e R$12,77 com lazer. Entre os domicílios que adquiriram psicotrópicos, a renda média mensal per capita foi de R$1.154,40 e, suas despesas mensais médias, per capita, de R$210,38 com saúde, R$162,08 com alimentação e R$15,45 com lazer. Conclusões: houve um aumento acima da inflação nos gastos com medicamentos psicotrópicos entre os anos avaliados. A aquisição desses medicamentos está relacionada a famílias de níveis socioeconômicos mais elevados. As diferenças encontradas podem representar diferentes níveis tanto de acesso aos serviços médicos de diagnóstico e tratamento quanto aos próprios medicamentos. O orçamento das famílias brasileiras não parece mostrar remanejamento de recursos em função da compra de psicotrópicos. Se a mudança epidemiológica, em sua primeira etapa, representou a transição das doenças infecciosas para as doenças crônicas não transmissíveis, o quadro que pode representar o futuro seriam as doenças neurodegenerativas, mantidas as tendências de aumento da expectativa de vida. / Introduction: over the past four decades the use of psychotropic drugs increased its relevancy to the lives of millions of people. The direct and indirect costs associated to psychotropics are usually unknown. Economic aspects of psychotropic medicine have been studied in other countries, although such information is still scarce in Brazil. A data source for studies about household expenditure and health care costs is the Survey on Household Budgets. Objectives: to draw a profile of Brazilian people that acquire psychotropic drugs, as well as evaluate spends with these medicine and its impacts on the Brazilian household budget on the recent years. Methods: a cross-sectional study, with data used are from the Survey on Household Budgets from 2002-2003 and from 2008-2009, which involved interviews of a complex sample made of 48,470 households on 2003, 128,300 people and 55.970 homes in 2009. Poisson multilevel regression models with robust variance were made by SAS/SUDAAN 10.0.1. All income and spends were adjusted to a monthly basis and indexed by inflation. Results: the prevalence of psychotropics acquisition in the Brazilian population in 2008-2009 was of 5.2% (CI95%=5.0-5.5), resulting in an annual expenditure of R$507 millions. The use of psychotropic drugs was more frequent among women, white people, older people, do not co-habit with a spouse or partner, more schooled and wealthier. Individuals that spent with psycotropics had more 11 spends with health insurance (PR=1.40, CI95%: 1.30-1.50) and medical consults (PR=2.51, CI95%: 2.32-2.72). The average monthly spends with psychotropics per household increased from R$54.38 in 2003 to R$78.73 in 2009, with values indexed by inflation. Among the households that did not purchase psychotropics, the average monthly per capita income was of R$1,026.73 and the monthly per capita spends were, in average, of R$73.92 with health care, R$103.17 with food and R$12.77 with leisure. Among the household that presented expenditure with psychotropics, the average monthly per capita income was of R$1,154.40 and its average monthly per capita spends were of R$210.38 with health care, R$162.087 with food and R$15.45 with leisure. Conclusion: there was an above inflation increase in the psychotropic drugs spends between the evaluated years. The psychotropics acquisition relates to higher socio-economic leveled families. The differences that were found may represent different levels of access to medical diagnose and treatment and to medication. The Brazilian household budgets do not seem to re-adequate resources to meet the purchase of psychotropics. If the epidemiologic change, at its first stage, represented the transition from infectious diseases to non-transmissive chronic illnesses. the picture that can represent the future would be the neurodegenerative diseases, if the trend of increasing life expectancy is kept.

In my diploma thesis, I researched the effect of mirtazapine on a developing embryo. Nowadays, new drugs are being developed and used for the treatment of depression. These drugs also include mirtazapine. The risk of using mirtazapine during pregnancy has not been documented yet and therefore it can not be used by pregnant women. These drugs are often very effective and well tolerated so it is very important to recognize the effect on a developing embryo. In our research, we used the method of CHEST (chick embryotoxicity screening test). We applied a dose of mirtazapine solution dissolved in DMSO to 4-day old chickens. The doses were 0.2µg, 0.15µg, 0.1µg, 0.05µg, 0.03µg in 3µl of the solution. As controls, we applied 3µl DMSO and 3µl destilled water. Embryos were being incubated for 5 days in an incubator and on the 9th day, we evaluated dead and malformed embryos and the spectrum of defects. From our observations, we have obtained the lethal dose, which was above 0.15µg and the dose that was equivalent to the LD50 - 0.05µg. Lower doses were safe, although these embryos were malformed. These malformations, however, were not statistically significantly different from the malformations occurring in controls. It is neccessary to continue and complete data for 2 -and 3-day old embryos, so that we cover all...

Introdução: nas quatro últimas décadas, os medicamentos psicotrópicos assumiram uma significativa importância na vida de milhões de pessoas. Os custos diretos e indiretos associados aos psicotrópicos são frequentemente desconhecidos. Aspectos econômicos dos psicotrópicos foram estudados em outros países, mas essas informações ainda são escassas no Brasil. Uma fonte de dados para estudos sobre despesas familiares e gastos em saúde é a Pesquisa de Orçamentos Familiares. Objetivos: desenhar o perfil de brasileiros que adquirem medicamentos psicotrópicos, bem como, avaliar o gasto com esses medicamentos e o seu impacto no orçamento familiar brasileiro nos últimos anos. Métodos: estudo transversal, onde os dados utilizados são provenientes da Pesquisa de Orçamentos Familiares de 2002-2003 e de 2008-2009, envolvendo entrevistas de uma amostra complexa, composta por 48.470 domicílios pesquisados em 2003, 128.300 pessoas e 55.970 domicílios visitados em 2009. Modelos de regressão multivariáveis de Poisson com variância robusta foram construídos através do SAS/SUDAAN 10.0.1. Todos os rendimentos e despesas foram convertidos para valores mensais e corrigidos para a inflação do período. Resultados: a prevalência de aquisição de psicotrópicos pela população brasileira em 2008-2009 foi de 5,2% (IC95%=5,0-5,5), resultando em um gasto anual de R$507 milhões. Essa aquisição foi mais frequente em mulheres, indivíduos brancos, de idades mais avançadas, que não vivem com o cônjuge, com grau mais 9 elevado de instrução e de maior renda. Indivíduos que gastaram com psicotrópicos apresentaram despesas maiores com plano de saúde (RP=1,40, IC95%: 1,30-1,50) e consultas médicas (RP=2,51, IC95%: 2,32-2,72). A média mensal de despesas com psicotrópicos, por domicílio, aumentou de R$ 54,38 em 2003 para R$ 78,73 em 2009, com os valores já corrigidos pela inflação. Entre os domicílios que não gastaram com psicotrópicos, a renda média mensal per capita foi de R$1.026,73 e os gastos mensais per capita foram de, em média, R$73,92 com saúde, R$130,17 com alimentação e R$12,77 com lazer. Entre os domicílios que adquiriram psicotrópicos, a renda média mensal per capita foi de R$1.154,40 e, suas despesas mensais médias, per capita, de R$210,38 com saúde, R$162,08 com alimentação e R$15,45 com lazer. Conclusões: houve um aumento acima da inflação nos gastos com medicamentos psicotrópicos entre os anos avaliados. A aquisição desses medicamentos está relacionada a famílias de níveis socioeconômicos mais elevados. As diferenças encontradas podem representar diferentes níveis tanto de acesso aos serviços médicos de diagnóstico e tratamento quanto aos próprios medicamentos. O orçamento das famílias brasileiras não parece mostrar remanejamento de recursos em função da compra de psicotrópicos. Se a mudança epidemiológica, em sua primeira etapa, representou a transição das doenças infecciosas para as doenças crônicas não transmissíveis, o quadro que pode representar o futuro seriam as doenças neurodegenerativas, mantidas as tendências de aumento da expectativa de vida. / Introduction: over the past four decades the use of psychotropic drugs increased its relevancy to the lives of millions of people. The direct and indirect costs associated to psychotropics are usually unknown. Economic aspects of psychotropic medicine have been studied in other countries, although such information is still scarce in Brazil. A data source for studies about household expenditure and health care costs is the Survey on Household Budgets. Objectives: to draw a profile of Brazilian people that acquire psychotropic drugs, as well as evaluate spends with these medicine and its impacts on the Brazilian household budget on the recent years. Methods: a cross-sectional study, with data used are from the Survey on Household Budgets from 2002-2003 and from 2008-2009, which involved interviews of a complex sample made of 48,470 households on 2003, 128,300 people and 55.970 homes in 2009. Poisson multilevel regression models with robust variance were made by SAS/SUDAAN 10.0.1. All income and spends were adjusted to a monthly basis and indexed by inflation. Results: the prevalence of psychotropics acquisition in the Brazilian population in 2008-2009 was of 5.2% (CI95%=5.0-5.5), resulting in an annual expenditure of R$507 millions. The use of psychotropic drugs was more frequent among women, white people, older people, do not co-habit with a spouse or partner, more schooled and wealthier. Individuals that spent with psycotropics had more 11 spends with health insurance (PR=1.40, CI95%: 1.30-1.50) and medical consults (PR=2.51, CI95%: 2.32-2.72). The average monthly spends with psychotropics per household increased from R$54.38 in 2003 to R$78.73 in 2009, with values indexed by inflation. Among the households that did not purchase psychotropics, the average monthly per capita income was of R$1,026.73 and the monthly per capita spends were, in average, of R$73.92 with health care, R$103.17 with food and R$12.77 with leisure. Among the household that presented expenditure with psychotropics, the average monthly per capita income was of R$1,154.40 and its average monthly per capita spends were of R$210.38 with health care, R$162.087 with food and R$15.45 with leisure. Conclusion: there was an above inflation increase in the psychotropic drugs spends between the evaluated years. The psychotropics acquisition relates to higher socio-economic leveled families. The differences that were found may represent different levels of access to medical diagnose and treatment and to medication. The Brazilian household budgets do not seem to re-adequate resources to meet the purchase of psychotropics. If the epidemiologic change, at its first stage, represented the transition from infectious diseases to non-transmissive chronic illnesses. the picture that can represent the future would be the neurodegenerative diseases, if the trend of increasing life expectancy is kept.

Atualmente os psicofármacos têm apresentado altas prevalências de consumo pela população. Visando fornecer subsídios para formulação de estratégias de gerenciamento de segurança no uso destes fármacos, o presente estudo teve como objetivos: identificar, entre pacientes internados em clínicas médica e cirúrgica de um hospital geral, a prevalência do uso de psicofármacos e, analisar a relação do uso destes fármacos com as variáveis demográficas, socioeconômicas e farmacoterapêuticas, com o histórico de saúde e com o resultado da aplicação do instrumento SRQ-20. Foi realizado estudo de corte transversal, com desenho correlacional descritivo e abordagem quantitativa, com 93 pacientes das clínicas em estudo. Para coleta dos dados utilizou-se a entrevista norteada por um questionário envolvendo as variáveis em estudo e pelo instrumento SRQ-20 (Self-Reporting Questionnaire), para a detecção de transtornos mentais comuns. Em seguida, foi verificado o prontuário destes pacientes, buscando a presença de prescrição de psicofármacos. Para avaliar a influência das variáveis independentes sobre o consumo de psicofármacos, foram investigadas associações estatísticas usando o teste Qui-quadrado. Para estimar a Razão de prevalência foi utilizado o modelo de regressão log-binomial simples e múltiplo. O ajuste do modelo foi feito através do procedimento PROC GENMOD do software SAS versão 9.0. Observou-se a prevalência de 38,71% de usuários de psicofármacos, evidenciando a associação do uso de psicofármacos com as variáveis sexo, custeio da internação, religião e resultado positivo no SRQ-20. Os benzodiazepínicos foram os psicofármacos mais consumidos pela amostra (64%), seguidos pelos antidepressivos (32%). As indicações dos benzodiazepínicos relatadas pelos pacientes foram: \"para dormir\" (54%), para \"depressão\" (14%), e para \"ansiedade\" (7%). A principal indicação dos antidepressivos foi a \"depressão\" (50%). Identificou-se que 25% e 22% dos pacientes estavam consumindo, respectivamente, benzodiazepínicos e antidepressivos, sem ter o conhecimento deste fato. Verificou-se que 70% das prescrições de psicofármacos foram realizadas por médicos não-psiquiatras, sendo os benzodiazepínicos a classe mais prescrita pelos não-psiquiatras e os antidepressivos os mais prescritos pelos psiquiatras. Dentre os pacientes em uso de psicofármacos, 59% realizavam apenas tratamento farmacológico, 27,8% possuíam diagnóstico de transtorno mental, 36,1% obtiveram resultado positivo e 36,1% obtiveram resultado negativo no SRQ-20. Foi identificada a automedicação em 5% dos pacientes. Espera-se que a presente pesquisa contribua para despertar a preocupação necessária relacionada ao tema, para a melhoria das informações que devem ser consideradas pelos profissionais de saúde quanto ao tratamento com psicofármacos bem como para implementação de estratégias direcionadas ao uso racional destes medicamentos. / Currently, psychotropic drugs have shown high prevalence rates of consumption by the population. Aiming to provide subsidies for formulation of strategies of security management in the use of these drugs, this study aimed to identify, among patients hospitalized in medical and surgical clinics of a general hospital, the prevalence of psychotropic use and analyze the relationship between the use of these drugs and the demographic, socioeconomic and pharmacotherapeutics variables, with the health history and the result of applying the SRQ-20. A cross sectional study with descriptive correlational design and quantitative approach was performed with 93 patients in the clinics. For data collection, an interview guided by a questionnaire involving the study variables and by the SRQ-20 (Self-Reporting Questionnaire) was used for the detection of common mental disorders. Then, the records of these patients were checked, looking for the presence of psychotropic prescription. To evaluate the influence of independent variables on the consumption of psychotropic drugs, statistical associations were investigated using Chi-square test. To estimate the prevalence ratio was used the simple and multiple log-binomial regression models. The model fit was achieved using the PROC GENMOD procedure of SAS software version 9.0. It was observed the prevalence of 38.71% of psychotropic drug users, showing the association between the use of psychiatric drugs and sex, cost of hospitalization, religion and positive result on the SRQ-20. Benzodiazepines were the most consumed psychotropic drugs by the individuals of the sample (64%), followed by antidepressants (32%). The indications of benzodiazepines reported by patients were: \"to sleep\" (54%), for \"depression\" (14%), and \"anxiety\" (7%). The main indication of antidepressants was \"depression\" (50%). It was found that 25% and 22% of the patients were taking, respectively, benzodiazepines and antidepressants, without having knowledge of this fact. It was found that 70% of prescriptions of psychotropic drugs were performed by physicians non-psychiatrists, and the most prescribed by non-psychiatrists were benzodiazepines and the most prescribed by psychiatrists were antidepressants. Among the patients using psychotropic drugs, 59% performed only pharmacological treatment, 27.8% had a diagnosis of mental disorder, 36.1% had positive outcome, and 36.1% had negative outcome in the SRQ- 20. Self-medication was identified in 5% of patients. It is expected that this research contributes to arouse the concern related to this theme required for the improvement of information that should be considered by health professionals regarding treatment with psychotropic drugs and to implement strategies aimed at the rational use of medicines.

Zinberg's Interaction Model implies that the content of a drug-induced experience is a function of the pharmacological properties of the drug, the set (the user’s characteristics e.g. motivation and personality), and the setting (the physical and social context). The current research investigated the function of the set and setting and their role in shaping the psychological effects of 3,4-methylenedioxmethamphetamine (MDMA), as well as their role in reducing the risk of drug abuse. An online survey was distributed among adult MDMA polydrug users (n = 158) and MDMA-naïve controls (alcohol, nicotine and cannabis users, n = 138). Participants answered questions regarding their pattern of drug use, their motivation for MDMA use and the setting (e.g. clubbing, home with friends), as well as the subjective effects of MDMA. Participants also completed a range of self-report measures of self-reflection and insight, emotional intelligence, and personality, as well as a drug dependency measure. MDMA users displayed higher levels of self-reflection and insight, openness to new experience and lower levels of neuroticism and conscientiousness, in comparison to the control group. The significant predictors of self-reflection and insight were openness, emotional intelligence, MDMA use, extraversion and neuroticism. When the analysis was rerun only for the MDMA group, the significant predictors of self-reflection and insight were openness, emotional intelligence and self-insight effects of MDMA. High levels of self-reported negative effects of MDMA were predictors of a problematic drug use. These findings suggest that there might be a relationship between MDMA use and higher levels of self-reflection and insight; however, longitudinal studies are required to further investigate the causality of this relationship. The results add to existing evidence that MDMA has potential for altering emotional experiences. Further research utilising a prospective design is warranted.

The purpose of this study was to identify barriers to psychotropic adherence regimens in clients with Severe and Persistent Mental Illness (SPMI). Medication non-adherence perpetuates the cycle of psychotic episodes, which leads to rehospitalization, incarceration, and homelessness.

The overall aim of this study was to investigate the association between family structure in childhood and mental health problems in young adulthood. A prospective cohort study was conducted with 481,777 individuals with complete follow-up information, which was obtained from national registers in Sweden. Individuals who were living with only one biological parent at age 17 were compared with those who grew up with two parents with regard to retrieval of prescribed psychotropic drugs at age 35. The association was examined by Cox regression analyses with equal survival time for all individuals included in the analyses. The results demonstrated a higher risk for retrieval of psychotropic medicines among the individuals who grew up with only one parent, with hazard ratio of 1,21 (95%CI: 1,19-1,23). The multivariate analyses showed that a part of the association was explained by familial and individual factors, namely parents’ country of origin, area of residence, parents’ and the individual’s educational attainment, receipt of social benefits and parents’ history of psychiatric disorder. The results indicated that the increased risk of mental health problems among individuals who grew up with only one parent might be accounted for by various psychological, social and economic factors associated to parental separation.

published_or_final_version / Social Work / Master / Master of Social Work