Submitted by Ismael Pereira (ismael@neuro.ufrn.br) on 2017-11-03T14:45:12Z No. of bitstreams: 1 Tese_AdrianoTort_2005.pdf: 1861214 bytes, checksum: 93eb092dffbce7414f26253895b0ad28 (MD5) / Approved for entry into archive by Ismael Pereira (ismael@neuro.ufrn.br) on 2017-11-03T14:46:05Z (GMT) No. of bitstreams: 1 Tese_AdrianoTort_2005.pdf: 1861214 bytes, checksum: 93eb092dffbce7414f26253895b0ad28 (MD5) / Made available in DSpace on 2017-11-06T11:41:34Z (GMT). No. of bitstreams: 1 Tese_AdrianoTort_2005.pdf: 1861214 bytes, checksum: 93eb092dffbce7414f26253895b0ad28 (MD5) Previous issue date: 2005-12 / Os objetivos da presente tese de doutorado foram os de buscar novos antipsic?ticos at?picos de baixo pre?o comercial e tamb?m procurar entender o mecanismo de a??o que leva a um perfil antipsic?tico at?pico. Os resultados da tese s?o divididos em duas partes, de acordo com sua natureza, em experimentais (primeira parte) e te?ricos (segunda parte). Para o desenvolvimento da primeira parte, foi necess?ria primeiramente a programa??o de um software para medir locomo??o em roedores ap?s filmagem com webcam. A seguir, foram investigados os efeitos da guanosina, flunarizina e cinarizina em modelos animais de psicose, bem como em outros paradigmas comportamentais. A guanosina foi escolhida para estudo uma vez que tem se mostrado que ela interage com o sistema glutamat?rgico ? que sabidamente est? envolvido na fisiopatologia da esquizofrenia ? promovendo a capta??o astrocit?ria de glutamato. J? a flunarizina e a cinarizina, dois bloqueadores de canal de c?lcio empregados para tratar enxaqueca e vertigem foram escolhidas pelo fato delas produzirem sinais e sintomas extrapiramidais em pacientes idosos, o que posteriormente foi relacionado ?s suas propriedades como antagonistas moderados dos receptores dopamin?rgicos do tipo D2. A guanosina diminuiu o aumento de locomo??o induzido por um antagonista NMDA (MK-801), enquanto que n?o apresentou efeito sobre o aumento de locomo??o induzido por anfetamina, de forma que sua utilidade como potencial antipsic?tico deve ser ainda melhor estudada. Tanto a flunarizina quanto a cinarizina foram capazes de diminuir o aumento de locomo??o induzido por MK-801 e por anfetamina em doses que n?o causam efeitos catal?pticos importantes. Portanto, foi conclu?do que estes dois compostos apresentam um potencial perfil de antipsic?tico at?pico, com as vantagens de j? estarem dispon?veis para uso comercial, boa tolerabilidade e baixo custo quando comparados com os antipsic?ticos at?picos dispon?veis comercialmente nos dias de hoje. A segunda parte da tese apresenta alguns resultados te?ricos matem?ticos que podem ser derivados da teoria da lei de a??o das massas aplicada ao binding de receptores, utilizando tamb?m resultados experimentais j? conhecidos de PET. Estes resultados apresentam insights ao entendimento das diferen?as entre os perfis antipsic?ticos at?picos e t?picos em rela??o ? gera??o de sinais extrapiramidais. ? discutido que fatores culturais e comerciais relacionados ? posologia atual empregada no tratamento com antipsic?ticos t?picos podem ser os respons?veis pelas diferen?as de perfis, uma vez que alguns deles s?o prescritos em doses proporcionalmente maiores em rela??o ? sua afinidade, atingindo assim maiores n?veis de bloqueio dopamin?rgico no estriado. Uma curta meia-vida plasm?tica tamb?m ? apontada como um poss?vel par?metro importante na gera??o de um perfil at?pico. ? mostrado ainda alguns erros de concep??o relacionados ao curso temporal da ocupa??o dopamin?rgica que tem sido atualmente cometidos na literatura cient?fica, como o conceito de meia-vida de ocupa??o de receptores. Como um ?ltimo resultado te?rico, ? proposto um algoritmo para a redu??o de dose em pacientes tratados com antipsic?ticos apresentando sinais e sintomas extrapiramidais. / The aims of this work were the search for new atypical antipsychotics presenting low cost and the understanding of the mechanism of action leading to atypical antipsychotic profile. The results obtained are presented in two distinct parts based on their nature, namely, experimental (first part) or theoretical (second part). For the development of the first part, a webcam based software to measure locomotion of rodents was programmed. After that, it was investigated the effect of guanosine, flunarizine and cinnarizine on animal models of psychosis, as well as in other behavioral tasks. Guanosine was chosen because it has been shown to interact with the glutamatergic system ? which is known to be involved in the pathophysiology of schizophrenia ? by promoting astrocytic glutamate reuptake. Flunarizine and cinnarizine, two calcium channel blockers commonly used in many countries to treat vertigo and migraine, were chosen because they were shown to induce extrapyramidal signs in elder patients, which was later related to moderate antagonist properties at dopamine D2 receptors. Guanosine was able to reduce a NMDA antagonist (MK-801) induced hyperlocomotion, whereas it had no effect on the hyperlocomotion induced by amphetamine, and it is discussed that its utility as antipsychotic drug should be further evaluated. Both cinnarizine and flunarizine were able to reduce the hyperlocomotion induced by MK-801 and amphetamine at doses that presented no significant cataleptic behavior. It was therefore concluded that these compounds have a potential atypical antipsychotic profile, with the advantage of already approved for commercial use, presenting well tolerability and very low cost when compared to current commercially available atypical antipsychotics. The second part of this thesis presents some theoretical mathematical results that can be derived from the law of mass action theory applied to receptor binding linked with known PET experimental data. These results present insights to the understanding of the differences between typical and atypical profile of antipsychotics regarding the generation of extrapyramidal syndrome. It is argued that cultural and commercial aspects related to the nowadays employed posology of typical antipsychotics can be responsible for the difference seen in profile, once some typical antipsychotics are prescribed in proportionally higher doses in relation to their affinities, leading therefore to higher dopaminergic blockade. A short plasmatic half-life is also pointed as a possible important factor leading to an atipical profile. Moreover, the second part of this thesis also points to some misconception currently being used in the scientific literature regarding the time-course of dopaminergic occupation, such as the concept of receptor occupation half-life. As a last theoretical based result, it is proposed an algorithm for antipsychotic dose reduction in patients presenting extrapyramidal signs and symptoms.

A esquizofrenia à uma doenÃa heterogÃnea quanto a caracterÃsticas e gravidade dos sintomas. Diversas alteraÃÃes relacionadas ao sono, com possÃveis efeitos sobre a capacidade funcional, foram descritas. Dentre os poucos estudos que registraram ritmo circadiano na esquizofrenia, alguns sugerem que os indivÃduos com alteraÃÃes de ritmo apresentam menor rendimento em testes neuropsicolÃgicos. Os estudos neuropsicolÃgicos com pacientes esquizofrÃnicos dÃo conta de um comprometimento de diversos tipos de funÃÃes incluindo a memÃria operacional tanto verbal quanto viso-espacial. Muitos desses testes sÃo considerados longos e complicados e a utilidade de cada um deles ainda nÃo està esclarecida. Este trabalho teve por objetivo: avaliar os padrÃes do sono, o cronotipo, o perfil neurocognitivo e as suas relaÃÃes com parÃmetros clÃnicos e funcionais. Trata-se de estudo observacional, transversal, de pacientes com esquizofrenia, em uso de antipsicÃticos convencionais ou de Ãltima geraÃÃo, quanto à capacidade funcional, alteraÃÃes do sono e perfil neurocognitivo. Foram utilizadas medidas para avaliaÃÃo da capacidade de funcionamento (Escala de AvaliaÃÃo Global do Funcionamento â AGF), gravidade das comorbidades (Cumulative Illness Rating Scale â CIRS), qualidade do sono (Ãndice de Qualidade de Sono de Pittsburgh â IQSP), sonolÃncia diurna (Escala de sonolÃncia de Epworth â ESE), cronotipo (QuestionÃrio de Horne e Ãstberg) e uma bateria de testes neurocognitivos incluindo os testes de Stroop, DÃgitos Direto e Indireto, Corsi Direto e Indireto e FluÃncia Verbal (CategÃrico). Foram estudados 82 pacientes (51,2% do sexo masculino) com idade entre 17 e 59 anos (35,2Â10,4) em uso de antipsicÃticos convencionais (N=22), olanzapina (N=30) ou risperidona (N=30). Observou-se mÃ-qualidade do sono (IQSP>5) em 41 (50%) e sonolÃncia excessiva diurna (ESE≥10) em 20 (24,4%) pacientes. A mà qualidade do sono associou-se com o gÃnero feminino (P=0,01). Uma tendÃncia de associaÃÃo entre a capacidade funcional e a qualidade do sono (P=0,07) foi registrada. Observou-se que a pior capacidade funcional associou-se com a idade mais avanÃada, um nÃmero reduzido de anos escolares e maior gravidade das comorbidades. Com relaÃÃo ao cronotipo e considerando o grupo total, 08 pacientes (9,8%) eram do tipo definitivamente vespertino, 39 (47,6%) eram do tipo moderadamente vespertino, 33 (40,2%) eram do tipo indiferente, dois (2,4%) eram moderadamente do tipo matutino e nenhum era definitivamente matutino. Os pacientes mais jovens e do sexo masculino apresentavam uma preferÃncia mais vespertina (F= 6,32; P= 0,01), de forma semelhante à populaÃÃo em geral. Os casos em uso de antipsicÃticos convencionais apresentaram uma tendÃncia para maior preferÃncia vespertina. As comorbidades mais frequentemente relatadas relacionaram-se a queixas osteoarticulares, sintomas psicolÃgicos e alteraÃÃes metabÃlicas. Os testes neurocognitivos apresentaram-se alterados na maioria dos casos, observando-se que a maioria dos pacientes apresentava escores inferiores a 80% dos valores historicamente normais. O teste de Stroop relacionou-se com a AGF apÃs controle para a idade e escolaridade (F= 6,43; P= 0,001). O teste de DÃgitos Indireto relacionou-se com a AGF apÃs controle para o gÃnero, a escolaridade e o tipo de antipsicÃtico (F= 4,76; P= 0,003). O teste de Corsi Direto relacionou-se com a capacidade global de funcionamento apÃs ajuste para o gÃnero (F= 3,68; P= 0,01). O teste de Corsi Indireto relacionou-se com a capacidade global de funcionamento apÃs ajuste para o gÃnero, escolaridade e tipo de tratamento (F=3,03; P= 0,02). Os testes de Stroop e DÃgitos Indireto associaram-se mais fortemente e de forma independente com a capacidade funcional seguidos pelo Teste de Corsi Direto e Indireto. Observou-se uma relaÃÃo entre o sexo feminino e a alteraÃÃo do Teste de Corsi Indireto que avalia memÃria espacial. Em conclusÃo, mà qualidade do sono à comum e associa-se ao sexo feminino. Observa-se uma tendÃncia de associaÃÃo entre a qualidade do sono e a capacidade funcional. No grupo geral, a preferÃncia vespertina foi predominante. Os testes neurocognitivos estavam alterados na maioria dos casos. Os testes de Stroop e DÃgitos Indireto, dois testes de realizaÃÃo rÃpida e fÃcil que avaliam a memÃria operacional, foram os que melhor se associaram com a capacidade funcional. / Clinical characteristics and symptom severity are heterogeneous in schizophrenia making the course and outcome less predictable. Sleep disturbances have been frequently described in association with this illness and may have deleterious effect on functional abilities. A few studies have described circadian changes in schizophrenia and some suggest a relationship between circadian alterations and poor performance after neuropsychological tests. Previously, it has been shown that patients with schizophrenia have impairment of verbal and visual-spatial working memory. However, many of these tests are laborious, complicated and time consuming. The utility of the several available neuropsychological tests in schizophrenia is not yet totally clarified. We have aimed to study sleep alterations, morning-evening preference, neurognitive function and their relationship with clinical variables. This is a cross-sectional study of patients with schizophrenia on use of conventional or atypical antipsychotic regarding functional abilities, sleep alterations and cognitive function. Assessment procedures involved the use of the Global Assessment of Functioning (GAF) Scale, Cumulative Illness Rating Scale (CIRS), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Horne e Ãstberg questionnaire, and a neuropsychological battery that included the WAIS Digit Span Forward and Backward, Corsi block-tapping task (Forward and Backward), Stroop Color Word Interference Test and the Phonemic Verbal Fluency Test. We studied 82 patients (51.2% male) aged 17 to 59 years (35.2Â10.4). Twenty-two were using conventional antipsychotic, 30 olanzapine and 30 risperidone. Poor sleep quality (PSQI>6) was observed in 41 subjects (50%) and excessive daytime sleepiness (ESE≥10) in 20 (24.4%). Female gender was associated with poor sleep quality (P=0.01). A trend of association between quality of sleep and GAF was observed (P=0.07). Worse disability, as evaluated by GAF, was associated with age, reduced number of school years and greater comorbidity severity. In relation to morning-evening preference, eight patients (9.8%) were definitely evening, 39 (47.6%) were moderately evening 33 (40.2%) were indifferent, 2 (2.4%) were moderately morning and none were definitely morning type. Younger patients and of male gender showed more evening preference (F= 6.32; P= 0.01) similar to previous reports in the literature. Frequent comorbidities were related to osteoarticular complaints, psychological symptoms, and metabolic alterations. Neuropsychological tests were altered in the vast majority of patients with values below 80% of historical normal values. The Stroop test was associated with GAF after controlling for age and school years (F= 6.43; P= 0.001). The Digit Span Backward was associated with GAF after controlling for gender, school years and type of antipsychotic (F= 4.76; P= 0.003). The Corsi block-tapping task Forward was associated with GAF after controlling for gender (F= 3.68; P= 0.01). The Corsi block-tapping task Backward was associated with GAF after controlling for gender, number of school years and type of antipsychotic (F=3.03; P= 0.02). The Stroop and Digit Span Backward were best associated with functional ability followed by the Corsi block-tapping task (Forward and Backward). A correlation between female gender and visual-spatial memory as evaluated by the Corsi Block-tapping Task Backward was observed. In conclusion, poor sleep quality is common and more present in women with schizophrenia. A trend between poor sleep quality and functional disability was observed. In general, an evening preference was predominant. Neurocognitive tests were altered in the majority of cases. The Stroop and Digit Span Indirect, two quick and easy to perform tests that evaluate working memory, were those that presented the greater association with global functional ability

INTRODUÇÃO: Acredita-se cada vez mais que o tempo para se observar a resposta ao antipsicótico é curto, sendo possível nas primeiras duas semanas já prever se o paciente responderá em 12 semanas. Entretanto, a maior parte das evidências que sustentam tal hipótese provém da análise de dados de estudos controlados duplo-cegos, que não definiam o conceito de início de ação de antipsicóticos, o que pode gerar uma certa confusão quanto às expectativas de resposta. Neste estudo, testamos se a ausência de melhora mínima de 20% da PANSS nas primeiras duas semanas correlacionava-se a ausência de resposta em 12 semanas. MÉTODOS: Foi feita a avaliação do tempo de resposta ao tratamento antipsicótico, utilizando o algoritmo de tratamento do IPAP, que recomenda o uso de monoterapia por 4 a 6 semanas, e troca por outro antipsicótico em caso de ausência de resposta. Os pacientes incluídos tinham esquizofrenia de início recente pelos critérios DSM-IV e foram aleatorizados para receber tratamento com antipsicótico de primeira geração (APG) ou de segunda geração (ASG). Foi considerada resposta ao tratamento a redução média de pelo menos 30% dos sintomas, em comparação com a PANSS inicial.Os pacientes foram avaliados pela PANSS a cada 2 semanas, durante 12 semanas. RESULTADOS: Foram incluídos 22 pacientes (APG, N=10 e ASG, N=12). Não houve diferença quanto ao tempo ou taxa de resposta entre os grupos; 20% (4) dos pacientes não responderam ao tratamento, enquanto 65% (13) responderam; 15% (3) abandonaram um tratamento. Um paciente não pôde ser avaliado pela PANSS e não teve seus dados incluídos na análise. Não houve correlação entre melhora nas primeiras 2 semanas e resposta em 12 semanas. A mudança média da 11 PANSS em relação ao basal foi significante a partir da 4a semana (p=0,43), e houve melhora progressiva ao longo das 12 semanas. Ambos os grupos tiveram a mesma proporção de substituições de medicamentos, sendo que não houve diferença, em termos de porcentagem de respondedores, entre os que trocaram o medicamento e entre os que permaneceram com a mesma medicação inicial. CONCLUSÕES: A ausência de resposta nas primeiras duas semanas não prediz ausência de resposta em 12 semanas. O tempo para avaliar a resposta clínica a um medicamento antipsicótico é de pelo menos quatro semanas. Aguardar o efeito do medicamento parece ser mais importante que trocar de medicamento nas primeiras 4 semanas / INTRODUCTION: It has been widely accepted that time to observe response to antipsychotic is short, with a response in 2 weeks predicting response or nonresponse in 12 weeks. However, most evidence for this hypothesis come from controlled doubleblind trials, which did not assess the onset of action, but clinical response, generating some false expectancies regarding clinical response. In this study, we assessed whether the lack of improvement in 2 weeks would predict nonresponse in 12 weeks. METHODS: We assessed time to response to antipsychotic through a treatment algorithm IPAP, which recommends monotherapy during 4-6 weeks and switch to another antipsychotic in case of nonresponse. Subjects with recent onset schizophrenia according to DSM-IV criteria were included and randomized to receive first generation antipsychotic (FGA) or second generation (SGA). Response was considered as at least 30% reduction of PANSS. Subjects were assessed every 2 weeks, during the 12-week study period. RESULTS: 22 subjects were included (FGA: 10; SGA: 12). There was no difference between groups in terms of response rate; overall 20% (4) did not respond in 12 weeks and 65% responded; 15% (3) dropped out. Data from one patient was not included in the analysis due to impossibility of assessment with PANSS. No correlation was found between response in 2 weeks and response in 12 weeks. Significant mean change at PANSS was observed in the fourth week (p= 0,43). The need for switch was similar in both groups, and improvement was progressive throughout the 12 weeks. Response rate was similar in the group that switched and the group that remained with first antipsychotic. CONCLUSIONS: Lack of response in 2 weeks does not predict lack 13 of response in 12 weeks. Time to assess clinical response é at least four weeks. Looking forward to drug effect seems to be more important for the outcome in 12 weeks than switching the drug in the first 4 weeks

Abstract Schizophrenia is associated with a shortened life expectancy and increased somatic comorbidity with e.g. cardiovascular disorders. The purpose of this study was to evaluate hyperlipidemia and metabolic syndrome in schizophrenia and thus find specific risk factors for excess mortality and morbidity. The study population was a subsample of the Northern Finland 1966 Birth Cohort, a general population-based birth cohort. In 1997, 8,463 members of the cohort were invited to a clinical examination, where e.g. blood samples were taken after an overnight fast. Total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglycerides (TG) were determined. The following psychiatric diagnostic categories were used: 1) DSM-III-R schizophrenia (n = 31), 2) other psychoses (n = 21), 3) non-psychotic disorders (n = 104), 4) comparison group (n = 5,498), having no psychiatric hospital treatment. Mean TC (5.5 mmol/l) and TG (1.5 mmol/l) were significantly higher in the schizophrenia group than in the comparison group (5.1 mmol/l and 1.2 mmol/l, respectively). To evaluate serum lipid levels in subjects with and without antipsychotic medication the sample was analyzed according to used medication. The prevalence of hypercholesterolemia, high LDL cholesterol and hypertriglyceridemia was high in persons using antipsychotic medication (31%, 20% and 22%, respectively) compared to persons without such medication (12%, 10% and 7%, respectively). We found higher triglyceride levels in patients who were ≤ 20 years old at the onset of schizophrenia (mean 1.7 mmol/l; N = 17) as compared with patients with later onset (mean 1.4 mmol/l; N = 14) or non-hospitalized controls (mean 1.2 mmol/l; N = 5,453). The difference between the first and third group was significant (p < 0.01), and there was a negative correlation between the age at onset and the level of serum triglycerides (r = -0.35, p = 0.05). To evaluate the prevalence of metabolic syndrome, the subjects were assessed for the presence of metabolic syndrome according to the criteria of the National Cholesterol Education Program. The prevalence of metabolic syndrome was high in subjects with schizophrenia compared with the comparison group (19% vs. 6%, p = 0.010). The results indicate an elevated risk for hyperlipidemia and metabolic syndrome in persons with schizophrenia or on antipsychotic medication. Regular monitoring of weight, serum lipid and glucose levels and blood pressure is important. Comprehensive efforts directed at controlling weight and improving physical activity are needed.

<p>Cilj: U istraživanju je posmatrana učestalost agresivnosti i hostilnosti kod osoba sa shizofrenim poremećajem, zatim povezanost težine kliniĉke slike shizofrenog poremećaja sa pojavom i stepenom agresivnosti i hostilnosti, povezanost doze ordiniranih antipsihotika sa stepenom agresivnosti i hostilnosti, kao i razlika u specifiĉnoj antiagresivnoj i antihostilnoj efikasnosti između risperidona i klozapina. Materijal i metode: Ova opservaciona studija je uključila 110 hospitalno lečenih bolesnika sa dijagnozom shizofrenog poremećaja koji su na prijemu u bolnicu imali vrednost ajtema P7 (hostilnost) skale PANSS &ge; 3 i vrednost skale MOAS &ge; 3. Bolesnici su procenjivani skalama PANSS i MOAS svakih sedam dana tokom njihovog bolničkog lečenja. Rezultati: Hostilnost i agresivnost su kao simptomi prisutni kod jedne trećine bolesnika sa dijagnozom shizofrenog poremećaja, a intenziteti hostilnosti i agresivnosti nisu povezani sa težinom kliničke slike poremećaja. Visine doza inicijalno ordiniranih antipsihotika su upravo srazmerne stepenu hostilnosti i agresivnosti bolesnika. Utvrđeno je da postoji specifično antiagresivno i antihostilno dejstvo i klozapina i risperidona, koje je nezavisno od njihovog antipsihotičnog dejstva, a klozapin je tokom posmatranog perioda imao bolju antihostilnu efikasnost. Zaključak: Agresivnost i hostilnost predstavljaju često prisutnu, značajnu, ali nezavisnu dimenziju shizofrenog poremećaja, a izbor antipsihotika se pored antipsihotične efikasnosti mora zasnivati i na njihovoj specifičnoj antiagresivnoj efikasnosti.</p> / <p>Objective: Frequency of aggression and hostility was observed in patients with schizophrenia, as well as the connection of symptom&rsquo;s severity with the appearance and level of aggression and hostility. The connection between the applied doses of antipsychotics with the level of aggression and hostility was observed, as well as differences in the specific antiagressive and antihostile efficacy of risperidone and clozapine. Materials and Methods: This observational study involved 110 hospitalized patients diagnosed with schizophrenia who had scores &ge; 3 on item P7 (hostility) of PANSS scale and score &ge; 3 on MOAS scale. Patients were evaluated every seven days during their hospitalization. Results: Hostility and aggression were present in one-third of schizophrenic patients on their hospital admission and their intensity was not related to the severity of the symptoms of schizophrenia. The dose of initially administered antipsychotics was proportional to the level of patient&rsquo;s hostility and aggression. It has been found that there is a specific antiaggressive and antihostile efficacy of clozapine and risperidone, which is independent of their antipsychotic efficacy, and that clozapine has a better antihostile efficacy during the observed period. Conclusion: Aggression and hostility are often present, important, but an independent dimension of schizophrenia, and the selection of antipsychotic must be based on it&rsquo;s specific antiaggressive efficacy, in addition to it&rsquo;s antipsychotic efficacy.</p>

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23408号 / 医博第4753号 / 新制||医||1052(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 中山 健夫, 教授 古川 壽亮, 教授 村井 俊哉 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Bakgrund: Forskning visar att antipsykotisk medicinering är en förutsättning för att upprätthålla hälsa och en god funktionsnivå hos patienter med psykossjukdom. Samtidigt är det vanligt att patienter slutar medicinera. Patienter har rätt att vara delaktiga i sin vård och behandling och psykiatrisjuksköterskan har ett ansvar att se till att dessa rättigheter uppfylls. Patienters upplevelser av delaktighet i samband med antipsykotisk medicinering är således viktiga att belysa. Syfte: Syftet var att beskriva patienters upplevelser av antipsykotisk läkemedelsbehandling med fokus på vad som påverkar patientens delaktighet Metod: Som metod valdes en litteraturöversikt med systematisk ansats. En litteratursökning genomfördes i tre olika databaser och 15 vetenskapliga originalartiklar inkluderades i resultatet. Dessa artiklar analyserades med tematisk analysmetod.  Resultat: Patienters upplevelser av vad som påverkar delaktighet i samband med antipsykotisk läkemedelsbehandling beskrevs genom fyra huvudteman; “Kommunikation och relationer med vårdpersonal”, “Upplevelser av maktlöshet vid medicinering”, “Bristfällig eller ingen information om antipsykotiska läkemedel från vården” samt “Hur läkemedlet i sig och dess biverkningar påverkar inställningen till medicinering”.  Slutsats: Patienters delaktighet i läkemedelsbehandlingen påverkas främst av dennes relation med läkare, sjuksköterskor och annan vårdpersonal. Individanpassad och tydlig läkemedelsinformation, en jämn maktbalans mellan patient och vårdpersonal samt patientens inställning till medicinering påverkar också delaktigheten men samtliga aspekter förutsätter att fungerande vårdrelationer existerar. / Background: Research shows that antipsychotic medication is a prerequisite for maintaining health and a good level of function in patients with psychosis. At the same time, it is common for patients to stop taking medication. Patients have the right to participate in their care and treatment and the psychiatric nurse has a responsibility to ensure that these rights are met. Patients' experiences of participation in connection with antipsychotic medication are thus important to shed light on.  Aim: The aim was to describe patients’ experiences of antipsychotic drug treatment with focus on what affects the patient’s participation Method: A literature review with a systematic approach was chosen as method. The literature search was performed in three databases and 15 original scientific articles were included. These articles were analysed with a thematic content analysis Results: Patients' experiences of what influences participation in connection with antipsychotic drug treatment were described through four main themes;"Communication and relationships with healthcare professionals", "Experiences of powerlessness during medication", "Inadequate or no information about antipsychotic drugs from healthcare" and "How the drug itself and its side effects affect the attitude towards medication" Conclusion: Patients' participation in drug treatment is mainly affected by their relationship with doctors, nurses and other healthcare professionals. Individualized and comprehensible drug information, an even balance of power between patient and healthcare staff and the patient's attitude to medication also affect participation, but all aspects presuppose that functioning healthcare relationships exist.

Background: The main aim of the studies in this thesis is to provide insights into the neonatal phencyclidine (PCP) induced deficits in male and female rats as a neurodevelopmental animal model of schizophrenia. Methods: Both male and female rats were treated with neonatal PCP on postnatal days (PNDs) 7,9 and 11 or vehicle, followed by weaning on PND 21-22. The rats were then tested in behavioural paradigms such as novel object recognition, spatial memory and social interaction in their adolescent and adult stages and were also tested with acute treatment of typical and atypical antipsychotic agents. Results: Neonatal PCP treatment (10 & 20 mg/kg in males and 10 mg/kg in females; once a day for 3 days on PND 7,9 and 11) caused novel object recognition and spatial memory impairment in male and female rats both in the adolescent (PND35-56) and in the adult stages (PND>56) (chapter 2) and robust deficits in social interaction behaviours in the adolescent stage. The SI deficits were observed in adulthood in female but not in male rats thereby establishing a sex-specific social behavioural deficit (chapter 3). The object memory and social interaction deficits induced by neonatal PCP treatment were reversed following acute risperidone but not haloperidol. Finally, the temporal profile of this treatment regime was investigated and the male and female animals were tested on PND 190 and PND 365. The animals did not have any challenge dose of PCP during their testing stage. The result showed that there was significant deficit in object and spatial recognition memory in both male and female animals at both time points, thereby establishing enduring deficits. Conclusion: Given the heterogeneity of the schizophrenic disorder and its complex aetiology, it is understandably difficult to find animal models that completely mimic most or all of the symptoms associated with the disorder. However, data from the studies in this thesis support the use of neonatal PCP as a valid animal model of cognitive and negative symptoms, and explores the effect of antipsychotics in understanding the model. Also, in light of the efficacy of neonatal PCP to produce robust object, spatial memory and social interaction deficits in rats, it appears that this model may be a useful tool to investigate the potential of novel therapeutic candidates that may help improve therapy and understand the illness.

No description available.

No description available.