<p>This thesis is based on two independent studies, the first in Stockholm County (index year 1984; n=302), and the second, a replication and validation study, in Uppsala County (index year 1991; n=455).</p><p>The general aim was to study all individuals with Long-term Functional Psychosis (LFP) within the two counties of Sweden from an epidemiological perspective and to perform specific studies on a subgroup of individuals with schizophrenia. In the Stockholm study, the total one-year LFP prevalence was 5.3/1 000; in the the rural, suburban and urban areas it was 3.4, 5.6 and 6.6/1 000, respectively. The total one-year prevalence of LFP in Uppsala was 7.3/1 000; in the rural, peripheral city and central city areas it was 6.0, 7.0, and 8.7/1 000, respectively.</p><p>Within the non-schizophrenic subpopulation, a pronounced difference was demonstrated between the two studies with substantially higher prevalence rates in the Uppsala study. The schizophrenic subgroup in Uppsala was re-diagnosed using parallel diagnostic systems (DSM-III, DSM-III-R, DSM-IV and ICD-10), and reasonably comparable prevalence estimates were obtained.</p><p>In both studies antipsychotic drugs were most frequently prescribed for the patients with schizophrenia, and the doses were considered as low to moderate. In the Uppsala study the doses of antipsychotic drugs decreased with a longer duration of illness, while the opposite was found in the Stockholm study.</p><p>The increased mortality rate among patients with schizophrenia was mainly due to unnatural causes of death and cardiovascular diseases, particularly among males.</p><p>The main methodological differences between the two studies were in the sampling procedures. In the Uppsala study, a larger number of care facilities were screened, and a broader set of diagnostic criteria were used for identifying cases from different registers.</p>

This thesis is based on two independent studies, the first in Stockholm County (index year 1984; n=302), and the second, a replication and validation study, in Uppsala County (index year 1991; n=455). The general aim was to study all individuals with Long-term Functional Psychosis (LFP) within the two counties of Sweden from an epidemiological perspective and to perform specific studies on a subgroup of individuals with schizophrenia. In the Stockholm study, the total one-year LFP prevalence was 5.3/1 000; in the the rural, suburban and urban areas it was 3.4, 5.6 and 6.6/1 000, respectively. The total one-year prevalence of LFP in Uppsala was 7.3/1 000; in the rural, peripheral city and central city areas it was 6.0, 7.0, and 8.7/1 000, respectively. Within the non-schizophrenic subpopulation, a pronounced difference was demonstrated between the two studies with substantially higher prevalence rates in the Uppsala study. The schizophrenic subgroup in Uppsala was re-diagnosed using parallel diagnostic systems (DSM-III, DSM-III-R, DSM-IV and ICD-10), and reasonably comparable prevalence estimates were obtained. In both studies antipsychotic drugs were most frequently prescribed for the patients with schizophrenia, and the doses were considered as low to moderate. In the Uppsala study the doses of antipsychotic drugs decreased with a longer duration of illness, while the opposite was found in the Stockholm study. The increased mortality rate among patients with schizophrenia was mainly due to unnatural causes of death and cardiovascular diseases, particularly among males. The main methodological differences between the two studies were in the sampling procedures. In the Uppsala study, a larger number of care facilities were screened, and a broader set of diagnostic criteria were used for identifying cases from different registers.

La aparición de los antipsicóticos atípicos o de segunda generación ha supuesto un gran cambio en el manejo de los pacientes con trastorno bipolar. Los ensayos controlados han demostrado la eficacia de prácticamente todos los antipsicóticos atípicos en la manía aguda. Además, la mayor parte de ellos disponen de datos positivos para el tratamiento de mantenimiento del trastorno bipolar, lo que sugiere propiedades normotímicas. E incluso algunos de ellos han mostrado datos positivos en la depresión bipolar. Sin embargo, apenas existen estudios independientes comparando la acción de los atípicos con la de los clásicos, mas allá del uso de haloperidol como comparador activo en algunos estudios de manía aguda. En este contexto, esta tesis tiene como objetivo evaluar el comportamiento de los antipsicóticos atípicos en las fases de manía aguda y depresión, en comparación con el de los antipsicóticos clásicos (haloperidol) y placebo respectivamente, para testar las posibles propiedades normoreguladoras en los episodios agudos. Se utilizaron para ello las técnicas de metanálisis, estructurándose la tesis en dos metanálisis separados. El primero en manía aguda, comparando antipsicóticos atípicos con antipsicóticos clásicos. Dentro de este metanálisis se escogieron dos variables principales: la velocidad de inicio de acción, operativizada como la disminución en la puntuación en la escala de manía a la primera semana, y el viraje depresivo. En los dos casos, se trata de variables de interés clínico, escasamente estudiadas hasta la actualidad, y que señalan el perfil de acción de los fármacos. En segundo lugar, se llevó a cabo un segundo metanálisis comparando la acción de los antipsicóticos atípicos con la del placebo (no existían estudios comparativos con antipsicóticos clásicos) en depresión bipolar. Los resultados de la primera variable del metanálisis en manía aguda, que dan lugar al primer artículo de esta tesis, confirman que el haloperidol muestra un inicio de acción más rápido que los antipsicóticos atípicos. El tamaño del efecto fue pequeño (SMD = 0,17 [0,01 - 0,32] tal como cabria esperar entre dos grupos de eficacia demostrada. Sin embargo, este resultado sugiere que el haloperidol puede seguir siendo un tratamiento de primera línea en la manía aguda en casos graves en los que se requiere una mejoría sintomática urgente, siempre y cuando el riesgo de efectos adversos extrapiramidales y de viraje depresivo sea bajo. El segundo artículo de la tesis analiza las diferencias en el riesgo de viraje depresivo tras el tratamiento de la manía aguda con antipsicóticos atípicos en comparación con haloperidol. El resultado del metanálisis es que los atípicos conllevan un 42% menos de riesgo de viraje que el haloperidol. No obstante, se observa heterogeneidad en este análisis y las diferencias entre grupos son atribuibles especialmente a la acción de tres de los atípicos: olanzapina, quetiapina, y ziprasidona. El segundo metanalisis, que da lugar al tercer lugar de la tesis, observa que existe un efecto positivo en la depresión bipolar, en comparacion con placebo, pero que solo es atribuible a algunos de los antipsicóticos atípicos, concretamente, a la olanzapina y la quetiapina. De modo que se concluye que no se trata de un efecto de clase de la familia. Analizando los resultados de los dos metanálisis en conjunto se observa que se puede establecerse un gradiente en función de la afinidad por el receptor dopaminergico D2, modulado por la acción sobre otros receptores, en el que la mayor afinidad y selectividad antiD2 supondría mayor potencia antimaníaca, inicio de acción antimaníaca más rápido, mayor riesgo de viraje depresivo, e ineficacia y/o agravamiento de la depresión bipolar. Haloperidol se situaría en el extremo izquierdo del gradiente y se propone la siguiente ubicación para los antipsicóticos atípicos: Risperidona – Aripiprazol – Ziprasidona – Olanzapina – Quetiapina. Además, este gradiente coincide con el de los valores del Índice de Polaridad obtenidos en los estudios de prevención de recurrencias con los antipsicóticos atípicos, de lo que se desprende que los efectos en los episodios agudos tiende a perdurar durante el tratamiento de mantenimiento. / Introduction of atypical antipsychotics has involved a great change in the management of bipolar disorder during last decade. Not only they show efficacy in mania, but also for recurrence prevention, and some of them have also been shown to work in bipolar depression. However, comparisons with classical neuroleptics to assess advantages and disadvantages are scarce. In this context, the goal of this thesis was to assess the behavior of atypical antipsichotics in the acute phases of mania and depression, compared to classical antipsychotics in the former and with placebo in the latter, and study their possible normothymic properties. Metanalysis techniques were used. The thesis was structured in two different metanalysis. The first one in acute mania, comparing atypical and classical antipyschotics. Two different outcomes were assessed: speed of onset of action and switch to depression. The second metanalysis studied the efficacy of atypical antipsychotics in bipolar depression versus placebo. The first article of the thesis shows that haloperidol has a faster onset of action than atypical antipsychotics in acute mania. The size of the effect was small (SMD = 0,17 [0,01 - 0,32] but could still be clinically significant in the subset of severe manic patients who require an urgent relief of symtpoms. On the other hand, as it is shown in the second paper of the thesis, treatment with atypicals involves a 42% reduction in the risk of switch to depression compared to haloperidol. However, heterogeneity was present which could be due to differences in the group of atypicals, as three of them (olanzapine, quetiapine, and ziprasidone) could explain the effect. The third article, corresponding to the second metanálisis, shows only some atypicals, namely olanzapine and quetiapine, are efficacious in bipolar depression. Therefore, there is no class effect. A global view of both metanalysis shows that dopaminergic D2 affinity is likely to be the most important factor over the different profile of antipsychotics, with lower affinity involving more clear normothymic actions.

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Objective: To evaluate trends in the use of antipsychotic drugs in Lithuania between 2003 and 2005 years. Methods: The data on total sales of antipsychotic drugs in all Lithuanian regions over three years (2003-2005) were obtained from IMS Health Inc. Drugs were classified according to the Anatomic Therapeutic Chemical system and use was quantified in terms of defined daily doses. Meta-analysis of observational studies retrieved through systematic search of all available electronic data sources. 1651 abstracts were found and checked. 76 randomised double-blind studies were identified for the met-analysis. Data were calculated by DDD methodology and expressed in DDDs per 1.000 inhabitants per day. The pharmacoeconomic analysis of antipsychotics was performed by cost minimization and reference price methodology. Results: In Lithuania the total antipsychotics consumption increased by 16% over three years (2003-2005) period reaching the value of 5,5 DDD/1000 inhabitants/day. Since 2003 the proportion of use of conventional antipsychotics has increased by 2%, while the use of atypical antipsychotics has increased by 14%. The expenditures of antipsychotics has reached 39 mln Litas (in 2005), of which 48% was costs for atypical antipsychotic agents. Setting the reference price of risperidone (according to the meta-analysis results of effectiveness) for atypical antipsychotics it would be possible to rationalize schizophrenia treatment using 10,68 mln Litas extra money. Conclusions:... [to full text]

Thesis (Ph.D.)--University of Alabama at Birmingham, 2008. / Title from first page of PDF file (viewed on June 24, 2009). Includes bibliographical references (p. 108-133).

The term splitting is defined as a process of formation of mental aggregates linked incompatible experiences producing numerous divisions in mental apparatus. Current findings indicate that psychological splitting in schizophrenia is likely specifically presented on a neural level as disrupted organization in neural communication. This disrupted neural communication likely underlies deficits in mental processing described by various neuroscientific concepts such as theories of disturbed connectivity, corollary discharges and dynamic complexity. In this context, a purpose of the theoretical part of the dissertation is to describe basic neuroscience theories that complementarily reflect interrelated processes between mind and brain underlying disturbances of mental integration that likely present a neural representation of the splitting. A purpose of the first part of the empirical research was to examine relationships between psychological process of splitting and disturbed cognitive and affective functions in schizophrenia. A sample of patients with borderline personality disorder (BPD) was used as a control group in this study. Methods: In the clinical study, we have assessed 30 patients with schizophrenia and 35 patients with BPD. The symptoms of splitting were measured using self- reported...

INTRODUÇÃO: Re-hospitalização é uma medida de desfecho reconhecida e utilizada em estudos para acessar prevenção de recaída que é considerada um dos principais indicadores de efetividade de um antipsicótico. Foi testada a hipótese que a clozapina seria superior aos demais antipsicóticos na prevenção de re-hospitalizações em pacientes com esquizofrenia que receberam alta do Instituto de Psiquiatria do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo entre 1 de dezembro de 1997 e 31 de dezembro de 2004. MÉTODOS: Este foi um estudo observacional de coorte, retrospectivo, desenhado para avaliar o tempo de re-hospitalização de pacientes que receberam alta em uso de antipsicóticos convencionais ou antipsicóticos de segunda geração, exceto clozapina ou clozapina, por um período de três anos. A análise de sobrevivência foi estimada pela fórmula produtolimite de Kaplan-Meier. Foi utilizado o modelo de regressão de Cox para identificar fatores associados à re-hospitalização. RESULTADOS: Dos 464 pacientes com esquizofrenia que receberam alta no período do estudo, foram selecionados 242 pacientes. A re-hospitalização foi observada em 12 (17%) pacientes em uso de antipsicóticos convencionais, 27 (24%) pacientes em uso de antipsicóticos de segunda geração, exceto clozapina, e nove (15%) pacientes em uso de clozapina. As análises de sobrevivência demonstraram uma diferença estatisticamente significante entre os três grupos e entre os grupos de antipsicóticos de segunda geração e clozapina. As variáveis clínico-demográficas não foram associadas à re-hospitalização. CONCLUSÕES: O grupo de pacientes que recebeu clozapina apresentou menor taxa de re-hospitalização do que os demais grupos. As diferenças entre tempo de rehospitalização foram estatisticamente significantes entre os três grupos e entre os grupos de pacientes que receberam clozapina e antipsicóticos de segunda geração. Os resultados são limitados pela heterogeneidade da gravidade do transtorno entre os grupos. / INTRODUCTION: An important outcome parameter of drug effectiveness in schizophrenia is relapse prevention which can be reliably measured by time to rehospitalization. We tested the hypothesis that clozapine was superior to other antipsychotics in preventing rehospitalization in patients with schizophrenia discharged from the Institute of Psychiatry. METHODS: This is a retrospective observational cohort study designed to evaluate rehospitalization rates of patients with schizophrenia discharged from the Institute of Psychiatry of the Hospital das Clínicas of the University of Sao Paulo between Dec 1, 1997 and Dec 31, 2004 on a regimen of either conventional antipsychotics or nonclozapine second generation antipsychotics or clozapine during a three years follow-up. Risk factors associated with rehospitalization were examined by Cox regression model and survival curves were estimated by the product-limit formula (Kaplan-Meier). RESULTS: Of the 464 patients with schizophrenia discharged from hospital 242 met criteria to enter the study. They were followed at IPq outpatient clinic for three years. Of these 12 (17%) patients discharged in use of conventional antipsychotic, 27 (24%) in use of non-clozapine second generation antipsychotic, and nine (15%) in use of clozapine were rehospitalized. Survival analysis demonstrated a significant difference in timeto-rehospitalization between groups and between clozapine and second generation antipsychotics groups. CONCLUSIONS: Patients with clozapine were less rehospitalized than the others groups. The differences in time to rehospitalization were statistically significant between the three groups and between clozapine and nonclozapine second generation antipsychotics groups. Results were limited due to the heterogeneity of severity of illness between groups.

Syfte: Syftet med arbetet är att fördjupa och undersöka relevanta kunskaper om patienters erfarenheter av omvårdnadsåtgärder som underlättar deras följsamhet vid antipsykotisk läkemedelsbehandling. Bakgrund: Sverige drabbas 1500–2000 människor av psykos varje år och forskning inom ämnet är viktigt då psykossjukdom utgör ett stort lidande för individen, dess anhöriga samt orsakar stora kostnader för samhället. Följsamheten vid antipsykotisk läkemedelsbehandling är ofta bristfällig vilket många gånger leder till återinsjuknande och inläggningar inom slutenvården. Metod: Systematisk litteraturstudie med kvalitativ ansats. Studiens resultat baserades på tio kvalitativa artiklar. Dataanalys: Latent innehållsanalys. Resultat: Analysen resulterade i fyra kärnteman. Dessa var; personcentrerad vård, coping-strategier, terapeutisk allians och självinsikt. Slutsats: Problematik framträder när vårdtagaren inte är delaktig i sin vård och när samsyn brister eller saknas vilket leder till negativ inverkan på följsamhet. Nyckeln till god följsamhet bygger på en kombination av de fyra kärnteman och det är viktigt att sjuksköterskan inger hopp och stöttar patienten genom behandlingen för ett positivt vårdförlopp. / Aim: The aim of the study was to explore patients’ experiences of nursing care measures that facilitate their adherence during antipsychotic treatment. Background: On a yearly basis about 1500-2000 people develop psychosis in Sweden. This leads to great suffering for the affected individual, their relatives and is also causing high economic burden on the society. The adherence during antipsychotic treatment is often poor which frequently leads relapse and rehospitalization. Method: Qualitative literature review. Data analysis: Latent content. Result: The result was based on ten qualitative articles whereof four main themes were found. These were; person-centered care, coping strategies, therapeutic alliance and self awareness. Conclusion: Poor patient involvement and lack of consensus between care providers and patients leads to negative impact on the treatment adherence. The key for successful medication adherence is based on the understanding and implementation of the four themes. It is also important for the nurse to provide hope, trust and security during the treatment.

The term splitting is defined as a process of formation of mental aggregates linked incompatible experiences producing numerous divisions in mental apparatus. Current findings indicate that psychological splitting in schizophrenia is likely specifically presented on a neural level as disrupted organization in neural communication. This disrupted neural communication likely underlies deficits in mental processing described by various neuroscientific concepts such as theories of disturbed connectivity, corollary discharges and dynamic complexity. In this context, a purpose of the theoretical part of the dissertation is to describe basic neuroscience theories that complementarily reflect interrelated processes between mind and brain underlying disturbances of mental integration that likely present a neural representation of the splitting. A purpose of the first part of the empirical research was to examine relationships between psychological process of splitting and disturbed cognitive and affective functions in schizophrenia. A sample of patients with borderline personality disorder (BPD) was used as a control group in this study. Methods: In the clinical study, we have assessed 30 patients with schizophrenia and 35 patients with BPD. The symptoms of splitting were measured using self- reported...