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>

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.

Bakgrund: Schizofreni är en kronisk sjukdom som kan resultera i förkortad livslängd, utanförskap, förhöjd suicidrisk och orsakar lidande för patienter och anhöriga. Dessutom innebär sjukdomen höga kostnader för samhället. Antipsykotiska läkemedel är en central del av behandlingen och nödvändig för återhämtning och att minska risk för recidiv. Bristande sjukdomsinsikt, otillräcklig effekt och svåra biverkningar kan påverka följsamheten. Psykiatrisjuksköterskan kan genom personcentrerad vård stödja patienter till förbättrad hälsa och minskat lidande. Syfte: Syftet var att beskriva upplevelser av behandling med antipsykotiska läkemedel  hos patienter med diagnosen schizofreni.   Metod: Litteraturöversikt med systematisk ansats valdes som metod. Sökningen genomfördes i databaserna CINAHL, PubMed och PsycInfo. Resultatet analyserades med hjälp av Thomas och Hardens tematiska syntes. Resultat: Resultatet baserades på analys av femton originalartiklar som berörde patienter med schizofreni och deras upplevelser av antipsykotisk läkemedelsbehandling. Teman som framkom var; Upplevelser av kontrollförlust och trygghet, Upplevelser av en förändrad vardag, samt Upplevelser av delaktighet. Slutsats: Patienter med schizofreni upplevde behandling med antipsykotiska läkemedel både som en hjälp och förlust med stor påverkan på daglig funktion och relationer. Patienterna beskrev svårigheter att vara delaktiga i sin behandling och vårdalliansen som central. Att finna en fungerande medicinering var en komplex process som förutsatte stöd från anhöriga och vårdpersonal. / Background: Schizophrenia is a chronic disease that can result in shortened lifespan, isolation, increased suicide risk and causes suffering for patients and relatives. In addition, the disease entails high costs for society. Antipsychotic drugs are a central part  of treatment and necessary for recovery and to reduce the risk of relapse. Lack  of insight, insufficient effect and severe side effects can affect compliance. Through person-centred care, the psychiatric nurse can support patients to improve their health and reduce suffering. Aim: The aim was to describe patients' experiences of treatment with antipsychotic  drugs in schizophrenia Methods: A literature review with a systematic approach was used as method. The search was undertaken in the databases CINAHL, PubMed and PsycInfo. The result was analysed using Thomas and Hardens thematic synthesis. Results: The result was based on the analysis of fifteen primary research articles concerning patients with schizophrenia and their experiences of antipsychotic drug treatment. Themes that emerged where; Experiences of losing control and feeling safe, Experiences of changes in everyday life, as well as Experiences of participation. Conclusions: Patients with schizophrenia experienced treatment with antipsychotic drugs both as a help and a loss with a major impact on daily functioning and relationships. The patients described difficulties in being involved in their treatment and the therapeutic alliance as central. To find a stable medication was a complex process that required support from relatives and healthcare professionals.

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 &amp; 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&gt;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.

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).

Thesis (Ph. D.)--West Virginia University, 2005. / Title from document title page. Document formatted into pages; contains xvii, 327 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references (p. 311-323).

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2005. / Härtill 5 uppsatser.