Doenças cardiovasculares e uso de antipsicóticos na esquizofrenia: uma revisão / Cardiovascular diseases and use of antipsychotics in schizophrenia: a review

RESUMO Objetivo Realizar uma revisão de escopo a respeito dos efeitos adversos cardiovasculares e metabólicos associados ao uso de antipsicóticos em pessoas com o diagnóstico de esquizofrenia. Métodos Foi realizada uma revisão de escopo utilizando-se da base de dados PubMed, com descritores MeSH relacionados às doenças cardiovasculares e antipsicóticos. Foram encontrados 976 artigos, os quais foram filtrados por títulos, seguidos dos resumos e, na sequência, lidos na íntegra. Ao final, foram selecionados 71 artigos para a análise. Resultados O uso de antipsicóticos típicos e atípicos para tratamento da esquizofrenia associa-se a alterações glicêmicas e lipídicas, síndrome metabólica, hipertensão, ganho de peso e morbidade cardiovascular. Os estudos evidenciaram a existência de subdiagnóstico e subtratamento de doenças crônicas nessa população. A mortalidade por doença cardiovascular demonstrou aumento considerável nos pacientes em tratamento com agentes antipsicóticos, em comparação com a população geral. Conclusão Alguns fatores dos antipsicóticos, ainda não completamente determinados na psicofarmacologia, vêm se mostrando relacionados a maior risco de distúrbios metabólicos, comportamentais e intrínsecos às pessoas diagnosticadas com esquizofrenia, os quais podem agravar o curso clínico de tais doenças. Reconhece-se a necessidade de aprimorar o acompanhamento e o diagnóstico de doenças cardiovasculares e metabólicas entre pessoas com diagnóstico de esquizofrenia em tratamento com antipsicóticos típicos e atípicos.

ABSTRACT Objective To perform a scoping review of cardiovascular and metabolic adverse effects associated with the use of antipsychotics in people diagnosed with schizophrenia. Methods A scoping review was conducted based on the PubMed database containing MeSH descriptors related to cardiovascular diseases and antipsychotics. At first moment, 976 articles were found, which were filtered by titles, followed by abstracts, and then fully read. In the end 71 articles were selected for the analysis. Results The use of typical and atypical antipsychotics for the treatment of schizophrenia is associated with glycemic and lipid abnormalities, metabolic syndrome, hypertension, obesity/weight gain, and cardiovascular morbidities. The literature showed underdiagnosis and undertreatment of chronic diseases in this population. Mortality from cardiovascular disease showed a considerable increase in patients under treatment with antipsychotic agents, compared to the general population. Conclusion Factors, still not entirely determined, in the psychopharmacology of antipsychotics have been shown to be related to an increased risk of metabolic, behavioral and intrinsic disorders in people diagnosed with schizophrenia, which may worsen the clinical course of such illnesses. It is recognized that there is a need to improve the monitoring and diagnosis of cardiovascular and metabolic diseases among people diagnosed with schizophrenia on treatment with typical and atypical antipsychotics.

Bilateral ocular deposit of chlorpromazine / Depósito ocular bilateral de clorpromazina

ABSTRACT Chlorpromazine is a medication widely used in psychiatry for the treatment of psychoses, especially schizophrenia. Since 1964, published articles have been correlating this medication with the appearance of ocular alterations. In this paper, we report the case of a 65-year-old patient with ocular effects due to long-term therapy with chlorpromazine. Biomicroscopy of both eyes presented diffuse granular brown deposits, most prominent at the deep stroma and corneal endothelium level. Also showed anterior subcapsular brown deposits with a stellate pattern in the lens. The total amount exceeds 2.000g (significant for the ocular alterations described) considering the patient's daily dosage of chlorpromazine of 300mg for ten years. After performing complete ophthalmic evaluation and discarding other causes for the ocular deposits, we diagnosed a secondary corneal deposit and cataract due to the use of chlorpromazine. This case reinforces the importance of periodic follow-up with an ophthalmologist for chlorpromazine users to trace ocular changes, heeding the exposure time and its dosage.

RESUMO A clorpromazina é uma medicação muito empregada na psiquiatria para tratamento de psicoses, especialmente em casos de esquizofrenia. Desde 1964 existem artigos publicados que correlacionam o uso dessa medicação com o aparecimento de alterações oculares. Neste trabalho, relatamos o caso de um paciente de 65 anos com efeitos oculares devido à terapia de longo prazo com clorpromazina. A biomicroscopia de ambos os olhos apresentou depósitos granulares difusos e de cor marrom, mais proeminente ao nível do estroma profundo e do endotélio da córnea, além de depósitos castanhos subcapsulares anteriores centrais em um padrão estrelado no cristalino. Considerando a dose diária de clorpromazina de 300mg por 10 anos usada pelo paciente, a quantidade total ultrapassa 2.000g (dose considerada significativa para as alterações oculares descritas). Após avaliação oftalmológica completa e descartado outras causas desses depósitos oculares, foram diagnosticados depósito corneano e catarata secundários ao uso de clorpromazina. O caso apresentado reforça a importância do acompanhamento oftalmolÓgico periÓdico de usuários de clorpromazina para o rastreio de alteraçÕes oculares, atentando-se ao tempo de exposição à droga e à posologia da mesma.

Adolescente varón con distonía abdominal secundaria al uso de haloperidol y confundida con abdomen agudo / Male adolescent with abdominal dystonia secondary to the use of haloperidol and misdiagnosed as an acute abdomen syndrome

En los últimos años se ha incrementado el uso de psicofármacos, específicamente antipsicóticos, para tratar cuadros no psicóticos en niños y adolescentes. El mayor uso de los antipsicóticos atípicos en desmedro de los clásicos ha influido en un menor conocimiento de sus usuales efectos extrapiramidales. Reportamos el caso de un adolescente varón de 15 años con diagnóstico de esquizofrenia paranoide quien presentó distonía abdominal luego de tratarlo con haloperidol. Atendido bajo la presunción de abdomen agudo, fue sometido a una serie de exámenes auxiliares que resultaron normales. Posteriormente presentó distonía cervical y agitación psicomotriz. Luego de cambiar la medicación inicial por ziprasidona y biperideno, el paciente logró la recuperación y fue dado de alta con el cuadro psicótico controlado. Deben reconocerse los efectos secundarios de los antipsicóticos y considerar su uso solo cuando no haya otras alternativas viables. La distonía de músculos abdominales debe incluirse en el diagnóstico diferencial del abdomen agudo

In the past few years, the use of psychotropic drugs, especially anti-psychotics, has increased, for the therapy of non-psychotic conditions in children and adolescents. The more frequent use of atypical anti-psychotic drugs replacing the classical ones has influenced in having less knowledge of their extra-pyramidal effects. We report the case of a 15-year old male adolescent diagnosed with paranoid schizophrenia who presented with abdominal dystonia after receiving haloperidol. He was taken care of with a presumptive diagnosis of acute abdomen syndrome, and he underwent some tests that turned out to have normal results. Later, he developed cervical dystonia and psychomotor agitation. After the initial medication was replaced with ziprasidone and biperiden, the patient fully recovered and he was discharged with his psychotic condition under control. Side effects of anti-psychotic drugs should always be recognized, and its use is to be considered only when no other viable option is available. Abdominal muscle dystonia should be included in the differential diagnosis of the acute abdominal syndrome

Cost variation of antipsychotics in the public health system in Brazil: the implication for health resource use / A variação de custos de antipsicóticos no sistema público de saúde do Brasil: as implicações para o uso de recursos

Objective: This study aimed to verify the variation on antipsychotics costs according to four unit costs paid by public health providers in Brazil. Methods: This cross-sectional study used the health provider perspective and bottom-up approach to evaluate 134 subjects with mental disorders, in regular use of antipsychotics, and living in 20 residential services in the city of Sao Paulo between 2011 and 2012. They were assessed for psychiatric diagnosis, the severity of symptoms, quality of life, independent living skills, pattern of health service use and treatments. The Brazilian version of Client Socio-demographic Services Receipt Inventory (ISDUCS) was used to assess health service and medication use. Four different values of unit costs for each antipsychotic were extracted from Medication Price Database (Banco de Preços de Saúde) by the Ministry of Health, Brazil. Results: Variability on the unit costs for chlorpromazine was found by 25,600 fold to the lowest values. Similarly, mean costs of chlorpromazine use per capita per diem varied between BRL 0.55 and BRL 357.87, that is, a difference by 650 fold to the lowest value. Conclusion: The great variability in the unit costs paid by public health providers for all antipsychotics hinders any guideline recommendation for the best cost-saving choice of antipsychotics. It is paramount to proceed cost-effectiveness studies verifying acceptable thresholds for treatments according to the national budget. Yet, monitoring public resource use on the antipsychotic purchasing is imperative to avoid waste of public resources.

Objetivo: Este estudo verificou a variação de custos do antipsicóticos de acordo com quatro valores de unidade de custos pagas pelos provedores públicos no Brasil. Métodos: Estudo transversal utilizou a perspectiva dos provedores públicos de saúde e abordagem bottom-up para avaliar 134 indivíduos com transtornos mentais em uso regular de antipsicóticos, residindo em 20 residências terapêuticas na cidade de São Paulo entre 2011 e 2012. Foram mensurados os diagnósticos psiquiátricos, a gravidade dos sintomas, a qualidade de vida, habilidades de vida independente. O Inventário Sociodemográfico de Utilização de Serviços e Custos ­ ISDUCS (versão do Client Socio-demographic Service Receipt Inventory) foi utilizado para mensurar a frequência de utilização de serviços e de medicamentos. Quatro valores de unidades de custo para os antipsicóticos foram extraídos do Banco de Preços de Saúde do Ministério da Saúde do Brasil. Resultados: A variabilidade entre as unidades de custo para a clorpromazina foi de 25.600 vezes comparada com o menor valor, e o custo médio da clorpromazina per capita por dia variou de R$ 0,55 a R$ 357,87, uma diferença de 650 vezes o menor valor. Conclusão: A grande variabilidade entre as unidades de custos pagas pelo provedor público de saúde dificulta as recomendações dos guias clínicos em termos de escolher o antipsicótico menos custoso como primeira linha, sendo necessários estudos de custo-efetividade para verificar o limite máximo aceitável para a unidade de custo compatível com o orçamento nacional. O monitoramento do uso de recursos públicos para a aquisição de antipsicóticos é imperativo para impedir o desperdício de recursos públicos.

Effects of different antipsychotics on sugar, lipid metabolism and body mass in female patients with first-episode schizophrenia / 中国基层医药

Objective To study the effects of atypical antipsychotic drugs on glucose and lipid metabolism and body weight in female patients with schizophrenia.Methods 120 patients with schizophrenia were randomly divided into three groups according to the number randomized method.Group 1 (olanzapine group) was treated with olanzapine,group 2(ziprasidone group) was treated with ziprasidone,group 3 (risperidone group) was treated with risperidone.The total cholesterol (TC),triglyceride (TG) and body mass index (BMI) in the three groups were analyzed retrospectively.Results After treatment for 8 weeks,the fasting blood glucose of the olanzapine group and risperidone group increased significantly compared with before treatment,the differences were statistically significant(t =-2.81,P ＜ 0.01;t =-1.76,P ＜ 0.05),the blood glucose of the ziprasidone group had no significant change (t =-0.56,P ＞ 0.05).After treatment for 8 weeks,the BMI of the olanzapine group and risperidone group had statistically significant difference compared with before treatment (t =-3.62,P ＜ 0.01;t =-2.95,P ＜ 0.01),the difference of the ziprasidone group was not significant in BMI (t =-1.26,P ＞ 0.05).After treatment for 8 weeks,the TG,TC levels of the olanzapine group had statistically significant differences compared with before treatment (t =-3.89,P ＜ 0.01;t =-3.89,P ＜ 0.01),which of the risperidone group and ziprasidone group had no statistically significant differences (t =-1.64,P ＞ 0.05;t =-1.06,P ＞ 0.05;t =-0.55,P ＞ 0.05;t =-0.62,P ＞ 0.05).Conclusion Ziprasidone in the treatment of female first episode schizophrenia,has less influence on sugar,lipid metabolism and weight,with high compliance and more advantages compared with other atypical antipsychotics.

Perfil metabólico y factores asociados en pacientes con esquizofrenia bajo tratamiento con antipsicóticos que acuden a consulta externa en el Instituto Nacional de Salud Mental (Perú) / Metabolic profile and associated factors among patients with schizophrenia under antipsychotic treatment attending an outpatient service at the National Institute of Mental Health (Perú)

Objetivo: Describir el perfil metabólico y factores asociados en pacientes con esquizofrenia bajo tratamiento conantipsicóticos que acudieron a consulta externa en el Instituto Nacional de Salud Mental “Honorio Delgado–HideyoNoguchi” durante un periodo de tres meses. Material y m‚todos: Estudio transversal, realizado entre mayo y julio del 2015. De manera consecutiva, fueron incluidos pacientes con esquizofrenia, en tratamiento con el mismo esquema antipsicótico por al menos 3 meses. Se tomaron medidas antropom‚tricas y se recogió información del paciente y de su historia cl¡nica. Se estimaron frecuencias y medidas de tendencia central para la estad¡stica descriptiva. Los factores asociados al perfil metabólico se establecieron mediante an lisis bivariado y multivariado, con el S¡ndrome Metabólico (SM) como variable dependiente. Resultados: De un total de 272 pacientes, 40,8% cumplieron criterios para SM seg£n la ATP-III modificada; 6,3% presentaron diabetes, 8,1% hipertensión arterial, 43% sobrepeso, 28,7% obesidad y 74,3% presentaron al menos una alteraci¢n lip¡dica. El SM estuvo significativamente asociado a edad,antecedente familiar de infarto de miocardio (IM), ¡ndice de masa corporal (IMC) y uso de politerapia con antipsicóticos at¡picos. Conclusiones: La frecuencia de SM hallada en esta muestra de pacientes esquizofr‚nicosfue elevada y estuvo asociada a una variedad de factores que es indispensable evaluar para un manejo integral y adecuado de cada paciente.

Objectives: To describe the metabolic profile and its associated factors among patients with schizophrenia underantipsychotic treatment, seen in the outpatient service at the National Institute of Mental Health “Honorio Delgado–Hideyo Noguchi”, during a period of 3 months. Material and Methods: Cross-sectional study, carried out from May to July 2015. By consecutive sampling, patients with schizophrenia who were receiving the same antipsychotic treatment for at least three months were included. Anthropometric measures were taken, and medical data were obtained from the patients and their medical records. For descriptive statistics purposes, frequencies and measures of central tendency were estimated. To determine the metabolic profile-associated factors, bivariate and multivariate analyses were performed with the Metabolic Syndrome (MS) as a dependent variable. Results: From a total of272 patients evaluated, 40.8% met the modified ATP-III criteria for MS, 6.3% had type 2 diabetes mellitus, 8.1%had hypertension, 43% were overweight, 28.7% were obese and 74.3% had at least one lipid disorder. MS was significantly associated with age, family history of myocardial infarction (MI), body mass index (BMI) and use of polytherapy with atypical antipsychotics. Conclusions: The frequency of MS found in our sample of schizophrenic patients was high and was associated to a variety of factors whose evaluation is indispensable for an integral and adequate treatment of every patient.

Effects of Antipsychotics on Bone Mineral Density in Patients with Schizophrenia: Gender Differences

Low bone mineral density (BMD) and osteoporosis are common in patients with schizophrenia and detrimental to illness prognosis and life quality. Although the pathogenesis is not fully clear, series of studies have revealed factors related to low BMD such as life style, psychotic symptoms, medication use and the activity of bone absorption markers. It has been known that antipsychotic-induced hyperprolactinemia plays a critical role on decreased BMD. However, it remains uncertain whether the risk factors differ between men and women. According to the effect on prolactin, antipsychotics can be classified into two groups: prolactin-sparing (PS) and prolactin-raising (PR). Our previous study has demonstrated that clozapine which is among the PS antipsychotics is beneficial for BMD when compared with PR antipsychotics in women with chronic schizophrenia. We have also found that risks factors associated with low BMD are different between men and women, suggesting that gender-specific risk factors should be considered for intervention of bone loss in patients with schizophrenia. This article reviews the effects of antipsychotics use on BMD with particular discussion for the differences on gender and age, which implicate the alterations of sex and other related hormones. In addition, currently reported protective and risk factors, as well as the effects of medication use on BMD including the combination of antipsychotics and other psychotropic agents and other potential medications are also reviewed.

Delirium na unidade de cuidados intensivos: uma realidade subdiagnosticada / Delirium in intensive care: an under-diagnosed reality

Entidade frequente em medicina intensiva, ocorrendo em até 80% dos doentes internados na unidade de cuidados intensivos, embora muito subdiagnosticado, o delirium está associado a aumento significativo da morbilidade e da mortalidade no doente crítico. No presente artigo, foram revistos os principais fatores de risco, manifestações clínicas e abordagens preventivas e terapêuticas (farmacológicas e não farmacológicas) nessa doença.

Delirium occurs in up to 80% of patients admitted to intensive care units. Although under-diagnosed, delirium is associated with a significant increase in morbidity and mortality in critical patients. Here, we review the main risk factors, clinical manifestations and preventative and therapeutic approaches (pharmacological and non-pharmacological) for this illness.

Association Study of Fat-mass and Obesity-associated Gene and Body Mass Index in Japanese Patients with Schizophrenia and Healthy Subjects

OBJECTIVE: Fat-mass and obesity-associated (FTO) gene is known to be involved in the pathophysiology of obesity and a single-nucleotide polymorphism (SNP) rs9939609 of FTO gene is repeatedly confirmed to be associated with body mass index (BMI) and obesity. The aim of this study is to elucidate effects of FTO gene polymorphism on BMI in Japanese patients with schizophrenia and healthy subjects. METHODS: Three hundred fifty one patients with schizophrenia and 342 age- and sex-matched healthy subjects participated in the study. Information on BMI and antipsychotic medication was also collected from patients and healthy subjects. Genotype of the FTO SNP rs9939609 was determined by TaqMan SNP Genotyping Assays. RESULTS: There was no significant difference in BMI between patients and healthy subjects. No significant difference in BMI was observed among any medications. We observed no significant difference in rs9939609 allele frequencies between patients and healthy subjects. There was a significant difference in BMI between healthy subjects with risk (AA or TA) genotypes and those with TT genotype. We also observed a significant positive correlation between the number of risk allele (A allele) and BMI in healthy subjects. CONCLUSION: Our study suggested that FTO rs9939609 polymorphism might have some impacts on the BMI in healthy subjects, but might not have same impacts on the BMI of patients with schizophrenia.

O uso de antipsicóticos em pacientes com diagnóstico de demência / The use of antipsychotics in patients with dementia

OBJETIVO: Revisar sistematicamente as evidências que sustentam o uso de antipsicóticos no tratamento dos sintomas comportamentais e psicológicos em pacientes com demência, assim como rever as controvérsias e desvantagens dessa prescrição, tendo em vista, por um lado, a elevada prevalência destas manifestações no curso clínico das demências e, por outro, a maior susceptibilidade do idoso aos eventos adversos desses medicamentos. MÉTODO: Revisão sistemática da literatura sobre o uso de antipsicóticos típicos e atípicos em pacientes portadores de síndromes demenciais. As bases de dados usadas para este fim foram o PubMed/Medline, Embase e SciELO. A busca por trabalhos se limitou aos anos de 1986 a 2007, selecionando-se ensaios clínicos randomizados e metanálises da literatura. RESULTADOS: Há evidências a partir de ensaios randomizados, duplamente encobertos, controlados por placebo, de que os antipsicóticos típicos e atípicos são eficazes no tratamento dos sintomas comportamentais que ocorrem nas síndromes demenciais, especialmente os quadros psicóticos e alterações do comportamento motor. Entretanto, o uso destas medicações está associado a eventos adversos importantes. Embora os antipsicóticos atípicos estejam menos associados aos efeitos colaterais extrapiramidais, comuns entre os neurolépticos de primeira geração, podem aumentar a incidência de eventos cerebrovasculares e do risco de morte, sobretudo em pacientes vulneráveis. CONCLUSÃO: Os antipsicóticos devem ser usados com cautela nos pacientes com demência, buscando otimizar o regime de dosagem e duração do tratamento, e avaliando-se individualmente a relação risco-benefício.

OBJECTIVE: The objective of the present study is to systematically review the supporting evidence for the use of antipsychotics in the treatment of behavioral and psychological symptoms in patients with dementia, as well as the controversies and limitations of this prescription. We discuss the available evidence in the light of the high prevalence of behavioral and psychological symptoms of dementia in this population, along with the greater susceptibility of elderly patients to adverse events. METHOD: Systematic literature review of the use of typical and atypical antipsychotics in patients with dementia was carried out in the databases PubMed/Medline, Embase and SciELO. The search was limited to clinical trials and meta-analysis of the literature published from 1986 to 2007. RESULTS: Evidence drawn from randomized, double-blind, placebo controlled trials support the use of both typical and atypical antipsychotics in the treatment of behavioral symptoms of dementia, especially psychotic symptoms and abnormal psychomotor activity. Nevertheless, the use of these drugs in demented patients is not devoid of important adverse events. Although the induction of extrapiramidal symptoms is not as frequent or severe with atypical antipsychotics as it is with first-generation neuroleptics, the former drugs may particularly increase the risk of cerebrovascular events and death. CONCLUSION: Although effective, antipsychotic drugs must be prescribed cautiously in patients with dementia. Dose regimens, duration of treatment and a cautious assessment of risk-benefit must be established for each patient.