Guía práctica para el uso de clozapina en niños/as y adolescentes / Practical guidelines for the use of clozapine in children and adolescents

El uso de clozapina (CZP) en niños/as y adolescentes ha estado históricamente limitado, debido a los efectos adversos y riesgos médicos asociados al fármaco, a pesar de ser una herramienta farmacológica de gran efectividad en la psiquiatría general. A continuación, se presenta una guía clínica con los siguientes objetivos: 1) identificar los criterios de indicación de CZP en niños, niñas y adolescentes (NNA) según la evidencia disponible; 2) entregar algunas directrices a los clínicos y profesionales de salud respecto a la prescripción de CZP y precauciones a tener en consideración en esta población y; 3) entregar algunos datos comparativos del uso de CZP entre población infantojuvenil y población adulta. Todo lo anterior tiene como finalidad poder entregar la información necesaria para que los clínicos no limiten el uso de este fármaco y puedan prescribirlo de acuerdo con la evidencia científica disponible.

The use of clozapine (CZP) in children and adolescents has historically been limited due to the adverse effects and medical risks commonly associated with the drug, despite being a highly effective pharmacological tool in general psychiatry. Below we developed a clinical guideline with the following objectives: 1) identify the indication criteria for CZP in children and adolescents (NNA) according to the available evidence; 2) provide some guidelines to clinicians and health professionals regarding the prescription of CZP and precautions to be taken into account in this population and; 3) provide some comparative data on the use of CZP between the pediatric and adult population. The purpose of the guideline is to provide the necessary information so that clinicians do not limit the use of CLZ when needed and can prescribe it safely and according to the available scientific evidence.

Posibles mecanismos de acción de la terapia electroconvulsiva en esquizofrenia: revisión de la evidencia disponible en investigación con seres humanos / A review about the putative mechanisms of action of electroconvulsive therapy in schizophrenia in human research

Electroconvulsive therapy (ECT) has multiple uses in psychiatry, but its mechanisms of action (MA) in patients with schizophrenia (PS) are poorly understood. We synthesize and discuss the available evidence in this regard. We conducted a search for primary human studies and systematic reviews searching MA of ECT in PS published in PubMed/Medline, SciELO, PsycInfo, and the Cochrane Library, including 24 articles. Genetic findings are scarce and inconsistent. At the molecular level, the dopaminergic and GABAergic role stands out. The increase in brain derived neurotrophic factor (BDNF) after ECT, is a predictor of positive clinical outcomes, while the change in N-acetyl aspartate levels would demonstrate a neuroprotective role for ECT. This intervention would improve inflammatory and oxidative parameters, thereby resulting in a symptomatic improvement. ECT is associated with an increase in functional connectivity in the thalamus, right putamen, prefrontal cortex and left precuneus, structures that play a role in the neural default mode network. A decrease in connectivity between the thalamus and the sensory cortex and an enhanced functional connectivity of the right thalamus to right putamen along with a clinical improvement have been reported after ECT. Moreover a volumetric increase in hippocampus and insula has been reported after ECT. These changes could be associated with the biochemical pathophysiology of schizophrenia. Most of the included studies are observational or quasi-experimental, with small sample sizes. However, they show simultaneous changes at different neurobiological levels, with a pathophysiological and clinical correlation. We propose that the research on ECT should be carried out from neurobiological dimensions, but with a clinical perspective.

Bacopa monnieri: historical aspects to promising pharmacological actions for the treatment on central nervous system diseases / Bacopa monnieri: aspectos históricos de las acciones farmacológicas prometedoras para el tratamiento de enfermedades del sistema nervioso central

Bacopa monnieri(L.) Wettst. (Plantaginaceae), also known as Brahmi, has been used to improve cognitive processes and intellectual functions that are related to the preservation of memory. The objective of this research is to review the ethnobotanical applications, phytochemical composition, toxicity and activity of B. monnieri in the central nervous system. It reviewed articles on B. monnieri using Google Scholar, SciELO, Science Direct, Lilacs, Medline, and PubMed. Saponins are the main compounds in extracts of B. monnieri. Pharmacological studies showed that B. monnieri improves learning and memory and presents biological effects against Alzheimer's disease, Parkinson's disease, epilepsy, and schizophrenia. No preclinical acute toxicity was reported. However, gastrointestinal side effects were reported in some healthy elderly individuals. Most studies with B. monnieri have been preclinical evaluations of cellular mechanisms in the central nervous system and further translational clinical research needs to be performed to evaluate the safety and efficacy of the plant.

Bacopa monnieri (L.) Wettst. (Plantaginaceae), también conocida como Brahmi, se ha utilizado para mejorar los procesos cognitivos y las funciones intelectuales que están relacionadas con la preservación de la memoria. El objetivo de esta investigación es revisar las aplicaciones etnobotánicas, composición fitoquímica, toxicidad y actividad de B. monnieri en el sistema nervioso central. Se revisaron artículos sobre B. monnieri utilizando Google Scholar, SciELO, Science Direct, Lilacs, Medline y PubMed. Las saponinas son los principales compuestos de los extractos de B. monnieri. Los estudios farmacológicos mostraron que B. monnieri mejora el aprendizaje y la memoria y presenta efectos biológicos contra la enfermedad de Alzheimer, la enfermedad de Parkinson, la epilepsia y la esquizofrenia. No se informó toxicidad aguda preclínica. Sin embargo, se informaron efectos secundarios gastrointestinales en algunos ancianos sanos. La mayoría de los estudios con B. monnieri han sido evaluaciones preclínicas de los mecanismos celulares en el sistema nervioso central y es necesario realizar más investigaciones clínicas traslacionales para evaluar la seguridad y eficacia de la planta.

Protocolo Clínico e Diretrizes Terapêuticas (PCDT) complementares de esquizofrenia no Estado de Goiás - versão 2022 / Clinical protocol and complementary therapeutic guidelines (PCDT) for schizophrenia in the State of Goiás - version 2022

Protocolo estadual que complementa o PCDT do Ministério da Saúde e ambos devem ser considerados como referência diagnóstica e terapêutica pelos profissionais de saúde, em Goiás, para o tratamento de pessoas com o transtorno de esquizofrenia. A esquizofrenia é um transtorno mental grave que ocorre em cerca de 1% da população, independente de nível sociocultural. É caracterizada por períodos de intensas distorções do pensamento e da percepção (surtos) e pela inadequação e embotamento do afeto. Ao longo do tempo, pode aparecer prejuízos cognitivos em uma parcela significativa dos pacientes , principalmente os que não seguem tratamento regular

State protocol that complements the Ministry of Health's PCDT and both should be considered as a diagnostic and therapeutic reference by health professionals in Goiás for the treatment of people with schizophrenia disorder. Schizophrenia is a serious mental disorder that occurs in around 1% of the population, regardless of sociocultural level. It is characterized by periods of intense distortions of thought and perception (outbreaks) and by inadequacy and blunting of affect. Over time, cognitive impairment may appear in a significant portion of patients, especially those who do not follow regular treatment

Estudio de utilización de psicofármacos en usuarios de la policlínica del Hospital Vilardebó con diagnóstico de esquizofrenia (años 2006 y 2016) / Study of the use of psychotropic drugs in users of the Vilardebó Hospital polyclinic with a diagnosis of schizophrenia (2006 and 2016)

El tratamiento farmacológico de demostrada eficacia en la esquizofrenia es el antipsicótico. Sin embargo, en muchas ocasiones se requiere medicación concomitante que depende de comorbilidades y efectos adversos. Se realizó un estudio cuantitativo, longitudinal, retrospectivo, considerando el año 2006 y 2016, en una población de usuarios con esquizofrenia de la Policlínica del Hospital Vilardebó, analizando los tratamientos con psicofármacos. Se diferenciaron los tratamientos según monoterapia antipsicótica y polifarmacia con 2 antipsicóticos, y polifarmacia con más de 2 antipsicóticos, antidepresivos, estabilizantes del humor, benzodiacepinas y anticolinérgicos. La población inicial en 2006 fue de 621 pacientes y 398 pacientes continuaban en tratamiento en 2016. Mantuvieron el trata-miento con antipsicóticos 377 pacientes; 184 mantuvieron benzodiacepinas; 59 se mantuvieron con anticolinérgicos; 49, con estabilizantes del humor y 47, con antidepresivos. La monoterapia antipsicótica se presentó en torno al 50 % de la población estudiada. Se deberían revisar aquellas prácticas que se infieren a partir de este estudio, como el uso prolongado de anticolinérgicos, benzodiacepinas, y polifarmacia con más de 2 antipsicóticos, que está extendida en los usuarios con esquizofrenia. El tratamiento con clozapina fue el más estable y no parece aumentar la mortalidad en estos pacientes

Antipsychotics are the proved effective therapy for schizophrenia. However, on many occasions, associated drugs are required depending on comorbidities and side effects. A retrospective longitudinal quantitative study of drug prescription for 2006 and 2016 in patients with schizophrenia diagnosis was carried out in an outpatient clinic at Hospital Vilardebó. Treatments were classified as antipsychotic monotherapy, two antipsychotic drugs polypharmacy and polypharmacy with two antipsychotic drugs, antidepressants, mood stabilizers, benzodiazepines and anticholinergic drugs. Initial population in 2006 included 621 patients, 398 were still being treated in 2016. Antipsychotic drugs were still being received in 377 patients, benzodiazepines in 184, anticholinergic drugs in 59, mood stabilizers in 49, and anti-depressants in 47. Antipsychotic monotherapy was 50% of the population. Those practices that can be inferred from this study, with lengthy use of anticholinergic drugs, benzodiazepines, and the use of more than 2 antipsychotic drugs in patients with schizophrenia diagnosis should be revised. Clozapine therapy was the most stable and does not seem to increase mortality.

Eficácia e segurança de Aripiprazol comparado aos antipsicóticos disponíveis no SUS para tratamento de Esquizofrenia em adultos: revisão rápida de evidências / Compared effectiveness and safety of Aripiprazol and antipsychotics available on Brazilian Public Health System for treatment of Schizophrenic adults: a rapid review of evidence

Tecnologia: Aripiprazol, antipsicóticos disponíveis no Sistema Único de Saúde (SUS). Indicação: Tratamento da esquizofrenia em adultos. Pergunta: O Aripiprazol é mais eficaz e seguro para promover controle sintomático, que os antipsicóticos disponíveis no SUS? Métodos: Levantamento bibliográfico foi realizado em bases de dados PUBMED, com estratégias estruturadas de busca, e a qualidade metodológica das revisões sistemáticas foi avaliada com a ferramenta AMSTAR II. Resultados: Foram identificados 109 resumos de revisões sistemáticas. Após leitura dos mesmos, foram selecionadas 2 revisões sistemáticas. Conclusão: Aripiprazol tem eficácia e segurança similar à Ziprasidona e Haloperidol, mas eficácia semelhante e maior segurança metabólica que a Quetiapina, Olanzapina, Clozapina e Risperidona. Ziprasidona apresenta vantagem sobre o Aripiprazol, pois tem menor risco de efeito colateral de mudanças na função sexual. Considerando que o perfil de eficácia e segurança do Aripiprazol é muito parecido com o dos outros antipsicóticos disponíveis no SUS, com mínimas diferenças, e seu custo de tratamento é inferior ao da Ziprasidona e Quetiapina, essa droga poderia estar disponível no SUS

Technology: Aripiprazole, antipsychotics available in the Brazilian Public Health System (BPHS). Indication: Treatment of schizophrenia in adults. Question: Is Aripiprazole more effective and safer to promote symptomatic control than antipsychotics available in BPHS? Methods: A bibliographic survey was carried out in PUBMED databases, with structured search strategies, and the methodological quality of systematic reviews was assessed using the AMSTAR II tool. Results: 109 abstracts of systematic reviews were identified. After reading them, 2 systematic reviews were selected. Conclusion: Aripiprazole has identical effectiveness and safety to Ziprasidone and Haloperidol, but similar efficacy and greater safety than Quetiapine, Olanzapine, Clozapine and Risperidone. Ziprasidone has an advantage over Aripiprazole as it has a lower risk of side effects of changes in sexual function. Since the Aripiprazole's effectiveness and safety profile is very similar to profile of others antipsychotics available in BPHS, with minimal differences, and it has cost lower than Ziprasidone and Quetiapine, this drug could be available in BPHS

Clozapine use decreases the number of hospitalizations per year in patients with treatment-resistant schizophrenia

For years, the management of schizophrenia has represented a challenge for clinicians, with antipsychotic treatments usually resulting in relapses and new hospitalizations. Clozapine has been shown to be an effective medication for treatment-resistant schizophrenia (TRS), but is currently underused due to its potential side effects. Nevertheless, research has suggested that clozapine reduces future hospitalizations in patients with TRS. This study aims to verify the rates of hospitalizations in patients with TRS under long-term use of clozapine. We retrospectively analyzed clinical data from 52 individuals with TRS before and after the use of clozapine. The mean duration of treatment with and without clozapine was 6.6 (± 3.9) and 8.5 years (± 6.6), respectively. Patients had a median of 0.5 (0.74) hospitalizations per year before the use of clozapine and 0 (0.74) hospitalizations after it (p = 0.001). Therefore, the use of clozapine resulted in an expected reduction in the number of hospitalizations per year in individuals with TRS. (AU)

A severe COVID-19 case with schizophrenia as well as other chronic diseases

The prognosis of COVID-19 (coronavirus disease 2019) is usually poor when it occurs in aged adults or in patients with chronic diseases, which brought a great challenge to clinical practice. Furthermore, widespread depression, anxiety, and panic related to SARS-CoV-2 (severe acute respiratory syndrome-coronavirus 2) infection affected treatment compliance and recovery. Here we report the successful treatment of a 57-year-old male with severe COVID-19, schizophrenia, hypertension, and type 2 diabetes. The patient's negative emotions (such as tension, panic, and anxiety), particularly his aggression and paranoia, seriously hindered treatment, leading to a deteriorating condition. Psychological counseling and supportive psychotherapy were given but the effect was weak. To improve adherence, risperidone and quetiapine fumarate were replaced by olanzapine for anti-schizophrenic treatment to reduce insomnia and anxiety side effects, associated with sedative-hypnotic drugs as well as psychological counseling. The treatment compliance of the patient improved significantly. The patient's serum alanine aminotransferase increased abnormally in the late stage of hospitalization, suggesting potential liver damage after complex medication strategies. We also monitored the changes of lymphocyte subsets and retrospectively analyzed the virus-specific antibody response. The results suggested that dynamic monitoring of lymphocyte subsets and virus-specific antibody response could facilitate disease progression evaluation and timely treatment plan adjustments. An effective psychotropic drug intervention associated with psychological counselling and psychotherapy are essential for the successful adherence, treatment, and rehabilitation of psychiatric disorders in COVID-19 patients.

Health-related quality of life in patients treated with atypical antipsychotics

Objective: To assess health-related quality of life and associated factors in patients treated with atypical antipsychotics, as well as to determine utility values using the EuroQol-5D-3L instrument. Methods: A cross-sectional study was conducted at a state-run pharmacy in the Brazilian National Health System. Individuals were included if they were using a single atypical antipsychotic and completed the EuroQol-5D-3L. Sociodemographic, behavioral, and clinical data were collected. The dependent variable was the EuroQol-5D-3L utility score. Associations between the independent variables and the dependent variable were analyzed in a multiple linear regression model. Results: A total of 394 patients were included, and their mean utility score was 0.664±0.232. Patients treated with clozapine had the highest mean score (0.762 [0.202]), followed by olanzapine (0.687 [0.230]), risperidone (0.630 [0.252]), ziprasidone (0.622 [0.234]), and quetiapine (0.620 [0.243]). The following variables were related to higher utility scores: income, employment, clozapine use, no illicit psychoactive substance use, no suicide attempts, and no comorbidities. Conclusion: Evaluating health-related quality of life differences in the available atypical antipsychotics can facilitate the choice of treatment, improve health outcomes, and ensure rational prescriptions.

Tratamento com aripiprazol para Esquizofrenia no contexto do Sistema Único de Saúde em Goiás: análise de impacto orçamentário e revisão de estudos de análise de custo-utilidade / Aripiprazol for Schizophrenia treatment in the Goiás Public Health System perspective: budget impact analysis and review of cost-utility analysis studies

Tecnologia: Aripiprazol, medicamento antipsicótico de segunda geração. Indicação: tratamento da esquizofrenia. Objetivos: Apresentar evidências de análise econômicas em saúde, no cenário do SUS e contextos internacionais, do tratamento com Aripiprazol para esquizofrenia, comparado a outros antipsicóticos de uso oral de primeira e segunda geração utilizados no SUS. Realizar uma análise de impacto orçamentário para o contexto do SUS em Goiás e estimar uma projeção de gastos diretos com aquisição de Aripiprazol pela Secretaria de Saúde de Goiás, em cenário de incorporação do Aripiprazol para tratamento de esquizofrenia, no período de 2021 a 2025. Materiais e Métodos: Levantamentos bibliográficos nas bases de dados PUBMED e Biblioteca Virtual em Saúde, no mês de junho de 2020. Realizada avaliação da qualidade metodológica das revisões sistemáticas e dos estudos econômicos com as ferramentas Assessing the Methodological Quality of Systematic Reviews (AMSTAR), e Quality of Health Economic Studies (QHES) checklist, respectivamente. Foi calculado o impacto orçamentário, seguindo diretrizes do Ministério da Saúde, e projeção de gastos para a Secretaria de Saúde de Goiás. Resultados: Foram selecionadas e incluídas 1 revisão sistemática e 1 estudo econômico brasileiro no estudo de revisão rápida de evidências. Conclusão: No contexto brasileiro, o Aripiprazol é custo-efetivo, quando comparado a Clorpromazina, Haloperidol, Quetiapina e Ziprasidona. Porém, é menos custo-efetivo que Risperidona e Olanzapina. Caso seja padronizado pela Secretaria de Saúde de Goiás, promoverá economia anual para o SUS de R$ 250.042,05 a R$ 407.418,41, em sua máxima difusão. A projeção de gastos diretos é estimada em R$1.582.115,24 a R$27.960.108,08

Technology: Aripiprazole, second generation antipsychotic medication. Indication: treatment of schizophrenia. Objectives: To show evidence of health economic analysis in the scenario of Brazilian Public Health System (BPHS) and international contexts, for schizophrenia treatment with Aripiprazole, compared to other oral antipsychotics used in BPHS. To make a budget impact analysis for the Goias Public Health System perspective and estimate direct expenditures for the acquisition of Aripiprazole by State Department of Health of Goias, in a scenario of technology incorporation of Aripiprazole for the treatment of schizophrenia, in the period from 2021 to 2025. Materials and Methods: Bibliographical searches were done in the PUBMED and Virtual Health Library databases, in 2020 June. An evaluation of the methodological quality of systematic reviews and economic studies was done using the tools AMSTAR (Assessing the Methodological Quality of Systematic Reviews), and QHES (Quality of Health Economic Studies) checklist, respectively. Calculation of budget impact, following guidelines of the Brazilian Health Ministry, and projection of expenditures for the State Department of Health of Goias. Results: 1 systematic review and 1 Brazilian economic study were selected and included in the study of rapid evidence review. Conclusion: In the Brazilian context, Aripiprazole is cost-effective when compared to Chlorpromazine, Haloperidol, Quetiapine and Ziprasidone. However, it is less cost-effective than Risperidone and Olanzapine. If it is standardized by State Department of Health of Goias, it will promote anual savings for BPHS from R$ 250,042.05 to R$ 407,418.41, in its maximum dissemination. The direct expenses are estimated at R$ 1,582,115.24 to R $ 27,960,108.08

Evaluation of nonadherence to treatment among patients with schizophrenia attending psychosocial care centers in the south region of Brazil

Abstract Introduction The treatment of schizophrenia aims to reduce symptoms, improve quality of life and promote recovery from debilitating effects. Nonadherence to treatment is related to several factors and may lead to persistence of symptoms and relapse. Worldwide, the rate of nonadherence to treatment in individuals with schizophrenia is around 50%. Objectives To compare the clinical profile of nonadherent and adherent patients among individuals diagnosed with schizophrenia receiving treatment at psychosocial care centers in a city in southern Brazil. Method The clinical-epidemiological profile of patients with schizophrenia was retrospectively analyzed based on medical records entered into the system between January and December 2016, evaluating data at one-year follow-up. Results 112 patients were included. The disease was more prevalent in men; mean age was 40.5 years, being lower among men. Most of the sample had a low level of education, was unemployed/retired, did not have children and resided with relatives. The highest rate of diagnosis was among young adults. Psychotic symptoms were most frequently described, and the most commonly prescribed antipsychotic was haloperidol. The nonadherence rate was 15.2%; only one patient required admission to a psychiatric hospital. Among nonadherent patients, the mean time of attendance was 6 months; there were more nonadherent women than men. The most prevalent age range of nonadherence was 41-64 years. Psychosocial and clinical data were similar across the whole sample. Conclusion A nonadherence rate of 15.2% was found among individuals receiving treatment for schizophrenia, suggesting that psychosocial care centers were effective in treating and monitoring these patients.

Combined influence of illness duration and medication type on visual sensitivity in schizophrenia

Objective: Patients with schizophrenia have visual processing impairments. The main findings from the literature indicate that these deficits may be related to differences in paradigms, medications, and illness duration. This study is part of a large-scale study investigating visual sensitivity in schizophrenia. Here we aimed to investigate the combined effects of illness duration and antipsychotic use on contrast sensitivity function. Methods: Data were collected from 50 healthy controls and 50 outpatients with schizophrenia (classified according to illness duration and medication type) aged 20-45 years old. The contrast sensitivity function was measured for spatial frequencies ranging from 0.2 to 20 cycles per degree using linear sine-wave gratings. Results: Patients with an illness duration > 5 years had more pronounced deficits. Differences in the combined effects of illness duration and antipsychotic use were marked in patients on typical antipsychotics who had been ill > 10 years. No significant differences were found between typical and atypical antipsychotics in patients with an illness duration < 5 years. Conclusion: Visual impairment was related to both long illness duration and medication type. These results should be tested in further studies to investigate pharmacological mechanisms.

Schneider's first-rank symptoms as predictors of remission in antipsychotic-naive first-episode psychosis

Objective: German psychiatrist Kurt Schneider proposed the concept of first-rank symptoms (FRS) of schizophrenia in 1959. However, their relevance for diagnosis and prediction of treatment response are still unclear. Most studies have investigated FRS in chronic or medicated patients. The present study sought to evaluate whether FRS predict remission, response, or improvement in functionality in antipsychotic-naive first-episode psychosis. Methods: Follow-up study of 100 patients at first episode of psychosis (FEP), with no previous treatment, assessed at baseline and after 2 months of treatment. The participants were evaluated with the standardized Positive and Negative Syndrome Scale (PANSS) and Global Assessment of Functioning (GAF) and for presence of FRS. Results: Logistic regression analysis showed that, in this sample, up to three individual FRS predicted remission: voices arguing, voices commenting on one's actions, and thought broadcasting. Conclusion: Specific FRS may predict remission after treatment in FEP patients. This finding could give new importance to Kurt Schneider's classic work by contributing to future updates of diagnostic protocols and improving estimation of prognosis.

Prevalência de coprescrição clinicamente significativa de psicofármacos inibidores da enzima CYP2D6 em usuários de um centro de atenção psicossocial / The prevalence of co-prescription of clinically relevant CYP enzyme inhibitor psychotropic drugs in psychosocial care center users

Objetivo: mensurar a prevalência da coprescrição de psicofármacos inibidores clinicamente significativos da enzima CYP2D6. Métodos: estudo transversal realizado com usuários do Centro de Atenção Psicossocial de um município da Amazônia Legal. Os dados foram coletados de prontuário (medicamentos e diagnóstico clínico) e questionário semiestruturado (sociodemográficos). As informações referentes às medicações (substrato/inibidor da CYP2D6) foram consultadas no Micromedex®, Drug Interaction Checker, Food and Drug Administration e The Pharmacogene Variation Consortium. Os dados foram interpretados utilizando estatística descritiva percentual simples, considerando a média e o desvio-padrão. Para a confecção do banco de dados, utilizou-se o Office Excel®2010. Estudo aprovado pelo Comitê de Ética em Pesquisa sob o Parecer nº 289.937. Resultados: participaram deste estudo 43 pessoas com média de idade de 40,98 (±11,04) anos, sendo 55,81% do sexo masculino, 81,39% solteiros, 88,37% não brancos (pretos/pardos), 58,14% estudaram até o ensino médio e 62,79% tiveram diagnóstico F20 (esquizofrenia e subdivisões). Entre a população estudada, 100% (43/43) faziam uso diário de haloperidol, e 95,34% (41/43) encontravam-se em uso rotineiro de mais de uma droga metabolizada pela enzima CYP2D6. Verificou-se que 93% (40/43) dos participantes continham coprescrição de substratos e inibidores da enzima CYP2D6, sendo a maior prevalência de prescrições envolvendo ácido valproico, clorpromazina, levomepromazina, prometazina e risperidona. Conclusão: o estudo pôde mensurar alta prevalência de coprescrição de psicofármacos inibidores clinicamente significativos da enzima CYP2D6.

Introduction: Clinically significant adverse drug reactions are seldomly frequent, but their incidence rises when there is co-prescription, especially psychoactive drugs metabolized by the enzyme CYP2D6. Objective: To measure the prevalence of co-prescription of clinically significant CYP2D6 enzyme inhibitors. Methods: Cross-sectional study conducted with users of the Center for Psychosocial Attention in a city of Legal Amazon. Sociodemographic, health and drug profile data were collected from patients' records. Possible enzymatic inductions or inhibitions were researched in Micromedex®, Drug Interaction Checker, Food and Drug Administration e The Pharmacogene Variation Consortium. The data were interpreted using simple percentage descriptive statistics, considering the mean and standard deviation. To make the database, Office Excel®2010 was used. The research has the approval of the Research Ethics Committee under opinion no. 289,937. Results: Forty-three people with a mean age of 40.98 (±11.04) years participated in this study, 24 (55.81%) men, 81,39% single, 88,37% non-white, 58,14% have high school and 62,79% were diagnosed with schizophrenia. Among the studied population, 100% (43/43) used haloperidol daily and 95.34% (41/43) used more than one drug inhibitor or metabolized by the CYP2D6 enzyme. It was found that 93% of the participants contained co-prescription of CYP2D6 substrates and inhibitors, with the highest prevalence of prescriptions involving valproic acid, chlorpromazine, levomepromazine, promethazine and risperidone. Conclusion: The study was able to measure the high prevalence of co-prescription of clinically significant CYP2D6 inhibitor drugs in the studied population.

Eficácia, segurança e efetividade comparada de palmitato de paliperidona e outros antipsicóticos injetáveis de efeito prolongado para tratamento de esquizofrenia: revisão rápida de evidências / Efficacy, safety and effectiveness in the real world for paliperidone palmitate compared to the others long acting injectable antipsychotics for schizophrenia treatment: rapid review of evidence

Tecnologia: Palmitato de Paliperidona (PP) é um antipsicótico injetáveis de efeito prolongado (AIEP). Indicação: Tratamento sintomático da esquizofrenia. Objetivo: Comparar a eficácia, segurança e efetividade terapêutica entre PP e outros AIEP para o tratamento de esquizofrenia em adultos. Pergunta: O PP é mais eficaz e seguro que os outros AIEP (Decanoato de Haloperidol, Enantato de Flufenazina, Decanoato de Zuclopentixol, Risperidona-IEP) para o tratamento sintomático de esquizofrenia em adultos? Métodos: Levantamento bibliográfico, com estratégias estruturadas de busca, na base de dados PUBMED. Foi feita avaliação da qualidade metodológica das revisões sistemáticas (RS), ensaios clínicos randomizados (ECR) e dos estudos observacionais de efetividade no mundo real (EOEMR) com as ferramentas Assessing the Methodological Quality of Systematic Reviews (AMSTAR), Delphi List e Newcastle-Ottawa Scale (NOS), respectivamente. Resultados: Foram selecionadas 3 RS, 1 ECR e 3 EOEMR. Conclusão: PP (de aplicação mensal) tem similar eficácia e segurança com a Risperidona-IEP para o tratamento de esquizofrenia, exceto que provoca menor incidência de sintomas extrapiramidais. PP e Decanoato de Haloperidol são similares na eficácia e segurança para o tratamento de esquizofrenia, inclusive no risco de sintomas extrapiramidais (discinesias tardias e parkinsonismo), exceto que PP tem menor incidência de acatisia. PP é similar aos outros AIEP nos vários desfechos de eficácia e segurança terapêutica, inclusive mortalidade

Technology: Paliperidone palmitate (PP) is a long-acting injectable (LAI) antipsychotics. Indication: Symptomatic treatment of schizophrenia. Objective: To compare the therapeutic efficacy, safety and effectiveness in the real world between PP and other LAI antipsychotics for the treatment of schizophrenia in adults. Question: Is PP more effective and safer than other LAI antipsychotics (Haloperidol Decanoate, Fluphenazine Enanthate, Zuclopentixol Decanoate, Risperidone-LAI), for the symptomatic treatment of schizophrenia? Methods: Bibliographic survey, with structured search strategies, in the PUBMED database. Na evaluation was made of the methodological quality of systematic reviews (SR), randomized clinical trials (RCT) and observational studies (OS) of effectiveness in the real world with Assessing the Methodological Quality of Systematic Reviews (AMSTAR), Delphi List and Newcastle-Ottawa Scale (NOS) tools, respectively. Results: 3 SR, 1 RCT and 3 OE were included. Conclusion: PP (monthly dose presentation) has similar efficacy and safety with Risperidone-LAI for the treatment of schizophrenia, except that it causes a lower incidence of extrapyramidal symptoms. PP and Haloperidol Decanoate are similar in efficacy and safety for the treatment of schizophrenia, including the risk of extra-pyramidal symptoms (tardive dyskinesias and parkinsonism), except that PP has a lower incidence of akathisia. PP has similar outcomes of efficacy and safety to the other LAI antipsychotics, including mortality risk

Terapia Electroconvulsiva y Estimulación Magnética Transcraneal Repetitiva en pacientes con esquizofrenia: una revisión sistemática / Electroconvulsive Therapy and Repetitive Transcranial Magnetic Stimulation in patients with schizophrenia: a systematic review

Cuando la esquizofrenia no responde satisfactoriamente a tratamiento farmacológico, alcanzar una terapia efectiva para el paciente es una tarea bastante frustrante para el médico psiquiatra. Es en este contexto que la terapia electroconvulsiva y la estimulación magnética transcraneal repetitiva han tomado fuerza en la investigación clínica, a pesar de los grandes cuestionamientos sobre su efectividad y mala reputación. Se realizó una revisión sistemática de la literatura en las principales bases de datos disponibles. Concluyendo que ambas terapias demuestran ser herramientas útiles en el tratamiento de la esquizofrenia resistente a tratamiento farmacológico, así como también complementarias a los antipsicóticos

When schizophrenia does not respond satisfactorily to pharmacological treatment, achieving effective therapy for the patient is quite a frustrating task for the psychiatrist. It is in this context that electroconvulsive therapy and repetitive transcranial magnetic stimulation have gained strength in clinical research, despite huge questions about its success and bad reputation. A systematic review of the literature was conducted in the main available databases. Concluding that both specific therapies will be useful tools in the treatment of schizophrenia resistant to pharmacological treatment, as well as complementary to antipsychotics.

Research advances in add-on treatment for negative symptoms and cognitive dysfunction in schizophrenia / 中南大学学报(医学版)

Antipsychotic medication is the primary treatment for schizophrenia, which is effective on ameliorating positive symptoms and can reduce the risk of recurrence, but it has limited efficacy for negative symptoms and cognitive dysfunction. The negative symptoms and cognitive dysfunction seriously affects the life quality and social function for the patients with schizophrenia. Currently, there is plenty evidence that antipsychotic drugs combined with adjuvant therapy drugs can effectively improve the negative symptoms and cognitive dysfunction. These drugs include anti-oxidants, nicotinic acetylcholine receptors and neuro-inflammatory drugs (anti-inflammatory drugs, minocycline), which show potential clinical effects.

The role of NMDA receptor antagonists, amantadine and memantine, in schizophrenia treatment: a systematic review

Abstract Objective Schizophrenia is a complex and chronic psychiatric disorder. In recent years, studies have found glutamatergic system participation in its etiopathogenesis, especially through aberrant NMDA receptors functioning. Thus, drugs that modulate this activity, as amantadine and memantine, could theoretically be used in its treatment. To perform a systematic literature review about memantine and amantadine use as adjunct in schizophrenia treatment. Methods A systematic review of papers published in English indexed in the electronic database PubMed ® using the terms "memantine", "amantadine" and "schizophrenia" published until October 2016. Results We found 144 studies, 8 selected for analysis due to meet the objectives of this review. Some of these have shown benefits from such drug use, especially in symptoms measured by PANSS and its subdivisions, while others do not. Discussion: The data in the literature about these drugs use for schizophrenia treatment is still limited and have great heterogeneity. Thus, assay with greater robustness are needed to assess real benefits of these drugs as adjuvant therapy.

Efficacy and safety of paliperidone palmitate 3-month formulation in Latin American patients with schizophrenia: A subgroup analysis of data from two large phase 3 randomized, double-blind studies

Objective: To analyze the efficacy and safety of paliperidone palmitate 3-monthly (PP3M) in Latin American patients with schizophrenia vs. rest-of-world (ROW). Methods: We analyzed data from two multinational, double-blind (DB), randomized, controlled phase 3 studies including patients with schizophrenia (DSM-IV-TR) previously stabilized on PP1M/PP3M (open-label [OL] phase). Patients were randomized to PP3M or PP1M (noninferiority study A) and PP3M or placebo (study B) in DB phase. The subgroup analysis included Latin American (Argentina, Brazil, Colombia, Mexico) patients. Primary efficacy endpoints were relapse-free rates (study A) and time-to-relapse (study B). Results: In study A, 63/71 (88.7%) and in study B 38/43 (88.4%) Latin American patients completed the DB phase. In study A, relapse-free percentage was similar in Latin America (PP3M: 97%, PP1M: 100%) and ROW (PP3M: 91%, PP1M: 89%). In study B, median time-to-relapse was not estimable in the Latin American subgroup for either placebo or PP3M groups, nor for the ROW PP3M group; the median time-to-relapse in the ROW placebo group was 395 days. Caregiver burden improved in patients switching from oral antipsychotics (OL baseline) to PP3M/PP1M in DB phase (Involvement Evaluation Questionnaire score mean ± SD change, -9.4±15.16; p < 0.001). Treatment emergent adverse events with PP3M during DB phase were similar in Latin America (study A: 24/34 [70.6%]; study B: 15/21 [71.4%]) and ROW (study A: 318/470 [67.7%]; study B: 84/139 [60.4%]) subgroups. Conclusion: PP3M was efficacious and showed no new safety concerns in patients with schizophrenia from Latin America, corroborating ROW findings. Clinical trial registration: NCT01515423, NCT01529515

Sex-differential effects of olanzapine vs. aripiprazole on glucose and lipid metabolism in first-episode schizophrenia

Abstract Objective To compare sex difference in metabolic effect of olanzapine versus aripiprazole on schizophrenia. Methods A twelve-week prospective open-label cohort study to compare four subgroups according to first-episode schizophrenia patients' type of drug usage and sex: female aripiprazole (n = 11), male aripiprazole (n = 11), female olanzapine (n = 10), and male olanzapine (n = 11) for body mass index, fasting serum triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and fasting glucose. Results Aripiprazole may be associated with weight gain in female patients with low-baseline weight. Aripiprazole may have an adverse effect of weight and favorable effects of circulating glucose and lipid on female over male schizophrenia patients. The aripiprazole-induced changes in glucose and lipid may be independent of body fat storage, especially for female schizophrenia patients. Olanzapine may have adverse effects of weight, glucose and lipid profiles on female over male schizophrenic patients. Discussion Our findings fill the gap in knowledge and provide a sex-specific guidance to psychiatrist better tailoring treatment to individual sex-differential characteristics and a key clue to understand the sex-differential mechanism of antipsychotics-induced metabolic dysfunction.