Clozapine prescription trends in Brazil in the last decade

Objective: Clozapine is a second-generation antipsychotic indicated for treatment-resistant schizophrenia. Studies in several countries have shown a low rate of clozapine use despite the fact that approximately 30% of schizophrenia cases are treatment-resistant. In Brazil, few studies have addressed the frequency and variety of antipsychotic use in individuals diagnosed with schizophrenia (ICD F20). The objective of this study was to measure the rates of clozapine use in this population in the last decade using Brazilian Ministry of Health data. Methods: Prescriptions made between 2010 and 2020 in all 26 states and the Federal District registered at the Outpatient Information System Database from the Brazilian Health System (SIASUS) were evaluated. Results: A total of 25,143,524 prescriptions were recorded in this period, with clozapine representing 8.86% of all antipsychotics. The most frequently prescribed antipsychotic for patients with schizophrenia was olanzapine (35.8%), followed by quetiapine (27.5%). From 2010 to 2020, the rate of clozapine prescriptions in Brazil increased from 7.2% to 10.9%. Conclusions: Despite a slight increase in prescriptions in the last decade, clozapine is still underutilized in Brazil

Biomarcadores periféricos nos transtornos psicóticos: a influência de características clínicas, estágio da doença e tratamento

INTRODUCTION: Schizophrenia is a chronic disease, with considerable impact on live of individuals and their families. Its origin is related to a complex interaction between genetic and environmental factors during brain development. Despite advances in research, there are no biological markers to confirm the diagnosis, indicate the prognosis, or assist in therapeutic decision. Changes in immune system and oxidation processes have been consistently associated with schizophrenia and markers of these processes emerge as promising biomarkers. However, the current literature is still heterogeneous, and the role of factors such as the use of medication or phenotypic variability remain a challenge to be surmounted. This thesis presents seven studies investigating biomarkers related to inflammation and oxidative stress in different aspects of the disorder. AIMS: To investigate psychotic disorders longitudinally, with a multi-phase and multimodal approach, taking into account clinical heterogeneity. Hence, it was explored the immunological profile and oxidative biomarkers, by evaluating different subgroups of the disease (first episode, drug-naïve patients, the presence of depression, before and after treatment, treatment-resistance). It was also evaluated the relationship between inflammation, oxidative and genetic biomarkers. METHODS: Patients were recruited in their first psychotic episode (FEP), drug-naïve, and followed for an average period of 8 weeks under risperidone. It was also evaluated patients in advanced stages, with more than 1 year of disease. Patients were diagnosed by SCID, with psychopathological evaluation by PANSS and CDSS. RESULTS: FEP patients have increased levels of interleukin (IL)-6, IL-10 and tumor necrosis factor (TNF)-alpha when compared to healthy controls. They also have increased total reactive antioxidant potential (TRAP) and decreased activity of paraoxonase (PON) 1. Those in FEP with depression had higher levels of IL-4 and TNFalfa compared to those without depression, and increased expression of COMT and decrease expression NDEL1. After treatment with risperidone, the three mentioned cytokines, and additionally, IL-4 reduced significantly, and lipid hydroperoxides (LOOH) levels decreased and PON1 activity increased. Next, it was demonstrated that the combination of five biomarkers (sTNF-R1, sTNF-R2, CCL11, IP-10, IL-4) may predict the diagnosis of schizophrenia with a sensitivity of 70.0% and a specificity of 89 4%. Treatment resistance patients showed distinct inflammatory profile, with an increase in increased levels of sTNF-R1, sTNF-R2, and MCP-1. Finally, increased levels of IL-6 was associated with reduced expression of AKT1 and DROSHA, while an increase of IL-10 was associated with increased expression NDEL1, DISC1 and MBP. IL-6 also significantly increased expression of AKT1, DICER1, DROSHA and COMT induced by risperidone. DISCUSSION: It was shown that a disorder in the immune system and oxidative balance is already present from the onset of schizophrenia, before the use of antipsychotic drugs. Moreover, it was suggested that risperidone has antioxidative and anti-inflammatory effects. Features such as depression and treatment resistance also presented a specific immunological profile. Finally, it was showed that inflammatory cytokines play an important role in the regulation of oxidative processes and gene expression. Using an innovative approach and seeking for convergence between different methodologies, the results generated new perspectives in understanding the pathophysiological mechanisms underpinning the neurobiology of schizophrenia.A esquizofrenia é uma doença crônica, com grande impacto na vida do indivíduo e de seus familiares. Sua origem está relacionada a uma complexa interação entre fatores genéticos e ambientais ao longo do desenvolvimento cerebral. Apesar dos avanços nas pesquisas, ainda não existem marcadores biológicos que confirmem o diagnóstico, indiquem o prognóstico, ou auxiliem na escolha terapêutica. Alterações no sistema imunológico e nos processos de oxidação tem sido consistentemente associadas à esquizofrenia e indicadores desses processos surgem como promissores biomarcadores. No entanto, a literatura atual ainda é bastante heterogênea, e o papel de fatores como o uso de medicação ou a variabilidade fenotípica da esquizofrenia, permanecem como desafios científicos a serem transpostos. Nesta tese são apresentados sete estudos que investigam biomarcadores relacionados à inflamação e ao estresse oxidativo em diferentes aspectos da doença. Objetivos: Investigar os transtornos psicóticos de maneira longitudinal, multifásica e multimodal, levando em consideração a heterogeneidade clínica presente. Para tanto, foi explorado o perfil de biomarcadores imunológicos e oxidativos, através da avaliação de diferentes subgrupos da doença (primeiro episódio, virgens de tratamento, presença de depressão, pré e pós tratamento, presença de refratariedade ao tratamento). Também foram avaliadas as relações entre biomarcadores inflamatórios, oxidativos e genéticos. MÉTODOS: Foram recrutados pacientes no primeiro episódio psicótico (PEP), virgens de tratamento, sendo acompanhados por período médio de 8 semanas, antes e depois do uso de risperidona. Também foram avaliados pacientes em estágios mais avançados, portadores de esquizofrenia, com mais de 1 ano de doença. Os pacientes receberam diagnóstico através da SCID, com avaliação psicopatológica através da PANSS e CDSS. Resultados: Pacientes no PEP apresentam aumento dos níveis de interleucina (IL)- 6, IL-10 e fator de necrose tumoral (TNF)-alfa quando comparados com controles xix xix saudáveis. Também apresentam aumento do potencial reativo antioxidante total (TRAP) e diminuição da atividade da paraoxonase (PON) 1. Aqueles no PEP com depressão apresentaram níveis mais altos de IL-4 e TNF-alfa em relação àqueles sem depressão, além de aumento da expressão da COMT e diminuição da expressão de NDEL1. Após o tratamento com risperidona, as três citocinas alteradas e, adicionalmente, IL-4 reduziram significativamente, além de diminuição dos níveis de hidroperóxidos de lipídios (LOOH) e aumento da atividade da PON1. A seguir, foi demonstrado que a combinação dos cinco biomarcadores (sTNF-R1, sTNF-R2, CCL11, IP-10, IL-4) podem prever o diagnóstico de esquizofrenia com uma sensibilidade de 70,0% e uma especificidade de 89,4%. Os pacientes refratários apresentaram perfil inflamatório distinto, com aumento nos níveis aumentados de sTNF-R1, sTNF-R2 e MCP-1. Por fim, níveis aumentados de IL-6 foi associado com expressão de AKT1 e DROSHA reduzida, enquanto aumento da IL-10 está associado com aumento da expressão de NDEL1, DISC1 e MBP. IL-6 também aumentou significativamente a expressão de AKT1, DICER1, DROSHA e COMT induzida por risperidona. Conclusão: Foi demonstrado que uma disfunção no sistema imunológico e no equilíbrio oxidativo já está presente desde o início da esquizofrenia, precedendo o uso de antipsicóticos. Além disso, foi apontado que a risperidona apresenta efeitos antiinflamatórios e antioxidantes. Características como a depressão e a refratariedade ao tratamento também apresentam um perfil imunológico específico. Por fim, foi proposto que as citocinas inflamatórias tem um importante papel na regulação de processos oxidativos e de expressão gênica. Utilizando uma abordagem inovadora e buscando convergência entre diferentes metodologias, os resultados obtidos geraram novas perspectivas na compreensão dos mecanismos fisiopatológicos associados à neurobiologia da esquizofrenia.Dados abertos - Sucupira - Teses e dissertações (2013 a 2016

Pharmacological treatment of schizophrenia

Background: A lack of human and financial resources, as well as effective health systems, leads to a worldwide treatment gap for schizophrenia. the aim of this paper is to propose evidence-based antipsychotics interventions for people with schizophrenia with special focus in low and middle income countries (LAMIC) reality. Method: A comprehensive search was conducted to locate the main clinical trials, reviews and relevant meta-analyses, and a number of the main recent international clinical practice guidelines. Results: First- and second-generation antipsychotics are similarly effective in the acute treatment of psychotic symptoms. in LAMIC, the treatment of choice for medical treatment of psychotic conditions is the group of so-called 'first generation antipsychotics' (FGAs) preferentially delivered in a community-based service model. Conclusions : Although the symptomatic control is essential, it is not the ultimate goal of treatment. the main aim of treatment is to improve functional recovery and social reintegration of patients.Universidade Federal de São Paulo, Dept Psychiat, BR-04038000 São Paulo, BrazilUniv London, Univ London Kings Coll, Inst Psychiat, Hlth Serv & Populat Res Dept, London WC1E 7HU, EnglandUniversidade Federal de São Paulo PROESQ, Schizophrenia Program, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychiat, BR-04038000 São Paulo, BrazilUniversidade Federal de São Paulo PROESQ, Schizophrenia Program, São Paulo, BrazilWeb of Scienc

Recognition of bipolar disorder type I before the first manic episode: challenges and developments

Bipolar disorder (BD) usually follows a neurobiological progression pathway, but a relatively long interval between the first symptoms of the disorder and the correct diagnosis and treatment takes place in most patients. Strategies used to recognize BD at an early stage and even prior to the first manic episode could help identify the risk and modifying factors that influence the onset and course of disease, and improve outcomes. Drawing on current research results, this article presents considerations on risk factors for the development of BD, including genetic/familial risk, endophenotypes and clinical characteristics. Taken together, this article provides a framework and tools for research on the BD prodrome, as well as for the early recognition and timely treatment of patients prior to and immediately after the emergence of BD.Universidade Federal de São Paulo, Dept Psychiat, Program Recognit & Intervent Individuals Risk Men, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychiat, Interdisciplinary Lab Clin Neurosci LINC, São Paulo, BrazilUniv Toronto, CAMH, Toronto, ON, CanadaUniv Toronto, Univ Hlth Network, Mood Disorders Psychopharmacol Unit, Toronto, ON, CanadaZucker Hillside Hosp, Div Psychiat Res, Glen Oaks, NY USAHofstra North Shore LIJ Sch Med, Hempstead, NY USAUniversidade Federal de São Paulo, Dept Psychiat, Program Recognit & Intervent Individuals Risk Men, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychiat, Interdisciplinary Lab Clin Neurosci LINC, São Paulo, BrazilWeb of Scienc

Evaluation of the efficacy of transcranial direct current stimulation in the treatment of cognitive symptomatology in the early stages of psychosis: study protocol for a double-blind randomized controlled trial

Abstract Background Cognitive deficits are core symptoms of schizophrenia that occur from the early stages of the disorder. There is reliable evidence that cognitive deficits are associated with outcomes in schizophrenia; thus, early treatment could be particularly important. Studies with different neuromodulation techniques involving subjects with schizophrenia suggest that application of transcranial direct current stimulation (tDCS) with inhibitory stimulation over the left temporo-parietal cortex and excitatory stimulation over the left dorsolateral prefrontal cortex could ameliorate positive, negative, and cognitive symptoms. The aim of the present study protocol is to evaluate the efficacy of tDCS in the treatment of cognitive symptomatology in the early stages of psychosis. Methods/design Seventy patients in the early stages of psychosis will be randomly allocated to receive 20 min of active 2-mA tDCS or sham stimulation once a day for 10 consecutive weekdays. The anode will be placed over the left dorsolateral prefrontal cortex and the cathode over the left temporo-parietal cortex. Neuropsychological and psychiatric assessments will be performed at baseline and at 1 and 3 months following the end of the intervention (sustained effect). Discussion The development and utilization of potentially effective neuroenhancement tools such as the non-invasive brain stimulation technique tDCS for the treatment and rehabilitation of cognitive impairment in the early stages of schizophrenia may contribute to improving outcomes of the disorder and eventually provide a further understanding of the nature of the complex and dynamic neural processes underlying those abnormalities. Trial registration ClinicalTrials.gov, NCT03071484. Registered on 7 March 2017

New evidence in support of staging approaches in schizophrenia: Differences in clinical profiles between first episode, early stage, and late stage

Few studies have examined the progression of symptom dimensions in schizophrenia patients over the course of the illness. The objective of this study was to investigate whether clinical and psychopathological differences exist between first-episode schizophrenia (FES) and multiple-episode patients in an inpatient setting. Patients (N = 203) were evaluated using the Positive and Negative Syndrome Scale (PANSS) overtime. Five different generalized estimating equations were built for the PANSS factors using the following as covariates: sex, patient's age, assessment time point (i.e., moment of patient's evaluation, with a minimum of two and a maximum of four assessments throughout the study timeframe). The FES group was used as the reference to which the groups with up to five years of illness and more than five years of illness were compared. Remission rates and treatment resistance (TRS) rates were also compared. Generalized estimating equations were used to allow for different numbers of assessments over the study period. Patients with FES showed significantly milder severity in positive, disorganized, and hostility factors. Also, FES patients were more likely to achieve remission (P = 0.002) and had lower rates of TRS (P = 0.001). First-episode schizophrenia seems to be the critical period to improve outcome, as multiple-episode patients were similar in clinical characteristics regardless of illness duration. (C) 2016 Elsevier Inc. All rights reserved.Univ Fed Sao Paulo, Dept Psychiat, Interdisciplinary Lab Clin Neurosci LiNC, Rua Pedro Toledo 669,3 Andar, BR-05039032 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Psychiat, Schizophrenia Program Proesq, Sao Paulo, SP, BrazilHosp Clin Luzia Pinho Melo SPDM, Dept Mental Hlth, Mogi das Cruzes Sch Med FMUMC, Mogi Das Crazes, SP, BrazilUniv Fed Sao Paulo, Dept Psychiat, Interdisciplinary Lab Clin Neurosci LiNC, Rua Pedro Toledo 669,3 Andar, BR-05039032 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Psychiat, Schizophrenia Program Proesq, Sao Paulo, SP, BrazilWeb of Scienc