Eficácia e segurança de Aripiprazol comparado a medicamentos disponíveis no SUS para o tratamento de transtorno de déficit de atenção com hiperatividade em crianças e adolescentes / Effectiveness and safety of aripiprazole compared to other medicines available in Brazilian Public Health for treatment of attention deficit disorder with hyperactivity: rapid review

Tecnologia: Aripiprazol. Indicação: Tratamento de transtorno de déficit de atenção com hiperatividade em crianças e adolescentes. Pergunta: O aripiprazol é mais eficaz e tolerável que os medicamentos disponíveis no SUS (bupropiona e antidepressivos (amitriptilina, nortriptilina, fluoxetina, clomipramina, risperidona) para o tratamento de transtorno de déficit de atenção e hiperatividade em crianças e adolescentes? Métodos: Revisão rápida de evidências de ensaios clínicos randomizados com levantamento bibliográfico realizado na base de dados PUBMED, EMBASE, Cochrane Library, PsycInfo, utilizando estratégia estruturada de busca. A qualidade metodológica dos ECR foi avaliada com a escala PEDro (Physiotherapy Evidence Database). Resultados: Foram selecionados dois estudos clínicos randomizados, que atendiam aos critérios de inclusão. Conclusão: As evidências demonstraram tanto o aripiprazol quanto a risperidona apresentam redução dos sintomas emocionais de déficit de atenção e hiperatividade mediante avaliação das escalas e ambas apresentaram taxa de abandono de tratamento devido a efeitos adversos e não se mostraram uma opção econômica

Technology: Aripiprazole. Indication: Treatment of attention deficit hyperactivity disorder in children and adolescents. Question: Is aripiprazole more effective and tolerable than drugs available in the SUS (bupropion and antidepressants (amitriptyline, nortriptyline, fluoxetine, clomipramine, risperidone) for the treatment of attention deficit hyperactivity disorder in children and adolescents? Methods: Rapid review of evidence of randomized clinical trials with a bibliographic search done in PUBMED, EMBASE, Cochrane Library and PsycInfo databases using a structured search strategy. The methodological quality of the randomized clinical trials was evaluated with the PEDro scale (Physiotherapy Evidence Database). Results: Two randomized clinical studies were selected, which met the inclusion criteria. Conclusion: The evidence showed that both aripiprazole and risperidone present a reduction in the emotional symptoms of attention deficit and yperactivity according to the scales and both presented a rate of abandonment of treatment due to and adverse effects and did not prove to be an economical option

Treatments for Tourette syndrome in children and young adults: a systematic review / Tratamento da síndrome de Tourette em crianças e jovens adultos: uma revisão sistemática

INTRODUCTION: Tourette's Syndrome (TS) is a neurodevelopmental disorder characterized by motor and / or vocal tics for more than 12 months. TS affects about 0.8% of pediatric patients and is associated with great functional impairment and psychological distress. The present study aims to list and compare the effectiveness of therapies used in children and young people with TS. METHODS: PubMed / MEDLINE, Cochrane Library, ScienceDirect, SciELO and Lilacs were used from September 2020 to April 2021 to search for randomized clinical trials with pharmacological, behavioral, physical or alternative interventions for tics in children and young people with ST. RESULTS: 13 clinical trials were included, of which six pharmacological, six behavioral and one of other conformation. The global score on the Yale Global Tic Severity Scale showed evidence in favor of Habit Reversal Training (HRT) and Comprehensive Behavioral Intervention for Tics (CBIT). Evidence from two studies suggests that antipsychotic medications improve tic scores. Evidence from other interventions has shown no conclusive benefit. CONCLUSIONS: The present study identified benefits with the use of antipsychotics. The study also found that HRT and CBIT showed improvement in reducing the severity of tics, in addition to not having any adverse effects. These therapies showed significant clinical improvement, but there is no comparison between the use of these isolated approaches in relation to their use associated with medications. In view of the different forms of therapy, further studies are needed to identify the effectiveness and the profile of adverse effects of these interventions.

INTRODUÇÃO: A Síndrome de Tourette (ST) é um distúrbio do neurodesenvolvimento caracterizado por tiques motores e/ou vocais por mais de 12 meses. A ST afeta cerca de 0,8% dos pacientes pediátricos e associa-se a grande comprometimento funcional e sofrimento psíquico. O presente estudo tem como objetivo listar e comparar a eficácia das terapias utilizadas em crianças e jovens com ST. MÉTODOS: PubMed/MEDLINE, Cochrane Library, ScienceDirect, SciELO e Lilacs foram usados desde setembro de 2020 até abril de 2021 para a busca de ensaios clínicos randomizados com intervenções farmacológicas, comportamentais, físicas ou alternativas para tiques em crianças e jovens com ST. RESULTADOS: 13 ensaios clínicos foram incluídos, dos quais seis farmacológicos, seis comportamentais e um de outra conformação. A pontuação global na Yale Global Tic Severity Scale, apresentou evidências a favor do Treinamento de Reversão de Hábito (TRH) e Intervenção Comportamental Abrangente para Tiques (ICAT). As evidências de dois estudos sugerem que medicamentos antipsicóticos melhoram os escores de tiques. Evidências de outras intervenções não mostraram nenhum benefício conclusivo. CONCLUSÕES: O presente estudo identificou benefícios com o uso do antipsicóticos. O estudo também identificou que a TRH e a ICAT apresentaram melhora na redução da gravidade dos tiques, além de não apresentarem efeitos adversos. Essas terapias mostraram importante melhora clínica, mas não há comparação entre o uso dessas abordagens isoladas em relação ao seu uso associado com medicamentos. Diante das diferentes formas de terapia, mais estudos são necessários para identificar a eficácia e o perfil de efeitos adversos dessas intervenções.

Aplicação da eletroforese capilar - espectrometria de massas para identificação dos produtos de degradação do aripiprazol em medicamentos / Application of capillary electrophoresis - mass spectrometry to identify aripiprazole degradation products in drugs

Diretrizes internacionais e nacionais como a FDA (Food and Drug Administration), ICH (International Council for Harmonisation) e ANVISA (Agência Nacional de Vigilância Sanitária) estabelecem a exigência de testes de estabilidade para entender melhor a qualidade de um medicamento. O estudo de estabilidade deve ser realizado usando métodos indicativos de estabilidade que possam qualificar e quantificar os insumos farmacêuticos do medicamento, bem como as impurezas e produtos de degradação nele contidos. O aripiprazol é um antipsicótico atípico de segunda geração aprovado para o tratamento de esquizofrenia, transtorno bipolar, depressão e transtornos do espectro do autismo. Os métodos oficiais descritos nas farmacopeias para avaliar o aripiprazol e suas impurezas utilizam a cromatografia líquida de alta eficiência (HPLC) como técnica principal. Nesta pesquisa, objetivou-se desenvolver um método indicativo de estabilidade por eletroforese capilar de zona (CZE) para o aripiprazol na forma farmacêutica de comprimidos, e identificação dos produtos de degradação por espectrometria de massas. O estudo de degradação forçada e a optimização do método desenvolvido por CZE foram realizados utilizando o conceito de delineamento de experimentos (DoE). A separação do aripiprazol de seus produtos de degradação foi conseguida usando uma coluna capilar de sílica fundida (30,2 cm x 75 µm ID), eletrólito de formiato de amônio 6 mmol/L (pH 3) com 5% de metanol sob um potencial de 15 kV e detecção em 214 nm. A capacidade indicativa de estabilidade do método foi investigada pela análise do aripiprazol após ser submetido a condições de estresse ácido, alcalino, térmico, fotolítico e oxidativo, de acordo com as diretrizes ICH. A oxidação foi a principal via de degradação entre as condições de estresse avaliadas. O aripiprazol foi separado dos seus produtos de degradação oxidativa em tempo de corrida abaixo de 5 minutos. O método por CZE mostrou ser linear na faixa de 60 - 140 µg/mL, R2 = 0,9980, precisão calculada como desvio padrão relativo (DPR) menor que 2% e exatidão calculada como recuperação média de 100,93 ± 0,77%. Os resultados obtidos demonstram que o método por HPLC-RP em modo gradiente, separou o aripiprazol e seus produtos de degradação em um tempo de corrida de 30 minutos. Quatro produtos de degradação foram detectados pelo método LC-MS e o principal produto de degradação oxidativo foi identificado. O aripiprazol mostrou-se suscetível à oxidação no grupo piperazina, gerando principalmente o composto aripiprazol-1-N-óxido

International and national guidelines such as the FDA (Food and Drug Administration), ICH (International Council for Harmonization) and ANVISA (National Health Surveillance Agency) establish the requirement for stability tests to better understand quality of a medicine. The stability study must be carried out using stability indicating methods that can qualify and quantify the pharmaceutical ingredients of the drug, as well as the impurities and degradation products contained therein. Aripiprazole is a second-generation atypic antipsychotic drug approved for the treatment of schizophrenia, bipolar disorder, depression, and autism spectrum disorders. The official method described in the pharmacopoeias to evaluate aripiprazole and its impurities is high performance liquid chromatography (HPLC) as the main technique. In this research, the objective was to develop an indicative method of stability by capillary zone electrophoresis (CZE) for aripiprazole in the pharmaceutical form of tablets, and identification of degradation products by mass spectrometry. The forced degradation study and the optimization of the method developed by CZE were carried out using the concept of design of experiments (DoE). The separation of aripiprazole from its degradation products was achieved using a fused silica capillary column (30,2 cm x 75 µm ID), 6 mmol/L ammonium formate electrolyte (pH 3) with 5% methanol under a potential of 15 kV and detection at 214 nm. The indicative stability of the method was investigated by analyzing aripiprazole after being subjected to acid, alkali, thermal, photolytic and oxidative stress conditions, according to the ICH guidelines. Oxidation was the main degradation pathway among the stress conditions evaluated. Aripiprazole was separated from its oxidative degradation products at run times below 5 minutes. The CZE method proved to be linear in the range of 60 - 140 µg/mL, R2 = 0,9980, precision calculated as a relative standard deviation (DPR) of less than 2% and accuracy calculated as a mean recovery of 100,93 ± 0,77%. The results obtained demonstrate that the HPLC-RP method in gradient mode separated aripiprazole and its degradation products in a run time of 30 minutes. Four degradation products were detected by the LC-MS method and the main oxidative degradation product was identified. Aripiprazole was shown to be susceptible to oxidation in the piperazine group, generating mainly the compound aripiprazole-1-N-oxide

Manía unipolar: un ineludible diagnóstico: revisión de la literatura a propósito de un caso / Unipolar mania: an unavoidable diagnosis: case report and literature review

Resumen Introducción: La manía unipolar (MU) es un trastorno que se comporta de manera distinta al trastorno bipolar-I (TB-I), sin embargo, no es considerado como una entidad independiente por los manuales diagnósticos vigentes, sino que es incluido dentro del diagnóstico de TB-I. Caso clínico: Hombre de 21 años presenta cuadro clínico de 3 meses de evolución caracterizado por ánimo exaltado y síntomas psicóticos congruentes al estado de ánimo. El paciente niega episodios depresivos previos. Se instaura tratamiento con litio y aripiprazol que resulta satisfactorio, sin presentar recurrencias tras 5 años de seguimiento. Revisión de la literatura y discusión: Los manuales diagnósticos describen que para diagnosticar TB-I no se requiere la presencia de un episodio depresivo mayor, lo que implica que pacientes con MU quedan dentro de la misma categoría diagnóstica que pacientes con TB-I. Diferencias entre MU y TB-I han sido demostradas en estudios epidemiológicos, clínicos y genéticos, por lo tanto, incluir pacientes heterogéneos dentro de la misma categoría podría dificultar la interpretación de estudios y limitar los avances en el conocimiento de ambos trastornos. Conclusión: De la revisión de la literatura se sugiere que la MU debe ser reconocida como un diagnóstico independiente. A pesar de su baja prevalencia, al validarlo como tal, en un futuro podríamos contar con mayor cantidad y mejor calidad de datos sobre este. De esta forma se podrá definir de manera más concreta sus características distintivas, y por consiguiente mejorar el abordaje clínico de estos pacientes.

Introduction: Unipolar mania (UM) is a disorder that behaves differently from bipolar-I disorder (BP-I), however, it is not considered an independent entity by current diagnostic manuals, but rather included within the diagnosis of BP-I. Case report: A 21-year-old man presented a 3-month-long episode characterized by exalted mood and mood-congruent psychotic symptoms. The patient denies previous depressive episodes. Treatment with lithium and aripiprazole was established, which was satisfactory, not showing recurrence after 5 years of follow-up. Literature review and discussion: Diagnostic manuals describe that to diagnose BP-I the presence of a major depressive episode is not required, which implies that patients with UM fall into the same diagnostic category as patients with BP-I. Differences between UM and BP-I have been demonstrated in epidemiological, clinical, and genetic studies, therefore, including heterogeneous patients within the same category could hinder the interpretation of studies and limit advances in the knowledge of both disorders. Conclusion: Based on the literature review, it is suggested that UM should be recognized as an independent diagnosis. Despite its low prevalence, by validating it as such, in the future we could have more and better-quality data about this diagnosis. In this way, its distinctive characteristics can be defined more concretely, and therefore improve the clinical approach of these patients.

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.

Para el abordaje de depresión en adolescentes: guía de práctica clínica / For the management of depression in adolescents: clinical practice guideline

Generar recomendaciones basadas en la mejor evidencia disponible acerca de la entrega de respecto a la pesquisa, diagnóstico y tratamiento de adolescentes con depresión. Adolescentes sospecha o diagnóstico de depresión, que reciben atención en el nivel primario, secundario y terciario de salud en el sector público y privado de salud. Todos los profesionales de salud con responsabilidades en la atención de adolescentes con depresión. Las recomendaciones de esta Guía fueron elaboradas de acuerdo al sistema "Grading of Recommendations Assessment, Development, and Evaluation" (GRADE). Luego de priorizadas las preguntas a responder, se realizó la búsqueda y la síntesis de evidencia, para finalmente generar las recomendaciones a través del juicio del Panel de Expertos.

Pathological Gambling Due to Aripiprazole: Two Cases

ABSTRACT Aripiprazole is an atypical antipsychotic agent which has a partial agonistic effect on dopamine D2 and D3 receptors. It is effective in the treatment of schizophrenia and bipolar disorder. Owing to its partial agonistic effect, hyperactivity of dopamine may occur in the mesolimbic pathway. In the literature, there are few case reports about pathological gambling due to aripiprazole. In this article, there are two case reports of patients who showed pathological gambling behaviour and alcohol abuse and who were under treatment with aripiprazole. The patient had a history of gambling in the past. With the use of aripiprazole, pathological gambling behaviour occurred quickly and with discontinuation of aripiprazole it ended completely. Aripiprazole causes pathological gambling by forming a hyperdopaminergic condition in the mesolimbic dopaminergic pathway. Aripiprazole should be recommended cautiously and carefully to patients who are impulsive and have a history of alcohol/substance abuse.

Eficácia e segurança de Aripiprazol comparado a outros agentes potencializadores no tratamento de depressão refratária revisão rápida de evidências / Effectiveness and safety of Aripiprazole compared to other augmentative agents for treatment of resistant depression: rapid review of evidence

Tecnologia: Aripiprazol, antipsicóticos atípicos disponíveis no Sistema Único de Saúde, outras classes de potencializadores de tratamento depressivo. Indicação: Depressão refratária. Pergunta: Há diferenças de eficácia e segurança entre o Aripiprazol, Ziprasidona, Olanzapina, Quetiapina e Risperidona como agente potencializador do tratamento de depressão refratária? Há diferenças de eficácia e segurança entre as principais classes de drogas potencializadoras do tratamento de depressão refratária? Métodos: Levantamento bibliográfico foi realizado na base de dados PUBMED, seguindo estratégias de buscas predefinidas. Foi feita a avaliação da qualidade metodológica das revisões sistemáticas com a ferramenta Assessing the Methodological Quality of Systematic Reviews version 2. Resultados: Foram selecionadas 3 revisões sistemáticas, que atendiam aos critérios de inclusão. Conclusão: Na potencialização do tratamento antidepressivo, o Aripiprazol, em dose padrão ou dose diária reduzida, não é superior à Quetiapina, Olanzapina/Fluoxetina ou Risperidona em desfechos de eficácia ou segurança para casos de depressão refratária com pelo menos uma falha terapêutica prévia. As diferentes classes de potencializadores de antidepressivos não diferem entre si nos desfechos de eficácia para casos de depressão refratária com duas ou mais falhas terapêuticas prévias. Ziprasidona e Quetiapina se mostraram mais eficazes que o placebo e seguros para promover remissão sintomática da depressão refratária

Technology: Aripiprazole, atypical antipsychotics available in the Brazilian Public Health System, other classes of augmentative antidepressant agent. Indication: Treatment-resistant depression (TRD). Question: Are there differences in efficacy and safety between Aripiprazole, Ziprasidone, Olanzapine, Quetiapine, and Risperidone as augmentative agent in the treatment of TRD? Are there differences in efficacy and safety between the main classes of augmentative drugs that enhance the treatment of TRD? Methods: A bibliographic survey was carried out in the PUBMED database, following predefined search strategies. The methodological quality of systematic reviews was assessed using the Assessing the Methodological Quality of Systematic Reviews version 2 tool. Results: 3 systematic reviews were selected that met the inclusion criteria. Conclusion: In potentiating antidepressant treatment, Aripiprazole, in standard dose or reduced daily dose, is not superior to Quetiapine, Olanzapine/fluoxetine or Risperidone in efficacy or safety outcomes for cases of TRD with at least one previous therapeutic failure. The different classes of antidepressant enhancers do not differ in efficacy outcomes for cases of TRD with two or more prior therapeutic failures. Ziprasidone and Quetiapine were more effective than placebo and safer for the outcome of symptomatic remission of TRD

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

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

Efeitos citotóxicos do aripiprazol nas linhagens celulares MKN45 e NIH3T3 e efeitos genotóxicos nos linfócitos sanguíneos periféricos humanos / Cytotoxic effects of aripiprazole on mkn45 and nih3t3 cell lines and genotoxic effects on human peripheral blood lymphocytes

ABSTRACT BACKGROUND: Gastric cancer is known as the fourth most common cancer. Current treatments for cancer have damaged the sensitive tissues of the healthy body, and in many cases, cancer will be recurrent. Therefore, need for treatments that are more effective is well felt. Researchers have recently shifted their attention towards antipsychotic dopamine antagonists to treat cancer. The anticancer activities of aripiprazole remain unknown. OBJECTIVE: This study aimed to evaluate the efficacy and safety of aripiprazole on gastric cancer and normal cell lines. METHODS: In this regard, the cytotoxicity and genotoxicity of aripiprazole were investigated in MKN45 and NIH3T3 cell lines by methyl tetrazolium assay and on peripheral blood lymphocytes by micronucleus assay. For this purpose, cells were cultured in 96 wells plate. Stock solutions of aripiprazole and cisplatin were prepared. After cell incubation with different concentrations of aripiprazole (1, 10, 25, 50, 100 and 200 μL), methyl tetrazolium solution was added. For micronucleus assay fresh blood was added to RPMI culture medium 1640 supplemented, and different concentrations of aripiprazole (50, 100 and 200 μL) were added. RESULTS: The finding of present study showed that the IC50 of aripiprazole in the cancer cell line (21.36 μg/mL) was lower than that in the normal cell line (54.17 μg/mL). Moreover, the micronucleus assay showed that the frequency of micronuclei of aripiprazole at concentrations below 200 μM was much less than cisplatin. CONCLUSION: Aripiprazole can be a good cytotoxic compound and good candidate for further studies of cancer therapy.

RESUMO CONTEXTO: O câncer gástrico é conhecido como o quarto câncer mais comum. Os tratamentos atuais para o câncer danificaram os tecidos sensíveis do corpo saudável e, em muitos casos, o cancro será recorrente. Portanto, a necessidade de tratamentos que são mais eficazes é desejada. Recentemente, os pesquisadores mudaram sua atenção para os antagonistas antipsicóticos da dopamina para tratar o câncer. As atividades anticâncer de aripiprazol permanecem desconhecidas. OBJETIVO: Este estudo objetivou avaliar a eficácia e a segurança do aripiprazol no câncer gástrico e nas linhagens celulares normais. MÉTODOS: A este respeito, a citotoxicidade e a genotoxicidade do aripiprazol foram investigadas em linhas celulares MKN45 e NIH3T3 por ensaio de metil tetrazólio e em linfócitos periféricos de sangue por ensaio de micronúcleos. Para este efeito, as células foram cultivadas em 96 placas. As soluções de estoque de aripiprazol e cisplatina foram preparadas. Após incubação celular com diferentes concentrações de aripiprazol (1, 10, 25, 50, 100 e 200 μL), a solução de metil tetrazólio foi adicionada. Para o ensaio do micronúcleo o sangue fresco foi adicionado ao meio de cultura RPMI 1640 suplementado, e as concentrações diferentes de aripiprazole (50, 100 e 200 μL) foram adicionadas. RESULTADOS: O presente estudo mostrou que o IC50 de aripiprazol na linhagem celular cancerosa (21,36 μg/mL) foi menor do que na linha celular normal (54,17 μg/ mL). Além disso, o ensaio de micronúcleos demonstrou que a frequência de micronúcleos de aripiprazol em concentrações inferiores a 200 μM foi muito inferior à cisplatina. CONCLUSÃO: O aripiprazol pode ser um bom composto citotóxico e bom candidato para estudos adicionais da terapia do câncer.

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.

Korean Treatment Guideline on Pharmacotherapy of Co-existing Symptoms and Antipsychotics-related Side Effects in Patients with Schizophrenia / 대한정신분열병학회지

OBJECTIVES: The current study covers a secondary revision of the guidelines for the pharmacotherapy of schizophrenia issued by the Korean Medication Algorithm for Schizophrenia (KMAP-SCZ) 2001, specifically for co-existing symptoms and antipsychotics-related side-effects in schizophrenia patients. METHODS: An expert consensus regarding the strategies of pharmacotherapy for positive symptoms of schizophrenia, co-existing symptoms of schizophrenia, and side-effect of antipsychotics in patients with schizophrenia was retrieved by responses obtained using a 30-item questionnaire. RESULTS: For the co-existing symptoms, agitation could be treated with oral or intramuscular injection of benzodiazepine or antipsychotics; depressive symptoms with atypical antipsychotics and adjunctive use of antidepressant; obsessive-compulsive symptoms with selective serotonin reuptake inhibitors and antipsychotics other than clozapine and olanzapine; negative symptoms with atypical antipsychotics or antidepressants; higher risk of suicide with clozapine; comorbid substance abuse with use of naltrexone or bupropion/ varenicline, respectively. For the antipsychotics-related side effects, anticholinergics (extrapyramidal symptom), propranolol and benzodiazepine (akathisia), topiramate or metformin (weight gain), change of antipsychotics to aripiprazole (hyperprolactinemia and prolonged QTc) or clozapine (tardive dyskinesia) could be used. CONCLUSION: Updated pharmacotherapy strategies for co-existing symptoms and antipsychotics-related side effects in schizophrenia patients as presented in KMAP-SCZ 2019 could help effective clinical decision making of psychiatrists as a preferable option.

Intramuscular Aripiprazole in the Therapy of Acute Mania for More than 24 hrs

No abstract available.

Amenorrhea as a Side Effect of Low Dose Aripiprazole: An Adolescent Case

No abstract available.

The Long-Acting Injectable Antipsychotics in Clinical Practice / 신경정신의학

Symptomatic relapse is observed frequently and often associated with social and/or occupational decline that can be difficult to reverse in patients with schizophrenia. Several atypical antipsychotics, including risperidone, olanzapine, paliperidone, and aripiprazole, have become available as long-acting injectable antipsychotics (LAIs), and new evidence has been accumulating. LAIs appear to have a significant role in at least a group of schizophrenia patients. Improving the adherence, continuous availability, managing changes in receptor sensitivity, and lowering the requirement of cumulative doses are some of the major advantages of LAIs. Patients with first episode psychosis, dopamine super-sensitivity syndromes, and comorbid substance abuse might particularly benefit. Delaying the initiation of LAI until the establishment of non-adherence is not recommended. The results of clinical trials comparing LAIs with oral antipsychotics (OAPs) are inconsistent because they are influenced considerably by the study design. On the other hand, several barriers to LAIs use in current practice include clinical lack of knowledge, and negative attitudes about LAIs. This article tries to help clinicians better characterize the role of LAIs in the treatment of schizophrenia.

Adjunctive Lurasidone Suppresses Food Intake and Weight Gain Associated with Olanzapine Administration in Rats

OBJECTIVE: Lurasidone is an antipsychotic drug that shows a relative lack of weight gain common to many antipsychotics. Aripiprazole and ziprasidone also show little weight gain and can reduce olanzapine-induced food intake and weight gain in animals, paralleling some clinical findings. We hypothesized that lurasidone would have similar actions. METHODS: Female Lister-hooded rats received intraperitoneal injection either 2× vehicle (saline), lurasidone (3 mg/kg) and vehicle, olanzapine (1 mg/kg) and vehicle, or olanzapine and lurasidone. Following drug administration food intake was measured for 60min. A further series of rats underwent a seven-day regime of once-daily administration of the above doses and free access to food and water. Weight gain over the course of the study was monitored. RESULTS: Olanzapine induced a significant increase in food intake while lurasidone showed no significant effect. Co-administration of lurasidone with olanzapine suppressed the increase in food intake. Repeated dosing showed an increase in body weight after seven days with olanzapine, and no significant effect observed with lurasidone, while repeated administration of lurasidone with olanzapine reduced the effect of olanzapine on the increase in body weight. CONCLUSION: These findings support our hypotheses in that lurasidone, in addition to a lack of effect on acute food intake and short term weight gain, can reduce olanzapine-induced food intake and weight gain in rats. This indicates the drug to have an active anti-hyperphagic mechanism, rather than solely the absence of a drug-induced weight gain that is such a severe limitation of drugs such as olanzapine.

Effects of Amisulpride Adjunctive Therapy on Working Memory and Brain Metabolism in the Frontal Cortex of Patients with Schizophrenia: A Preliminary Positron Emission Tomography/Computerized Tomography Investigation

OBJECTIVE: Dopamine plays a significant role in working memory by acting as a key neuromodulator between brain networks. Additionally, treatment of patients with schizophrenia using amisulpride, a pure dopamine class 2/3 receptor antagonist, improves their clinical symptoms with fewer side effects. We hypothesized that patients with schizophrenia treated with amisulpride and aripiprazole show increased working memory and glucose metabolism compared with those treated with cognitive behavioral therapy (CBT) and aripiprazole instead. METHODS: Sixteen patients with schizophrenia (eight in the amisulpride group [aripiprazole+amisulpride] and eight in the CBT group [aripiprazole+CBT]) and 15 age- and sex-matched healthy control subjects were recruited for a 12-week-long prospective trial. An [18F]-fluorodeoxyglucose-positron emission tomography/computerized tomography scanner was used to acquire the images. RESULTS: After 12 weeks of treatment, the amisulpride group showed greater improvement in the Letter-Number Span scores than the CBT group. Additionally, although brain metabolism in the left middle frontal gyrus, left occipital lingual gyrus, and right inferior parietal lobe was increased in all patients with schizophrenia, the amisulpride group exhibited a greater increase in metabolism in both the right superior frontal gyrus and right frontal precentral gyrus than the CBT group. CONCLUSION: This study suggests that a small dose of amisulpride improves the general psychopathology, working memory performance, and brain glucose metabolism of patients with schizophrenia treated with aripiprazole.

Korean Medication Algorithm for Bipolar Disorder 2018: Comparisons with Other Treatment Guidelines

The objective of this study was to compare recommendations of the Korean Medication Algorithm Project for Bipolar Disorder 2018 (KMAP-BP 2018) with other recently published guidelines for treating bipolar disorder. We reviewed a total of five recently published global treatment guidelines and compared treatment recommendation of the KMAP-BP 2018 with those of other guidelines. For initial treatment of mania, there were no significant differences across treatment guidelines. All guidelines recommended mood stabilizer (MS) or atypical antipsychotic (AAP) monotherapy or a combination of an MS with an AAP as a first-line treatment strategy for mania. However, the KMAP-BP 2018 did not prefer monotherapy with MS or AAP for psychotic mania. Quetiapine, olanzapine and aripiprazole were the first-line AAPs for nearly all phases of bipolar disorder across guidelines. Most guidelines advocated newer AAPs as first-line treatment options for all phases while lamotrigine was recommended for depressive and maintenance phases. Lithium and valproic acid were commonly used as MSs in all phases of bipolar disorder. As research evidence accumulated over time, recommendations of newer AAPs (such as asenapine, cariprazine, paliperidone, lurasidine, long-acting injectable risperidone and aripiprazole once monthly) became prominent. KMAP-BP 2018 guidelines were similar to other guidelines, reflecting current changes in prescription patterns for bipolar disorder based on accumulated research data. Strong preference for combination therapy was characteristic of KMAP-BP 2018, predominantly in the treatment of psychotic mania and severe depression. Further studies were needed to address several issues identified in our review.