Uso de antipsicóticos atípicos no tratamento da esquizofrenia no Sistema Único de Saúde do Brasil: estudo de coorte, 2008-2017 / Uso de antipsicóticos atípicos en el tratamiento de la esquizofrenia en el Sistema Único de Salud de Brasil: estudio de 2008 a 2017 / Use of atypical antipsychotics in the treatment of schizophrenia in the Brazilian National Health System: a cohort study, 2008-2017

Objective: to investigate sociodemographic and clinical characteristics of users of atypical antipsychotics receiving care via the Specialized Component of Pharmaceutical Assistance (Componente Especializado da Assistência Farmacêutica - CEAF), for the treatment of schizophrenia in Brazil, between 2008 and 2017. Methods: this was a retrospective cohort study using records of the authorizations for high complexity procedures retrieved from the Outpatient Information System of the Brazilian National Health System, from all Brazilian states. Results: of the 759,654 users, 50.5% were female, from the Southeast region (60.2%), diagnosed with paranoid schizophrenia (77.6%); it could be seen a higher prevalence of the use of risperidone (63.3%) among children/adolescents; olanzapine (34.0%) in adults; and quetiapine (47.4%) in older adults; about 40% of children/adolescents were in off-label use of antipsychotics according to age; adherence to CEAF was high (82%), and abandonment within six months was 24%. Conclusion: the findings expand knowledge about the sociodemographic and clinical profile of users and highlight the practice of off-label use.

Objetivo: investigar las características sociodemográficas y clínicas de los usuarios de antipsicóticos atípicos, atendidos por el Componente Especializado de Asistencia Farmacéutica (CEAF) para el tratamiento de la esquizofrenia en Brasil, de 2008 a 2017. Métodos: estudio de cohorte retrospectivo utilizando registros de autorizaciones de trámites de alta complejidad del Sistema de Información Ambulatorio del SUS, de todos los estados brasileños. Resultados: de los 759.654 usuários identificados, el 50,5% era del sexo feminino de la región Sudeste (60,2%), diagnosticadas con esquizofrenia paranoide (77,6%). Hubo una mayor prevalencia de risperidona (63,3%) entre niños y adolescentes; de olanzapina (34,0%) en adultos; y quetiapina (47,4%) en ancianos. Alrededor del 40% de los niños/adolescentes estaba bajo uso no autorizado de antipsicóticos según la edad. La adherencia al CEAF fue alta (82%), y la deserción a los seis meses fue del 24%. Conclusión: los hallazgos amplían el conocimiento sobre el perfil sociodemográfico y clínico de los usuarios y destacan la práctica del uso off-label.

Objetivo: investigar características sociodemográficas e clínicas de usuários de antipsicóticos atípicos assistidos pelo Componente Especializado da Assistência Farmacêutica (CEAF), para tratamento da esquizofrenia no Brasil, de 2008 a 2017. Métodos: estudo de coorte retrospectivo utilizando registros das autorizações de procedimentos de alta complexidade do Sistema de Informações Ambulatoriais do Sistema Único de Saúde, de todos os estados brasileiros. Resultados: dos 759.654 usuários, 50,5% eram do sexo feminino, da região Sudeste (60,2%), diagnosticados com esquizofrenia paranoide (77,6%); observou-se maior prevalência de uso da risperidona (63,3%) entre crianças/adolescentes; de olanzapina (34,0%), em adultos; e quetiapina (47,4%), nos idosos; cerca de 40% das crianças/ adolescentes estavam sob uso off-label de antipsicóticos segundo a idade; a adesão ao CEAF foi alta (82%), e o abandono em seis meses foi de 24%. Conclusão: os achados ampliam o conhecimento sobre perfil sociodemográfico e clínico dos usuários e destacam a prática do uso off-label.

Risperidone as a galactogogue of choice in peripartum: A concise review / Philippine Journal of Obstetrics and Gynecology

@#Human lactation is a dynamic physiological process that produces a complex biological fluid that provides nutritive and nonnutritive factors for an optimal child growth and well-being. Several factors play a formidable role in maternal breast milk production with respect to quality, and quantity, which will adequately sustain the child for at least the first 6 months after delivery. Evidence has shown majority of new mothers who wished to immediately commence exclusive breastfeeding after birth as recommended by the WHO, are unable to initiate lactation immediately. In view of this lactation insufficiency, health-care personnel have not only been campaigning on appropriate breastfeeding education but also offer early lactation support such as encouraging liberal fluid intake, dietary modifications, and in a worst-case scenario, administering agents/drugs such as galactogogue. Orthodox galactogogues in current use are either hormonal or antipsychotics; most of them have relative efficacy and safety limitations. Risperidone is an atypical antipsychotic which has been used for decades with established safety in lactating mothers and the highest propensity to induce galactorrhea as a secondary effect when compared to other antipsychotics that are currently being used as galactogogues. We call the attention of the medical community in conducting further researches on its possible adoption as a galactogogue, using this review as an insight.

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

Anorexia nervosa e o efeito no quadro clínico com o uso dos antipsicóticos / Anorexia nervosa and the effect on the clinical framework with the use of antipsychotics / Anorexia nervosa y el efecto sobre el marco clínico con el uso de antipsicóticos

Introdução:aanorexia nervosa caracteriza-se por um transtorno alimentar com quadro clínico típico de restrição dietética e desnutrição. Objetivo:verificar a eficácia do uso dos fármacos antipsicóticos olanzapina, quetiapina, risperidonano aumento ponderal de pacientes com tal patologia.Metodologia:utilizou-se de 9 Ensaios Clínicos Randomizados anexados na plataforma Medical Literature Analysis and Retrieval System Online/PubMed, sendo todos analisados a partir de critérios de inclusão e exclusão feitos aos pares para a realização de uma Revisão Sistemática de Literatura.Os artigos foram avaliados através do sistema Grading of Recommendatons AssessmentDevelopment and Evaluaton/GRADE. Resultadose discussão:Percebeu-se a prevalência da olanzapina sobre o aumento do peso entre os pacientes com anorexia comparado ao placebo. Pouca eficácia sobre o ganho ponderal com relação a quetiapina. A risperidona não demonstroualteração do peso ao utilizá-ladurante o tratamento da anorexia nervosa.Conclusões:Os achados sugeriram que aolanzapina, apresentou oefeito mais significativo sobre o ganho de peso em um menor intervalo de tempo (AU).

Introduction:Anorexia nervosa is characterized by an eating disorder with a typical clinical of food restriction and malnutrition. Objective:to verify the effectiveness of the use of the antipsychotic drugs olanzapine, quetiapine, risperidone in the weight gain of patients with this pathology. Methodology:9 Randomized Clinical Trials (RCT) were used attached to the Medical Literature Analysis andRetrieval System Online/PubMed/MEDLINE platform, all of which were analyzed based oninclusion and exclusion criteria made in pairs to carry out a Systematic Literature Review. Results and discussion:It was noticed the prevalence of olanzapine on weight gain among patients with anorexia compared to placebo. Little diligence on weight gain with regard to quetiapine. Risperine showed no weight change when used during the treatment of anorexia nervosa. Conclusions:The findings suggest that olanzapine had the most significant effect on weight gain in a short period (AU).

Introducción: La anorexia nerviosa se caracteriza por un trastorno alimentario con un cuadro clínico típico de restricción alimentaria y desnutrición. Objetivo: verificar la efectividad del uso de los medicamentos antipsicóticos olanzapina, quetiapina, risperidonaem el aumento de peso de pacientes con esta patología.Metodología: Se utilizaron 9 Ensayos Clínicos Aleatorizados (RCT) adjuntos a la plataforma Medical Literature Analysis and Retrieval System Online / PubMed (MEDLINE), todos fueron analizados en base a criterios de inclusión y exclusión realizados en pares para realizar una Revisión Sistemática de la Literatura. Resultados y discusión:Se notó la prevalencia de la olanzapina en la ganancia de peso entre pacientes con anorexia en comparación con el placebo. Poca diligencia en la ganancia de peso con respecto a la quetiapina. Risperine no mostró cambios de peso cuando se usó durante el tratamiento de la anorexia nerviosa. Conclusiones:Los hallazgos sugieren que la olanzapina tuvo el efecto más significativo sobre el aumento de peso en un lapso de tiempo más corto (AU).

Formulation development and pharmacokinetic studies of long acting in situ depot injection of risperidone

Abstract Risperidone is an atypical antipsychotic drug widely prescribed all over the world due to its clinical advantages. The currently available long acting marketed depot formulation of risperidone is a microsphere based preparation using poly-[lactide-co-glycolide] (PLGA) as drug release barrier. It is however, a cold chain product due to thermal instability of PLGA at room temperature. After beginning the depot injection therapy it is administered every two weeks but associated with another drawback of about 3 weeks lag time due to which its tablets are also administered for three weeks so as to attain and maintain therapeutic drug concentration in the body. The present work attempts to develop a long acting depot delivery system of risperidone for once a month administration based on the combination of sucrose acetate isobutyrate and polycaprolactone dissolved in benzyl benzoate to provide an effective drug release barrier for one month without any lag time and which can be stored at room temperature precluding the requirement of cold supply chain. The developed depot formulation showed a sustained in vitro drug release profile with 88.95% cumulative drug release in 30 days with little burst release. The in vivo pharmacokinetic studies of the developed formulation conducted on rats showed attainment of mean peak plasma drug concentration of 459.7 ng/mL in 3 days with a mean residence time of 31.2 days, terminal half-life of 20.6 days, terminal elimination rate constant of 0.0336 per day, and a good in vitro- in vivo correlation.

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

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

High Doses of Drugs Extensively Metabolized by CYP3A4 Were Needed to Reach Therapeutic Concentrations in Two Patients Taking Inducers / Dos pacientes que tomaban inductores necesitaron dosis altas de medicamentos metabolizados en gran medida por el CYP3A4 para alcanzar concentraciones terapéuticas

ABSTRACT Introduction: In the last 20 years of clinical practice, the senior author has identified these 2 rare cases in which the patients needed extremely high doses of drugs metabolized by CYP3A4 to reach and maintain serum therapeutic concentrations. Methods: The high metabolic ability of these 2 patients was demonstrated by the low concentration-to-dose ratios (C/D ratios) of several drugs metabolized by CYP3A4. Results: Case 1 was characterized by a history of high carbamazepine doses (up to 2,000 mg/day) and needed 170 mg/day of diazepam in 2 days to cooperate with dental cleaning. The high activity of the CYP3A4 isoenzyme was manifested by fast metabolism for quetiapine and diazepam, which took more than 1 year to normalize after the inducer, phenytoin, was stopped. Case 2 was also very sensitive to CYP3A4 inducers as indicated by very low C/D ratios for carbamazepine, risperidone and paliperidone. The carbamazepine (2,800 mg/day) and risperidone (20 mg/day) dosages for this second patient are the highest doses ever seen for these drugs by the senior author. Risperidone induction appeared to last for many months and metabolism was definitively normal 3 years after stopping carbamazepine. On the other hand, olanzapine C/D ratios were normal for induction. Conclusions: The literature has never described similar cases of very high doses of drugs metabolized by CYP3A4. We speculate that these 2 patients may have unusual genetic profiles at the nuclear receptor levels; these receptors regulate induction of drugs.

RESUMEN Introducción: Durante sus últimos 20 años de práctica, el último autor ha identificado estos 2 infrecuentes casos que necesitaban dosis extremadamente altas de medicaciones metabolizadas por el CYP3A4 para alcanzar y mantener concentraciones séricas terapéuticas. Métodos: La gran capacidad metabólica de estos 2 pacientes se demostró por los bajos cocientes entre concentración y dosis (C/D) de varias medicaciones metabolizadas por el CYP3A4. Resultados: El caso 1 se caracterizaba por una historia de altas dosis de carbamazepina (1.500 mg/día) y la necesidad de tomar 170 mg de diazepam en 2 días para facilitar una limpieza dental. La gran actividad de la isoenzima CYP3A4 se manifestó por una gran capacidad metabólica de quetiapina y diazepam, cuya normalización tardó más de 1 año tras la toma de un inductor, fenitoína. El caso 2 tambien era muy sensible a la inducción, lo cual se demuestra por los bajos cocientes C/D de carbamazepina, risperidona y paliperidona. Las dosis de carbamazepina (2.800 mg/día) y risperidona (20 mg/día) de este segundo paciente son las más altas nunca vistas por el último autor. La inducción de risperidona duró muchos meses y su metabolismo era normal 3 años después de interrumpir la carbamazepina. El cociente C/D de olanzapina era normal para la inducción. Conclusiones: Nunca se habían descrito casos similares de dosis tan altas de medicaciones metabolizadas por el CYP3A4. Se especula con que estos pacientes podrían tener unos perfiles genéticos inusuales en los receptores nucleares que regulan la inducción de medicamentos.

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

Effect of risperidone on proliferation and apoptosis of MC3T3-E1 cells

This aim of this study was to assess the molecular mechanism of osteoporosis in schizophrenia patients with risperidone use. Here, we investigated the effects of risperidone on cellular proliferation and apoptosis of a preosteoblast cell line, MC3T3-E1. Cell viability and apoptotic rate of MC3T3-E1 were detected by cell counting kit-8 and flow cytometry at a serial dose of risperidone and at different time points, respectively. Bone transformation relevant gene serum osteocalcin (BGP), collagen 1, tumor necrosis factor-α (TNF-α), osteoprotegerin (OPG), and receptor activator of nuclear factor-κB ligand (RANKL) mRNA levels were determined by real-time PCR (qPCR). Their protein expression patterns were evaluated using western blot. The results revealed that risperidone dramatically inhibited MC3T3-E1 cell proliferation in a dose-dependent manner. It also significantly induced MC3T3-E1 cell apoptosis. TNF-α gene and protein levels were greatly enhanced after risperidone treatment. In contrast, BGP, collagen 1, OPG, and RANKL gene and protein levels were markedly downregulated. Our study indicated that risperidone suppressed MC3T3-E1 cell proliferation and induced apoptosis. It also regulated BGP gene and protein expression.

Psychotic Symptoms of Hashimoto's Encephalopathy: A Diagnostic Challenge

Hashimoto's encephalopathy (HE) is a rare and underdiagnosed neuropsychiatric illness. We present the case of a 17-year-old girl who was admitted to a tertiary-care psychiatric center with acute onset psychosis and fever. Her psychotic symptoms were characterized by persecutory and referential delusions, as well as tactile and visual hallucinations. Her acute behavioral disturbance warranted admission and treatment in a psychiatric setting (risperidone tablets, 3 mg/day). She had experienced an episode of fever with a unilateral visual acuity defect approximately 3 years before admission, which was resolved with treatment. Focused clinical examination revealed an enlarged thyroid, and baseline blood investigations, including thyroid function test results were normal. Abnormal laboratory investigations revealed elevated anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-TG) levels (anti-TPO of 480 IU/mL; anti-TG of 287 IU/mL). Results of other investigations for infection, including cerebrospinal fluid examination, electroencephalography, and brain magnetic resonance imaging were normal. She was diagnosed with HE and was treated with intravenous corticosteroids (methylprednisolone up to 1 g/day; tapered and discontinued after a month). The patient achieved complete remission of psychotic symptoms and normalization of the anti-thyroid antibody titers. Currently, at the seventh month of follow-up, the patient is doing well. This case highlights the fact that in the absence of well-defined clinical diagnostic criteria, a high index of suspicion is required for early diagnosis of HE. Psychiatrists need to explore for organic etiologies when dealing with acute psychiatric symptoms in a younger age group.

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.

Long-term Effects of Aripiprazole Treatment during Adolescence on Cognitive Function and Dopamine D2 Receptor Expression in Neurodevelopmentally Normal Rats

OBJECTIVE: This study aimed to investigate the long-term effects of aripiprazole treatment during adolescence on behavior, cognitive function, and dopamine D2 receptor (D2R) expression in adult rats. METHODS: Adolescent male Sprague-Dawley rats were injected intraperitoneally with aripiprazole, risperidone, or vehicle control for 3 weeks (postnatal day 36–56). After a 2-week washout period, locomotion, anxiety, and spatial working memory were evaluated in adulthood (postnatal day 71–84), using an open field test, elevated plus maze, and Y-maze, respectively. In addition, we assessed D2R levels in the dorsolateral and medial prefrontal cortex (PFC), dorsal and ventral striatum, and hippocampus using western blot analysis. RESULTS: Spontaneous alternation performance (SAP) in the Y-maze, a measure of spatial working memory, differed significantly among the 3 groups (F = 3.89, p = 0.033). A post-hoc test confirmed that SAP in the aripiprazole group was significantly higher than that in the risperidone group (post-hoc test p = 0.013). D2R levels in the medial PFC (F = 8.72, p = 0.001) and hippocampus (F = 13.54, p < 0.001) were different among the 3 groups. D2R levels in the medial PFC and hippocampus were significantly lower in the aripiprazole-treated rats than that in the risperidone-treated rats (post-hoc test p = 0.025 and p < 0.001, respectively) and controls (post-hoc test p < 0.001, all). CONCLUSION: This study showed that aripiprazole treatment in adolescence could influence cognitive function and dopaminergic neurotransmission into early adulthood.

Rhabdomyolysis and Neuroleptic Malignant Syndrome Associated with Very Low-dose Antipsychotics in Children and Adolescent

Along with the field of adult psychiatry, antipsychotic agents are increasingly used in the field of child and adolescent psychiatry. Although neuroleptic malignant syndrome (NMS) and rhabdomyolysis are rare complication associated with antipsychotic agent, clinicians should need to pay attention to all potential adverse drug reaction (ADR). Also, ADRs in child and adolescent could show different signs and symptoms compared with those in adult. In this case report, we present a case of NMS in a child which occurred shortly after the resolution of rhabdomyolysis which was induced by low-dose risperidone.

Pharmacological Therapy in Panic Disorder: Current Guidelines and Novel Drugs Discovery for Treatment-resistant Patient

Panic disorder (PD) being one of the most intensively investigated anxiety disorders is considered a heterogeneous psychiatric disease which has difficulties with early diagnosis. The disorder is recurrent and usually associated with low remission rates and high rates of relapse which may exacerbated social and quality of life, causes unnecessary cost and increased risk for complication and suicide. Current pharmacotherapy for PD are available but these drugs have slow therapeutic onset, several side effects and most patients do not fully respond to these standard pharmacological treatments. Ongoing investigations indicate the need for new and promising agents for the treatment of PD. This article will cover the importance of immediate and proper treatment, the gap in the current management of PD with special emphasis on pharmacotherapy, and evidence regarding the novel anti-panic drugs including the drugs in developments such as metabotropic glutamate (mGlu 2/3) agonist and levetiracetam. Preliminary results suggest the anti-panic properties and the efficacy of duloxetine, reboxetine, mirtazapine, nefazodone, risperidone and inositol as a monotherapy drug. Apart for their effectiveness, the aforementioned compounds were generally well tolerated compared to the standard available pharmacotherapy drugs, indicating their potential therapeutic usefulness for ambivalent and hypervigilance patient. Further strong clinical trials will provide an ample support to these novel compounds as an alternative monotherapy for PD treatment-resistant patient.

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.

First Manic Episode in a Young Woman with Schizophrenia after Initiation of Oral Aripiprazole and Aripiprazole Long-Acting Injection / 우울ㆍ조울병

A woman in her twenties with schizophrenia developed immediate-onset mania after taking oral aripiprazole and receiving aripiprazole long-acting injection (ALAI). The dosage of aripiprazole was rapidly increased due to inadequate stimulating effect of low-dosage aripiprazole, but her manic symptomatology worsened. Clinicians should therefore carefully monitor for the induction of mania by oral aripiprazole and ALAI. Her manic symptomatology improved after adding 20 mg of blonanserin, 3 mg of risperidone, and 300 mg of quetiapine.

Evaluation of drug interventions for the treatment of sleep disorders in children with autism spectrum disorders: a systematic review / 소아과

A structured review study of drug interventions on sleep disorders in patients with autism spectrum disorders (ASD) has not been published to date. This systematic review aimed to investigate drug interventions for the treatment of sleep disorders in children with ASD. The Web of Science, PubMed, and Scopus databases were searched until March 2019. Study quality was assessed using the Delphi checklist. Due to the heterogeneity of the findings, a meta-analysis was not possible. Drug interventions for the treatment of sleep disorders in patients with ASD included melatonin, atomoxetine, and risperidone. Atomoxetine had no effect on sleep disorders in patients with ASD. A total of 10 studies were reviewed. Melatonin appears to be useful for the treatment of sleep problems in patients with ASD, but further studies are needed to determine the effects of other drugs.