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

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

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

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

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

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

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

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

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

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

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

Informe diário de evidências COVID-19: busca referente aos dias 20, 21 e 22 de junho de 2020 / COVID-19 daily evidence report: search for June 20, 21 and 22, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referente ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 13 artigos e 9 protocolos.

Psicosis, Discapacidad intelectual y trastornos conductuales: enfoque biopsicosocial / Psychosis, intellectual disability and behavioral disorders: biopsychosocial approach

Caso Clínico: Mujer, 23 años. Discapacidad intelectual. Asiste a colegio especial (no lee ni escribe). Institucionalizada. Motivo de ingreso: Paciente ingresa en octubre del 2017 traída por carabineros por ser encontrada en la calle bajo el efecto de múltiples sustancias, con ideación suicida. Días antes fue expulsada del hogar por agresión a cuidadoras. Diagnósticos de ingreso: Discapacidad intelectual moderado. Síndrome suicidal, Trastorno por dependencia a drogas. ¿Esquizofrenia hebefrénica? Evolución: Mantiene desajustes conductuales severos fluctuantes, con serias dificultades para manejar la rabia, lo que la lleva a tener conductas hetero y autoagresivas. Plan de tratamiento: Farmacológico (clozapina), Psicológico (TCC), Social (dispositivo adecuado post-alta). Clozapina para trastornos psicóticos en adultos con discapacidad intelectual. El principal riesgo de atribuir alguno de estos comportamientos a una supuesta "psicosis", es el de "medicalizar" y tratar de forma poco acertada. Es importante descartar factores ambientales y del aprendizaje (hábitos y conductas aprendidas, institucionalización, reacciones ante el estrés agudo.) La prevalencia de abuso y dependencia de sustancias en población con DI va desde el 0,5% al 2,6%. Lo cual es menor que la población general. Pacientes con DI y dependencia a drogas se asocia a otras enfermedades psiquiátricas (42-54%). Se ha informado que las personas con discapacidad intelectual en América Latina a menudo están institucionalizadas y escondidas de la sociedad en instalaciones deficientes y superpobladas.

Clinical Case: Female, 23 years old. Intellectual disability. He attends a special school (she does not read or write). Institutionalized. Reason for admission: Patient enters in October 2017 brought by police officers to be found in the street under the effect of multiple substances, with suicidal ideation. Days before she was expelled from the home because of assaulting caregivers. Admission diagnoses: Moderate intellectual disability. Suicidal syndrome, Disorder due to drug dependence. Hebephrenic schizophrenia? Evolution: Maintains fluctuating severe behavioral imbalances, with serious difficulties in managing rage, which leads to hetero and self-aggressive behaviors. Treatment plan: pharmacological (clozapine), Psychological (CBT), Social (adequate post-hospitalization discharge device). Clozapine for psychotic disorders in adults with intellectual disabilities. The main risk of attributing some of these behaviors to a supposed "psychosis" is that of "medicalizing" and dealing inappropriately. It is important to rule out environmental and learning factors (habits and behaviors learned, institutionalization, reactions to acute stress. The prevalence of substance abuse and dependence in the population with ID ranges from 0.5% to 2.6%. Which is less than the general population. Patients with ID and drug dependence are associated with other psychiatric illnesses (42-54%). It is reported that people with intellectual disabilty in Latin America are often institutionalized and hidden from society in poor and overcrowded facilities.

A propósito de un caso complejo: agitación psicomotora: ¿TEC y clozapina, sala de aislamiento? / About a complex case: psychomotor agitation: TEC and clozapine, isolation room?

Paciente de 25 años. Ingreso a Servicio de Urgencia. Paciente viene solo, desaseado, relata múltiples ideas bizarras, no sistematizadas. Pensamiento laxo, musita, interferido, a ratos discordante. Diagnóstico: Síndrome esquizomorfo. Antecedentes judiciales: Informe cumplimiento condena en Puerto Montt: Lesiones menos graves y Robo con violencia. Persiste amenazante, exaltado. Paranoide. Durante la tarde amenaza con colgase, cortarse o quemar colchón, cuelga sabana de ventana e intenta ahorcarse. Primera sesión de TEC, Cisordinol accutard. Contención física, Sujeciones. Modecate. Cortes en antebrazo, Amenaza con matar otros pacientes, al apagar las luces se sienta en cama de otro paciente en actitud intimidante, lo agrede con lápiz en ojo derecho. Reinicia TEC, Inicia clozapina 25mg/día. Hostil y desafiante ante funcionarios por el encuadre, Baja en recuento de blancos, inicia litio. Algo hostil y querellante con personal, probablemente relacionado con suspensión de TEC (20 sesiones). Clozapina 450mg/día, Litio 600 mg/día. Traslado de paciente para sala de aislamiento, Se retira chapa de aislamiento ­ Sala de observación, Cuidador especial constante, hombre, Mitones, solicitud a UGC apoyo

Patient of 25 years old. Entrance to Emergency Service. Patient comes alone, untidy, reports multiple bizarre ideas, not systematized. Lax thought, mumble, interfered, discordant at times. Diagnosis: Schizomorphic syndrome. Legal background: Condemning Report in Puerto Montt: Less serious injuries and robbery with violence. He persists threatening, exalted. Paranoid. During the afternoon threatens to hang, cut or burn mattress, hangs a blanket in window and tries to hang himself. First session of TEC, Cisordinol accutard. Physical restraint, Supports. Modecate. Cuts in forearm. Threat to kill other patients, when turning off lights sits in bed of another patient in intimidating attitude, strikes him with pencil in right eye. Restart TEC, Starts clozapine 25mg / day. Hostile and challenging with officials because of setting, White cells: Low counting, initiating lithium. Somehow hostile and prosecuting with staff, probably related to ECT suspension (20 sessions). Clozapine 450mg / day, Lithium 600mg / day. Transfer of patient to isolation room, Removal of insulation sheet - Observation room, Special caregiver constant, male, Mittens, request to UGC support.

Actualización en enfermedad con cuerpos de Lewy / Update in Lewy body disease

La enfermedad con cuerpos de Lewy incluye 2 entidades que podrían ser consideradas variantes clínicas de una misma patología: la demencia con cuerpos de Lewy y la demencia en enfermedad de Parkinson. Con la finalidad de describir correctamente lo que sucede en la evolución de la enfermedad se divide el cuadro en etapa prodrómica y de demencia propiamente dicha. La primera está clínicamente representada por aquel período en el cual, si bien el paciente exhibe algunos signos y síntomas propios de la enfermedad, no reúne criterios de demencia. A pesar de ser difícil de definir y por carecerse todavía de contundentes datos clínicos y biomarcadores, se caracteriza principalmente por deterioro leve selectivo en función atencional ­ visuoespacial, trastorno del sueño REM y disautonomía‒. La segunda etapa está claramente caracterizada en los criterios de consenso del año 2005. Recientemente hemos publicado la validación de un instrumento llamado ALBA Screening Instrument, que permite diagnosticar con alta sensibilidad y especificidad la enfermedad aun en etapas tempranas y diferenciarla de otras patologías semejantes. La tomografía por emisión de positrones (PET) para transportador de dopamina es el procedimiento de referencia (gold standard) del diagnóstico. El tratamiento sintomático con anticolinesterásicos y neurolépticos atípicos favorece una buena evolución de la enfermedad y es fundamental tener en cuenta evitar medicamentos que pueden dañar gravemente a los pacientes como los anticolinérgicos y antipsicóticos típicos. Los avances en el diagnóstico y la difusión del impacto de esta enfermedad en la población contribuirán a generar mayores esfuerzos de investigación para hallar un tratamiento eficaz, preventivo o curativo o de ambas características. (AU)

Lewy body disease includes 2 entities that could be considered clinical variants of the same pathology: Dementia with Lewy bodies and Parkinson's disease Dementia. Two stages of the disease are described in this review, a prodromal stage and one of explicit dementia. The first one is clinically represented by that period in which, the patient exhibits some typical features of the disease, but not dementia criteria. Despite being difficult to define the prodromal stage and that strong clinical data and biomarkers are still lacking, there is evidence to characterize it mainly by mild selective impairment in attention and visuo-spatial function, REM sleep disorder and dysautonomia. The second stage is clearly characterized in the known consensus criteria of 2005. We have recently published the validation of an instrument called ALBA Screening Instrument which showed a high sensitivity and specificity for diagnosis of the disease even in the early stages. It´s useful to differentiate the disease from other similar pathologies. Positron Emission Tomography for dopamine transporter is the gold standard of diagnosis in life. Symptomatic treatment with anticholinesterases and atypical neuroleptics help patients in their evolution of the disease. Anticholinergics and typical antipsychotics are agents to avoid in the treatmen of the disease because can severely damage patients. Future advances in the diagnosis and dissemination of the knowledge of the disease will contribute to generate greater research efforts to find an effective preventive and / or curative treatment. (AU)

Trends in the prescription of clozapine in a psychiatric hospital: a 5-year observational study / Tendência na prescrição de clozapina em um hospital psiquiátrico: estudo observacional de 5 anos

Abstract Introduction Clozapine is a well-recognized effective treatment for some patients with treatment-resistant schizophrenia (TRS). Although it has potential benefits and approximately 30% of patients have a clinical indication for clozapine use, prescription rates are low. Objective To evaluate clozapine prescription trends over a 5-year period in a tertiary psychiatric hospital. Methods In this observational study, data prospectively collected by the Medical and Statistical File Service (Serviço de Arquivo Médico e Estatístico) and the Pharmacy Division of Instituto de Psiquiatria de Santa Catarina between January 2010 and December 2014 were summarized and analyzed by investigators blinded to data collection. The number of 100 mg clozapine pills dispensed by the Pharmacy Division to the inpatient units was the outcome and considered a proxy measure of clozapine prescriptions. The number of occupied inpatient unit beds and the number of patients admitted with F20-F29 (ICD-10) diagnoses during the study period were considered to be possible confounders. Results A multiple linear regression model showed that time in months was independently associated with an increase in the number of clozapine pills dispensed by the Pharmacy Division (β coefficient = 15.82; 95% confidence interval 10.88-20.75). Conclusion Clozapine prescriptions were found to have increased during the 5-year period studied, a trend that is opposite to reports from several other countries.

Resumo Introdução Clozapina é um medicamento reconhecidamente eficaz para alguns pacientes com esquizofrenia refratária ao tratamento. Apesar dos seus potenciais benefícios e de sua indicação clínica para aproximadamente 30% dos pacientes, a frequência de prescrição de clozapina é baixa. Objetivos Avaliar a tendência na prescrição de clozapina durante um período de 5 anos em um hospital psiquiátrico. Métodos Neste estudo observacional, dados coletados prospectivamente pelo Serviço de Arquivo Médico e Estatístico e pela Divisão de Farmácia (DF) do Instituto de Psiquiatria de Santa Catarina foram analisados por pesquisadores cegos para a coleta de dados. O número de comprimidos de clozapina 100 mg dispensados pela DF às enfermarias foi considerado a variável dependente e a medida de prescrição de clozapina. Número de leitos de internação ocupados e número de pacientes admitidos com diagnósticos F20-F29 (CID-10) durante o período de estudo foram considerados possíveis confundidores. Resultados Após análise com modelo de regressão linear múltipla, tempo em meses foi independentemente associado com aumento do número de comprimidos de clozapina 100 mg dispensados pela DF (coeficiente β = 15,82; intervalo de confiança de 95% 10,88-20,75). Conclusão Houve um aumento na prescrição de clozapina durante o período de 5 anos estudado, uma tendência oposta à relatada em vários outros países.

Clozapina na psicose associada à doença de Parkinson / Clozapine in psychosis associated with Parkinson's disease

Contexto: Ao se delinear a revisão do Protocolo Clínico e Diretrizes Terapêuticas (PCDT) da doença de Parkinson (DP), observou-se a necessidade de garantir também o acesso ao tratamento com o antipsicótico clozapina, hoje disponível no SUS para o tratamento de esquizofrenia e transtorno esquizoafetivo. A clozapina é um antipsicótico atípico, assim denominado por não possuir quase nenhum efeito extrapiramidal, possibilitando o tratamento da psicose na DP, sem reduzir a função motora destes pacientes. No Brasil, possui registro e comercialização aprovados pela Anvisa para, dentre outras indicações, a psicose na DP[1] Pergunta: A clozapina é eficaz e segura no tratamento da psicose associada à doença de Parkinson? Evidências científicas: A maioria dos estudos selecionados tem graves problemas metodológicos, incluindo um pequeno número de participantes, avaliação contra medicamentos não considerados padrão-ouro ou comprovadamente ineficazes, como o caso da olanzapina, e delineamento aberto. A melhor evidência atualmente disponível sobre eficácia e segurança deste medicamento no tratamento de sintomas psicóticos associados à DP é baseada em dois estudos clínicos randomizados contra placebo, com tempo de seguimento relativamente curto. Todavia, poderia dar suporte à recomendação o fato de que essa situação clínica é um fator que influencia negativamente no desfecho da doença de base, com aumento da dependência, das hospitalizações em casas de saúde e da mortalidade, e ainda que não há alternativas com maior evidência de benefício e segurança. Decisão: Incorporar a clozapina para o tratamento de psicose relacionada à doença de Parkinson, conforme Protocolo Clínico do Ministério da Saude, no âmbito do Sistema Único de Saúde ­ SUS, dada pela Portaria SCTIE-MS nº 22 publicada no Diário Oficial da União (D.O.U.) nº 106, de 06 de junho de 2016.

Heat stroke during long-term clozapine treatment: should we be concerned about hot weather? / Heat stroke durante tratamento de longo prazo com clozapina: devemos nos preocupar com o tempo quente?

Objective To describe the case of a patient with schizophrenia on clozapine treatment who had an episode of heat stroke. Case description During a heat wave in January and February 2014, a patient with schizophrenia who was on treatment with clozapine was initially referred for differential diagnose between systemic infection and neuroleptic malignant syndrome, but was finally diagnosed with heat stroke and treated with control of body temperature and hydration. Comments This report aims to alert clinicians take this condition into consideration among other differential diagnoses, especially nowadays with the rise in global temperatures, and to highlight the need for accurate diagnosis of clinical events during pharmacological intervention, in order to improve treatment decisions and outcomes.

Objetivo Descrever o caso de um paciente com esquizofrenia em tratamento com clozapina acometido por um episódio de heat stroke. Descrição do caso Durante uma onda de calor em janeiro e fevereiro de 2014, um paciente com esquizofrenia em tratamento com clozapina foi inicialmente encaminhado para diagnóstico diferencial de infecção sistêmica e síndrome neuroléptica maligna, tendo obtido o diagnóstico final de heat stroke, tratado com controle de temperatura corporal e hidratação. Comentários Este relato de caso tem como objetivo alertar os clínicos para este diagnóstico diferencial, que pode surgir com mais frequência à medida que as temperaturas globais continuarem a aumentar, e também destacar a importância da realização de um diagnóstico mais acurado, que possa melhorar as decisões de tratamento e os desfechos clínicos para os pacientes.

Rabdomiólise recorrente secundária à hiponatremia em doente com polidipsia psicogênica primária / Recurrent rhabdomyolysis secondary to hyponatremia in a patient with primary psychogenic polydipsia

A rabdomiólise é caracterizada por destruição de tecido muscular esquelético, sendo as suas principais causas o trauma, os tóxicos e os distúrbios hidroeletrolíticos. Entre esses últimos, inclui-se a rabdomiólise induzida por hiponatremia, uma situação rara, que ocorre principalmente em doentes com polidipsia psicogênica. Esta acomete maioritariamente doentes com esquizofrenia, cursando com hiponatremia em quase 25% dos casos. É também nesse contexto que a rabdomiólise secundária a hiponatremia ocorre mais frequentemente. Neste artigo, descreveu-se o caso de um homem de 49 anos, com antecedentes de esquizofrenia, medicado com clozapina, trazido ao serviço de urgência por quadro de coma e convulsões. Foi objetivada hiponatremia hiposmolar grave, com edema cerebral em tomografia computorizada, sendo feito posteriormente o diagnóstico de hiponatremia secundária à polidipsia psicogênica. Foi iniciada terapêutica de correção de hiponatremia e internado em unidade de terapia intensiva. Feita correção de hiponatremia, contudo apresentou analiticamente marcada rabdomiólise, de agravamento crescente, com creatinofosfoquinase de 44.058UI/L no 3º dia de internação. Houve posterior redução progressiva com a terapêutica, sem ocorrência de lesão renal. Este caso alerta para a necessidade de monitorização dos marcadores de rabdomiólise na hiponatremia grave, ilustrando um quadro de rabdomiólise secundária à hiponatremia induzida por polidipsia psicogênica, situação a considerar em doentes sob terapêutica com neurolépticos.

Rhabdomyolysis is characterized by the destruction of skeletal muscle tissue, and its main causes are trauma, toxic substances and electrolyte disturbances. Among the latter is hyponatremia-induced rhabdomyolysis, a rare condition that occurs mainly in patients with psychogenic polydipsia. Psycogenic polydipsia mostly affects patients with schizophrenia, coursing with hyponatremia in almost 25% of the cases. It is also in this context that rhabdomyolysis secondary to hyponatremia occurs most often. In this article, the case of a 49-year-old male with a history of schizophrenia, medicated with clozapine, and brought to the emergency room in a state of coma and seizures is described. Severe hypoosmolar hyponatremia with cerebral edema was found on a computed tomography examination, and a subsequent diagnosis of hyponatremia secondary to psychogenic polydipsia was made. Hyponatremia correction therapy was started, and the patient was admitted to the intensive care unit. After the hyponatremia correction, the patient presented with analytical worsening, showing marked rhabdomyolysis with a creatine phosphokinase level of 44.058UI/L on day 3 of hospitalization. The condition showed a subsequent progressive improvement with therapy, with no occurrence of kidney damage. This case stresses the need for monitoring rhabdomyolysis markers in severe hyponatremia, illustrating the condition of rhabdomyolysis secondary to hyponatremia induced by psychogenic polydipsia, which should be considered in patients undergoing treatment with neuroleptics.

Patterns of Antipsychotic Prescription to Patients with Schizophrenia in Korea: Results from the Health Insurance Review & Assessment Service-National Patient Sample

This study aimed to analyze the patterns of antipsychotic prescription to patients with schizophrenia in Korea. Using the Health Insurance Review & Assessment Service-National Patients Sample (HIRA-NPS), which was a stratified sampling from the entire population under the Korean national health security system (2009), descriptive statistics for the patterns of the monopharmacy and polypharmacy, neuropsychiatric co-medications, and prescribed individual antipsychotic for patients with schizophrenia were performed. Comparisons of socioeconomic and clinical factors were performed among patients prescribed only with first- and second-generation antipsychotics. Of 126,961 patients with schizophrenia (age 18-80 yr), 13,369 were prescribed with antipsychotic monopharmacy and the rest 113,592 with polypharmacy. Two or more antipsychotics were prescribed to 31.34% of the patients. Antiparkinson medications (66.60%), anxiolytics (65.42%), mood stabilizers (36.74%), and antidepressants (25.90%) were co-medicated. Patients who were prescribed only with first-generation antipsychotics (n=26,254) were characterized by significantly older age, greater proportion of male, higher proportion of medicaid, higher total medical cost, lower self-payment cost, and higher co-medication rates of antiparkinson agents and anxiolytics than those who were prescribed only with second-generation antipsychotics (n=67,361). In this study, it has been reported substantial prescription rates of first-generation antipsychotics and antipsychotic polypharmacy and relatively small prescription rate of clozapine to patients with schizophrenia. Since this study has firstly presented the patterns of antipsychotic prescription to schizophrenic patients in Korean national population, the findings of this study can be compared with those of later investigations about this theme.

Is disorganized schizophrenia a predictor of treatment resistance? Evidence from an observational study

Objective: To investigate whether inpatients with disorganized schizophrenia are more resistant to treatment. Method: Eighty-five inpatients were assessed at admission and at discharge for schizophrenia subtype, symptom severity, and treatment resistance criteria. Results: Disorganized patients were significantly more treatment-resistant than paranoid patients (60%, p = 0.001), and presented worse scores on the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression Scale (CGI-S), and the Global Assessment of Functioning Scale (GAF) (p < 0.001). Although the difference was not significant, 80% of treatment-resistant patients with disorganized schizophrenia responded to clozapine. Conclusion: Patients with the disorganized subtype of schizophrenia should benefit from clozapine as a second-line agent. .

Pharmacogenetics in schizophrenia: a review of clozapine studies

Objectives: Clozapine is quite effective to treat schizophrenia, but its use is complicated by several factors. Although many patients respond to antipsychotic therapy, about 50% of them exhibit inadequate response, and ineffective medication trials may entail weeks of unremitted illness, potential adverse drug reactions, and treatment nonadherence. This review of the literature sought to describe the main pharmacogenetic studies of clozapine and the genes that potentially influence response to treatment with this medication in schizophrenics. Methods: We searched the PubMed database for studies published in English in the last 20 years using keywords related to the topic. Results and Conclusions: Our search yielded 145 studies that met the search and selection criteria. Of these, 21 review articles were excluded. The 124 studies included for analysis showed controversial results. Therefore, efforts to identify key gene mechanisms that will be useful in predicting clozapine response and side effects have not been fully successful. Further studies with new analysis approaches and larger sample sizes are still required. .

Experiencia clínica con el antipsicótico clozapina en niños y adolescentes menores de 18 años en Chile / Clinical experience in Chile with clozapine in child and adolescents under 18 years

Objective: Increase in severe psychopathology in adolescents who are resistant to common treatment creates a need to search new alternatives in pharmacological treatment. Background: To describe a sample 47 child and adolescent patients treated with clozapine between 1985 and 2010, indicating: age, gender, diagnoses, hospitalization, electroconvulsive therapy, dosing, adverse effects specially hematological ones. Methods: 47patients between the ages of 10 and 18 were treated with clozapine. Review of clinical charts, protocol investigation and Excel statistic analysis. Results: The sample consisted in: male: 40 percent, female: 60 percent, the youngest was 10 and the oldest 17years and 11 months old; the most frequent age was 15 years. The mean number of hospitalization was 1.5. Diagnosis Axis I,DSM IV: Affective disorders 64 percent, Schizophreniform disorder 23 percent. Electroconvulsive Therapy: 57 percent. Treatment indications: irreducible psychosis 23 percent, suicidability: 33 percent. Average dosing 200 mg. Adverse effects: sedation: 76 percent, hypersalivation: 68 percent, increase in weight: 66 percent. Neutropenia: not severe (more than 2000/ mm³): 17 percent; severe 1:15 percent, severe II: 2 percent, severe III: 2 percent. Conclusions: Clozapine appears as an effective drug, with moderate but frequent adverse effects. Hematologic adverse effects where transient; only one in 47 patients presented a severe neutropenia and require cancellation of treatment, which was reinstalled after three month without mayor side effects. There is a need for control studies with larger population and a longer period of time.

Introducción: El aumento de psicopatología severa en la clínica infanto-juvenil y la resistencia a los tratamientos habituales, lleva a los clínicos buscar nuevas alternativas farmacológicas. Surge entonces la clozapina como una alternativa útil, avalada por la literatura para tratamiento de estas patologías. Objetivos: Describir una muestra de 47 pacientes niños y adolescentes entre 10 y 18 años tratados con clozapina entre los años 1985 y 2010. Se indican: variables demográficas, diagnósticos, hospitalizaciones, dosis y efectos adversos, especialmente los hematológicos. Material y Método: Estudio descriptivo, retrospectivo consistente en revisión de fichas clínicas, protocolo de investigación y análisis estadístico con plantilla Excel. Resultados: Muestra de 47 pacientes; 40 por ciento hombres, 60 por ciento mujeres, el menor de 10 años y el mayor de 17 años y 11 meses; la edad más frecuente fue de 15 años. El 80 por ciento presentó al menos una hospitalización. Diagnósticos agrupados: Trastornos a predominio afectivo el 64 por ciento, Trastornos esquizomorfo el 23 por ciento y Trastornos a predominio del descontrol de los impulsos y agresión 9 por ciento. Un 57 por ciento recibió TEC. Causa de indicación: psicosis irreductible 36 por ciento, suicidalidad alta 33 por ciento, conducta heteroagrsiva 25 por ciento, efectos laterales con otros fármacos 23 por ciento. La dosis promedio de mantención fue de 200 mg. Los efectos adversos más frecuentes fueron: sedación 76 por ciento, salivación 68 por ciento, alza peso 66 por ciento. Baja inespecífica de neutrófilos: 17 por ciento, alarma 1:15 por ciento, alarma II: 2 por ciento, alarma III: 2 por ciento. Discusión: Clozapina aparece como fármaco útil, con efectos adversos frecuentes, pero en nuestra muestra fueron graves no y transitorios. Hubo un caso con alarma III que requirió de suspensión, pero se reinstaló 3 meses después; sin reincidir, ni presentar otros efectos adversos de gravedad...

Uso de clozapina en trastorno bipolar refractario / Clozapine in refractory bipolar disorder

Background: The combination of multiple agents including lithium, mood stabilizers and antipsychotics, represents the most commonly strategy in bipolar disorder treatment. Lack of response, breakthrough episodes during adequate maintenance treatment, functional impairment, including re-hospitalization, suicide attempts and intolerance of medication are considered clinical inclusion criteria for treatment resistance in bipolar disorder. In bipolar disorder, Clozapine as mono-therapy or in combination treatment, remains as a efficacious second line agent, with few clinical data available, mainly including short observational periods, small samples and uncontrolled trials. Methods: We analyze retrospectively clinical data about five female bipolar refractory patients who were under combined treatment including atypical antipsychotics. Due to this combined first line treatment resistance, Clozapine was indicated as an add-on agent. Equivalent analysis periods were established for each patient, previous and under Clozapine use. These periods extends from 8 months to 5 years and 2 months. Results: Clozapine average daily dose was 260 mgs. No adverse effects were noticed. Total hospitalization days decrease from 979 days to 118 days andsu icide attempts decrease from 14 ep isodes in pre Clozap ine period to 1 episode in the Clozapine treatment period. No re-hospitalization neither self harm attempts with Clozapine add on treatment were reported in 3 patients. Conclusion: Clozapine efficacy, in treatment resistance bipolar patients, should be considered as a second line option in combination therapy with insufficient response. Therapeutic benefits of Clozapine may include potential decrease of self harm conduct in bipolar patients as in schizophrenia and schizoaffective disorder.

Antecedentes: La combinación de múltiples agentes incluyendo el litio, los estabilizadores del ánimo y los antipsicóticos, representa la estrategia más común en el tratamiento del trastorno bipolar. La falta de respuesta, la irrupción de nuevos episodios durante un adecuado tratamiento de mantención, el deterioro funcional incluyendo la re-hospitalización, los intentos de suicido y la intolerancia a la medicación se consideran criterios clínicos de inclusión para establecer la resistencia al tratamiento en el trastorno bipolar. En el trastorno bipolar, la Clozapina como terapia única o en tratamiento combinado, se mantiene como un agente de segunda línea eficaz, con pocos datos clínicos disponibles, incluyendo principalmente períodos cortos de observación, muestras pequeñas y ensayos no controlados. Métodos: Analizamos datos clínicos en forma retrospectiva de cinco pacientes mujeres bipolares refractarias que se sometieron a tratamiento combinado que incluyó antipsicóticos atípicos. Debido a resistencia a este tratamiento de primera línea, se indicó Clozapina como antipsicótico asociado al tratamiento. Se establecieron períodos de análisis equivalentes para cada paciente, previo y durante el uso de Clozapina. Estos períodos se extendieron de 8 meses a 5 años y 2 meses. Resultados: La dosis diaria promedio de Clozapina fue de 260 mg. No se observaron efectos adversos. Los días de hospitalización totales disminuyeron de 979 días a 118 días y los intentos de suicidio disminuyeron de 14 episodios en el período previo a Clozapina a 1 episodio durante el período de tratamiento con Clozapina. En tres pacientes no se informó de re-hospitalizaciones ni de intentos de auto agresiones con el tratamiento agregado de Clozapina. Conclusión: La eficacia de Clozapina en pacientes bipolares con resistencia al tratamiento debiera considerarse como una opción de segunda línea en terapia combinada con respuesta insuficiente. Los beneficios terapéuticos de Clozapina pueden inclui...