Miocarditis inducida por Clozapina: Revisión y protocolo de Screening

Clozapina, el gold standard en esquizofrenia refractaria, presenta algunos efectos adversos que ocasionalmente pueden ser graves. Entre ellos, la miocarditis precoz es un efecto cardiovascular severo poco frecuente que puede aparecer en las primeras 4-6 semanas. Las cifras de incidencia oscilan entre el 0,015-0.188% en el mundo, siendo más altas en Australia. La etiología es desconocida, postulándose hipersensibilidad mediada por Ig E; hipereosinofilia y hiperadrenergia. Múltiples investigaciones avalan a la ecocardiografía como una de las técnicas más útiles para el diagnóstico. La biopsia endomiocárdica es definitoria pero no viable. Existen, asimismo, criterios de RNM indicativos de inflamación miocárdica. Para facilitar el diagnóstico, se han propuesto criterios clínicos y analíticos de screening (hemograma, ECG, CK, PCR, troponinas). En caso de sospecha de miocarditis, el cese de clozapina y el tratamiento de soporte es la actitud a seguir, habitualmente con buenos resultados.

Although Clozapine is the gold standard treatment in resistant-schizophrenia, severe or even life-threatening adverse effects must be taked into account. Early myocarditis, a severe but unusual cardiovascular effect, can appear in the first 4-6 weeks of initiation. Incidence rates of myocarditis are about 0,015-0,188% around the world, being more elevated in Australia. Aethiology is unknown, suggesting Ig E mediated hipersensibility, hiperaeosinophilia and hiperadrenergy. Echocardiography seems to be one of the most helpful tools for diagnosing myocarditis. Endomyocardial biopsy is definitive, but not usually available. A role for cardiac magnetic resonance imaging (MRI) also has been proposed (findings of inflammation). In order to make an early diagnosis, several screening-criteria, considering clinical and laboratory ones, have been proposed: aeosinophylia, creatininkinase, C Reactive Proteine, troponin, and EKG. If we suspected clozapine-induced myocarditis, the drug must be removed and support medical treatment must be indicated.

Esquizofrenia resistente al tratamiento. I, concepto e impacto clínico / Treatment resistant schizophrenia. I, concept and clinical impact

La esquizofrenia es una psicosis crónica que se caracteriza por tres dominios sintomáticos: síntomas positivos, síntomas negativos y síntomas cognitivos. Se estima que afecta al 1 % de la población. El desarrollo de la psicofarmacología y del tratamiento de la esquizofrenia ha permitido distinguir genios evolutivos según la respuesta terapéutica. En este sentido es que se delinea el concepto de esquizofrenia resistente al tratamiento (ERT). Se estima ERT en un 30 % aproximadamente de los sujetos que padecen esquizofrenia. La identificación temprana y adecuada de este subgrupo de individuos se relaciona con una mejor respuesta. Este artículo es una narrativa sobre el concepto de ERT y su impacto clínico.

Schizophrenia is a chronic psychosis characterized by three symptom domains: positive symptoms, negative symptoms and cognitive symptoms. Its prevalence is about 1 % of the general population. The development of psychopharmacology and schizophrenia treatment have made possible the distinction between different clinical courses and outcomes according to treatment response. This is the basis for the concept of treatment resistant schizophrenia (TRS), which can be present in 30 % of schizophrenic patients. Early and adequate identification of this subgroup is related to better outcomes. Authors analyze the previously mentioned concept and its clinical impact.

Concentrations in plasma clozapine levels in schizophrenic and schizoaffective patients. / Variaciones en las concentraciones plasmáticas de clozapina en pacientes con esquizofrenia y trastorno esquizoafectivo.

INTRODUCTION: There is great variability in plasma levels of clozapine. The objective of this study is to know the characteristics of patients treated with clozapine and the relationship between them and the variability of plasma levels. MATERIAL AND METHODS: Descriptive, cross-sectional study of all patients currently treated with clozapine in a Psychiatric Service with a diagnosis of schizophrenic psychosis or schizoaffective disorder. The present study assessed physical situation, psychopathology and functionality of the patients and explored the associations and correlations between clinical variables and plasma levels. RESULTS: We studied 39 patients, predominantly men, with negative and depressive symptoms and cardiovascular risk factors (metabolic syndrome and smoking). Significant variability in dose and even greater in clozapine levels were observed. The levels of clozapine at equal doses/kg of body weight were higher in non-smokers, they had positive correlation with BMI and negative correlation with systolic BP, disruptive behaviors and number of cigarettes consumed. CONCLUSION: Plasma level monitoring clozapine is an important tool to avoid clozapine plasma levels monitoring and minimize undesirable clinical situations (metabolic syndrome, sedation, negative symptoms and functional impairment). It is also important to control the effects of a smoking habit for optimum drug bioavailability.

Esquizofrenia resistente al tratamiento: ¿hemos tomado una decisión? / Treatment-resistant schizophrenia: have we made a decision?

Introduction: For decades, the term refractory psychosis has been widely used, but not clearly defined. Although the exact mechanisms by which treatment-resistance is developed are unknown, some factors will lead to bigger vulnerability to present it. It remains unclear if it is just a severe extreme at the end of the psychosis spectrum, or a subtype of schizophrenia. Objective: To determine if there is current consensus in the concept of refractory psychosis. Methods: Review of different guidelines about it (EMEA, SIGN, NICE, BPA, APA, CPA and WFSBP) and comparison of their definitions and approach designs. Results: Consulted guidelines show differences in the way they define refractory psychosis, but uniformity in their management proposal. Conclusion: There is no consensus in the operational definition of treatment resistant psychosis.

Introducción: Por décadas, el término de esquizofrenia refractaria ha sido ampliamente usado, pero no adecuadamente definido. Aunque no se conocen los mecanismos exactos por los cuales se desarrolla resistencia a la terapia antipsicótica, algunos factores condicionarán mayor probabilidad de fallo terapéutico. No se sabe, a punto fijo, si el cuadro se trata sólo de un extremo severo al final del continuum del espectro psicótico, o si es un subtipo de esquizofrenia. Objetivo: Determinar si existe consenso actual sobre el concepto de esquizofrenia refractaria. Metodología: Revisión de distintas guías clínicas sobre el tema (EMEA, SIGN, NICE, BPA, APA, CPA y WFSBP) y comparación de sus definiciones y sus diseños de abordaje. Resultados: Las guías consultadas muestran diferencias respecto al modo en que definen esquizofrenia refractaria, pero uniformidad en su planteamiento de manejo. Conclusión: No existe consenso en la definición operacional de esquizofrenia resistente al tratamiento.

Evaluation of the efficacy of the continuation electroconvulsive therapy in treatment-resistant schizophrenia / Avaliação da eficácia da eletroconvulsoterapia contínua para esquizofrenia resistente ao tratamento

Background: Electroconvulsive therapy (ECT) has been reported being a safe and effective treatment in schizophrenia. However, there are a limited number of studies assessing continuation ECT utilization in patients with schizophrenia giving partial response to pharmacological treatment. Objective: The aim of this study is to evaluate the effectiveness of continuation ECT in preventing relapse in patients with treatment-resistant schizophrenia. Methods: In this retrospective analysis, schizophrenia patients (n = 73) were defined in three groups such as patients who received only AP treatment (only AP), patients who received acute ECT only during hospitalization (aECT+AP), patients who received acute ECT and continuation ECT (a-cECT+AP). Three groups were compared according to positive and negative syndrome scale (PANSS) and Brief Psychiatric Rating Scale (BPRS) scores. Results : As per comparison of only AP group, aECT+AP group and a+cECT+AP groups in terms of after discharge PANSS and after discharge BPRS scores for 1st month, 3rd month and 6th month; 3rd and 6th month’s PANSS scores of a+cECT+AP group were statistically significantly lower than other two groups. Discussion: Although this study suffers the limitations of retrospective medical chart analysis, results suggest that, in patients with a diagnosis of schizophrenia who have responded to an acute course of ECT, continuation ECT in combination with antipsychotics is more effective than antipsychotics alone in preventing relapse...

Contexto: A eletroconvulsoterapia (ECT) tem mostrado ser um tratamento seguro e eficaz para esquizofrenia. No entanto, o número de estudos que avaliam a utilização contínua de ECT em pacientes com esquizofrenia e a resposta parcial ao tratamento farmacológico é limitado. Objetivo: O objetivo deste estudo é avaliar a eficácia da ECT de continuação na prevenção de recaída em pacientes com esquizofrenia resistente ao tratamento. Métodos: Nesta análise retrospectiva, pacientes com esquizofrenia (n = 73) foram alocados em três grupos: pacientes que receberam apenas o tratamento AP (somente AP), pacientes que receberam um curso agudo de ECT durante a hospitalização (aECT+AP) e pacientes que receberam um curso agudo de ECT durante a hospitalização e ECT de continuação (a-cECT+AP). Esses três grupos foram comparados de acordo com a pontuação atribuída na Positive and Negative Syndrome Scale (PANSS) e na Brief Psychiatric Rating Scale (BPRS). Resultados: De acordo com a comparação dos grupos, somente em AP, aECT+AP e a+cECT+AP, em termos de PANSS e BPRS, após descarga no primeiro, terceiro e sexto mês, as pontuações na PANSS no terceiro e sexto mês no grupo a+cECT+AP foram estatística e significativamente menores do que nos outros dois grupos. Conclusões: Embora este estudo mostre limitações causadas pela análise retrospectiva de prontuários, os resultados sugerem que a continuação da ECT em combinação com antipsicóticos é mais eficaz do que somente os antipsicóticos, na prevenção da recaída em pacientes com diagnóstico de esquizofrenia que responderam ao curso agudo de ECT...