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Although commonly used in clinical practice, scientific literature about clozapine prescription patterns in Colombia is scarce. A cross-sectional observational study was conducted in an outpatient clinic in Bogotá, Colombia. Between 2016 and 2018, clozapine was prescribed to 2603 patients, mainly for Schizophrenia Spectrum Disorders and Bipolar and Depressive Disorders, at a median dose of 100mg/day. After controlling for other variables, older age was the only variable that explained the use of doses lower than 100mg/day. Clozapine was not only used for Treatment-Resistant Schizophrenia, and further studies are needed to explain these differences.

Aunque se utiliza comúnmente en la práctica clínica, la literatura científica sobre los patrones de prescripción de clozapina en Colombia es escasa. Se realizó un estudio observacional transversal en el servicio ambulatorio de una clínica de referencia en Bogotá, Colombia. Entre 2016 y 2018, se recetó clozapina a 2603 pacientes, principalmente para esquizofrenia y trastornos relacionados, trastorno afectivo bipolar y trastornos depresivos, a una dosis media de 100 mg/día. Después de controlar otras variables, la edad avanzada fue la única variable que explicó el uso de dosis inferiores a 100 mg/día. La clozapina no se utilizó sólo para la esquizofrenia resistente al tratamiento, y se necesitan estudios adicionales para explicar estas diferencias.

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Patient response to antipsychotic drugs varies and may be related to clinical and genetic heterogeneity. This study aimed to determine the performance of clinical, genetic, and hybrid models to predict the response of first episode of psychosis (FEP). patients to the antipsychotic risperidone. We evaluated 141 antipsychotic-naïve FEP patients before and after 10 weeks of risperidone treatment. Patients who had a response rate equal to or higher than 50% on the Positive and Negative Syndrome Scale were considered responders (n = 72; 51%). Analyses were performed using a support vector machine (SVM), k-nearest neighbors (kNN), and random forests (RF). Clinical and genetic (with single-nucleotide variants [SNVs]) models were created separately. Hybrid models (clinical+genetic factors) with and without feature selection were created. Clinical models presented greater balanced accuracy 63.3% (confidence interval [CI] 0.46-0.69) with the SVM algorithm than the genetic models (balanced accuracy: 58.5% [CI 0.41-0.76] - kNN algorithm). The hybrid model, which included duration of untreated psychosis, Clinical Global Impression-Severity scale scores, age, cannabis use, and 406 SNVs, showed the best performance (balanced accuracy: 72.9% [CI 0.62-0.84] - RF algorithm). A hybrid model, including clinical and genetic predictors, can provide enhanced predictions of response to antipsychotic treatment.

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OBJECTIVES: The primary objective was to describe the standardized body mass index (z-BMI) trajectory of children and adolescents admitted to a psychiatric reference center in Mexico City according to their diagnosis and medication use. The secondary objective was to compare z-BMI between antipsychotic users and non-users. METHODS: This is a retrospective cohort study. The psychiatric diagnosis, prescribed medications, serial heights, and weights were collected from the medical records. RESULTS: The median baseline z-BMI of the 129 analyzed cases was 0.88 (interquartile range [IQR]: 0-1.92), and the prevalence of excessive weight (obesity or overweight) was 46.8 %. At the end of follow-up (median 50.3 weeks), the median change in z-BMI was -0.09 (IQR: -0.68 to 0.42). New long-term users of antipsychotics (n=29) had an increase in their z-BMI, in contrast to never-users (median difference 0.73, p=0.01) and to previous users (median difference 0.92, p=0.047). The 59 subjects with excessive weight at admission had a median z-BMI change of -0.39 (IQR: -0.81 to -0.04). Among patients with excessive weight and depression, there was a greater decrease in z-BMI in sertraline users (n=13) compared with fluoxetine users (n=15) (median -0.65 vs. 0.21, p<0.001). CONCLUSIONS: New long-term users of antipsychotics showed a significant increase in their z-BMI. Patients with depressive disorders and obesity on sertraline therapy tended to show a decrease in their z-BMI.

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INTRODUCTION: Clozapine, a second-generation antipsychotic (SGA), is considered the gold standard medication to treat patients with treatment-resistant schizophrenia (TRS). Despite its efficacy, clozapine is associated with adverse effects, notably neutropenia and agranulocytosis. Other hematological adverse effects are less common. Severe anemia is a rare adverse effect seldom reported in the literature and is typically associated with pure red cell aplasia (PRCA). Nevertheless, the benefits of clozapine in managing TRS make rechallenge a reasonable option. CASE REPORT: We present the case of a 35-year-old man with TRS, resistant to previous antipsychotics, who experienced severe anemia during clozapine treatment. An investigation for clozapine-induced anemia revealed PRCA on myelogram. After discontinuing clozapine, the patient's hemoglobin levels recovered. Subsequent treatments with olanzapine, zuclopenthixol, and aripiprazole proved ineffective, leading us to consider a clozapine rechallenge. The rechallenge, monitored for 58 days, resulted in improved psychiatric symptoms and stable hemoglobin levels. The patient remained stable during 6 months of follow-up, with no hematological changes. DISCUSSION: PRCA is a very rare adverse effect of clozapine. The cause of drug-induced PRCA is still unknown; for clozapine, there are no studies. Rechallenge after a severe and rare adverse effect is a complex decision. This case is the first to report a successful clozapine rechallenge following severe anemia without other blood dyscrasias, emphasizing the imperative need for close monitoring during the rechallenge process. Further study is warranted to understand the predictive factors for a successful outcome in clozapine rechallenges.

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RESUMEN Introducción: Las reacciones adversas a medicamentos (RAM) son manifestaciones clínicas o de laboratorio no deseadas que se relacionan con el consumo de medicamentos. Las RAM se asocian con un riesgo significativo de morbimortalidad e ingresos hospitalarios. Los antipsicóticos poseen una reducida ventana terapéutica y se han relacionado con la manifestación de una diversidad de RAM. Objetivo: Evaluar el patrón de las RAM debido a fármacos antipsicóticos, detectadas en pacientes atendidos en el Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz entre diciembre de 2021 y mayo de 2022. Métodos: Estudio observacional, descriptivo, prospectivo y transversal de una serie de casos. La gravedad, la severidad y la calidad de la información de la notificación de las RAM se definieron conforme a la NOM-220-SSA1-2016, instalación y operación de la farmacovigilancia, mientras que la causalidad se determinó mediante el algoritmo de Naranjo. Resultados: La incidencia de las RAM fue del 59% y se detectó una o más RAM en 52 de los 88 pacientes que estaban en tratamiento antipsicótico durante el periodo de estudio. El 45% de las RAM tuvo una causalidad probable y el 55%, posible; únicamente tres RAM se clasificaron como graves, debido a que prolongaron la estancia hospitalaria y pusieron en peligro la vida del paciente. Conclusiones: Las RAM de los sistemas gastrointestinal y endocrino fueron las más incidentes, y la hiperprolactinemia fue la más frecuente. La olanzapina y clozapina fueron los medicamentos que más RAM provocaron. Se recomienda fomentar la cultura de notificación y seguimiento de RAM causadas por fármacos antipsicóticos.

ABSTRACT Introduction: Adverse Drug Reactions (ADR) are unwanted clinical or laboratory manifestations that are related to drug use. ADR are common and are associated with significant risk of morbidity, mortality and hospital admissions. Antipsychotics have a reduced therapeutic window, and have been related to the manifestation of a variety of ADR. Objetive: To evaluate the pattern of ADRs due to antipsychotic drugs detected in patients treated at the Ramón de la Fuente Muñiz National Institute of Psychiatry between December 2021 and May 2022. Methods: Observational, descriptive, prospective and cross-sectional study of a series of cases. The seriousness, severity, and quality of the information in the notification of the ADR were defined in accordance with NOM-220-SSA1-2016, Installation and Operation of Pharmacovigilance, while causality was determined using the Naranjo algorithm. Results: The incidence of ADRs was 59%, with one or more ADR detected in 52 of the 88 patients who were receiving antipsychotic treatment during the study period. Forty-five percent of the ADR had probable causality and 55% possible; only three ADR were classified as serious as they prolonged the hospital stay and endangered the patient's life. Conclusions: The ADR of the gastrointestinal and endocrine systems were the most incidental, with hyperprolactinemia being the most frequent. Olanzapine and clozapine were the medications that caused the most ADR. It is recommended to promote the culture of notification and follow-up of ADR caused by antipsychotic drugs.

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ABSTRACT Neuroleptic malignant syndrome (NMS) is a neurologic emergency potentially fatal. This rare side effect is most commonly associated with first-generation antipsychotics and less frequently with atypical or second-generation antipsychotics. The diagnosis relies on both clinical and laboratory criteria, with other organic and psychiatric conditions being ruled out. CASE REPORT: A 39-year-old female patient, who is institutionalized and completely dependent, has a medical history of recurrent urinary infections and colonization by carbapenem-resistant Klebsiella pneumoniae. Her regular medication regimen included sertraline, valproic acid, quetiapine, risperidone, lorazepam, diazepam, haloperidol, baclofen, and fentanyl. The patient began experiencing dyspnea. Upon physical examination, she exhibited hypotension and a diminished vesicular murmur at the right base during pulmonary auscultation. Initially, after hospitalization, she developed high febrile peaks associated with hemodynamic instability, prompting the initiation of antibiotic treatment. Despite this, her fever persisted without an increase in blood inflammatory parameters, and she developed purulent sputum, necessitating antibiotherapy escalation. The seventh day of hospitalization showed no improvement in symptoms, suggesting NNMS as a differential diagnosis. All antipsychotic and sedative drugs, as well as antibiotherapy, were discontinued, after which the patient showed significant clinical improvement. CONCLUSION: Antipsychotic agents are commonly employed to manage behavioral changes linked to various disorders. However, their severe side effects necessitate a high degree of vigilance, the cessation of all medications, and the implementation of supportive care measures. A prompt and accurate diagnosis of NMS is crucial to alleviating the severe, prolonged morbidity and potential mortality associated with this syndrome.

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Introducción: Los antipsicóticos son medicamentos que pueden producir elevaciones transitorias de las enzimas hepáticas. La clozapina es un antipsicótico atípico usado en el tratamiento de la esquizofrenia refractaria a los antipsicóticos convencionales y existe evidencia que puede producir elevaciones de las transaminasas hepáticas, expresión de dafño hepático con patrón hepatocelular. Métodos: Reporte de caso y revisión no sistemática de la literatura relevante. Presentación del caso: Una mujer de 39 años con diagnóstico de esquizofrenia paranoide acudió a un servicio de urgencias de un hospital general por náuseas, vómitos e ictericia que apareció tras el inicio de clozapina. No hubo mejoría clínica de la paciente durante la hospitalización, que falleció a los 44 días de su ingreso. Revisión de la literatura: La clozapina puede elevar las cifras de función hepática de manera transitoria y asintomática. Hay criterios clínicos para recomendar la suspensión de este antipsicótico. Conclusiones: Este caso es el tercero en la literatura que registra un desenlace fatal tras un cuadro de hepatotoxicidad inducido por clozapina. © 2021 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España, S.L.U. Todos los derechos reservados.

Introduction: Antipsychotics are drugs that can produce transient elevations of hepatic enzymes. Clozapine is an atypical antipsychotic used in treatment-resistant schizophrenia and there is evidence that it can produce elevations of hepatic transaminases, expression of liver damage in a hepatocellular pattern. Methods: Case report and non-systematic review of the relevant literature. Case presentation: A 39-year-old woman with a diagnosis of paranoid schizophrenia attended the emergency department of a general hospital for nausea, vomiting and jaundice that appeared after the initiation of clozapine. There was no clinical improvement during hospitalization, and death occurred after 44 days. Literature review: Clozapine can increase the liver enzyme levels transiently and asymptomatically; however, there are clinical criteria that recommend the withdrawal of the antipsychotic. Conclusions: This is the third case reported in the literature of a fatal outcome of clozapine-induced hepatotoxicity.

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INTRODUCTION: Neuroleptic malignant syndrome (NMS) is uncommon, with an incidence of 0.01%-3.23%, and is associated with the use of drugs that intervene with dopamine, causing hyperthermia, muscular rigidity, confusion, autonomic instability and death. CASE REPORT: A 35-year-old man with a history of catatonia, refractory epilepsy and functional impairment, required frequent changes in his anticonvulsant and antipsychotic treatment, due to adverse effects. During 2019, in the month of July, clozapine was changed to amisulpride, in September he developed fever, muscle stiffness, stupor, diaphoresis and tachypnea over a two-week period; paraclinical tests showed elevated creatine phosphokinase (CPK) and leukocytosis, so NMS was considered. The antipsychotic was withdrawn and he was treated with bromocriptine and biperiden, with a good response. Ten days after discharge, he began treatment with olanzapine, which generated a similar episode to the one described in December, with subsequent management and resolution. DISCUSSION: The diagnosis is based on the use of drugs that alter dopamine levels, plus altered state of consciousness, fever, autonomic instability and paraclinical tests showing leukocytosis and elevated CPK. Differential diagnoses must be ruled out. Early diagnosis generally leads to total remission, although some patients will suffer complications, long-term sequelae or recurrences. The recurrence in this case derived from the early reintroduction of the neuroleptic after the first episode. Treatment should be individualised according to severity to avoid mortality. CONCLUSIONS: Atypical antipsychotics are rarely suspected of generating NMS. Moreover, the time to reintroduction after an episode must also be taken into account.

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Introducción: El síndrome neuroléptico maligno (SNM) es infrecuente, con una incidencia del 0,01 al 3,23%, y tiene relación con el consumo de fármacos que interfieren con la dopamina; genera hipertermia, rigidez muscular, confusión, inestabilidad autonómica y la muerte. Caso clínico: Un varón de 35 arios, con antecedentes de catatonía, epilepsia refractaria y deterioro funcional, en tratamiento anticonvulsivo y antipsicótico, requirió cambio frecuente por efectos adversos de este. En julio de 2019 se cambió la clozapina por amisulprida; en septiembre se inicia un cuadro de 2 semanas de fiebre, rigidez muscular, estupor, diaforesis y taquipnea; los paraclínicos mostraron aumento de la creatininasa (CK) y leucocitosis, por lo que se consideró SNM. Se retiró el antipsicótico y se trató con bromocriptina y biperideno, que obtuvieron buena respuesta. A los 10 días del egreso, se inició tratamiento con olanzapina, que generó en diciembre un cuadro clínico similar al descrito, con posterior tratamiento y resolución. Discusión: El diagnóstico se basa en la toma de fármacos que alteren la dopamina, más alteración del estado de conciencia, fiebre e inestabilidad autonómica, junto con paraclínicos como leucocitosis y elevación de la CK. Se debe descartar diagnósticos diferenciales. El diagnóstico temprano generalmente lleva a la remisión total; algunos tendrán complicaciones, secuelas a largo plazo o recidivas. La recurrencia en este caso derivó de la reintroducción temprana del neuroléptico después del primer episodio. El tratamiento se debe individualizar según la gravedad para evitar la muerte. Conclusiones: Rara vez se sospecha que los antipsicóticos atípicos generen SNM; a su vez se debe tener en cuenta el tiempo a la reintroducción después de un episodio.

Introduction: Neuroleptic malignant syndrome (NMS) is uncommon, with an incidence of 0.01% to 3.23%, and is associated with the use of drugs that intervene with dopamine, causing hyperthermia, muscular rigidity, confusion, autonomic instability and death. Case report: A 35-year-old man with a history of catatonia, refractory epilepsy and functional impairment, required frequent changes in his anticonvulsant and antipsychotic treatment, due to adverse effects. During 2019, in the month of July, clozapine was changed to amisul-pride, in September he developed fever, muscle stiffness, stupor, diaphoresis and tachypnea over a two-week period; paraclinical tests showed elevated creatine phosphokinase (CPK) and leukocytosis, so NMS was considered. The antipsychotic was withdrawn and he was treated with bromocriptine and biperiden, with a good response. Ten days after discharge, he began treatment with olanzapine, which generated a similar episode to the one described in December, with subsequent management and resolution. Discussion: The diagnosis is based on the use of drugs that alter dopamine levels, plus altered state of consciousness, fever, autonomic instability and paraclinical tests showing leukocy-tosis and elevated CPK. Differential diagnosis must be ruled out. Early diagnosis generally leads to total remission, although some patients will suffer complications, long-term sequelae or recurrences. The recurrence in this case derived from the early reintroduction of the neuroleptic after the first episode. Treatment should be individualised according to severity to avoid mortality. Conclusions: Atypical antipsychotics are rarely suspected of generating NMS. Moreover, the time to reintroduction after an episode must also be taken into account.

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Introducción: los adultos mayores son una población de riesgo para el desarrollo de reacciones adversas a los medicamentos. Los medicamentos potencialmente inapropiados son aquellos que representan mayores riesgos que beneficios en este grupo etario. Se cuenta con herramientas de apoyo a la prescripción en geriatría que permiten identificar a estos medicamentos y mediante la aplicación de estudios de utilización de medicamentos, podemos describir o analizar el uso de los mismos en una población. Objetivos: reconocer disponibilidad de medicamentos potencialmente inapropiados para adultos mayores en la RAP metropolitana de ASSE durante 2019 y establecer un diagnóstico de situación de consumo de los mismos durante ese año. Método: se realizó un análisis del vademécum institucional mediante la aplicación de los Criterios de Beers 2019 y dos escalas de riesgo anticolinérgico para identificar medicamentos potencialmente inapropiados. Posteriormente se realizó un estudio de utilización de los medicamentos identificados, mediante datos de dispensación de farmacia entre el 1 de enero y 31 de diciembre de 2019. El consumo se expresó en Dosis Diarias Definidas por cada 1000 adultos mayores-año (DHD). Resultados: se identificaron 16 medicamentos potencialmente inapropiados, de los cuales los más usados fueron clonazepam (DHD 69), quetiapina (65,6), alprazolam (DHD 43,7), flunitrazepam (DHD 42,7) y zolpidem (DHD 36,4). Conclusiones: la aplicación de herramientas explícitas facilita la identificación de medicamentos potencialmente inapropiados para adultos mayores y se evidenció un consumo elevado de los mismos durante el año 2019 a expensas de derivados benzodiazepínicos y quetiapina.

Introduction: older adults are at higher risk for developing adverse drug reactions. Potentially inappropriate medications are drugs that have more risks than benefits in this age group. There are a number of tools to support the prescription of medication in geriatrics that allow the identification of these medications, and by applying studies developed on the use of medications we may describe or analyze their impact on a given population. Objectives: to recognize availability of potentially inappropriate medications in older adults in ASSE's Metropolitan RAP during 2019 and to draw conclusions about the current situation in terms of the consumption of this kind of medications. Method: an institutional analysis of medications available in each healthcare provided was conducted through the application of Beers Criteria 2019, and two anticholinergic risk scales were used to identify potentially inappropriate medications. Subsequently, the use of the medications identified was studied by applying pharmacy dispensing data between January 1 and December 31, 2019. Consumption was expressed in defined daily doses every 1000 adults per year (DHD). Results: 16 potentially inappropriate medications were identified, the most widely used of which were clonazepam (DHD 69), quetiapine (65.6), alprazolam (DHD 43.7), flunitrazepam (DHD 42.7) and zolpidem (DHD 36.4). Conclusions: Applying explicit tools makes it easier to identify potentially inappropriate medications for older adults. An increased consumption of these kinds of drugs was noticed during 2019, as a result of benzodiazepine derivatives and quetiapine.

Introdução: os idosos são uma população de risco para o desenvolvimento de reações adversas a medicamentos. Medicamentos potencialmente inapropriados são aqueles que apresentam maiores riscos do que benefícios nessa faixa etária. Existem ferramentas de apoio à prescrição em geriatria que permitem identificar esses medicamentos e, por meio da aplicação de estudos de utilização de medicamentos, descrever ou analisar seu uso em uma população. Objetivos: reconhecer a disponibilidade de medicamentos potencialmente inapropriados para idosos na RAP metropolitana da ASSE durante o ano de 2019 e estabelecer um diagnóstico de consumo durante esse ano. Método: o formulário institucional foi analisado utilizando os Critérios de Beers 2019 e duas escalas de risco anticolinérgico para identificar medicamentos potencialmente inapropriados. Posteriormente, foi realizado um estudo de consumo dos medicamentos identificados, através dos dados de dispensação da farmácia entre 1 de janeiro e 31 de dezembro de 2019. O consumo foi expresso em Doses Diárias Definidas por 1000 idosos-ano (DHD). Resultados: foram identificados 16 medicamentos potencialmente inapropriados, sendo clonazepam (DHD 69), quetiapina (65,6), alprazolam (DHD 43,7), flunitrazepam (DHD 42,7) e zolpidem (DHD 36,4) os mais utilizados Conclusões: a aplicação de ferramentas explícitas facilita a identificação de medicamentos potencialmente inapropriados para idosos; foi observado um alto consumo dos mesmos em detrimento dos derivados benzodiazepínicos e da quetiapina durante o período do estudo.

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