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Introduction: Currently, 21 million people live with the disease, mostly in low to middle-income countries. We aimed to assess the survival of patients with schizophrenia using clozapine compared with non-clozapine atypical antipsychotics provided by the Brazilian National Health System using real-world data. Materials and methods: This is an open retrospective cohort study of patients diagnosed with schizophrenia to whom atypical antipsychotics were dispensed by the Brazilian National Health System between 2000 and 2015, based on deterministic-probabilistic pairing of administrative data records. The Kaplan-Meier method was used to estimate the cumulative probability of survival and the Cox proportional hazards model was adjusted to assess the risk factors for survival via the hazard ratio (HR). Result: Participants were 375,352 adults with schizophrenia, with an overall survival rate of 76.0% (95%CI 75.0-76.0) at the end of the cohort. Multivariate analysis indicated a greater risk of death for men (HR=1.30; 95%CI 1.27-1.32), older adults (HR=17.05; 95%CI 16.52-17.60), and in the Southeast region of Brazil (HR=1.20; 95%CI 1.17-1.23). Patients who used non-clozapine atypical antipsychotics had a 21% greater risk of death when compared to those taking clozapine (HR=1.21; 95%CI 1.14-1.29). Additionally, a history of hospitalization for pneumonia (HR=2.17; 95%CI 2.11-2.23) was the main clinical variable associated with increased risk of death, followed by hospitalization for lung cancer (HR=1.82; 95%CI 1.58-2.08), cardiovascular diseases (HR=1.44; 95%CI 1.40-1.49) and any type of neoplasia (HR=1.29; 95%CI 1.19-1.40). Discussion: This is the first published Brazilian cohort study that evaluated survival in people with schizophrenia, highlighting the impact of atypical antipsychotics. In this real-world analysis, the use of clozapine had a protective effect on survival when compared to olanzapine, risperidone, quetiapine, and ziprasidone.
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RESUMEN: Introducción: Lograr la recuperación funcional lo más rápido posible en el tratamiento de la depresión unipolar es un reto que la práctica clínica debe tratar de afrontar en la actualidad, ya que cualquier retraso en lograr la remisión de los síntomas es predictivo de un mayor número de recurrencias y mayores tasas de morbimortalidad. En esta revisión comprensiva, nuestro objetivo es guiar a los clínicos en su elección de aumentar con antipsicóticos atípicos o combinar el fármaco de referencia con un segundo antidepresivo, después de que se haya optimizado la dosis del antidepresivo seleccionado inicialmente y/o se haya cambiado el antidepresivo, sin lograr remisión, o bien cuando solo han obtenido una respuesta parcial después de un tiempo suficiente a una dosis apropiada. Estas decisiones surgen con frecuencia en la práctica clínica diaria. Metodología: Se realizó una búsqueda sistemática en PubMed bajo varias combinaciones clave de palabras, resultando en 230 informes. Después de aplicar los criterios de inclusión y según el título y el resumen, el número final de informes seleccionados para la revisión completa fue de 113. Se respondieron dos preguntas principales con base en estos estudios: 1) ¿Existe evidencia para recomendar claramente la combinación de antidepresivos versus potenciación con antipsicóticos (y el momento correcto para hacerlo) en la depresión unipolar no respondedora, una vez que las estrategias de optimización o de cambio han fallado en obtener la remisión? y 2) ¿Es posible identificar algunas características clínicas para guiar la decisión de combinación de antidepresivos versus potenciación con agentes antipsicóticos? Resultados: Según nuestro análisis, no hay datos disponibles para seleccionar una estrategia de otra de manera clara. Sin embargo, sugerimos favorecer una combinación o estrategia de aumento, basada en un enfoque de "tratamiento contra objetivos dianas" para perfilar al paciente, considerando una o dos características clínicas predominantes que permanecen activas como parte de una depresión mayor con respuesta parcial. Un adecuado análisis de los dominios sintomáticos presentes, una visión crítica de las guías clínicas actuales y de las opciones preferidas, considerar la bipolaridad oculta como uno de los principales diagnósticos diferenciales y adoptar una actitud enérgica pero lúcida en esta etapa del tratamiento son, a nuestro juicio, fundamentales para lograr recuperación ad integrum del paciente.
ABSTRACT Introduction: achieving functional recovery as quickly as possible in the treatment of unipolar depression is a challenge that clinical practice must try to meet nowadays, since any delay in accomplishing remission of the symptoms is predictive of a larger number of recurrences and higher morbidity and mortality rates. In this topical review we aim to guide clinicians in their choice to augment with atypical antipsychotics or to combine the baseline drug with a second antidepressant, after the dose of the antidepressant initially selected has been optimized and/or the antidepressant has been changed, not achieving remission, or resulting only in a partial response after sufficient time at an appropriate dose. These decisions arise frequently in everyday clinical practice. Methodology: a systematic search in PubMed was performed under several key combinations of words, resulting in 230 reports. After applying inclusion criteria and based in title and abstract, the final number of reports selected for full revision were 113. Two main questions were answered based on these studies: 1) Is there evidence to clearly recommend combination of antidepressants vs. augmentation with antipsychotics (and the correct moment to do it) in non-responsive unipolar depression, once optimization or switching strategies have failed to obtain remission? and 2) Is it possible to identify some clinical features to guide the decision of combination of antidepressants vs. augmentation with antipsychotic agents? Results: According to our analysis, there is no data available to select one strategy from another in a clear-cut manner. Nevertheless, we suggest favoring a combination or augmentation strategy, based in a "treating to target" approach to profile the patient, considering one or two predominant clinical features that remain active as part of a major depression with partial response. Proper analysis of the symptomatic domains present, a critical view of current clinical guidelines and preferred options, considering hidden bipolarity as one of the main differential diagnoses and adopting an energetic but lucid attitude at this stage of treatment are, in our view, fundamental for achieving ad integrum patient recovery.
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Humanos , Antipsicóticos/uso terapêutico , Indução de Remissão/métodos , Transtorno Depressivo/tratamento farmacológico , Antidepressivos/uso terapêutico , Sinergismo Farmacológico , Quimioterapia CombinadaRESUMO
INTRODUCTION: For the pharmacotherapy of delirium in elderly adults who are hospitalized, atypical antipsychotics are used. Currently, there is insufficient evidence on the effectiveness of this treatment in low complexity units. METHODS: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE/PubMed, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis, and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified 13 systematic reviews that included three randomized trials. We concluded that the use of atypical antipsychotics in hospitalized patients likely increases the risk of mortality compared to placebo and could decrease the response rate associated with reducing the risk of adverse effects. Furthermore, using atypical antipsychotics probably results in low or no difference in the severity of delirium.
INTRODUCCIÓN: Para el tratamiento farmacológico de delirium en pacientes adultos mayores hospitalizados se plantea el uso de antipsicóticos atípicos. Actualmente, existe poca evidencia sobre la efectividad y los resultados de estos fármacos en pacientes adultos hospitalizados en unidades de baja complejidad. MÉTODOS: Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el tamizaje de múltiples fuentes de información, incluyendo MEDLINE/PubMed, EMBASE y Cochrane. Extrajimos los datos desde las revisiones sistemáticas identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos 13 revisiones sistemáticas que en conjunto incluyeron tres estudios primarios, de los cuales todos corresponden a ensayos aleatorizados. Concluimos que el uso de antipsicóticos atípicos en pacientes hospitalizados probablemente aumenta el riesgo de mortalidad en comparación con el placebo, y podría disminuir la tasa de respuesta asociado a disminuir el riesgo de efectos adversos. Además, probablemente resulta en poca o nula diferencia en la severidad del delirium.
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Antipsicóticos/uso terapêutico , Delírio/tratamento farmacológico , Adulto , Idoso , Antipsicóticos/efeitos adversos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Revisões Sistemáticas como Assunto , Resultado do TratamentoRESUMO
Atypical antipsychotics (AAP) or second-generation antipsychotics are the clinical option for schizophrenia treatment during acute psychoses, but they are also indicated for maintenance during lifetime, even though they are being used for other psychiatric conditions in clinical practice such as affective disorders and autism spectrum disorder, among others. These drugs are differentiated from typical antipsychotics based on their clinical profile and are a better choice because they cause fewer side effects regarding extrapyramidal symptoms (EPS). Even though they provide clear therapeutic benefits, AAP induce peripheral effects that trigger phenotypic, functional, and systemic changes outside the Central Nervous System (CNS). Metabolic disease is frequently associated with AAP and significantly impacts the patient's quality of life. However, other peripheral changes of clinical relevance are present during AAP treatment, such as alterations in the immune and endocrine systems as well as the intestinal microbiome. These less studied alterations also have a significant impact in the patient's health status. This manuscript aims to revise the peripheral immunological, endocrine, and intestinal microbiome changes induced by AAP consumption recommended in the clinical guidelines for schizophrenia and other psychiatric disorders.
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Antipsicóticos/efeitos adversos , Sistema Endócrino/efeitos dos fármacos , Neuroimunomodulação/efeitos dos fármacos , Animais , Sistema Endócrino/fisiologia , Humanos , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/epidemiologia , Transtornos Psicóticos/imunologia , Transtornos Psicóticos/fisiopatologiaRESUMO
A major hurdle faced by most schizophrenia patients is the poor efficacy of current antipsychotic medications. This stems from a poor understanding of the underlying pathophysiology and the lack of biomarkers for the prediction of a positive medication response. By employing state-of-the-art proteomic analysis of blood plasma from 58 patients who were either drug-naive or drug-free at the time of sample collection, we identified potential biomarkers that were predictive of a positive response after 6 weeks of treatment with antipsychotics. Complement and coagulation cascades were the most over-represented biological pathways among these proteins, consistent with the importance of these processes in schizophrenia. Although preliminary, these findings are novel and may drive future efforts in the development of predictive tests for medication efficacy and thereby have a positive influence on disease outcome.
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Antipsicóticos/farmacologia , Proteoma , Proteômica/métodos , Esquizofrenia/sangue , Esquizofrenia/tratamento farmacológico , Adulto , Biomarcadores/sangue , Seguimentos , Humanos , Avaliação de Resultados em Cuidados de Saúde , Projetos PilotoRESUMO
Atypical antipsychotics is being considered in the treatment of "negative" symptoms of psychoses, such as schizophrenia. In this case report, we presented a case of a patient with psychiatric disorder who developed hypertension soon after starting using atypical antipsychotic. A 53-year-old woman had reported having episodes of tachycardia, nausea, headache and high blood pressure. At the time of the doctor's appointment, the blood pressure was 210/110 mmHg. According to the patient, she made use of simvastatin for dyslipidemia and started taking aripiprazole, an antipsychotic for approximately 40 days before the symptoms. The initial treatment was 20 mg of olmesartan, and examinations were requested. After 2 months, the patient returned with the examinations: altered serum lipids and the other results were normal. Ambulatory blood pressure monitoring showed an average of 24 h of 150/100 mmHg. Blood pressure was measured at the doctor's office; in regular use of 20 mg of olmesartan, it was 156/92 mmHg. The dosage of olmesartan was increased to 40 mg and 1.5 mg of indapamide was initiated. The patient returned after 20 days with a blood pressure of 146/90 mmHg. After approval from the psychiatrist, the Aripiprazole was stopped, and the patient returned 15 days later with blood pressure of 120/80 mmHg. The ambulatory blood pressure monitoring control showed an average of 24 h of 130/78 mmHg. The Dopamine receptors play a role in the regulation of the blood pressure and the alterations in this system can lead to hypertension. D1, D3 and D4 receptors interact with the renin-angiotensin-aldosterone system, while D2 and D5 interact with the sympathetic nervous system in the regulation of PA. The case reported and the literature review bring to light the discussion of the use of atypical antipsychotics and its adverse events. If necessary, the use of these drugs should be followed by careful monitoring of blood pressure.
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Después de varias décadas de desarrollo de los fármacos antipsicóticos, la esquizofrenia sigue siendo en gran medida una enfermedad crónica con muchos pacientes que experimentan una mala calidad de vida. En este contexto, la aparición de los llamados antipsicóticos de segunda generación fue recibida con gran entusiasmo. Los clínicos esperaban que los nuevos antipsicóticos causaran no solamente menos efectos secundarios motores que los más antiguos, tal como la clorpromazina, sino también que mejoraran los síntomas y la funcionalidad general de los pacientes. Este artículo, de carácter narrativo, revisa cómo inicialmente la evidencia de un gran número de ensayos controlados aleatorios pareció favorecer muchas de estas suposiciones. Esta visión, sin embargo, no era universal, y algunos investigadores destacaron el potencial efecto del diseño de los estudios en los resultados. Un aspecto importante dice relación con la dosis utilizada de antipsicóticos de primera generación, siendo aquellos ensayos que usaron mayores dosis los que apoyaron el uso de antipsicóticos de segunda generación. Esta controversia se resolvió después de la publicación de tres estudios a gran escala, que incluían pacientes menos seleccionados y que enfocaban los resultados a largo plazo en un entorno clínico más "típico", los cuales no encontraron diferencias significativas entre los dos tipos de antipsicóticos. Desde entonces, las discusiones sobre la elección de los antipsicóticos han girado en torno a otros factores tales como los efectos secundarios, más que en su capacidad para controlar los síntomas.(AU)
After several decades of antipsychotic medication development, schizophrenia has largely remained a chronic disease with many patients experiencing poor quality of life. In this context, the appearance of so-called second generation antipsychotics was received with great enthusiasm. Clinicians hoped that the new antipsychotics would not only cause less motor side effects than older ones such as Chlorpromazine, but also improve patients' symptoms and overall functioning. In this narrative article we review how initially the vidence of a large number of randomized controlled trials appeared to favour many of these claims. This view was not universal though, and some researchers highlighted the potential effect of some design aspects of the trials in the results. A particular concern related to the dose of first generation antipsychotic used, with trials favouring second generation frequently using higher doses. This controversy was resolved after the publication of three large studies, including less selected patients and looking at longer-term outcomes in a more "typical" clinical setting, which failed to find significant differences between the two types of antipsychotics. Since then, discussions about the choice of antipsychotic revolve more around other factors such as side-effects than their capacity to control symptom.(AU)
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Humanos , Masculino , Feminino , Terapêutica , Antipsicóticos , Esquizofrenia , Efeitos Colaterais Metabólicos de Drogas e SubstânciasRESUMO
Myocarditis occurs more frequently during clozapine (CLZ) administration than during treatment with other antipsychotic drugs (APs). In this observational study, we transversally screened outpatients for myocarditis by comparing a CLZ group of 132 subjects, with a non-CLZ group taking other APs (n = 371) only, and in 21 CLZ-treated patients and 18 subjects treated with other APs who had been followed for more than one year. The protocol included a) assessment of symptoms such as dyspnea, tachycardia, chest discomfort, fever, cough, and edema, b) blood pressure and heart auscultation; c) a standard electrocardiogram after a 5-minute rest, d) white cell count, and qualitative determination of troponin I, creatine-kinase-MB and myoglobin, and e) a cardiologist evaluation of subjects with suspected myocarditis. Only one case of myocarditis was detected, providing an approximation of the frequency of myocarditis of 1.6% in the first month of treatment. This was a 30-year-old man with schizophrenia who developed symptoms at day 6 after starting a treatment with 200 mg of CLZ a day without titration. Myocarditis was not observed during prolonged CLZ or other AP administration. These results support the proposal of starting CLZ treatment with a low dose and the feasibility of a simple protocol for myocarditis detection in psychiatry primary care.
El desarrollo de miocarditis ocurre con más frecuencia durante el tratamiento con clozapina (CLZ) que durante el uso de otros antipsicóticos (APs). En el presente estudio observacional evaluamos la presencia de miocarditis mediante un protocolo transversal comparando 132 sujetos tratados con CLZ con 371 pacientes tratados con otro AP, y en 21 sujetos tratados con CLZ y 18 pacientes tratados con otro AP en un protocolo longitudinal mayor 1 año de duración. La evaluación incluyó: a) detección de síntomas como disnea, taquicardia, malestar torácico, fiebre, tos y edema; b) presión arterial y auscultación cardiaca; c) electrocardiograma estándar luego de un reposo de 5 minutos; d) contaje de glóbulos blancos y determinación cualitativa de troponina I, creatin-kinasa-MB y mioglobina, y e) evaluación por un cardiólogo en sujetos sospechosos para miocarditis. Detectamos un solo caso de miocarditis, lo que permite una aproximación sobre la frecuencia de miocarditis de 1,6 % durante el primer mes de tratamiento. Se trató de un sujeto masculino con esquizofrenia que desarrolló síntomas durante el día 6 después de haber iniciado el tratamiento con CLZ a la dosis de 200 mg por día sin titulación. No se detectaron sujetos sospechosos de miocarditis durante el tratamiento prolongado con CLZ u otro AP. Estos resultados sustentan la recomendación de comenzar el tratamiento con clozapina a dosis bajas, y la factibilidad de utilizar un protocolo sencillo para detectar miocarditis en la atención psiquiátrica primaria.
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Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Antipsicóticos/efeitos adversos , Clozapina/efeitos adversos , Miocardite/induzido quimicamente , Estudos Transversais , Estudos LongitudinaisRESUMO
A eficácia da clozapina(CLZ)como um agente antipsicótico atípico foi reconhecida desde o início dos anos 1960, sendo ainda nos dias atuais a droga de escolha no tratamento de casos de esquizofrenia refratários a outros antipsicóticos. Dentre os efeitos adversos da CLZ, a constipaçãoé relatada com frequência, podendo progredir para obstruçãointestinal, necrose intestinal,sepse intrabdominale morte. O presente estudoavaliou o mecanismo de ação da CLZsobre a motilidade gastrintestinalatravés da análise da taxa de trânsito intestinal (TI) e da excreção de pelotas fecais em camundongos. Foram utilizados camundongos Swiss, machos, peso 25-30g, provenientes do Biotério Central da UFC e o projeto foi aprovado pela CEPA/UFC (Proc. No. 57/2014).As drogas utilizadas foram: CLZ (2,5; 5; 10; 20mg/kg), neostigmina (NEO, 1mg/kg i.p.), serotonina (5-HT, 10mg/kg v.o.), alilisitiocianato (AITC 10mg/kg v.o.), domperidona (DOM, 20mg/kg v.o.), L-NAME (80 mg/kg i.p.), naloxona (2mg/kg s.c.), glibenclamida (5mg/kg i.p.) e AM251 (1mg/kg i.p.).A administração oral de CLZ 10 e 20 mg/kgreduziusignificativamente(p<0,05) o transito gastrintestinal (TI) em relação ao veículoa partir desse resultado optou-se pela menor dose efetiva de CLZ sobre a função motora intestinal para as avaliações subsequentes...
Clozapine (CLZ)an atypicalantipsychotic agentrecognized for its efficacy since the early 1960s stillsnowadays the drug of choice in treating refractory schizophrenia cases to other antipsychotics. Among the adverse effects of CLZ, constipation, often reported, may progress to bowel obstruction, intestinal necrosis, intraabdominal sepsis and death. This study evaluated the mechanism of action of CLZ on gastrointestinal motility by analyzingthe intestinal transit rate (IT) and excretionof fecal pellets in mice. Animals usedwereSwiss males, weight 25-30g, from the UFC Central Animal Facility and the project approved by the CEPA / UFC (Proc. No. 57/2014). The drugs used were: CLZ (2.5, 5, 10, 20mg/kgp.o.), neostigmine (NEO 1mg /kg i.p.), serotonin (5-HT, 10mg/kg p.o.), alilisotiocianate(AITC 10mg/kg p.o.) , domperidone (DOM 20mg/kg p.o.), L-NAME (80 mg/kg i.p.), naloxone (2 mg/kg s.c.), glibenclamide (5 mg/kg i.p.) and AM251 (1 mg/kg i.p.). Oral administration of CLZ 10 and 20 mg/kg significantly (p <0.05) inhibited ITfrom the vehicle.Based on the results we decided forthe smallest effective dose of CLZ active on intestinal motor function(10mg/kg)for subsequent evaluations...
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Humanos , Clozapina , Constipação Intestinal , Receptor CB1 de CanabinoideRESUMO
El presente trabajo consiste en una revisión de la evidencia que existe hasta la fecha respecto a tratamientos psicosociales y farmacológicos para el trastorno de ánimo bipolar (TAB) en población pediátrica. En cuanto a tratamientos psicosociales destacan: Grupo Psicoeducativo Multifamiliar de Fristad, el Programa Rainbow de Pavuluri, Terapia Focalizada en la Familia para adolescentes, Terapia Interpersonal y de Ritmos Sociales para Adolescentes y la Terapia Dialéctica Comportamental para adolescentes (DBT). Se ha visto que los tratamientos comparten ciertas características, tales como, psicoeducación, establecimiento de hábitos y rutinas, y el trabajo con las familias en términos de desarrollo de habilidades sociales, habilidades de comunicación, afrontamiento al estrés y resolución de conflictos, que serían de relevancia para la mejoría de la sintomatología anímica, la recurrencia de los cuadros anímicos, la adherencia al tratamiento y la prevención de recaídas. Las investigaciones realizadas en intervenciones farmacoterapéuticas muestran que los antipsicóticos atípicos son eficaces en el tratamiento de episodios agudos (maníacos o mixtos), y que podrían ser superiores a los estabilizadores del ánimo en este grupo etáreo. La escasez de estudios en el tratamiento de depresión bipolar y de largo plazo limitan las conclusiones del tratamiento farmacológico en estas fases. Tanto para intervenciones psicosociales como farmacológicas se necesita mayor investigación, ya que existen pocos estudios que aborden el tratamiento del TAB pediátrico, y faltan ensayos controlados aleatorios.
This article is an updated revision of the psychosocial and pharmacological treatments for Pediatric Bipolar Disorder (PBD). Psychosocial treatments include: Fristad Multi-family Psychoeducation Groups, Pavuluri's Rainbow Program, Family Focused Therapy for adolescents, Interpersonal and Social Rhythm Therapy for adolescents and the Dialectical Behavior Therapy for adolescents. These interventions have common characteristics: psychoeducational interventions, habit and routine establishment, social and communication skills training and problem solving skills training. The evidence suggests that these characteristics would help to recover from mood symptoms, delay recurrent episodes, contribute to treatment adherence, and prevent recurrence. Research in pharmacologic interventions shows that atypical antipsychotics are efficacious in treating acute episodes (manic or mixed states), and could be superior to mood stabilizers in this age group. Lack of studies regarding treatment of bipolar depression and long-term treatment limit the conclusions for these pha- ses. Further research is warranted for both psychosocial and pharmacological interventions, specially randomized controlled trials.
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Humanos , Criança , Adolescente , Transtorno Bipolar/terapia , Medicina Baseada em Evidências , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/tratamento farmacológico , Terapia Cognitivo-Comportamental , Relações Familiares , Terapia do Comportamento Dialético , Psicoterapia Interpessoal , Relações InterpessoaisRESUMO
We assessed the efficacy and tolerability of the augmentation of antidepressants (ATDs) with atypical antipsychotics (AAPs) to treat patients with major depressive disorder. A retrograde study to identify relevant patient data included databases of PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Database of Abstracts of Reviews of Effects. Data from 17 trials, involving 3807 participants, were identified. The remission rate (RR) and overall response rate (ORR) of adjunctive treatment with AAPs were significantly higher than placebo treatment: RR=1.90 (95%CI=1.61-2.23, z=7.74, P<0.00001) and ORR=1.68 (95%CI=1.45-1.94, z=7.07, P<0.00001). We found that the short-term (4 weeks) treatment [ORR=1.70 (95%CI=0.98-2.95, Z=1.89, P=0.06)] was significantly different from the long-term (6-12 weeks) treatment [ORR=1.68 (95%CI=1.45-1.94, z=7.07, P<0.00001)]. No significant difference in ORR was observed between groups with or without sedative drugs. The discontinuation rate due to adverse effects was higher for adjunctive treatment with AAPs: ORR=3.32 (95%CI=2.35-4.70, z=6.78, P<0.00001). These results demonstrate that the augmentation of ATDs with AAPs (olanzapine, quetiapine, aripiprazole, and risperidone) was more effective than a placebo in improving response and remission rates, although associated with a higher discontinuation rate due to adverse effects.
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Adolescente , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Antidepressivos/administração & dosagem , Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Transtorno Depressivo Maior/tratamento farmacológico , Antidepressivos/efeitos adversos , Benzodiazepinas/administração & dosagem , Benzodiazepinas/efeitos adversos , Quimioterapia Adjuvante , Método Duplo-Cego , Sinergismo Farmacológico , Dibenzotiazepinas/administração & dosagem , Dibenzotiazepinas/efeitos adversos , Piperazinas/administração & dosagem , Piperazinas/efeitos adversos , Quinolonas/administração & dosagem , Quinolonas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão , Risperidona/administração & dosagem , Risperidona/efeitos adversos , Resultado do TratamentoRESUMO
Objective: To review the options for acute and maintenance pharmacological treatment of bipolar disorder in children and adolescents, including the treatment of bipolar depression and comorbid attention deficit/hyperactivity disorder (ADHD). Methods: Narrative review of randomized clinical trials and open-label studies published from 2000 to 2012. The PubMed and PsycINFO websites were queried. Case series were included when a higher level of evidence was not available. Results: Published data from randomized controlled trials (RCTs) in acute mania/hypomania with significant responses are available for lithium, topiramate, risperidone, olanzapine, and aripiprazole. Open trials of lithium and lamotrigine show that these drugs may be effective in the treatment of depressive episodes. No trials of selective serotonin reuptake inhibitors (SSRIs) have been conducted. In the treatment of comorbid ADHD, there are encouraging findings with mixed amphetamine salts and atomoxetine; conflicting results are observed with methylphenidate. Conclusions: Published RCTs of traditional mood stabilizers are scarce, but the best available evidence (results from meta-analytic regression) suggests that second-generation antipsychotics (SGAs) as a group are more effective in reducing manic symptoms. Risperidone was the only one included in head-to-head comparisons (vs. lithium and divalproex), showing superiority in terms of efficacy, but with more metabolic side effects, which were also more common in most of the SGAs. There are few studies addressing the treatment of ADHD and depression. Brazilian guidelines for the treatment of pediatric bipolar disorder should also include some SGAs (especially risperidone and aripiprazole) as first-line treatment, and these drugs should be provided by the public health services. .
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Adolescente , Criança , Humanos , Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Transtorno Bipolar/psicologia , Comorbidade , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
The use of atypical antipsychotics as an adjunctive therapy to antidepressants for treating non-psychotic major depressive disorder (MDD) has been a common practice long before large-scale randomized double-blind placebo-controlled clinical trials demonstrated their efficacy. In this study, we aimed to study the frequency with whichpatients with non-psychotic major depression were prescribed antipsychotics (AP) and to examine the effect of age, race, and ethnicity on the type and dose of individual antipsychotics prescribed, in a cohort of patients before the recent Food and Drug Administration (FDA) approval of adjunctive aripiprazole. The charts of 1537 patients with unipolar depression were analyzed. 1376 had non-psychotic depression; among them 466 (33.9%) patients were prescribed antipsychotics with a significant predilection towards males (males vs. females: 41.7% vs. 27.8%. z=2.4, p<.02; odds ratio=1.97 with a standard error of 0.57) of Hispanic origin (X 2 = 35.8, df = 1, p < 0.0001).Quetiapine was the most commonly prescribed antipsychotic (n=209, 44.8%) with a mean (±SEM) 195.1±13.1 mg. Our results confirm previous reports of the common clinical practice of the use of atypical antipsychotics, specifically quetiapine, as adjunctive treatment for non-psychotic patients with unipolar depression. Further research is required to study the long term effect of this class of medications in patients without a primary psychotic disorder.
El uso de antipsicóticos atípicos como terapia adjunta a antidepresivos en el tratamiento del trastorno depresivomayor (TDM) no psicótico fue práctica común por un largo periodo antes de que los ensayos clínicos a doble-ciego,controlados (con placebo) y al azar, llevados a cabo a gran escala, demostraran su eficacia. El presente estudio se propuso evaluar la frecuencia con la cual pacientes diagnosticados con TDM recibieron tratamiento con agentes antipsicóticos (AP) y examinar los efectos de edad, raza y etnicidad sobre el tipo y dosis de los anti-psicóticos prescritos a una cohorte de pacientes antes de la reciente aprobación de aripiprazole por la Administración de Alimentos y Drogas (FDA), como medicación adjunta para el manejo de esta entidad clínica. Se analizaron lashistorias clínicas de 1537 pacientes portadores del diagnóstico de depresión unipolar. 1376 presentaron depresiónno psicótica y de ellos, 466 (33,9%) recibieron antipsicóticos con predominio de pacientes varones (hombres vs. mujeres: 41,7% vs. 27,8%. z=2,4, p<0,02; odds ratio (OR)=1,97, con error estándar (SE) de 0,57) de origen Hispánico (X2= 35,8, df = 1, p < 0,0001). Quetiapina fue el antipsicótico más comúnmente prescrito (n=209,44,8%) con una dosis promedio (±SEM) de 195,1±13,1 mg. Nuestros resultados confirman reportes previos del uso de antipsicóticos (específicamente quetiapina) en la práctica clínica habitual, como tratamiento adjunto en pacientesno psicóticos con diagnóstico de depresión unipolar. Se requiere investigación adicional que indague los efectos a largo plazo de este tipo de medicación en pacientes sin un diagnóstico de trastorno psicótico primario.
Assuntos
Antipsicóticos/uso terapêutico , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/terapia , Estudos RetrospectivosRESUMO
Objective: To review the literature about the use of atypical antipsychotics in the treatment of pathological aggression in children and adolescents. Method: The databases MEDLINE, SciELO, and LILACS were searched for publications in Portuguese or English from 1992 to August 2011 using the following keywords: mental disease, child, adolescent, treatment, atypical antipsychotic, aggressive behavior, aggression, and violent behavior. Results: Sixty-seven studies of good methodological quality and clinical interest and relevance were identified. Studies including children and adolescents were relatively limited, because few atypical antipsychotics have been approved by the Food and Drug Administration (FDA). All the medications included in this review (risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole and clozapine) have some effectiveness in treating aggression in children and adolescents, and choices should be based on clinical indications and side effects. Conclusions: There are few studies about the effectiveness and safety of atypical antipsychotics for the pediatric population, and further randomized controlled studies with larger groups of patients and more diagnostic categories, such as severe conduct disorder and oppositional defiant disorder, should be conducted to confirm the results reported up to date and to evaluate the impact of long-term use.
Objetivo: Realizar uma revisão sistemática da literatura científica sobre o uso de antipsicóticos atípicos (APAs) no tratamento da agressividade patológica em crianças e adolescentes. Método: Foi realizada busca eletrônica nas bases de dados MEDLINE, SciELO e LILACS, de 1992 a agosto 2011, considerando artigos publicados em língua inglesa e portuguesa. Foram utilizadas associações das seguintes expressões: mental disease, child, adolescent, treatment, atypical antipsychotic, aggressive behaviour, aggression e violent behavior. Resultados: Foram identificados 67 artigos de boa qualidade metodológica, de relevância e interesse clínico para o tema em foco. De modo geral, os estudos são relativamente limitados para esta faixa etária, resultado do fato de poucos APAs terem sido aprovados pela Food and Drug Administration (FDA). Dentre as medicações consideradas nesta revisão (risperidona, olanzapina, quetiapina, ziprazidona, aripiprazol e clozapina), todas elas podem ter alguma efetividade no tratamento da agressividade em crianças e adolescentes, ficando a escolha baseada na indicação clínica e perfil de efeitos colaterais. Conclusão: O número ainda limitado de estudos acerca da efetividade e segurança na população pediátrica demanda pesquisas futuras com grupos maiores de pacientes e com mais categorias diagnósticas (como, por exemplo, as formas graves de transtorno de conduta e transtorno desafiador de oposição), desenhadas de forma randomizada e controlada. Assim poderão ser confirmados os achados até o momento e o impacto do uso em longo prazo.
Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Antipsicóticos/farmacologia , Antipsicóticos/uso terapêutico , Transtorno da Personalidade Passivo-Agressiva/diagnóstico , Transtorno da Personalidade Passivo-Agressiva/patologia , Literatura de Revisão como Assunto , Metanálise como Assunto , Transtorno da Conduta/patologia , Transtorno da Personalidade Passivo-Agressiva/epidemiologiaRESUMO
BACKGROUND AND OBJECTIVE: This review article aims to discuss and evaluate the risk factors for the development of violence and homicidal behaviour and the effectiveness and outcomes of the preferred atypical antipsychotics in patients diagnosed with schizophrenia. METHOD: For this purpose, the psychiatry literature was comprehensively reviewed. A screening of the articles in the international databases covering the period between 1970 and 2010 was performed. RESULTS: Although the risk of homicidal behaviours is higher in patients with schizophrenia compared to the overall population, little is known about the relevant conditions triggering acts of violence among the patients with schizophrenia. The available results suggest that certain factors including some socio-demographic characteristics, young age, alcoholism, substance abuse, noncompliance with treatment, fulfillment of the criteria for antisocial personality disorder and paranoid subtype, history of suicidal ideation and attempts and history of frequent hospitalization increase the potential for violent episodes. Available data show clozapine to be the most rational therapeutic choice in preventing violent behaviour in patients with schizophrenia. There is evidence from randomized controlled trials in support of the specific anti-aggressive effect of clozapine. CONCLUSION: In clinical practice, patients with a risk of committing homicide should be detected and monitored closely. There are many trials showing the efficacy of clozapine on violent and aggressive behaviour.
ANTECEDENTES Y OBJETIVO: Este artículo de revisión esta dirigido a discutir y evaluar los factores de riesgo en el desarrollo de la violencia y el comportamiento homicida, frente a la efectividad y los resultados de los antipsicóticos atípicos preferidos en pacientes diagnosticados con esquizofrenia. MÉTODOS: Para este propósito, se procedió a hacer una revisión exhaustiva de la literatura psiquiátrica. Asimismo se realizó un análisis y selección de los artículos en los bancos de datos internacionales, abarcando el periodo entre 1970 y 2010. RESULTADOS: Aunque el riesgo de comportamiento homicida es más alto en los pacientes con esquizofrenia si se le compara con la población mundial, poco se sabe de las condiciones pertinentes que desatan actos de violencia entre los pacientes con esquizofrenia. Los resultados disponibles sugieren que ciertos factores - que incluyen algunas características sociodemográficas, edad juvenil, alcoholismo, abuso de substancias, no cumplimiento con el tratamiento, correspondencia con los rasgos de desorden de personalidad antisocial y el subtipo paranoico, historia de ideación e intentos suicidas, así como antecedentes de hospitalizaciones frecuentes - aumentan la potencialidad de los episodios violentos. Los datos disponibles muestran la clozapina como la opción terapéutica más racional para prevenir el comportamiento violento en los pacientes con esquizofrenia. Hay evidencias provenientes de ensayos controlados aleatorios que fundamentan el efecto anti-agresivo específico de la clozapina. CONCLUSIÓN: La práctica clínica debe detectar y monitorear de cerca a los pacientes con riesgo de cometerr homicidio. Hay muchos ensayos que muestran la eficacia de la clozapina en controlar el comportamiento violento y agresivo.
Assuntos
Humanos , Antipsicóticos/uso terapêutico , Homicídio/prevenção & controle , Esquizofrenia/tratamento farmacológico , Transtornos do Comportamento Social/tratamento farmacológico , Comportamento Perigoso , Fatores de Risco , Esquizofrenia/complicações , Transtornos do Comportamento Social/complicaçõesRESUMO
Medications are being used with greater frequency to address pediatric mental health problems, and in recent years atypical antipsychotic (AAP) prescriptions have increased more than any other class. Acute care practitioners must be aware of the pharmacology of AAPs and the conditions, on- and off-label, for which they are prescribed. This involves identifying and managing side effects that manifest both mentally and physically. Although "atypicality" confers a lower risk of movement side effects compared to conventional agents, children are more sensitive than adults to extrapyramidal reactions. Like adults, they also may present with toxic sedation, confusion, cardiovascular dysfunction, and metabolic derangements. Evaluation and management of these toxicities requires an index of suspicion, a careful symptom and medication history, physical examination, and targeted interventions. This review is designed to orient the emergency practitioner to the challenging task of recognizing and treating adverse effects related to acute and chronic atypical antipsychotic exposure in children.
RESUMO
Neuroleptic malignant syndrome (NMS) is a potentially fatal adverse event associated with the use of antipsychotics (AP). The objective of this study was to investigate the profile of cases of NMS and to compare our findings with those published in similar settings. A series of 18 consecutive patients with an established diagnosis of NMS was analyzed, gathering data on demography, symptoms and signs. Two thirds of all cases involved woman with a past medical history of psychiatric disorder receiving relatively high doses of AP. The signs and symptoms of NMS episodes were similar to those reported in other series and only one case had a fatal outcome, the remaining presenting complete recovery. As expected, more than two thirds of our cases were using classic AP (68 percent), however the clinical profile of these in comparison with those taking newer agent was similar. Newer AP also carry the potential for NMS.
A síndrome neuroléptica maligna (SNM) é um evento adverso potencialmente fatal associado ao uso de antipsicóticos (AP). O objetivo deste estudo foi investigar as características clínicas de cases da SNM e comparar nossos resultados com os publicados na literatura. Uma série de 18 pacientes com diagnóstico confirmado de SNM foram analisados, associando dados demográficos, apresentação clínica, diagnóstico e tratamento. Dois terços dos casos envolveram mulheres com antecedentes psiquiátricos que recebeceram doses relativamente altas de AP. Os sinais e sintomas foram semelhantes àqueles já relatados na literatura e a maioria dos pacientes teve uma recuperação completa, exceto por um caso com desfecho fatal. Houve predomínio de pacientes que usam medicamentos neurolépticos clássicos (68 por cento), porém não houve diferença nas manifestações destes casos em relação àqueles que usavam AP novos. AP mais novos também têm o potencial de causar SNM.
Assuntos
Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Antipsicóticos/efeitos adversos , Síndrome Maligna Neuroléptica/diagnóstico , Estudos Transversais , Síndrome Maligna Neuroléptica/etiologiaRESUMO
The use of atypical antipsychotics is associated with metabolic side effects including weight gain, diabetes mellitus and an atherogenic lipid profile. These adverse effects are not only the risk factors for cardiovascular disease, insulin resistance and diabetes mellitus, leading to increased morbidity and mortality; but may also impair the patients adherence to treatment. The increasing numbers of reports of diabetes and ketoacidosis have raised concerns about the association and it is still unclear whether it is a class or single drug effect. Two groups of patients have been recognized. The first and smaller one with a rapid onset of diabetes and ketoacidosis debut were made of younger people, less overweight and include a higher proportion of women. The second and larger group has a more classical onset in witch weight gain, abdominal fat deposition and other major risk factors played an important role. Although not fully scientifically proven yet, available evidence suggests that clozapine and olanzapine have a higher propensity to induce diabetes and metabolic syndrome compared with other atypical antipsychotic drugs, risperidone and quetiapine. Despite more limited available data, amisulpride, aripiprazole and ziprazidone showed less likelihood of precipitating diabetes. The metabolic effects of antipsychotic drugs should be of concern when planning a patients treatment strategy. Baseline screening and regular follow-up monitoring whose intervals should depend on the individual predisposition are advised. Possible therapeutic strategies for the management of drug-induced obesity include therapeutic approaches, such as life style change and pharmaceutical intervention. Drugs with a weight reducing effect become more important because of the lack of compliance and short duration of behavioral intervention.
El uso de Antipsicóticos Atípicos se asocia a efectos metabólicos que incluyen aumento de peso, diabetes mellitus y perfil lipídico aterogénico. Estos efectos adversos no sólo son factores de riesgo cardiovascular e insulino-resistencia asociados a morbilidad y mortalidad sino que también disminuyen la adherencia del paciente al tratamiento. El incremento de reportes de casos de diabetes y cetoacidosis ha aumentado el interés por este efecto secundario y aún no queda claro si se trata de un efecto de clase o asociado sólo a algunos fármacos. Se han reconocido dos grupos de pacientes; el primero y menor, caracterizado por la presentación súbita de diabetes y debut cetoacidótico corresponde a pacientes más jóvenes, con menor sobrepeso y mayor proporción de mujeres. El segundo grupo y de mayor amplitud tiene un inicio más clásico de la enfermedad con aumento de peso, deposito visceral de grasa y otros factores de riesgo. Todavía no existe evidencia científica suficiente, sin embargo, la existente sugiere que clozapina y olanzapina tienen mayor propensión a inducir diabetes y síndrome metabólico en comparación con otros antipsicóticos atípicos tales como quetiapina y risperidona y aparentemente amisulpirida, ziprazidona y aripiprazol involucrarían menor riesgo. Los efectos metabólicos de los antipsicóticos deben ser tomados en cuenta al iniciar tratamiento y deben ser evaluados al inicio y durante el seguimiento según la predisposición de cada sujeto. Las posibles estrategias de tratamiento incluyen cambios en el estilo de vida y el uso de fármacos. Éstos últimos adquieren especial importancia ante la corta duración y falta de adherencia a las intervenciones conductuales. Topiramato, agentes dopaminérgicos y serotoninérgicos han mostrado posible utilidad en el manejo del aumento de peso secundario al uso de fármacos. Se requieren, sin embargo, mayores estudios antes de recomendar el uso de cualquier fármaco.
Assuntos
Humanos , Masculino , Feminino , Adulto , Antipsicóticos/efeitos adversos , Antipsicóticos/metabolismo , Antipsicóticos/uso terapêutico , Diabetes Mellitus , Obesidade , Síndrome MetabólicaRESUMO
El Clinical Antipsychotic Trials of lntervention Effectiveness-Alzheimer Disease (CATIE-AD) es el primer estudio de efectividad que investiga por 36 semanas la respuesta a los antipsicóticos atípicos en los pacientes con Enfermedad de Alzheimer que se presentan con síntomas conductuales y psicológicos asociados a la demencia (SCPD). No se encontraron diferencias estadísticamente significativas entre los antipsicóticos atípicos y placebo en las medidas de efectividad que también incluyeron un análisis costo-beneficio. Este artículo no solo examina este importante estudio sino que resume la compleja relación de los antipsicóticos y los SCPD a lo largo de los últimos años.
The Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer Disease (CATIE-AD) is the first 36 weeks effectiveness trial of atypical antipsychotics in patients with Alzheimer's disease presenting with behavioral and psychiatric symptoms of dementia (BPSD). There were no significant differences between atypical antipsychotics and placebo in effectiveness measures which also included a cost-benefit analysis. This article not only reviews this landmark study but also summarizes the complex relationship between antipsychotics and BPSD during the last years.
Assuntos
Humanos , Antipsicóticos , Doença de Alzheimer , Ensaios Clínicos como Assunto , Sintomas Comportamentais , Sintomas PsíquicosRESUMO
El Clinical Antipsychotic Trials of lntervention Effectiveness-Alzheimer Disease (CATIE-AD) es el primer estudio de efectividad que investiga por 36 semanas la respuesta a los antipsicóticos atípicos en los pacientes con Enfermedad de Alzheimer que se presentan con síntomas conductuales y psicológicos asociados a la demencia (SCPD). No se encontraron diferencias estadísticamente significativas entre los antipsicóticos atípicos y placebo en las medidas de efectividad que también incluyeron un análisis costo-beneficio. Este artículo no solo examina este importante estudio sino que resume la compleja relación de los antipsicóticos y los SCPD a lo largo de los últimos años.(AU)
The Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer Disease (CATIE-AD) is the first 36 weeks effectiveness trial of atypical antipsychotics in patients with Alzheimers disease presenting with behavioral and psychiatric symptoms of dementia (BPSD). There were no significant differences between atypical antipsychotics and placebo in effectiveness measures which also included a cost-benefit analysis. This article not only reviews this landmark study but also summarizes the complex relationship between antipsychotics and BPSD during the last years.(AU)