Metabolic Effects of Antipsychotics in Children

抗精神病药物对儿童的代谢影响

• 批准号: 7096128
• 负责人: JOHN W. NEWCOMER
• 金额: $ 107.06万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-05 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7096128
• 关键词: adipose tissue; adolescence (12-20); antipsychotic agents; bioenergetics; calorimetry; child behavior disorders; clinical research; clinical trial phase I; drug adverse effect; glucose metabolism; glucose tolerance test; glucose transport; human subject; human therapy evaluation; insulin sensitivity /resistance; lipid metabolism; magnetic resonance imaging; middle childhood (6-11); obesity; patient oriented research; pharmacokinetics; photon absorptiometry; risperidone; serotonin inhibitor

DESCRIPTION (provided by applicant): The prevalence of overweight and obesity, insulin resistance, hyperglycemia, dyslipidemia and type 2 diabetes mellitus (T2DM) are increasing in children, with epidemic rates reported in children in the United States. Increased adiposity and related reductions in insulin sensitivity are major risk factors for the development of dyslipidemia, metabolic syndrome, T2DM, cardiovascular disease (e.g., risk of myocardial infarction and stroke), other adverse health outcomes, and reduced psychosocial function. Reductions in lifespan attributable to obesity impact younger individuals most measurably such that, for example, a severely obese 20 year-old African American male is expected to lose 20 years of life. Certain medications can increase regional adipose tissue mass and insulin resistance, contributing to short- and long-term metabolic risk. Antipsychotic medications are extensively used in children, with certain agents producing greater increases in weight and adiposity than any other commonly used drugs in this age group. Recent studies also indicate that some antipsychotics may affect insulin sensitivity independent of adiposity, suggesting a potential additional mechanism for metabolic risk. The use of atypical antipsychotics in children is increasing, and has been stimulated by reported efficacy for aggression and irritability in a variety of psychiatric conditions. However, no study in children has sensitively quantified the adverse metabolic effects of widely used atypical antipsychotics despite reports of alarming levels of weight gain. The proposed randomized clinical trial aims to assess the metabolic safety of atypical antipsychotics in antipsychotic-naive children aged 7-18 with aggression in the setting of various childhood psychiatric disorders during 12 weeks of prospective, randomized treatment with olanzapine (Zyprexa), risperidone (Risperdal) or aripiprazole (Abilify). The primary aims are to evaluate antipsychotic treatment effects on 1) insulin action in skeletal muscle (glucose disposal), liver (glucose production) and adipose tissue (lipolysis) by measuring whole-body glucose and lipid kinetics with stable isotope tracer methodology, and 2) on total body fat and abdominal fat mass using whole body dual energy x-ray absorptiometry (DEXA) and abdominal magnetic resonance imaging (MRI). Secondary aims of the study include the assessment of the effectiveness for treatment of symptoms of aggression and irritability. Relevant data are critically needed to assess the risks of antipsychotic therapy in children, to identify targets for additional basic research, and to guide clinical decision-making.

描述（由申请人提供）：儿童的超重和肥胖症，胰岛素抵抗，高血糖，血脂异常和2型糖尿病（T2DM）的患病率正在增加，在美国儿童中报道了流行病。胰岛素敏感性增加的肥胖和相关降低是发育异常血症，代谢综合征，T2DM，心血管疾病（例如，心肌梗死和中风的风险），其他不良健康欧现代和降低的心理社会社会社会社会心理功能的主要危险因素。可归因于肥胖的寿命的降低影响年轻的个体，以便例如，预计一名肥胖的20岁非洲裔美国男性将损失20年的生命。某些药物可以增加区域脂肪组织肿块和胰岛素抵抗，从而导致短期和长期代谢风险。与该年龄段的任何其他常用药物相比，抗精神病药被广泛用于儿童，某些药物的体重和肥胖性增加。最近的研究还表明，某些抗精神病药可能会影响胰岛素敏感性与肥胖无关，这表明具有代谢风险的潜在附加机制。在儿童中使用非典型抗精神病药的使用正在增加，并且在各种精神疾病中的侵略性和易怒的疗效刺激了。然而，尽管有报道称体重增加水平令人震惊，但对儿童的研究尚未敏感地量化了广泛使用的非典型抗精神病药的不良代谢作用。提议 随机临床试验旨在评估7-18岁的抗精神病药抗精神病药的代谢安全性，并在各种儿童期精神疾病中进行侵略性，并在前瞻性，随机治疗奥氮平（Zypredxa），Risperidone（Risperidone（Risperidone）或Aripipififififife（Abilipiprififife）的各种儿童精神疾病中。主要目的是评估对抗精神病药物对1）骨骼肌中的胰岛素作用（葡萄糖处置），肝脏（葡萄糖产生）和脂肪组织（脂肪分解），通过测量全身脂肪和脂肪的脂肪方法，以及使用整体脂肪的脂肪量（使用总体脂肪量），通过测量全体体葡萄糖和脂质动力学（使用全体脂肪量）来促进整个体体量，并促进整个体体量x，并促进整个体体X型刺激量。和腹部磁共振成像（MRI）。该研究的次要目的包括评估治疗侵略性和易怒症状的有效性。需要非常需要数据来评估儿童抗精神病药疗法的风险，以确定其他基础研究的目标，并指导临床决策。