NALTREXONE FOR ANTIPSYCHOTIC-INDUCED WEIGHT GAIN

纳曲酮用于抗精神病药引起的体重增加

基本信息

批准号：
8437335
负责人：
CENK TEK
金额：
$ 47.9万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-03-01 至 2018-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8437335
关键词：
Accounting Affect Affinity Antipsychotic Agents Attenuated Behavior Therapy Body Weight decreased Body mass index Brain Cardiovascular Diseases Cardiovascular system Cessation of life Communities Desire for food Development Diabetes Mellitus Diet Dopamine D2 Receptor Dose Double-Blind Method Eating Eating Behavior Economics Endorphins Epidemic Food Funding General Population Generations Glycosylated Hemoglobin Glycosylated hemoglobin A Guidelines Haloperidol Health Health Food Health Insurance Histamine H1 Receptors Hyperphagia Individual Intervention Knowledge Life Style Lipids Mediating Mentally Ill Persons Modeling Morbidity - disease rate Naltrexone Narcotic Antagonists Obesity Opioid Receptor Patients Pharmaceutical Preparations Physical activity Pilot Projects Placebo Control Placebos Population Prevalence Proteins Psychiatric therapeutic procedure Public Health Randomized Randomized Clinical Trials Request for Applications Rest Rewards Risk Marker Risk Reduction Running Scheme Schizophrenia Serum Smoking Symptoms System United States Vulnerable Populations Weight Weight Gain Work arm bariatric surgery base clinically significant cost cost effective diabetic diabetic patient effective intervention fasting glucose fighting health disparity improved increased appetite mortality non-diabetic nutrition obesity treatment physical conditioning prevent programs public health relevance receptor severe mental illness therapy development trend waist circumference

项目摘要

DESCRIPTION (provided by applicant): People with severe mental illness (SMI) die 25 years earlier, mostly due to cardiovascular disease and diabetes, which are directly related to obesity. Obesity is a leading cause of preventable death in the US, second only to smoking. There is an urgent need for the development of interventions for the growing problem of obesity as well as related morbidity and mortality in this vulnerable population. Poor knowledge about nutrition, lack of access to healthy foods, and the increased costs of healthy foods contribute to increased prevalence of obesity among SMI patients. Regardless, the most important contributor to the obesity epidemic in this population is antipsychotic-induced weight gain. Behavioral interventions are necessary to fight obesity, but are insufficient, as patients continue to need their psychiatric medications, which in turn increase their appetite and make the task of losing weight extremely difficult. We have developed a working model of antipsychotic-induced weight gain. We hypothesized that antipsychotic medications attenuate the rewarding effects of food, thus causing SMI patients to eat more to get the same level of reward. To prove the concept, we completed a pilot study using naltrexone, a medication which blocks the effects of endorphins, the brain proteins which mediate the reward. If the additional reward is not gained with eating more, patients should stop doing so. Indeed, the pilot study showed that naltrexone stopped the weight gain trend in a group of patients taking antipsychotics and, in fact, produced significant weight loss for non- diabetic patients, while the placebo group continued to gain weight during the trial. This is an indirect evidence to support our hypothesis, as naltrexone does not produce weight loss in standard obesity treatment. Based on this evidence, naltrexone may be a useful, easy to use and cost effective medication to counteract antipsychotic-induced weight gain. In this application, we propose a large double blind, randomized clinical trial utilizing two doses of naltrexone compared to placebo over a period of one year (52 weeks) to counteract antipsychotic induced weight gain and obesity among a group of patients with SMI.

描述（申请人提供）：患有严重精神疾病（SMI）的人会提前25年死亡，主要是由于心血管疾病和糖尿病，而这些疾病与肥胖直接相关。肥胖是美国可预防死亡的主要原因，仅次于吸烟。迫切需要制定干预措施来解决这一弱势群体中日益严重的肥胖问题以及相关的发病率和死亡率。营养知识匮乏、无法获得健康食品以及健康食品成本增加导致 SMI 患者肥胖患病率增加。无论如何，导致该人群肥胖流行的最重要因素是抗精神病药物引起的体重增加。行为干预对于对抗肥胖是必要的，但还不够，因为患者继续需要精神药物，这反过来又增加了他们的食欲，使减肥任务变得极其困难。我们开发了一种抗精神病药物引起的体重增加的工作模型。我们假设抗精神病药物会减弱食物的奖励作用，从而导致 SMI 患者吃更多的东西以获得相同水平的奖励。为了证明这个概念，我们使用纳曲酮完成了一项试点研究，纳曲酮是一种阻断内啡肽（介导奖赏的大脑蛋白质）作用的药物。如果吃得更多并没有获得额外的奖励，患者应该停止这样做。事实上，初步研究表明，纳曲酮阻止了一组服用抗精神病药物的患者体重增加的趋势，并且实际上使非糖尿病患者的体重显着减轻，而安慰剂组在试验期间体重继续增加。这是支持我们假设的间接证据，因为纳曲酮在标准肥胖治疗中不会产生体重减轻。基于这一证据，纳曲酮可能是一种有用、易于使用且经济有效的药物，可以抵消抗精神病药物引起的体重增加。在本申请中，我们提出了一项大型双盲、随机临床试验，使用两种剂量的将纳曲酮与安慰剂进行为期一年（52 周）的比较，以抵消抗精神病药物引起的一组 SMI 患者的体重增加和肥胖。