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Medication Effects on Sleep in Alcoholics

药物对酗酒者睡眠的影响

基本信息

批准号：
7667287
负责人：
KIRK J BROWER
金额：
$ 17.89万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-09-27 至 2011-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7667287
关键词：
Abstinence Age Alcohol dependence Alcoholism Alcohols Anticonvulsants Antidepressive Agents Award Behavior Therapy Characteristics Circadian Rhythms Clinical Clinical Trials Development Electroencephalography Fellowship Frequencies Functional disorder Funding Goals Heavy Drinking Hour Hyperactive behavior K-Series Research Career Programs Knowledge Laboratories Left Measures Mediating Medicine Melatonin Mental disorders Methods Mirtazapine Naltrexone Neuraxis Neurobiology Patients Pharmaceutical Preparations Pharmacotherapy Phase Placebos Population Property REM Sleep Randomized Randomized Controlled Trials Reading Regulation Relapse Research Research Methodology Research Personnel Running Sleep Sleep Disorders Sleep Stages Sleep disturbances Sleeplessness Slow-Wave Sleep Time Training Trazodone Upper arm Work acamprosate actigraphy base career design gabapentin impaired driving performance improved indexing neurotoxic novel pilot trial problem drinker psychosocial response sex skills sleep abnormalities stressor symposium

项目摘要

DESCRIPTION (provided by applicant): This is a renewal of a K24 Career Investigator Award on sleep disturbances in alcohol-dependent patients. Insomnia is common, frequently persistent in newly recovering patients, and associated with relapse. In the first 5 years, the investigator acquired knowledge about sleep medicine, sleep research methods, traditional sleep stage scoring, and pharmacotherapy trial methods. He then designed and conducted a randomized, controlled pilot trial to study night-time administration of the sedating anticonvulsant drug, gabapentin, for its effects on both sleep and relapse to alcohol. This work produced the first evidence from a randomized controlled trial that gabapentin was superior to placebo for reducing time to relapse. Although robust effects on traditional measures of subjective and objective sleep were not found, analysis of sleep microarchitecture revealed that gabapentin increased delta (slow frequency) activity during rapid eye movement sleep, the period of sleep during which the cortex is paradoxically activated. Thus, gabapentin may have exerted its effect on daytime abstinence by slowing cortical hyperactivity during sleep. The current proposal builds on this work by investigating potential mechanisms for sleep disturbance in alcohol-dependent patients that could be targeted by medications. A novel sleep laboratory paradigm is described (and will be refined) that can inform the field about mechanisms of alcohol-related sleep disturbances as well as screen for medications that improve sleep. To demonstrate proof-of-concept, two medications with known potential for treating either alcohol dependence or insomnia (gabapentin, trazodone) will be studied for their short-term effects on disregulated sleep in alcohol-dependent patients. Training will comprise 10-15% effort for 5 years including mostly time in the sleep lab, but also local and national conferences on the neurobiology of sleep and alcoholism, and selected readings. Another 5-10% effort is for training new investigators supported by T32 and other fellowships. With Drs. Armitage and Hoffmann, the candidate will acquire new knowledge and skills about quantitative sleep EEG analysis and interpretation, as well as methods for measuring and analyzing homeostatic sleep drive and circadian rhythm regulation. He will apply these methods to alcohol dependent patients, an understudied population that may benefit clinically from a more sophisticated understanding of their sleep problems.

描述（由申请人提供）：这是一个K24职业研究者奖在酒精依赖患者睡眠障碍的更新。在新近康复的患者中，胰岛素抵抗是常见的，经常持续存在，并与复发有关。在前5年，研究者获得了有关睡眠医学、睡眠研究方法、传统睡眠阶段评分和药物治疗试验方法的知识。然后，他设计并进行了一项随机对照试验，研究夜间服用镇静抗惊厥药物加巴喷丁对睡眠和酒精复发的影响。这项工作从一项随机对照试验中首次获得证据，表明加巴喷丁在减少复发时间方面上级安慰剂。虽然没有发现对主观和客观睡眠的传统测量的强大影响，但睡眠微结构分析显示，加巴喷丁增加了快速眼动睡眠期间的δ（慢频率）活动，在此期间，大脑皮层被反常地激活。因此，加巴喷丁可能通过减缓睡眠期间的皮质过度活跃来对白天禁欲产生影响。目前的建议建立在这项工作的基础上，通过调查酒精依赖患者睡眠障碍的潜在机制，这些机制可能是药物治疗的目标。描述了一种新的睡眠实验室范式（并将被完善），可以告知该领域有关酒精相关的睡眠障碍的机制，以及筛选改善睡眠的药物。为了证明概念验证，将研究两种已知具有治疗酒精依赖或失眠潜力的药物（加巴喷丁，曲唑酮）对酒精依赖患者睡眠失调的短期影响。培训将包括10-15%的努力，为期5年，主要包括在睡眠实验室的时间，但也包括关于睡眠和酗酒的神经生物学的地方和国家会议，以及选定的阅读材料。另外5-10%的努力是培训由T32和其他奖学金支持的新调查员。与阿米蒂奇和霍夫曼博士一起，候选人将获得有关定量睡眠脑电图分析和解释的新知识和技能，以及测量和分析稳态睡眠驱动和昼夜节律调节的方法。他将把这些方法应用于酒精依赖患者，这是一个研究不足的人群，可能会从对他们睡眠问题的更复杂的理解中受益。