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）：这是对酒精依赖患者睡眠障碍的K24职业调查员奖的续签。失眠很常见，在新康复的患者中经常持续，并且与复发有关。在最初的5年中，研究人员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，受控的试验试验，以研究镇静剂抗惊厥药Gabapentin的夜间给药，因为它对睡眠和对酒精的复发的影响。这项工作从随机对照试验中产生了第一个证据，即加巴喷丁优于安慰剂，以减少复发时间。尽管找不到对主观和客观睡眠的传统措施的强大影响，但对睡眠微体系结构的分析表明，加巴喷丁在快速眼动睡眠期间增加了三角洲（缓慢的频率）活动，这是矛盾地激活皮质的睡眠时期。因此，加巴喷丁可能通过减慢睡眠过程中的皮质多动症来对白天的戒烟产生影响。当前的提案是基于这项工作的基础，该提案通过调查可能针对药物针对的酒精依赖性患者的睡眠障碍的潜在机制。描述了一种新型的睡眠实验室范例（并将进行完善），该范例可以告知该领域与酒精相关的睡眠障碍的机制以及改善睡眠的药物的筛查。为了证明概念验证，将研究两种具有已知潜力的药物治疗酒精依赖或失眠（加巴喷丁，曲唑酮）的药物，以便它们对酒精依赖性患者的无调睡眠的短期影响进行研究。培训将在5年中占10-15％的努力，包括大多数时间在睡眠实验室中，以及关于睡眠和酒精中毒神经生物学的本地和民族会议，以及精选的阅读。另外5-10％的努力是培训T32和其他奖学金支持的新调查人员。与博士。候选人Armitage和Hoffmann将获得有关定量睡眠脑电图分析和解释的新知识和技能，以及测量和分析体内稳态睡眠驱动器和昼夜节律调节的方法。他将把这些方法应用于依赖酒精的患者，这是一个研究的人群，可能会从对其睡眠问题的更复杂的理解中受益。