Pharmacotherapy and Mechanisms of Sleep Disturbance in Alcohol Dependence

酒精依赖睡眠障碍的药物治疗和机制

• 批准号: 7547076
• 负责人: KIRK J BROWER
• 金额: $ 39.45万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-01-20 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7547076
• 关键词: Abstinence; Acute; Adult; Affect; Age; Alcohol dependence; Alcohol or Other Drugs use; Alcohol withdrawal syndrome; Alcoholism; Biological; Brain; Cessation of life; Characteristics; Chronic Disease; Circadian Rhythms; Clinical; Data; Diagnosis; Double-Blind Method; Electroencephalography; Functional disorder; Gender; Hour; Hyperactive behavior; Laboratories; Measures; Melatonin; Monitor; Neuraxis; Outcome; Patients; Pharmaceutical Preparations; Pharmacotherapy; Phase; Phase I Clinical Trials; Placebos; Psyche structure; Public Health; Randomized; Recording of previous events; Regulation; Relapse; Research; Research Personnel; Risk; Risk Factors; Science; Screening procedure; Sleep; Sleep Apnea Syndromes; Sleep Disorders; Sleep disturbances; Sleeplessness; Slow-Wave Sleep; Time; Visit; Wakefulness; actigraphy; base; cost; design; drinking; effective therapy; follow-up; gabapentin; impaired driving performance; improved; indexing; insight; problem drinker; programs; response; sex; sleep abnormalities

Project Summary: Insomnia and other sleep abnormalities are common, persistent, and, as a key component of protracted alcohol withdrawal, associated with relapse in alcohol-dependent patients. Both subjective and objective sleep measures can predict relapse; however, objective measures provide additional insight into the potential mechanisms underlying disrupted sleep. The overall, long-term objectives of the proposed research are to investigate the neurophysiologic mechanisms ~ofsleep disturbance that are associated with relapse in patients with alcohol dependence, and to target those mechanisms with medication in order to reduce relapse risk. The specific research aims are 1) to investigate three potential mechanisms of sleep disturbance in alcoholic patients with insomnia: impaired homeostatic drive, impaired circadian regulation, and brain hyperactivation; 2) to investigate short-term effects of medication on sleep and its regulatory mechanisms in alcoholics; and 3) to investigate the short-term clinical course of alcoholism as a function of baseline sleep parameters. In Study Phases I & II (Screening & Baseline; 10+ days), subjects are characterized clinically to diagnose insomnia and alcohol dependence; determine baseline values for drinking and sleeping; and rule out confounding sleep-impairing causes such as acute alcohol withdrawal, other substance use, and/or physical, mental, and other sleep disorders, e.g., sleep apnea. Phase III (Medication; 10 days), is a randomized, double-blind parallel design comparison of gabapentin vs. placebo. Phases II & III each have 7 days of monitoring with sleep logs and actigraphy, followed by 3 nights in the sleep laboratory: an adaptation night, a baseline sleep night, and a challenge night in which sleep is recorded after a 3-hour extension of prior wakefulness. Dim-light melatonin onset (DLMO), a measure of circadian phase is also assessed. Power spectral analysis is used to quantify all-night EEG activity. On each challenge night, homeostatic sleep drive is assessed by evaluating the time course and distribution of delta power in NREM sleep after delay, compared to baseline levels. Phase IV is a 2-day med taper, & Phase V (Follow-up) consists of one visit after 12 weeks to assess course of drinking. In summary, sleep disturbance in alcoholic patients reflects neurophysiologic dysfunction, increases risk of relapse, and may be amenable to pharmacotherapy. Targeting treatment to the specific sleep regulatory disturbance is likely to improve alcoholism outcomes. Relevance: Alcoholism is a devastating chronic disorder that in any one year affects -10% of adults, costs over $185 billion, and causes more than 100,000 deaths in the U.S. Despite treatment, most alcoholic patients achieve only short-term abstinence, and medically based treatment improvements are needed that target biological risk factors for relapse. Overall public health will be improved by developing science-based treatments that can augment existing, but only partially effective, treatment approaches.

项目摘要：失眠和其他睡眠异常是常见的、持续的、关键的 长期酒精戒断的组成部分，与酒精依赖患者的复发有关。两者都有 主观和客观的睡眠测量可以预测复发；然而，客观的测量提供 对睡眠中断潜在机制的更多洞察力。总体的、长期的目标 建议的研究是调查睡眠障碍的神经生理学机制，这些机制是 与酒精依赖患者的复发相关，并针对这些机制 用药以降低复发风险。具体的研究目标是：1)调查三个方面的潜力 酒精性失眠症患者睡眠障碍的机制：体内平衡驱动力受损 昼夜节律与大脑过度激活；2)研究药物对睡眠的短期影响 3)研究酒精中毒的短期临床病程 作为基线睡眠参数的函数。在研究阶段I和II(筛选和基线；10天以上)， 受试者的临床特征是诊断失眠和酒精依赖；确定基线 饮酒和睡眠的价值观；并排除急性酒精等混杂的睡眠障碍原因 戒断、其他物质使用和/或身体、精神和其他睡眠障碍，例如睡眠呼吸暂停。 第三阶段(服药；10天)，是一项随机、双盲、平行设计的加巴喷丁与 安慰剂。第二阶段和第三阶段每个阶段都有7天的睡眠记录和活动记录监测，然后是3个晚上 在睡眠实验室：适应之夜、基线睡眠之夜和挑战之夜 在之前的清醒状态延长3小时后录制。暗光褪黑素发作(DLMO)，一种衡量 昼夜节律也被评估。功率谱分析被用来量化整夜的脑电活动。在每一个上 挑战之夜，通过评估三角洲的时间进程和分布来评估动态平衡睡眠驱动力 延迟后NREM睡眠中的电量，与基线水平相比。第四阶段是为期两天的医学缩减，第五阶段 (随访)包括12周后的一次访问，以评估饮酒过程。总而言之，睡眠障碍 酒精中毒患者反映神经生理功能障碍，增加复发的风险，并可能是顺从的。 去接受药物治疗。针对特定睡眠调节障碍的靶向治疗可能会有所改善 酒精中毒的后果。相关性：酗酒是一种毁灭性的慢性疾病，任何一年都会影响到 -10%的成年人，花费超过1850亿美元，在美国导致超过10万人死亡，尽管接受了治疗， 大多数酗酒患者只能实现短期戒酒，并在药物治疗方面有所改善 需要针对复发的生物风险因素。通过发展公共卫生事业，提高公众健康水平 以科学为基础的治疗方法可以加强现有的但仅部分有效的治疗方法。