Effect of Prazosin on Alcohol Craving, Stress Dysregulation and Alcohol Relapse

哌唑嗪对酒精渴望、压力失调和酒精复吸的影响

基本信息

批准号：
8297322
负责人：
Helen Cecilia Fox
金额：
$ 54.48万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-01 至 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8297322
关键词：
Address Adrenal Glands Adrenergic Antagonists Aftercare Alcohol abuse Alcohol consumption Alcohol dependence Alcoholism Alcohols American Anxiety Anxiety Disorders Basic Science Blood Pressure Cessation of life Characteristics Chronic Clinical Clinical Research Comorbidity Corticotropin Cues Data Disease Double-Blind Method Drug usage Exposure to FDA approved Family history of Gender Health Care Costs Heavy Drinking Hospitals Human Hydrocortisone Imagery Individual Laboratories Laboratory Study Light Measures Methods Modeling Norepinephrine Outcome Outcome Measure Outcome Study Pathway interactions Patients Pharmaceutical Preparations Placebo Control Placebos Play Prazosin Randomized Rattus Recruitment Activity Relative (related person)Research Risk Role Sleep Smoking Stress Surgeon Symptoms Traumatic Stress Disorders Treatment outcome Up-Regulation Woman Work alcohol abuse therapy alcohol craving alcohol cue alcohol misuse alcohol relapse alcohol seeking behavior alcoholism therapy base craving efficacy testing executive function follow-up hypothalamic-pituitary-adrenal axis improved men negative mood noradrenergic problem drinker reduced alcohol use secondary outcome treatment effect

项目摘要

ABSTRACT This revised application proposes to conduct a randomized, double blind, placebo-controlled combined laboratory and clinical outcome study to test the efficacy of Prazosin (PZ) in decreasing alcohol craving, anxiety, stress dysregulation and alcohol use outcomes in treatment seeking alcohol dependent (AD) individuals with and without current anxiety disorders (+Anx/-Anx). In previous research we've shown that laboratory exposure to stress and alcohol cues increases alcohol craving, anxiety and stress dysregulation, which in turn, are predictive of subsequent alcohol relapse outcomes. Prazosin, an alpha-1 adrenergic antagonist, known to decrease central norepinephrine and CRF upregulation, decreases stress-induced alcohol reinstatement and alcohol consumption in both dependent rats and in a preliminary study with alcoholic patients. However, the specific mechanisms by which PZ may be decreasing alcohol consumption in humans is not understood. Our preliminary data show that PZ relative to Placebo (PL) decreases stress and cue- induced alcohol craving, anxiety and stress dysregulation in AD individuals, and that such decreases are more pronounced in AD individuals with current anxiety disorders than those without such comorbidity. Thus, in light of previous research and our preliminary findings, we propose a 5-year study that will recruit 150 AD individuals (evenly split by those with and without any current anxiety disorders) to participate in a randomized, double blind, placebo-controlled 12-week clinical laboratory and outcome study. The following specific aims will be addressed: 1) To evaluate the effects of PZ (16 mg, tid) on stress and cue-induced alcohol craving and anxiety, stress dysregulation in the laboratory in AD patients with and without current anxiety disorders; (2)To evaluate the effects of 16mg PZ on alcohol craving, anxiety and stress dysregulation in AD patients with current anxiety disorders as compared to those without anxiety disorders; (3) To determine the efficacy of 12- week PZ treatment on primary alcohol use outcomes, and secondary outcomes including alcohol craving, negative mood symptoms, smoking and sleep; (4) To assess the efficacy of 12-week PZ versus PL treatment on primary alcohol use and secondary outcomes in alcoholics with/without any current anxiety disorders. (5) To examine one-month post-treatment follow-up alcohol use outcomes for enduring short term treatment effects. The role of patient characteristics and laboratory-based craving and stress dysregulation in predicting alcohol treatment outcome will also be explored. If the proposed hypotheses are supported, it will provide evidence for efficacy of Prazosin as a medication for alcoholism, particularly for those with co-morbid anxiety disorders.

摘要该修订后的应用建议进行随机，双盲，安慰剂对照的合并实验室和临床结果研究，以测试prazosin（PZ）减少酒精饮酒，焦虑，压力失调和酒精饮酒结果在治疗中寻求依赖酒精（AD）患者（AD）患者与当前焦虑症和当前焦虑症（+Ancor Ancearters（+Ancearders）（+Ancearders）（+Ancearders）（+Ancearders）（+Ancearders）（+Ancearderss）（+Ancearders）（+Ancearders）（+Ancress/-Ancanx）（+Ancriant-Ancranders）（+Ancress/-Ancanx）（+Ancress/-Ancanx）。在先前的研究中，我们已经表明，实验室承受压力和酒精提示会增加酒精的渴望，焦虑和压力失调，这反过来又可以预测随后的酒精复发结果。普唑嗪是一种α-1肾上腺素能拮抗剂，已知可降低中央去甲肾上腺素和CRF上调，可降低依赖大鼠的应激诱导的酒精恢复和酒精消耗，并在对酒精患者的初步研究中降低了胁迫诱导的饮酒。但是，尚不了解PZ可能降低人类饮酒的特定机制。我们的初步数据表明，相对于安慰剂（PL）的PZ降低了压力和提示诱发的AD个体中的酒精渴望，焦虑和压力失调，并且在当前患有焦虑症患者的AD患者中，这种减少比没有这种合并症的AD焦虑症更为明显。因此，鉴于以前的研究和我们的初步研究结果，我们提出了一项为期5年的研究，该研究将招募150个公元个人（由有或没有的人平均分配当前的任何焦虑症）参加了一项随机，双盲，安慰剂对照的12周临床实验室和结果研究。将解决以下具体目的：1）评估PZ（16 mg，TID）对压力和提示引起的酒精渴望和焦虑的影响，在患有和没有当前焦虑症的AD患者中实验室的压力失调；（2）与没有焦虑症的患者相比，评估16mg PZ对当前焦虑症患者的饮酒，焦虑和压力失调的影响；（3）确定12周PZ治疗对主要酒精使用结果的功效，以及包括饮酒，消极情绪症状，吸烟和睡眠在内的次要结果；（4）评估12周PZ与PL治疗对初次饮酒的功效和患有/没有任何当前焦虑症的酒精中毒的次要结果。（5）检查治疗后一个月的随访饮酒结果，以忍受短期治疗效果。还将探索患者特征和基于实验室的渴望和压力失调在预测酒精治疗结果中的作用。如果支持所提出的假设，它将为prazosin作为酒精中毒药物的功效提供证据，特别是对于患有焦虑症的人。