Optimizing Pharmacotherapy for Bipolar Alcoholics

优化双相酗酒者的药物治疗

• 批准号: 7576202
• 负责人: IHSAN M SALLOUM
• 金额: $ 51.36万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7576202
• 关键词: Abstinence; Acute; Address; Adult; Advocate; Affect; Age of Onset; Alcohol consumption; Alcohol dependence; Alcohol withdrawal syndrome; Alcoholism; Alcohols; Anxiety Disorders; Applications Grants; Area; Bipolar Disorder; Clinical; Combined Modality Therapy; Comorbidity; Controlled Study; Counseling; DSM-IV; Diagnosis; Disease; Double-Blind Method; Drug Addiction; Evaluation; Evidence based treatment; Frequencies; General Population; Hand; Heavy Drinking; Hospitalization; Individual; Intervention; Maintenance; Major Depressive Disorder; Manic; Mediating; Mediator of activation protein; Mental disorders; Moods; Morbidity - disease rate; NIH Program Announcements; Naltrexone; Naltrexone hydrochloride; Narcotic Antagonists; National Institute of Drug Abuse; National Institute of Mental Health; National Institute on Alcohol Abuse and Alcoholism; Opioid; Outcome; Patients; Pharmaceutical Preparations; Pharmacotherapy; Phase; Pilot Projects; Placebo Control; Placebos; Population; Psychiatry; Psychopathology; Public Health; Publishing; Randomized; Randomized Controlled Trials; Recruitment Activity; Recurrence; Relapse; Research; Research Personnel; Research Proposals; Rest; Review Literature; Schizophrenia; Severities; Social support; Stabilizing Agents; Stress; Substance Use Disorder; Substance abuse problem; Symptoms; Syndrome; System; Testing; Therapeutic; Time; Valproate Sodium; Woman; Work; addiction; alcohol abstinence; alcohol abuse therapy; alcohol effect; base; compliance behavior; craving; depressed; depressive symptoms; design; disability; disorder later incidence prevention; drinking; dual diagnosis; effective therapy; efficacy testing; efficacy trial; experience; follow-up; high risk; improved; medication compliance; men; mortality; open label; placebo controlled study; problem drinker; prospective; response; suicidal risk; therapy adherence; treatment adherence; treatment response; treatment strategy; valproate

This is a revision of application 1 R01 AA015385-01 that focuses on the evaluation of a promising pharmacological intervention for patients with alcoholism complicated by comorbid bipolar disorder, an area of major unmet treatment needs. We propose a double-blind, placebo-controlled, randomized, parallel group trial to test the efficacy of the combination of the opioid antagonist, naltrexone, and the antikindling mood stabilizing agent valproate, versus valproate alone, in the treatment of patients with comorbid alcoholism and bipolar disorder. With nearly two million affected individuals in the U.S., comorbid alcoholism and bipolar disorder represents a significant public health challenge. This comorbidity is associated with severe disability, morbidity, and heightened risk for suicide. Surprisingly, little research and limited evidence-based treatment options exist for this high-risk population. Our recently published randomized controlled trial of valproate efficacy in bipolar alcoholics remains the only such study completed to date (Arch Gen Psychiatry 2005; 62:37-45). The results of that study suggested an advantage of valproate over placebo in reducing heavy alcohol use. However, a significant proportion of valproate treated subjects continued to consume alcohol at abusive levels. There are compelling theoretical, and accruing clinical evidence suggesting that combined valproate + naltrexone may have synergistic effects on decreasing alcohol use. Valproate, may decrease alcohol use by stabilizing pathological mood states, and by dampening the negative reinforcing effects of acute and protracted alcohol withdrawal. Conversely, naltrexone would decrease the positive reinforcing effects of alcohol by decreasing the desire to drink alcohol. The results of our open-label, randomized, pilot study suggests that valproate + naltrexone robustly enhances abstinence from alcohol, decreases craving, and improves mood and functioning. All are particularly desirable outcomes in patients suffering from severe psychopathology. These results provide compelling evidence for testing this approach in a randomized, controlled trial. We propose the following aims: 1) Examine the efficacy of naltrexone plus valproate compared to valproate and placebo in the treatment of patients with DSM-IV alcohol dependence and comorbid bipolar I disorder; 2) Assess the effects of primary vs. secondary alcoholism, bipolar subtype (depressed vs. manic/mixed subtype), and the presence of another substance use disorder (SUD) as moderators of alcohol use outcome; 3) Assess the effects of medication compliance, persistence of mood symptoms or SUD, and social support as mediators of alcohol use outcome. One hundred and four acutely ill and actively drinking adult subjects will be randomized and prospectively followed during a 3-month double-blind study, and a 3-month follow-up phase. All subjects will receive individual counseling designed to enhance treatment adherence.

这是应用程序1 R01 AA015385-01的修订，重点是评估有希望的 酗酒患者的药理干预因合并症躁郁症而复杂（一个地区） 主要未满足的治疗需求。我们提出了双盲，安慰剂对照，随机，平行的 小组试验测试阿片类药物拮抗剂，纳曲酮和抗鉴定的疗效 在合并症患者的治疗中，情绪稳定剂量丙戊酸酯，单独与丙戊酸盐 酒精中毒和躁郁症。在美国有近200万受影响的人，合并症酒精中毒 躁郁症是一项重大的公共卫生挑战。这种合并症与 严重的残疾，发病率和自杀风险增加。令人惊讶的是，研究很少，有限 这个高危人群存在基于证据的治疗选择。我们最近出版的随机出版 双极酒精中毒的丙戊酸疗效的对照试验仍然是迄今唯一完成的研究（Arch Gen Psychiatry 2005; 62：37-45）。该研究的结果表明丙戊酸的优势超过了 安慰剂减少大量饮酒。但是，丙戊酸酯处理的受试者很大一部分 继续在滥用水平上食用酒精。有令人信服的理论和临床 证据表明丙戊酸 +纳曲酮组合可能对减少有协同作用 饮酒。丙戊酸盐，可以通过稳定病理情绪状态和通过 抑制急性和旷日持久的酒精戒断的负增强作用。反过来， 纳曲酮通过减少饮酒的欲望来降低酒精的积极增强作用 酒精。我们的开放标签，随机，试点研究的结果表明丙戊酸 +纳曲酮稳健 提高酒精的禁欲，减少渴望并改善情绪和功能。所有人都是 患有严重心理病理学的患者特别是理想的结果。这些结果提供了 在随机对照试验中测试这种方法的令人信服的证据。我们提出以下内容 目的：1）检查纳曲酮和丙戊酸的疗效与丙戊酸和安慰剂相比 DSM-IV酒精依赖性和合并双相情感障碍患者的治疗； 2）评估 初级酗酒，双极亚型（抑郁症与躁狂/混合亚型）的影响，以及 存在另一种药物使用障碍（SUD）作为饮酒结果的主持人； 3）评估 药物依从性，情绪症状或SUD的持久性以及作为调解人的社会支持的影响 酒精使用结果。一百四个急性病，积极饮用成人受试者 在3个月的双盲研究中随机和前瞻性遵循，并进行了3个月的随访 阶段。所有受试者都将获得旨在增强治疗依从性的个人咨询。