Optimizing Pharmacotherapy for Bipolar Alcoholics

优化双相酗酒者的药物治疗

• 批准号: 7432310
• 负责人: IHSAN M SALLOUM
• 金额: $ 40.45万
• 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/7432310
• 关键词: Abstinence; Acute; Address; Adherence; 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; Depressed mood; Diagnosis; Disease; Double-Blind Method; Drug Addiction; Evaluation; Evidence based treatment; Frequencies; General Population; Hand; Heavy Drinking; Hospitalization; Individual; Intervention; Label; 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; Rate; Recruitment Activity; Recurrence; Relapse; Research; Research Personnel; Research Proposals; Rest; Review Literature; Risk; Schizophrenia; Severities; Social support; Stabilizing Agents; Stress; Substance Use Disorder; Substance abuse problem; Symptoms; Syndrome; System; Testing; Therapeutic; Time; Valproate Sodium; Week; Woman; Work; addiction; alcohol abstinence; alcohol abuse therapy; alcohol effect; base; compliance behavior; craving; day; depressive symptoms; design; desire; disability; disorder later incidence prevention; drinking; dual diagnosis; efficacy trial; experience; follow-up; improved; medication compliance; men; mortality; placebo controlled study; problem drinker; prospective; response; suicidal risk; therapy adherence; 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.

这是申请1 R 01 AA 015385 -01的修订版，重点是评价一种有前景的 酒精中毒合并双相情感障碍共病患者的药物干预，一个领域 未满足的治疗需求。我们提出了一个双盲，安慰剂对照，随机，平行 测试阿片类拮抗剂纳洛酮和抗点燃药物组合的功效的组试验 情绪稳定剂丙戊酸盐与丙戊酸盐单药治疗共病患者的比较 酗酒和躁郁症美国有近两百万人受影响，共病酒精中毒 躁郁症是一个重大的公共卫生挑战。这种并发症与 严重残疾、发病率和自杀风险增加。令人惊讶的是，很少有研究和有限的 针对这一高危人群，存在循证治疗方案。我们最近发表的随机 丙戊酸盐在双相性酗酒者中疗效的对照试验仍然是迄今为止唯一完成的此类研究（Arch Gen Psychiatry 2005; 62：37-45）。该研究的结果表明，丙戊酸盐优于 安慰剂减少重度酒精使用。然而，相当比例的丙戊酸盐治疗受试者 继续滥用酒精有令人信服的理论，并积累临床 有证据表明，丙戊酸盐+纳曲酮联合用药可能对降低 饮酒丙戊酸盐可能通过稳定病理性情绪状态和通过 抑制急性和长期酒精戒断的负面强化作用。相反地， 纳洛酮通过降低饮酒欲望， 酒精我们的开放标签、随机、初步研究结果表明，丙戊酸盐+纳曲酮 增强戒酒，减少渴望，改善情绪和功能。都是 在患有严重精神病理学的患者中特别期望的结果。这些结果提供 在随机对照试验中测试这种方法的有力证据。我们提议下列 目的：1）检查纳洛酮+丙戊酸盐与丙戊酸盐和安慰剂相比在以下患者中的疗效： DSM-IV酒精依赖和共病双相I型障碍患者的治疗; 2）评估 原发性与继发性酒精中毒、双相亚型（抑郁与躁狂/混合亚型）以及 存在另一种物质使用障碍（SUD）作为酒精使用结果的调节剂; 3）评估 药物依从性、情绪症状或SUD的持续性和社会支持作为中介的影响 酒精使用的结果。104名患有急性疾病并主动饮酒的成年受试者将被 在为期3个月的双盲研究和为期3个月的随访期间进行随机化和前瞻性随访 相位所有受试者将接受旨在提高治疗依从性的个体化咨询。