权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Optimizing Pharmacotherapy for Bipolar Alcoholics

优化双相酗酒者的药物治疗

基本信息

批准号：
7778938
负责人：
IHSAN M SALLOUM
金额：
$ 48.23万
依托单位：
UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-03-01 至 2013-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7778938
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 Depressed mood 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 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

项目摘要

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的修订版，其重点是评估一个有前景的酒精中毒合并双相情感障碍患者的药物干预未得到满足的主要治疗需求。我们提出了双盲、安慰剂对照、随机、平行的测试阿片类拮抗剂纳曲酮和抗点燃药联合的疗效的团体试验心境稳定剂丙戊酸盐与单用丙戊酸盐治疗合并症的疗效比较酗酒和躁郁症。在美国有近200万受影响的个人，共同患有酒精中毒而双相情感障碍是一个重大的公共卫生挑战。这种共病与严重的残疾、发病率和高自杀风险。令人惊讶的是，几乎没有研究，而且有限对于这一高危人群，存在循证治疗选择。我们最近出版的随机化丙戊酸盐对双相酒精患者疗效的对照试验仍然是迄今为止唯一完成的此类研究(ARCH 《普通精神病学》2005；62：37-45)。这项研究的结果表明丙戊酸盐比丙戊酸盐有优势安慰剂在减少大量酒精使用中的作用。然而，丙戊酸盐治疗的受试者中有相当大比例继续以滥用的水平饮酒。有令人信服的理论和不断积累的临床有证据表明丙戊酸盐和纳曲酮联合应用可能具有协同作用。酗酒。丙戊酸盐，可以通过稳定病理情绪状态来减少酒精使用，并通过抑制急性和长期戒酒的负面强化作用。相反，纳曲酮可以通过降低饮酒欲望来减少酒精的积极强化作用酒精。我们的开放、随机、先导研究的结果表明丙戊酸盐+纳曲酮疗效显著。促进戒酒，减少饥饿感，改善情绪和功能。都是在患有严重精神病的患者中尤其令人满意的结果。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。我们提出以下建议目的：1)比较纳曲酮联合丙戊酸盐与丙戊酸盐和安慰剂治疗慢性前列腺炎的疗效。 DSM-IV酒精依赖和共病双相I型障碍患者的治疗；2)评估原发与继发性酒精中毒、双相亚型(抑郁与躁狂/混合亚型)的影响，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因素；3)评估服药依从性、情绪症状的持续性和社会支持作为中介的影响酒精使用结果。104名病情严重且经常饮酒的成年受试者在为期3个月的双盲研究和3个月的随访中，进行了随机和前瞻性的随访相位。所有受试者都将接受旨在提高治疗依从性的个别咨询。