Dopamine-2 Receptor Partial Agonist for Bipolar Disorder and Alcohol Use Disorder

多巴胺 2 受体部分激动剂治疗双相情感障碍和酒精使用障碍

• 批准号: 9352266
• 负责人: E SHERWOOD BROWN
• 金额: $ 56.38万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-15 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9352266
• 关键词: Acute; Adverse effects; Agonist; Alanine Transaminase; Alcohol consumption; Alcohol-Related Disorders; Alcohols; Algorithms; Anti-Inflammatory Agents; Anti-inflammatory; Antidepressive Agents; Antipsychotic Agents; Aspartate Transaminase; Benefits and Risks; Biological Markers; Bipolar Disorder; Bipolar I; Bipolar II; Blood Glucose; Blood specimen; C-reactive protein; Clinical; Clinical Trials; Conduct Clinical Trials; DRD4 gene; Data; Depressed mood; Development; Disease; Dopamine; Dose; Double-Blind Method; Enzymes; FDA approved; Gamma-glutamyl transferase; Genetic Polymorphism; Genotype; Geographic Locations; Hamilton Rating Scale for Depression; Heavy Drinking; Hospitalization; Impulsivity; Inflammation; Inflammatory; Laboratories; Literature; Liver; Manic; Mental Depression; Mental disorders; Methods; Modeling; Monitor; Mood Disorders; Mood stabilizers; Moods; Morbidity - disease rate; Naltrexone; Outcome; Outcome Measure; Outpatients; Participant; Patient Self-Report; Patients; Persons; Pharmaceutical Preparations; Phase; Placebos; Population; Prevalence; Public Health; Publishing; Randomized; Research; Research Design; Role; Safety; Sampling; Serum; Standardization; Substance Use Disorder; Symptoms; TimeLine; Titrations; Violence; adverse outcome; alcohol abuse therapy; alcohol craving; alcohol research; alcohol use disorder; aripiprazole; atypical antipsychotic; base; blood lipid; carbohydrate-deficient transferrin; control trial; depressive symptoms; design; disability; double-blind placebo controlled trial; drinking; dual diagnosis; effective therapy; experience; inclusion criteria; inventory of depressive symptomatology; mood symptom; placebo controlled study; predicting response; primary outcome; quetiapine; receptor; response; secondary outcome; statistics

Abstract Bipolar disorder is a severe, persistent, and common psychiatric illness that is associated with a staggering 46% lifetime prevalence of alcohol-related disorders. Alcohol use disorder in patients with bipolar disorder is associated with numerous adverse consequences including increased hospitalization, poor outcome during hospitalization, violence towards self and others, and treatment nonadherence. Thus, the development of effective treatments for patients with bipolar and alcohol use disorder is a major public health concern. However, to date, few placebo-controlled trials have been conducted in patients with bipolar disorder and alcohol use disorder. Our group conducts clinical trials in persons with bipolar disorder and substance use disorders. A particularly promising medication that we have investigated is the atypical antipsychotic aripiprazole. A 12-week, randomized, double-blind, placebo-controlled study of aripiprazole is proposed in 132 outpatients with bipolar I or II disorder (depressed or mixed mood state) and alcohol use disorder, with active alcohol use. Alcohol use will be the primary outcome, with alcohol craving and mood symptoms as secondary outcomes. To reflect the diversity of our geographic region, both English- and Spanish-speaking participants will be included. The study design includes a 12-week acute phase with a maximum aripiprazole dose of 15 mg/day. A 4-week extension phase for completers with at least one heavy drinking day at week 12 will explore an aripiprazole titration up to 30 mg/day. To standardize management of other psychotropic medications (e.g. mood stabilizers, antidepressants), concomitant medication changes will be managed in both groups using a treatment algorithm. Relationships between changes in alcohol use and changes in mood will be explored. Outcome measures will include alcohol use assessed with the Timeline Followback method, Hamilton Rating Scale for Depression, Inventory of Depressive Symptomatology–Self-report, Young Mania Rating Scale, Penn Alcohol Craving Scale, as well as liver enzyme and carbohydrate deficient transferrin levels. Side effects, including those associated with antipsychotics, will be monitored. Additionally, blood samples will be obtained for genotype analysis, as well as laboratory values including blood sugar and lipid levels. A research team with extensive experience in dual diagnosis, mood disorders, clinical trials, statistics, and alcohol research will conduct the trial.

抽象的 躁郁症是一种严重，持久和常见的精神病，与 与酒精相关疾病的终生患病率惊人的46％。双极患者的饮酒障碍 疾病与许多不利后果有关，包括增加住院，差 住院期间的结果，对自我和他人的暴力行为以及不遵守治疗。那， 为双极和饮酒障碍患者开发有效治疗是一种主要的公共卫生 忧虑。但是，迄今为止，对躁郁症患者的安慰剂对照试验很少 和饮酒障碍。我们的小组在患有躁郁症和药物使用的人中进行临床试验 疾病。我们已经研究的一种特别有希望的药物是非典型抗精神病药 阿立哌唑。 在132中提出了一项为期12周的，随机的，双盲的，安慰剂对照研究的研究 患有双极I或II障碍（抑郁症或混合情绪状态）和酒精使用障碍的门诊患者 饮酒。饮酒将是主要结果，渴望酒精和情绪症状作为次要 结果。为了反映我们地理区域的多样性，包括英语和西班牙语的参与者 将包括在内。研究设计包括一个为12周的急性期，最大阿立哌唑剂量为15 毫克/天。第12周至少一个大量饮酒日的完成者为期4周的延长阶段将探索 Aripiprazole滴定最高30毫克/天。标准化其他精神药物的管理（例如 情绪稳定剂，抗抑郁药），两组都将使用 处理算法。将探讨酒精使用变化与情绪变化之间的关系。 结果指标将包括使用时间轴后卫方法评估的饮酒，汉密尔顿评级 抑郁症的比例，抑郁症状学 - 自我报告，年轻躁狂评级量表，宾夕法尼亚 酒精渴望量表，以及肝酶和碳氢化物缺乏转铁蛋白水平。副作用， 包括与抗精神病药相关的那些，将受到监控。另外，将获得血液样本 用于基因型分析以及包括血糖和脂质水平在内的实验室值。一个研究团队 在双重诊断，情绪障碍，临床试验，统计和酒精研究方面的丰富经验将 进行试验。