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: 9976319
• 负责人: E SHERWOOD BROWN
• 金额: $ 47.56万
• 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 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9976319
• 关键词: Acute; Agonist; Alanine Transaminase; Alcohol consumption; Alcohol-Related Disorders; Alcohols; Algorithms; Antidepressive Agents; Antiinflammatory Effect; 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; 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; placebo controlled trial; predicting response; primary outcome; quetiapine; receptor; response; safety outcomes; secondary outcome; side effect; 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.

摘要 双相情感障碍是一种严重、持续和常见的精神疾病， 酒精相关疾病的终生患病率高达46%。双相情感障碍患者的酒精使用障碍 疾病与许多不良后果有关，包括住院率增加， 住院期间的结果，对自己和他人的暴力，以及治疗不依从性。因此 为双相情感障碍和酒精使用障碍患者开发有效的治疗方法是一项重要的公共卫生 关心然而，迄今为止，很少有安慰剂对照试验在双相情感障碍患者中进行 和酒精使用障碍我们的小组在双相情感障碍和物质使用者中进行临床试验 紊乱一个特别有前途的药物，我们已经调查是非典型抗精神病药 阿立哌唑。 一项为期12周、随机、双盲、安慰剂对照的阿立哌唑研究在132 患有双相I型或II型障碍（抑郁或混合情绪状态）和酒精使用障碍的门诊患者， 饮酒酒精使用将是主要结果，酒精渴望和情绪症状是次要结果 结果。为了反映我们地理区域的多样性，讲英语和西班牙语的与会者 将包括在内。研究设计包括12周的急性期，最大阿立哌唑剂量为15 mg/天。对于在第12周至少有一天重度饮酒的完成者，将进行为期4周的扩展阶段， 阿立哌唑滴定至30 mg/天。规范其他精神药品的管理。 情绪稳定剂、抗抑郁药），两组的伴随用药变化将使用 处理算法将探讨酒精使用变化与情绪变化之间的关系。 结果测量将包括使用时间轴随访方法评估的酒精使用情况，汉密尔顿评分 抑郁量表、抑郁症状自评量表、Young躁狂评定量表，宾夕法尼亚大学 酒精渴望量表，以及肝酶和碳水化合物缺乏转铁蛋白水平。副作用， 包括与抗精神病药物有关的药物。此外，还将采集血样 用于基因型分析，以及包括血糖和血脂水平的实验室值。一个研究小组， 在双重诊断、情绪障碍、临床试验、统计学和酒精研究方面的丰富经验将 进行审判。