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: 9522094
• 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/9522094
• 关键词: Acute; Adverse effects; 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; 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 双相情感障碍是一种严重、持续且常见的精神疾病，与 酒精相关疾病的终生患病率为 46%，令人震惊。双相情感障碍患者的酒精使用障碍 该疾病与许多不良后果相关，包括住院率增加、贫困 住院期间的结果、对自己和他人的暴力以及治疗不依从。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大的公共卫生事业 忧虑。然而，迄今为止，很少有针对双相情感障碍患者进行的安慰剂对照试验 和酒精使用障碍。我们小组对双相情感障碍和药物滥用患者进行临床试验 失调。我们研究的一种特别有前途的药物是非典型抗精神病药 阿立哌唑。 132 提出了一项为期 12 周、随机、双盲、安慰剂对照的阿立哌唑研究 患有 I 型或 II 型双相情感障碍（抑郁或混合情绪状态）和酒精使用障碍且活动活跃的门诊患者 酒精的使用。饮酒将是主要结果，其次是对酒精的渴望和情绪症状 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参与者 将被包括在内。研究设计包括为期 12 周的急性期，阿立哌唑最大剂量为 15 毫克/天。对于第 12 周至少有一天酗酒的完成者，将探讨为期 4 周的延长阶段 阿立哌唑滴定至 30 mg/天。规范其他精神药物的管理（例如 情绪稳定剂、抗抑郁药），同时药物的改变将在两组中使用 治疗算法。将探讨饮酒变化与情绪变化之间的关系。 结果衡量标准将包括使用时间线追踪方法、汉密尔顿评级评估饮酒情况 抑郁量表、抑郁症状量表 - 自我报告、年轻躁狂评定量表、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相关的药物，将受到监测。此外，还将获取血液样本 用于基因型分析以及实验室值，包括血糖和血脂水平。一个研究团队与 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。