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

摘要 双相情感障碍是一种严重的、持续的和常见的精神疾病，与 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 精神障碍与许多不良后果有关，包括增加住院、贫穷 住院期间的结局，对自己和他人的暴力，以及不坚持治疗。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健康 担忧。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身上进行。 和酒精使用障碍。我们小组在双相情感障碍和药物滥用患者身上进行临床试验 精神错乱。我们研究的一种特别有前景的药物是非典型抗精神病药物 阿立哌唑。 阿立哌唑的一项为期12周的随机、双盲、安慰剂对照研究于132年被提出。 患有双相I或II障碍(抑郁或混合情绪状态)和酒精使用障碍的门诊患者，有活跃 酗酒。饮酒将是主要结果，其次是酒精渴求和情绪症状 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。对于在第12周至少有一天大量饮酒的完成者，将进行为期4周的延长阶段 阿立哌唑滴定高达30毫克/天。为了规范其他精神药物的管理(例如 情绪稳定剂，抗抑郁剂)，伴随的药物变化将在两组中使用 处理算法。本课程将探讨饮酒习惯的变化与情绪变化之间的关系。 结果衡量标准将包括用时间线回溯方法、哈密尔顿评级评估酒精使用情况 抑郁量表，抑郁症状自评量表，宾夕法尼亚大学青年躁狂评定量表 酒精渴求量表，以及肝脏酶和碳水化合物缺乏的转铁蛋白水平。副作用， 包括那些与抗精神病药物有关的药物，将受到监测。此外，还将采集血液样本 用于基因分析，以及包括血糖和血脂水平在内的化验值。一个研究团队，拥有 在双重诊断、情绪障碍、临床试验、统计学和酒精研究方面有丰富经验 进行审判。

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.