Topiramate for co-occurring alcohol use and bipolar disorders in adolescents

托吡酯治疗青少年同时发生的饮酒和双相情感障碍

• 批准号: 7386326
• 负责人: Melissa P Delbello
• 金额: $ 22.43万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-15 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7386326
• 关键词: Abstinence; Adherence; Adolescence; Adolescent; Adult; Affective; Age; Alcohol abuse; Alcohol consumption; Alcohol dependence; Alcohol or Other Drugs use; Alcoholism; Antiepileptic Agents; Bipolar Disorder; Clinical Trials; Cognitive Therapy; Condition; Controlled Study; Data; Dependence; Disease; Dopamine; Double-Blind Method; Exhibits; Future; Goals; Grant; Heavy Drinking; High Prevalence; Individual; Intervention; Knowledge; Lead; Left; Life; Manic; Manuals; Medical; Midbrain structure; Mind; Moods; Morbidity - disease rate; Numbers; Outcome; Outcome Measure; Patients; Pharmacological Treatment; Pilot Projects; Placebo Control; Placebos; Public Health; Randomized; Rate; Recovery; Recurrence; Refractory; Relapse; Research; Rewards; Sampling; Score; Standards of Weights and Measures; Suicide; Symptoms; Time; United States Food and Drug Administration; Week; Work; alcohol prevention; alcohol relapse; alcohol use disorder; base; craving; day; depressive symptoms; design; drinking; mortality; neurotransmission; quetiapine; suicidal risk; topiramate; underage drinking

DESCRIPTION (provided by applicant): There is a bidirectional overlap between alcohol use and bipolar disorders, with a particularly severe illness course for individuals with both conditions. Specifically, patients with co-occurring alcohol use and bipolar disorders exhibit slower recovery, worse treatment adherence, increased suicidality, and higher rates of relapse of both illnesses compared with individuals with either illness alone. Adolescents with co-occurring alcohol use and bipolar disorders have a poorer outcome of both disorders than even occurs in similar adults. However, adolescents with co-occurring alcohol use and bipolar disorders are routinely excluded from controlled pharmacological treatment studies of either condition. Thus, clinicians have no evidence-based guidance on how to treat these adolescents. Research on the treatment of adolescents with co-occurring alcohol use and bipolar disorders is critical because adolescence may be the best time to interrupt the progression of these illnesses into lifelong alcohol dependence and treatment refractory bipolar disorder, both of which are associated with significant morbidity and mortality. Topiramate is an antiepileptic agent with a dual mechanism of action that leads to reduction of midbrain dopamine neurotransmission, and therefore, may be useful to reduce the reward and craving associated with alcohol use. Indeed, topiramate has been found to be safe and efficacious for reducing alcohol consumption and craving in adults. Our preliminary work suggests that topiramate also may be effective for the treatment of mania in adolescents with bipolar disorder. However, the efficacy of topiramate as a treatment for alcohol use disorders in bipolar adolescents has not been explored. Therefore, the goal of this two-year exploratory R21 proposal is to conduct a double-blind placebo-controlled, 12-week pilot study examining the efficacy and tolerability of topiramate as a treatment for reducing alcohol consumption in adolescents with co-occurring alcohol use and bipolar disorders. In order to accomplish this goal, we will randomize a total of 50 bipolar adolescents (ages 12-20 years) with an active alcohol use disorder to topiramate or placebo. All adolescents will also receive quetiapine and a manual-driven Cognitive Behavioral Therapy, as standard treatments for bipolar and alcohol use disorders, respectively. Change in alcohol consumption is the primary outcome measure. We will also examine the efficacy of topiramate in combination with quetiapine for the treatment of manic and depressive symptoms and explore the relationship between changes in alcohol use and mood symptoms. The proposed study would be the first to examine a pharmacological intervention for the treatment of alcohol consumption in adolescents with alcohol use and bipolar disorders. The preliminary data from this pilot project will inform and guide the design of future larger, more definitive, controlled studies of topiramate as a treatment for adolescent alcohol use disorders.

描述（由申请人提供）：饮酒和双相情感障碍之间存在双向重叠，患有这两种疾病的个体的病程尤其严重。具体来说，与单独患有其中一种疾病的患者相比，同时患有酗酒和双相情感障碍的患者表现出恢复较慢、治疗依从性较差、自杀倾向增加以及两种疾病的复发率较高。同时患有酗酒和双相情感障碍的青少年的两种疾病的结果甚至比类似的成年人更差。然而，同时患有酗酒和双相情感障碍的青少年通常被排除在这两种疾病的对照药物治疗研究之外。因此，临床医生对于如何治疗这些青少年没有基于证据的指导。对同时患有酒精使用和双相情感障碍的青少年的治疗研究至关重要，因为青春期可能是阻止这些疾病发展为终身酒精依赖和治疗难治性双相情感障碍的最佳时机，这两种疾病都与显着的发病率和治疗效果相关。死亡。托吡酯是一种抗癫痫药，具有双重作用机制，可减少中脑多巴胺神经传递，因此可能有助于减少与饮酒相关的奖赏和渴望。事实上，托吡酯已被发现对于减少成年人的饮酒和渴望是安全有效的。我们的初步工作表明托吡酯也可能有效治疗患有双相情感障碍的青少年的躁狂症。然而，托吡酯治疗双相情感障碍青少年酒精使用障碍的疗效尚未被探索。因此，这项为期两年的探索性 R21 提案的目标是进行一项双盲安慰剂对照、为期 12 周的试点研究，检验托吡酯作为减少同时饮酒的青少年饮酒量的治疗方法的有效性和耐受性和双相情感障碍。为了实现这一目标，我们将总共 50 名患有活动性酒精使用障碍的躁郁症青少年（年龄 12-20 岁）随机分为托吡酯或安慰剂。所有青少年还将接受喹硫平和手动认知行为疗法，分别作为双相情感障碍和酒精使用障碍的标准治疗方法。酒精消费量的变化是主要的结果指标。我们还将研究托吡酯与喹硫平联合治疗躁狂和抑郁症状的疗效，并探讨饮酒变化与情绪症状之间的关系。拟议的研究将是第一个检查药物干预治疗青少年饮酒和双相情感障碍的饮酒的研究。该试点项目的初步数据将为未来更大规模、更明确的托吡酯治疗青少年酒精使用障碍的对照研究的设计提供信息和指导。