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: 7614263
• 负责人: Melissa P Delbello
• 金额: $ 18.53万
• 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 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7614263
• 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; 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; Outcome; Outcome Measure; Patients; Pharmacological Treatment; Pilot Projects; Placebo Control; Placebos; Public Health; Randomized; Recovery; Recurrence; Refractory; Relapse; Research; Rewards; Sampling; Suicide; Symptoms; Time; United States Food and Drug Administration; Work; alcohol prevention; alcohol relapse; alcohol use disorder; cognitive behavior therapy; craving; depressive symptoms; design; drinking; effective therapy; evidence base; mortality; neurotransmission; primary outcome; quetiapine; standard care; suicidal risk; topiramate; treatment adherence; 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）：酒精使用和双相情感障碍之间存在双向重叠，对这两种情况的人来说，疾病特别严重。具体而言，与仅患有任何一种疾病的人相比，同时发生的酒精使用和双相性疾病的患者表现出较慢的康复，较差的治疗依从性，增加的自杀性和两种疾病复发率的较高。同时发生的酒精使用和双相情感障碍的青少年的两种疾病的结果都比在类似成年人中差的差。但是，经常将同时发生的酒精使用和双相性疾病的青少年排除在两种疾病的受控药理治疗研究之外。因此，临床医生没有关于如何治疗这些青少年的循证指导。关于同时发生饮酒和躁郁症的青少年治疗的研究至关重要，因为青春期可能是中断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，这两者都与显着的发病率和死亡率相关。托吡酯是一种具有双重作用机理的抗癫痫剂，可减少中脑多巴胺神经传递，因此可能有助于减少与酒精使用相关的奖励和渴望。实际上，已经发现托吡酯可以安全有效地减少成人的饮酒和渴望。我们的初步工作表明，托吡酯也可能有效地治疗双相情感障碍青少年的躁狂症。然而，尚未探索托吡酯作为对双极青少年酒精使用障碍的治疗方法的疗效。因此，这项为期两年的探索性R21提案的目的是进行一项双盲安慰剂对照，为期12周的试点研究，研究了托托乳木酯的疗效和耐受性，作为减少同时发生酒精使用和双极疾病的青少年饮酒的一种治疗方法。为了实现这一目标，我们将对托吡酯或安慰剂进行积极的饮酒障碍，将总共50个双相青少年（12-20岁）随机。所有青少年还将分别接受喹硫平和手动驱动的认知行为疗法，分别作为双极和酒精使用障碍的标准治疗方法。饮酒的变化是主要的结果指标。我们还将检查托吡酯与喹硫平对躁狂和抑郁症状的治疗的功效，并探索酒精使用变化与情绪症状的变化之间的关系。拟议的研究将是第一个研究药物干预措施，用于治疗酒精饮酒和双相情感障碍的青少年饮酒。该试点项目的初步数据将为您的未来更大，更确定的，更明确的对照研究的设计提供信息，以培育托吡酯作为青少年饮酒障碍的治疗方法。