Topiramate for Co-occurring Cannabis Use and Bipolar Disorders in Adolescents

双相情感障碍和大麻使用障碍之间存在双向重叠，特别是 两种情况下的严重疾病课程。具体而言，患有双相情感障碍和 大麻使用障碍显示出两种疾病的复发率都高于任何一种疾病的患者。 疾病独自同时使用大麻和双相情感障碍的青少年的结果较差， 这两种疾病甚至比发生在类似的成年人，并有更高的风险发展其他物质 使用障碍。然而，患有双相情感障碍和大麻使用障碍的青少年通常被排除在 两种情况的对照药物治疗研究。因此，临床医生没有证据- 指导如何治疗这些青少年。共沉淀法处理废水的研究 发生躁郁症和大麻使用障碍是至关重要的，因为青春期可能是最好的时间， 阻止这些疾病发展为终身物质依赖和治疗难治性 双相情感障碍，两者都与显著的发病率和死亡率相关。 托吡酯是一种具有双重作用机制的抗癫痫药物，可导致癫痫发作减少。 中脑多巴胺神经传递，因此，可能有助于减少奖励和渴望 与大麻使用有关。最近，托吡酯已被发现是安全和有效的减少 酒精和可卡因的消费和成年人的渴望。我们的初步研究表明，托吡酯也 可能对治疗青少年双相情感障碍的躁狂症有效。然而， 尚未探索托吡酯作为双相青少年大麻使用障碍的治疗。 因此，本提案的目标是进行一项为期16周的双盲安慰剂对照初步研究 研究托吡酯作为减少大麻消费的治疗的有效性和耐受性， 患有双相情感障碍和大麻使用障碍的青少年。这项建议的目的是一贯的 根据RFA-DA-06-002的目标，其中包括进行“药物治疗的试点临床试验， 物质相关疾病”。我们将随机抽取90名患有双相情感障碍的青少年， 使用托吡酯或安慰剂治疗。所有的青少年也将获得quetiabelanda 一次激励性访谈，然后是手动驱动的依从性增强疗法， 躁狂症和大麻使用障碍的标准化治疗。大麻的变化 消费是主要的结果测量。我们还将检查托吡酯在以下方面的疗效： 联合奎替利治疗躁狂症状，并探讨其与 大麻使用，情绪症状和其他物质使用的变化。拟议的研究将是第一个 研究治疗双相情感障碍患者大麻使用障碍的药物干预 青少年。该项目的初步数据为未来更大、更先进的建筑设计提供了信息和指导。 托吡酯治疗青少年物质使用障碍的确定性对照研究

There is a bidirectional overlap between bipolar and cannabis use disorders, with a particularly severe illness coursefor individuals with both conditions. Specifically, patients with co-occurring bipolar and cannabis use disorders exhibit higher relapse rates of both illnesses compared with individuals witheither illness alone. Adolescents with co-occurring cannabis use and bipolar disorders have a poorer outcome of both disorders than even occurs in similar adults and have an elevated risk of developing othersubstance use disorders. However, adolescents with bipolar and cannabis use disorders are routinely excludedfrom controlled pharmacological treatment studies of either condition. Thus, clinicians are left with noevidence- based guidance on how to treat these adolescents. Researchon the treatment of adolescentswith co- occurring bipolar and cannabis use disorders is critical because adolescence may be the best time to interrupt the progression of these illnesses into lifelong substance use 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 cannabis use. Recently, topiramate has been found to be safe and efficacious for reducing alcohol and cocaine 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 efficacyof topiramate as a treatment for cannabis use disorders in bipolar adolescents has not been explored. Therefore, the goal of this proposal is to conduct a double-blind placebo-controlled 16-week pilot study examining the efficacy and tolerability of topiramate as a treatment for reducing cannabis consumption in adolescents with co-occurring bipolar and cannabis use disorders. The aims of this proposal are consistent with the goals of RFA-DA-06-002,which include conducting "pilot clinical trials of pharmacotherapies for substance related disorders". We will randomize a total of 90 bipolar adolescents with a currentcannabis use disorder to treatment with topiramate or placebo. All adolescents will also receive quetiapine anda single Motivational Interview followed by Compliance Enhancement Therapy that is manual-driven, as standardized treatments for mania and cannabis use disorders, respectively. Change in cannabis consumption is the primary outcome measure. We will also examine the efficacy of topiramate in combination with quetiapine for the treatment of manic symptoms and explore the relationships among changes in cannabis use, mood symptoms, and other substance use. The proposed study would be the first to examine a pharmacological intervention for the treatment of cannabis use disorders in bipolar adolescents. The preliminary data from this projectwill inform and guide the design of future larger, more definitive, controlled studies of topiramate as a treatment for adolescent substance use disorders.