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

躁郁症和大麻使用障碍之间存在双向重叠，尤其是 有这两种情况的人都会患上严重的疾病。具体地说，同时患有双相情感障碍和 与有大麻使用障碍的个人相比，大麻使用障碍显示出这两种疾病的复发率更高 一个人生病。同时吸食大麻和双相情感障碍的青少年预后较差 这两种疾病甚至在相似的成年人中都会发生，并且发展为其他物质的风险更高 使用障碍。然而，患有躁郁症和大麻使用障碍的青少年通常被排除在 任何一种情况的对照药物治疗研究。因此，临床医生没有留下任何证据- 基于如何治疗这些青少年的指导。青春期精神分裂症的治疗研究 出现双相情感障碍和大麻使用障碍是至关重要的，因为青春期可能是 阻止这些疾病的发展成为终生的物质使用依赖和治疗难治 双相情感障碍，两者都与显著的发病率和死亡率有关。 托吡酯是一种抗癫痫药，具有双重作用机制，可减少 因此，中脑多巴胺的神经传递可能有助于减少奖赏和渴望 与大麻使用有关。最近，托吡酯被发现是安全和有效的减少 成年人对酒精和可卡因的消费和渴求。我们的初步工作表明托吡酯也 可能对治疗患有双相情感障碍的青少年躁狂症有效。然而，它的有效性 托吡酯作为治疗双相青少年大麻使用障碍的方法尚未被探索过。 因此，这项建议的目标是进行一项为期16周的双盲安慰剂对照先导性研究 检查托吡酯作为减少大麻消费的治疗方法的有效性和耐受性 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致的。 以RFA-DA-06-002的目标，其中包括进行药物疗法的试点临床试验 我们将对90名目前服用大麻的双相情感障碍青少年进行随机分组 使用托吡酯或安慰剂治疗精神障碍。所有青少年也将接受奎硫平和安非他明。 单次激励性访谈，之后是手动推动的遵从性增强疗法，如 分别对躁狂症和大麻使用障碍进行标准化治疗。大麻的变化 消费是衡量结果的主要指标。我们还将检查托吡酯在 奎硫平联合治疗躁狂症状的临床研究 大麻使用、情绪症状和其他物质使用的变化。这项拟议的研究将是第一次 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。该项目的初步数据将为未来更大、更多的 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.