Confirmatory Safety and Efficacy Trial of Magnetic Seizure Therapy for Depression

项目总结/摘要 本研究的目的是进行一项双中心、双盲、随机、非劣效性临床试验， 一种实验性治疗方法，以开发磁癫痫治疗（MST）作为一种有效和安全的方法， 治疗难治性抑郁症（TRD）。在这项研究中，我们建议比较MST的疗效 右侧单侧超短脉冲电休克治疗（RUL-UB-ECT）在自杀意念方面的作用， 抑郁症状和认知不良反应。重要的是，对于这两个 惊厥疗法，我们将确定与自杀意念相对应的神经生理学靶点 减少和认知不良影响。 ECT是一种成熟的TRD治疗方法，但在加拿大和美国，不到1%的患者 患有TRD的患者主要由于其认知不良影响而接受ECT（即，健忘症）。因此，新的治疗 迫切需要TRD的替代品。其中一种治疗方法是MST。MST涉及应用一系列高 频率磁刺激诱发癫痫发作（与ECT相比，ECT涉及应用一系列高频率磁刺激， 频率电刺激以诱发癫痫发作）。我们的试点数据表明，MST可以达到疗效 与ECT相当，但对认知的不良影响可以忽略不计。 了解TRD的神经生物学，重点是自杀意念，可以帮助加速治疗 发展在本提案中，我们将评估MST的自杀意念缓解率， ECT检查并结合经颅多普勒超声评价脑梗死患者是否存在背外侧前额叶皮质改变 磁刺激和脑电图与自杀意念的缓解有关。我们还将 确定ECT疗程后的认知不良反应及其神经生理学靶点， TRD患者进行脑电图检查。 这项试验的积极结果可能对TRD患者产生巨大的直接影响。首先，如果MST 显示出与ECT相当的治疗效果，但神经认知副作用较少， 应用于临床实践。事实上，由于MST的管理与ECT几乎相同，所有 北美的ECT设施将能够随时采用MST。第二，神经认知的缺失 副作用也将导致治疗可接受性的提高。最后，通过研究关键的神经生理学 这些治疗的机制，我们希望得到关键的机制信息TRD治疗。

Project Summary/Abstract The goal of this study is to conduct a two-site, double-masked, randomized, non-inferiority clinical trial through an experimental therapeutics approach to develop magnetic seizure therapy (MST) as a useful and safe treatment for treatment resistant depression (TRD). In this study, we propose to compare the efficacy of MST to right unilateral ultrabrief pulse electroconvulsive therapy (RUL-UB-ECT) in regards to suicidal ideation, depressive symptoms, and cognitive adverse effects in 260 patients with TRD. Importantly, for these two convulsive therapies, we will identify the neurophysiological targets corresponding with suicidal ideation reduction and cognitive adverse effects. ECT is a well-established treatment for TRD, but in Canada and the United States, less than 1% of patients with TRD receive ECT mainly due to its cognitive adverse effects (i.e., amnesia). Thus, new treatment alternatives for TRD are urgently needed. One such treatment is MST. MST involves applying a train of high frequency magnetic stimuli to induce a seizure (compared with ECT that involves applying a train of high frequency electrical stimuli to induce a seizure). Our pilot data demonstrated that MST can achieve efficacy that is comparable to ECT but with negligible cognitive adverse effects. Understanding the neurobiology of TRD, with an emphasis on suicidal ideation, can help accelerate treatment development. In this proposal, we will evaluate the rates of remission of suicidal ideation of MST compared to ECT and evaluate whether change in CI from the dorsolateral prefrontal cortex using combined transcranial magnetic stimulation and electroencephalography is associated with remission of suicidal ideation. We will also determine the cognitive adverse effects and their neurophysiological targets following a course of ECT in patients with TRD through electroencephalography. Positive results from this trial may have tremendous and immediate impact for patients with TRD. First, if MST demonstrates comparable treatment efficacy to ECT, but with fewer neurocognitive side effects, it could rapidly be adopted into clinical practice. Indeed, given that the administration of MST is nearly identical to ECT, all ECT facilities in North America would be able to readily adopt MST. Second, the absence of neurocognitive side effects will also lead to improved treatment acceptability. Lastly, by investigating key neurophysiological mechanisms of these treatments, we hope to derive critical mechanistic information underlying TRD treatment.