Confirmatory Safety and Efficacy Trial of Magnetic Seizure Therapy for Depression

项目摘要/摘要 本研究的目标是进行一项两点、双掩蔽、随机、非劣势的临床试验，通过 将磁癫痫疗法(MST)发展为一种有效和安全的实验治疗方法 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 关于自杀意念的右侧超短脉冲电休克治疗(RUL-UB-ECT)， 260例TRD患者的抑郁症状和认知不良反应。重要的是，对于这两个人 抽搐治疗，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是一种成熟的治疗TRD的方法，但在加拿大和美国，只有不到1%的患者 接受ECT治疗的TRD患者主要是由于其认知不良影响(即健忘症)。因此，新的治疗方法 迫切需要TRD的替代方案。MST就是这样一种治疗方法。MST涉及到应用一系列高强度 频率磁刺激以诱发癫痫(与ECT相比，ECT需要施加一系列高强度的 频率电刺激以诱发癫痫发作)。我们的试验数据表明，MST可以达到疗效 这与ECT相当，但对认知的不利影响可以忽略不计。 了解TRD的神经生物学，重点是自杀意念，有助于加速治疗 发展。在这项提案中，我们将评估MST自杀意念的缓解率与 联合经颅ECT检查并评估前额叶背外侧皮质CI是否发生改变 磁刺激和脑电检查与自杀意念的缓解有关。我们还将 电休克治疗1个疗程后认知不良反应及其神经生理指标的测定 TRD患者均经脑电检查证实。 这项试验的积极结果可能会对TRD患者产生巨大而直接的影响。首先，如果MST 显示出与ECT相当的治疗效果，但神经认知副作用更少，它可以迅速 可应用于临床实践。事实上，鉴于MST的管理几乎与ECT相同，所有 北美的ECT设施将能够很容易地采用MST。第二，神经认知的缺失 副作用也将导致治疗接受度的提高。最后，通过研究关键的神经生理学 通过对这些治疗机制的研究，我们希望能得出TRD治疗的关键机制信息。

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.