Electroconvulsive therapy amplitude titration for improved clinical outcomes in late-life depression

电休克治疗(ECT)刺激参数的选择反映了疗效和 认知不良影响。与更多抗抑郁疗效相关的ECT刺激参数(非焦点 电极位置、脉冲宽度较长)与认知不良影响的风险增加有关。 在标准的临床实践中，幅度目前固定在800或900毫安(MA)，没有临床或 科学依据。幅度决定了电场(电场)空间分布的强度。使用一个 固定的颅外幅度，由于解剖结构的不同，由电磁场表示的ECT“剂量”是高度可变的 皮肤、头骨、体液和脑组织的差异。这种解剖变异在老年人(50岁以上)中表现突出。 抑郁症患者和可折衷的抗抑郁药效(与情绪刺激不足相关 和安全性(由于过度刺激认知相关的回路而导致认知损害)。 本提案中提出的幅度滴定可以减少与固定幅度相关的变异性 给药并优化临床和认知结果。该项目的目标是改变标准的ECT 参数选择从固定幅度到个性化和经验性确定的幅度。要实现 这一目标，我们将重点放在之间的关系，幅度滴定和治疗反应的变化 RUL固定幅度电刺激对海马神经可塑性的影响。固定幅度ECT导致可变电场或 ECT剂量。在ECT系列过程中，可变的ECT剂量将导致不一致的变化 海马神经可塑性。相比之下，翻译前的调查已经证明了这种幅度 滴定产生一致的电场或ECT“剂量”。癫痫发作滴定幅度(基于历史数据，233至 544 mA)低于FDA批准的ECT设备的幅度范围(500至900 mA)，并将需要 降低输出幅度的适配器(调查设备除外)。波幅滴定也将低于 海马神经可塑性阈值和抗抑郁反应不足。两者之间的区别 RUL幅度滴定和RUL固定幅度(800 MA)ECT将决定目标的接合程度 通过海马体。举例而言，受试者的低幅度滴定为~250 mA(800/250，高固定/滴定 波幅比)会对海马神经可塑性产生明显的影响。高幅受试者 滴定~500 mA(800/500，低固定/滴定比)对海马神经可塑性的影响很小。 将利用幅度滴定和固定幅度海马神经可塑性的关系来 开发一致和临床有效的ECT剂量所需的幅度倍增器。一个随机化的 然后，对照试验将比较海马神经可塑性、抗抑郁药物和认知结果 神经可塑性倍增器(固定脉冲数)与传统固定幅度ECT的幅度滴定 (800 mA，可变脉冲数)。

Electroconvulsive therapy (ECT) stimulation parameter selection reflects a balance between efficacy and cognitive adverse effects. ECT stimulation parameters associated with more antidepressant efficacy (non-focal electrode placement, longer pulse width) are associated with increased risk of cognitive adverse effects. Amplitude is currently fixed at 800 or 900 milliamperes (mA) in standard clinical practice with no clinical or scientific basis. Amplitude determines the intensity of the spatial distribution of the electric field (E-field). With a fixed extracranial amplitude, the ECT “dose” as represented by the E-field is highly variable due to anatomic differences in skin, skull, fluid, and brain tissue. This anatomic variability is prominent in older (age 50+) depressed patients and can compromise both antidepressant efficacy (insufficient stimulation of mood-related circuitry) and safety (inducing cognitive impairment due to excessive stimulation of cognitive related circuitry). Amplitude titration, as proposed in this current proposal, can reduce the variability related to fixed amplitude dosing and optimize clinical and cognitive outcomes. The goal of this project is to change standard ECT parameter selection from a fixed amplitude to an individualized and empirically determined amplitude. To achieve this goal, we will focus on the relationship between amplitude titration and treatment-responsive changes in hippocampal neuroplasticity with RUL fixed amplitude ECT. Fixed amplitude ECT results in variable E-field or ECT dose. Over the course of an ECT series, the variable ECT dose will result in inconsistent changes in hippocampal neuroplasticity. In contrast, pre-translational investigations have demonstrated that amplitude titration results in a consistent E-field or ECT “dose”. Seizure titration amplitudes (based on historic data, 233 to 544 mA) are below the amplitude range of FDA-approved ECT devices (500 to 900 mA) and will require an adaptor to reduce the output amplitude (Investigational Device Exemption). Amplitude titration will also be below the hippocampal neuroplasticity threshold and insufficient for antidepressant response. The difference between RUL amplitude titration and RUL fixed amplitude (800 mA) ECT will determine the degree of target engagement with the hippocampus. To illustrate, subjects with low amplitude titration of ~250 mA (800/250, high fixed/titration amplitude ratio) will have significant changes in hippocampal neuroplasticity. Subjects with high amplitude titration ~500 mA (800/500, low fixed/titration ratio) will have minimal changes in hippocampal neuroplasticity. The relationship between amplitude titration and fixed amplitude hippocampal neuroplasticity will be used to develop the amplitude multiplier required for consistent and clinically effective ECT dosing. A randomized controlled trial will then compare hippocampal neuroplasticity, antidepressant, and cognitive outcomes between amplitude titration with neuroplasticity multiplier (fixed pulse number) and traditional fixed amplitude ECT (800 mA, variable pulse number) in older depressed subjects.