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

电惊厥治疗振幅滴定可改善晚年抑郁症的临床结果

• 批准号: 10341165
• 负责人: Christopher C Abbott
• 金额: $ 68.77万
• 依托单位: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-04 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10341165
• 关键词: Adverse effects; Age; Anatomy; Antidepressive Agents; BRAIN initiative; Brain; Clinical; Cognitive; Cognitive deficits; Data; Depressed mood; Depressive disorder; Devices; Dose; Effectiveness; Elderly; Electroconvulsive Therapy; Electrodes; Equilibrium; FDA approved; Frequencies; Goals; Hippocampus (Brain); Impaired cognition; Investigation; Liquid substance; Memory; Mental Depression; Methods; Modeling; Moods; Neuronal Plasticity; Outcome; Output; Physiologic pulse; Procedures; Randomized; Randomized Controlled Trials; Recovery; Research; Risk; Safety; Seizures; Series; Skin; Spatial Distribution; Spottings; Stimulus; Titrations; Training; Width; Work; arm; base; brain tissue; clinical practice; cranium; depressed patient; depressive symptoms; electric field; functional disability; geriatric depression; improved; neuroimaging; neuroregulation; novel; response; treatment arm; Adverse effects; Age; Anatomy; Antidepressive Agents; BRAIN initiative; Brain; Clinical; Cognitive; Cognitive deficits; Data; Depressed mood; Depressive disorder; Devices; Dose; Effectiveness; Elderly; Electroconvulsive Therapy; Electrodes; Equilibrium; FDA approved; Frequencies; Goals; Hippocampus (Brain); Impaired cognition; Investigation; Liquid substance; Memory; Mental Depression; Methods; Modeling; Moods; Neuronal Plasticity; Outcome; Output; Physiologic pulse; Procedures; Randomized; Randomized Controlled Trials; Recovery; Research; Risk; Safety; Seizures; Series; Skin; Spatial Distribution; Spottings; Stimulus; Titrations; Training; Width; Work; arm; base; brain tissue; clinical practice; cranium; depressed patient; depressive symptoms; electric field; functional disability; geriatric depression; improved; neuroimaging; neuroregulation; novel; response; treatment arm

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.

电抽搐治疗（ECT）刺激参数选择反映了有效性和 认知不利影响。 ECT刺激参数与更具抗抑郁药效率相关（非焦源 电极放置，较长的脉冲宽度）与认知不良反应的风险增加有关。 目前，在没有临床或 科学基础。振幅决定了电场（电子场）的空间分布的强度。与 固定颅外放大器，由于解剖学，由电子场代表的ECT“剂量”高度变化 皮肤，头骨，液体和脑组织的差异。这种解剖学变异性在较旧（50岁以上）中很明显 抑郁症患者，可能会损害抗抑郁药效率（与情绪相关的刺激不足 电路）和安全性（由于过度刺激认知相关电路而引起认知障碍）。 正如当前建议中提出的那样，振幅滴定可以降低与固定放大器相关的可变性 给药并优化临床和认知结果。该项目的目的是更改标准ECT 从固定放大器到个性化且紧急确定的放大器的参数选择。实现 这个目标，我们将重点介绍放大器滴定与治疗响应性变化之间的关系 带有RUL固定放大器ECT的海马神经可塑性。固定放大器ECT导致可变的电子场或 剂量。在ECT系列的过程中，变量ECT剂量将导致不一致的变化 海马神经塑性。相比之下，预先调查表明放大器 滴定会导致一致的电子场或“剂量”。癫痫发作滴定放大器（基于历史数据，233 544 MA）低于FDA批准的ECT设备的放大器范围（500至900 mA），将需要一个 减少输出放大器的适配器（研究设备豁免）。振幅滴定也将在下面 海马神经可塑性阈值，不足以抗抑郁反应。之间的区别 RUL放大器滴定和RUL固定放大器（800 MA）ECT将确定目标参与程度 与海马。在说明时，〜250 Ma的低放大器滴定受试者（800/250，高固定/滴定 放大器比）将在海马神经塑性上有重大变化。具有高放大器的受试者 滴定〜500 mA（800/500，低固定/滴定比）的海马神经可塑性的变化最小。 放大器滴定与固定放大器海马神经可塑性之间的关系将用于 开发需要一致和临床有效剂量的放大器乘数。一个随机 然后，对照试验将比较海马神经塑性，抗抑郁药和认知结果 具有神经可塑性乘数（固定脉冲数）和传统固定放大器ECT的放大器滴定器 （800 mA，可变脉冲数），较老的受试者。