AFFECTIVE AND COGNITIVE CONSEQUENCES OF ECT

ECT 的情感和认知后果

• 批准号: 6647038
• 负责人: HAROLD A. SACKEIM
• 金额: $ 39.4万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-08-01 至 2004-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6647038
• 关键词: antidepressants; antipsychotic agents; bipolar depression manic phase; brain circulation; clinical research; clinical trials; cognition; electroconvulsive therapy; electroencephalography; gender difference; human subject; human therapy evaluation; major depression; mental disorder chemotherapy; neuropsychological tests; remission /regression; schizophrenia; seasonal affective disorder

DESCRIPTION (Adapted from the Applicant's Abstract): This R01 is a competitive renewal of a MERIT Award. When this project started (1981), the universal view was that the efficacy of ECT was dependent on the generalized seizure, while its cognitive effects were largely determined by electrical dosage. Nonetheless, standard practice involved treating all patients with the same electrical dose, typically at device maximum. Across three studies, we demonstrated marked individual differences in seizure threshold (ST). Many patients were treated orders of magnitude above ST, accounting for much of the adverse cognitive effects of ECT. We also demonstrated that the efficacy of right unilateral (RUL)ECT is highly dependent on the degree to which dosage exceeds ST. These findings have been widely replicated. In our most recent study (started and completed during the MERIT Award period), high dosage RUL ECT equaled the efficacy of a robust form of bilateral (BL) ECT, and had clinically significant advantages in acute, short-term, and long-term cognitive side effects. These findings have already had impact on practice, and should help resolve the > 40 year controversy regarding the relative merits of RUL and BL ECT. The proposed study (Study 4) began during the MERIT Award period, and this application requests support for its completion. In addition to replicating the key findings regarding the relative merits of high dosage RUL compared to BL ECT, this study takes a new direction. The traditional ECT stimulus configuration is nonphysiologic. The standard pulse width (PW) used in ECT (1-2 ms) greatly exceeds the chronaxie for the optimal stimulation necessary for neuronal depoladzation and seizure production (eg, 0.04-0.2 ms). Excessive PW results in stimulation during refractory periods long following neuronal discharge. By reducing the PW of the ECT stimulus, we should maintain efficacy, but substantially reduce cognitive side effects. Our preliminary data suggest that the magnitude of this effect equals or exceeds the difference in cognitive effects between RUL and BL ECT, and, in fact, the extraordinary difference between sine wave and brief pulse stimulation. This new study uses a randomized, double-masked, parallel group, fully factorial [RUL vs. BL ECT and ultrabrief PW (0 ms) vs. traditional PW (1.5 ms)] design, with both RUL conditions treated at 6 times initial ST and both BL conditions treated at 2.5 times initial ST. We hypothesize that high dose RUL ECT has significant advantages over moderate dose BL ECT [with both at traditional PW]. Most critically, use of an ultrabrief PW is equally effective as a long PW, but markedly reduces the short- and long-term cognitive burden of ECT, and is also superior in effects on functional status, subjective cognitive outcome, and neurophysiological alterations. Such findings should have fundamental impact on our understanding of mechanisms and on the practice of ECT.

描述（改编自申请人的摘要）：此 R01 是一款具有竞争力的产品 续订优异奖。当这个项目开始时（1981 年），普遍的观点 ECT 的疗效取决于全身性癫痫发作，而 其认知效果很大程度上取决于电剂量。 尽管如此，标准做法是用相同的方法治疗所有患者 电剂量，通常为设备最大值。通过三项研究，我们 癫痫阈值（ST）表现出明显的个体差异。许多 患者接受的治疗数量级高于 ST，占大部分 ECT 的不良认知影响。我们还证明了 右单侧 (RUL)ECT 高度依赖于剂量的程度 超过ST。这些发现已被广泛复制。在我们最近的 研究（在优异奖期间开始和完成），高剂量 RUL ECT 与双侧 (BL) ECT 的效果相当，并且 在急性、短期和长期认知方面具有临床显着优势 副作用。这些发现已经对实践产生了影响，应该 帮助解决关于 RUL 和 RUL 的相对优点的超过 40 年的争​​议 BL ECT。 拟议的研究（研究 4）在优异奖期间开始，并且该研究 应用程序请求支持其完成。除了复制 关于高剂量 RUL 与 BL 相比的相对优点的主要发现 ECT，这项研究迈出了新的方向。传统ECT刺激 配置是非生理的。 ECT中使用的标准脉冲宽度（PW）（1-2 ms）大大超过了最佳刺激所需的时间 神经元去极化和癫痫发作（例如，0.04-0.2 ms）。密码过多 导致神经元在不应期很长一段时间内受到刺激 释放。通过减少 ECT 刺激的 PW，我们应该保持疗效， 但大大减少认知副作用。我们的初步数据表明 这种效应的程度等于或超过认知差异 RUL 和 BL ECT 之间的影响，以及事实上的非凡差异 介于正弦波和短暂脉冲刺激之间。这项新研究使用了 随机、双盲、平行组、完全析因 [RUL 与 BL ECT 和 超短 PW (0 ms) 与传统 PW (1.5 ms)] 设计，同时具有 RUL 初始 ST 条件为 6 倍，BL 条件为 2.5 倍 倍初始 ST。我们假设高剂量 RUL ECT 对 优于中等剂量 BL ECT [均采用传统 PW]。最多 关键的是，使用超短密码与长密码同样有效，但是 显着减轻了 ECT 的短期和长期认知负担，并且 对功能状态、主观认知结果和 神经生理学改变。这些发现应该会对 我们对 ECT 机制和实践的理解。