AFFECTIVE AND COGNITIVE CONSEQUENCES OF ECT

ECT 的情感和认知后果

• 批准号: 6391861
• 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 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6391861
• 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）：该R 01是一种具有竞争力的 再次获得MERIT奖。当这个项目开始时（1981年）， ECT的疗效取决于全身性癫痫发作， 其认知效果主要取决于电剂量。 尽管如此，标准的做法是用同样的药物治疗所有患者。 电剂量，通常为器械最大值。在三项研究中，我们 癫痫发作阈值（ST）的个体差异显著。许多 患者的治疗数量级高于ST，占大多数 ECT对认知的不良影响我们还证明， 右侧单侧（RUL）ECT高度依赖于剂量 这些发现已被广泛复制。日的最新 研究（在MERIT奖励期间开始和完成），高剂量RUL ECT等同于强有力的双侧（BL）ECT形式的疗效， 在急性、短期和长期认知方面具有临床显著优势 副作用.这些发现已经对实践产生了影响， 帮助解决关于RUL的相对优点的40多年的争议， BL ECT。 拟议的研究（研究4）在MERIT奖期间开始， 申请书要求支持其完成。除了复制 关于高剂量RUL与BL相比的相对优点的关键发现 ECT，这项研究采取了新的方向。传统的ECT刺激 配置是非生理性的。ECT（1-2）中使用的标准脉冲宽度（PW ms）大大超过了最佳刺激所需的时值， 神经元去极化和癫痫发作产生（例如，0.04-0.2 ms）。PW过多 导致在神经元兴奋后的长时间不应期期间的刺激 放电通过减少ECT刺激的PW，我们应该保持疗效， 但大大减少了认知副作用。我们的初步数据显示 这种影响的大小等于或超过认知差异， RUL和BL ECT之间的影响，事实上， 正弦波和短脉冲刺激之间的差异。这项新研究使用了 随机化、双盲、平行组、全析因[RUL vs. BL ECT和 超短PW（0 ms）与传统PW（1.5 ms）]设计，具有两种RUL 以6倍初始ST处理的条件和以2.5倍初始ST处理的两种BL条件 我们假设高剂量RUL ECT具有显著的 优于中等剂量BL ECT [两者均在传统PW下]。最 关键是，使用超短PW与长PW同样有效，但 显著降低ECT的短期和长期认知负担， 对功能状态、主观认知结果的影响上级，和 神经生理学改变这些发现应该对 我们对机制的理解和ECT的实践。