Simulated ECT: A Novel Approach to a Control Group in Clinical Trials

• Type of Material: Article
• Authors: Kaitlin R. McManus, McLean Hospital; Maria I. Lapid, Mayo Clinic, Rochester, MN; Brent P. Forester, Harvard Medical School; Martina Mueller, Medical University of South Carolina; Adriana P Hermida, Emory University; Louis Nykamp, Pine Rest Christian Mental Health Services; David G. Harper, Harvard Medical School; Stephen J. Seiner, Harvard Medical School; Sohang Shanghani, Zucker School of Medicine at Hofstra/Northwell; Regan Patrick, Harvard Medical School; Melanie T. Gentry, Mayo Clinic, Rochester, MN; Simon Kung, Mayo Clinic, Rochester, MN; Janette C. Leal, Mayo Clinic, Rochester, MN; Emily K. Johnson, Mayo Clinic, Rochester MN; Georgios Petrides, Zucker School of Medicine at Hofstra/Northwell
• Language: English
• Date: 2022-03-01
• Publisher: Wolters Kluwer Health, Inc.
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2022 Wolters Kluwer Health, Inc. All rights reserved.
• Final Published Version (URL): https://doi.org/10.1097%2FYCT.0000000000000832
• Title of Journal or Parent Work: The Journal of ECT
• Volume: 38
• Issue: 3
• Start Page: 165
• End Page: 170
• Grant/Funding Information: The ECT-AD project described is supported by the National Institutes of Health through Grant R01 AG061100.
• Keywords: agitation; behavioral symptoms; Dementia; Alzheimer's disease; electroconvulsive therapy
• Research Categories: Psychology, Cognitive; Biology, Neuroscience

Abstract

Objectives: Agitation is the most common behavioral symptom of Alzheimer’s disease (AD) affecting about 40–60% of the AD population, yet there are no FDA approved therapies for the myriad of behavioral or psychological symptoms of dementia. There is growing evidence from naturalistic studies that electroconvulsive therapy (ECT) is a safe and effective treatment for agitation in AD patients who are refractory to pharmacotherapy and behavioral interventions. Despite the existing evidence, ECT remains underutilized due to stigma, lack of education, and concerns regarding adverse cognitive effects. Randomized controlled clinical trials of ECT are an opportunity to provide high quality evidence of ECT as a safe and efficacious treatment for agitation in the AD population. We describe the methods for the Electroconvulsive Therapy in Alzheimer’s Dementia (ECT-AD) study, which utilizes a novel, simulated ECT control group to conduct a single-blind efficacy study of ECT for the treatment of agitation and aggression in individuals with moderate to severe AD. Methods: We discuss the rationale, study design, methodology, ethical and practical challenges, and management strategies in utilizing a simulated ECT group as the comparator arm in this randomized controlled trial of ECT in AD-related treatment refractory agitation and aggression. Conclusions: Validation of the safety and efficacy of ECT in patients with advanced AD with refractory agitation and aggression is necessary. This can be accomplished through creative formulation of simulated ECT groups that effectively maintain the blind while providing scientific integrity.