Journal article
A Randomized Controlled Trial of Prazosin for Disruptive Agitation in Alzheimer’s Disease: PEACE-AD
The American journal of geriatric psychiatry. Open science, education, and practice, v 11, pp 15-27
Sep 2026
Abstract
•What is the primary question addressed in the study?Safety and efficacy of prazosin, an alpha-1 adrenoreceptor (AR) antagonist, in the treatment of disruptive agitation in Alzheimer’s disease (AD).•What is the main finding of this study?There is some potential efficacy of prazosin for disruptive agitation in this fully remote small randomized controlled trial. There are important safety considerations in the use of prazosin in the late-stage AD population, particularly in women that are consistent with its mechanism of action and its bioavailability.•What is the meaning of the finding?This study supports further investigation of this repurposed medication as a potentially efficacious treatment for the challenging problem of disruptive agitation in AD.
PEACE-AD was a 12-week placebo-controlled multisite randomized clinical trial testing the efficacy and safety of prazosin, an alpha-1 adrenoreceptor antagonist, in treating disruptive agitation in Alzheimer’s disease (AD). It was initially designed to enroll long-term care residents. Due to the COVID-19 pandemic, it was redesigned to be remote for home-dwelling participants. Randomization was 2:1 prazosin:placebo with 4-week flexible dose titration to a maximum of 4 mg A.M. and 6 mg bedtime, with 8 weeks maintenance. The primary outcome was the Alzheimer’s Disease Cooperative Study (ADCS) Clinical Global Impression of Change-Agitation (CGIC-A), with secondary outcomes including the Neuropsychiatric Inventory and the ADCS Activities of Daily Living-Severe Dementia Version, with the Cohen-Mansfield Agitation Inventory (CMAI) as exploratory. There were 35 participants aged 80 ± 10 years (mean ± SD), 27 randomized to prazosin and eight to placebo. Prazosin completion rate was 59.2% (16/27); placebo 37.5% (3/7). There were no significant treatment differences on the primary or secondary outcomes. Prazosin showed higher odds of response of moderate or marked improvement on CGIC-A (OR = 2.89 [0.37,22.9], p = 0.314). CMAI scores significantly favored prazosin at week 12 (p = 0.034). There were no significant differences in treatment-emergent adverse events. Seven serious adverse events occurred in five women on prazosin, none on placebo (p = 0.309). This RCT supports the possible efficacy of prazosin in treating disruptive agitation in AD, with important safety considerations with its use. This trial provides feasibility data on conducting a remote trial in home dwellers with disruptive agitation.
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Details
- Title
- A Randomized Controlled Trial of Prazosin for Disruptive Agitation in Alzheimer’s Disease: PEACE-AD
- Creators
- Elaine R. Peskind - VA Puget Sound Health Care SystemMurray A. Raskind - VA Puget Sound Health Care SystemMichelle A. Herman - Alzheimer’s Disease Cooperative Study, University of California San Diego, La Jolla, CARosemary Morrison - Alzheimer’s Disease Cooperative Study, University of California San Diego, La Jolla, CAGenevieve Matthews - Alzheimer’s Disease Cooperative Study, University of California San Diego, La Jolla, CAA. Carol Evans - Alzheimer’s Disease Cooperative Study, University of California San Diego, La Jolla, CABen Boyarko - Alzheimer’s Disease Cooperative Study, University of California San Diego, La Jolla, CAGuerry Peavy - Alzheimer’s Disease Cooperative Study, University of California San Diego, La Jolla, CAGabriel C. Léger - Alzheimer’s Disease Cooperative Study, University of California San Diego, La Jolla, CAGregory A. Jicha - University of KentuckyNeela Patel - The University of Texas at San Antonio Health Science CenterSharon A. Brangman - Department of Geriatrics, State University of New York, Syracuse, NYAimee L. Pierce - University of PortlandLon S. Schneider - Alzheimer’s Disease Cooperative Study, University of California San Diego, La Jolla, CAShelia Jin - Alzheimer’s Disease Cooperative Study, University of California San Diego, La Jolla, CAJing Zhang - Biostatistics Shared Resource, Moores Cancer Center, University of California San Diego, La Jolla, CARonald G. Thomas - Alzheimer’s Disease Cooperative Study, University of California San Diego, La Jolla, CAKaren Messer - Biostatistics Shared Resource, Moores Cancer Center, University of California San Diego, La Jolla, CAHyunkeun Ryan Cho - Alzheimer’s Disease Cooperative Study, University of California San Diego, La Jolla, CAHoward H. Feldman - Alzheimer’s Disease Cooperative Study, University of California San Diego, La Jolla, CA
- Publication Details
- The American journal of geriatric psychiatry. Open science, education, and practice, v 11, pp 15-27
- Publisher
- Elsevier I
- Number of pages
- 13
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine
- Other Identifier
- 991022234644804721