A Randomized Controlled Trial of Prazosin for Disruptive Agitation in Alzheimer’s Disease: PEACE-AD

Abstract 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 only long-term care residents, however due to the COVID-19 pandemic, it was redesigned to be fully remote with 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 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 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 was 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; however, 7 serious adverse events occurred in 5 women on prazosin, none on placebo (p=0.309). This small RCT supports the possible efficacy of prazosin in treating disruptive agitation in AD, with important safety considerations with its use. This trial provides some feasibility data on conducting a fully remote trial in home dwellers with disruptive agitation.