Prazosin for Agitation in Alzheimer’s Disease: PEACE‐AD

Abstract

AbstractBackgroundDisruptive agitation is a major source of distress to patients/caregivers and is a common precipitant of long‐term care placement. High CNS noradrenergic signaling at the alpha‐1 adrenoreceptor (AR) in AD appears contributes to disruptive agitation. Prazosin, a CNS active alpha‐1 AR antagonist, was effective for reducing disruptive agitation and was well tolerated in our previous pilot study. The objective of this study was to evaluate efficacy and safety of prazosin for disruptive agitation in AD participants residing at home or in long‐term care in a multicenter RCT conducted by the NIA‐funded Alzheimer’s Disease Cooperative Study.MethodIn this multi‐site RCT recruitment was substantially handicapped by COVID‐19. Participants were randomized to prazosin or placebo 2:1 for 12 weeks. Prazosin was titrated over 4 weeks to a maximum possible dose of 4 mg mid‐morning and 6 mg at bedtime based on tolerability and persistent agitation. Adverse events and orthostatic blood pressure and heart rate were monitored. Primary outcome: ADCS‐Clinical Global Impression of Change‐Agitation (CGIC‐A) targeting disruptive agitation. Secondary outcomes: 17‐item Neuropsychiatric Inventory (NPI), Cohen Mansfield Agitation Inventory (CMAI), and total # study days completed. An exploratory outcome was the NPI 5‐item subscale reflecting agitation. Methods were adapted to allow for remote consent, participant screening, and outcome and safety assessments.Result35 participants were randomized. MMRM analysis revealed: no significant differences in CGIC‐A or total NPI scores; 7 of 18 prazosin participants were moderately‐markedly improved on the CGIC‐A compared to 1 of 4 placebo participants (NS); change from BL in the CMAI significantly favored prazosin (p = 0.04) and the 5‐item NPI Agitation subscale numerically favored prazosin (NS); 63% of prazosin participants completing compared to 38% of placebo participants (NS). Adverse events were as anticipated for prazosin. Remote consent and assessments allowed continuation of the study without the necessity of in‐person clinic visits.ConclusionAssessments were limited by the small # of participants. There was some benefit with prazosin with the expected safety profile. Feasibility of performing an RCT for disruptive agitation in AD using remote technology was demonstrated. A larger study of prazosin for moderate‐severe disruptive agitation in AD is necessary.