Disruptive agitation frequently emerges as a troublesome and often chronic clinical problem during the course of Alzheimer's disease (AD). It dramatically increases caregiver burden in both home and long term care settings, is distressing to patients and others in the patient's environment, and is a common precipitant of long-term care placement. Current psychopharmacologic approaches to agitation in AD and related dementing disorders, particularly the widely-prescribed antipsychotics, are of limited demonstrated efficacy and are associated with substantial adverse effects. The latter include increased risk for stroke and death, excessive sedation and pseudoparkinsonism. The development of more effective and safer pharmacologic approaches to the treatment of disruptive agitation in AD is an important clinical goal. Neurobiologic studies in the clinic and in postmortem brain tissue provide rationale for involvement of enhanced central nervous system (CNS) responsiveness to norepinephrine (NE) at the alpha-1 adrenoreceptor (AR) in the pathophysiology of disruptive agitation in AD. Our preliminary placebo-controlled clinical trial feasibility data support potential efficacy of the generically available brain active alpha-1 AR antagonist, prazosin for agitation in AD and good tolerability of this drug in this elderly and often frail population. We propose a placebo-controlled trial of prazosin, for disruptive agitation in AD.
Agitation in dementia is a major cause of morbidity and excess disability. It places great burden on caregivers and is probably the most common precipitant of long term care placement. Demonstrating an effective and well tolerated medical treatment for this problem would be a great benefit.
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