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Prazosin for the Treatment of Behavioral Symptoms in Patients With Alzheimer Disease With Agitation and Aggression

Objectives: Agitation/aggression in Alzheimer disease (AD) is a major cause of patient distress, caregiver burden, and institutionalization. Enhanced behavioral responsiveness to central nervous system norepinephrine (NE) release may contribute to the pathophysiology of agitation/aggression in AD. P...

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Published in:The American journal of geriatric psychiatry 2009-09, Vol.17 (9), p.744-751
Main Authors: Wang, Lucy Y., M.D, Shofer, Jane B., M.S, Rohde, Kirsten, R.N, Hart, Kim L., P.A.-C, Hoff, David J., P.A.-C, McFall, Yun H., R.Ph, Raskind, Murray A., M.D, Peskind, Elaine R., M.D
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Language:English
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Summary:Objectives: Agitation/aggression in Alzheimer disease (AD) is a major cause of patient distress, caregiver burden, and institutionalization. Enhanced behavioral responsiveness to central nervous system norepinephrine (NE) release may contribute to the pathophysiology of agitation/aggression in AD. Prazosin, a nonsedating generic medication used for hypertension and benign prostatic hypertrophy, antagonizes NE effects at brain postsynaptic alpha-1 adrenoreceptors. This pilot study examined the efficacy and tolerability of prazosin for behavioral symptoms in patients with agitation/aggression in AD. Design: Double-blind, placebo controlled, parallel group study. Setting: A university AD center and a nursing home in Seattle, WA. Participants: Twenty-two nursing home and community-dwelling participants with agitation/aggression and probable or possible AD (mean age: 80.6 ± 11.2). Intervention: Randomization to placebo (N = 11) or prazosin (N = 11). Medication was initiated at 1 mg/day and increased up to 6 mg/day using a flexible dosing algorithm. Measurements: The Brief Psychiatric Rating Scale (BPRS) and Neuropsychiatric Inventory (NPI) at Weeks 1, 2, 4, 6, and 8. The Clinical Global Impression of Change (CGIC) at Week 8. Results: Participants taking prazosin (mean dose: 5.7 ± 0.9 mg/day) had greater improvements than those taking placebo (mean dose: 5.6 ± 1.2 mg/day) on the NPI (mean change: −19 ± 21 versus −2 ± 15, χ2 = 6.32, df = 1, p = 0.012) and BPRS (mean change: −9 ± 9 versus −3 ± 5, χ2 = 4.42, df = 1, p = 0.036) based on linear mixed effects models and the CGIC (mean: 2.6 ± 1.0 versus 4.5 ± 1.6, z = 2.57, p = 0.011 [Mann-Whitney test]). Adverse effects and blood pressure changes were similar between prazosin and placebo groups. Conclusion: Prazosin was well tolerated and improved behavioral symptoms in patients with agitation/aggression in AD.
ISSN:1064-7481
1545-7214
DOI:10.1097/JGP.0b013e3181ab8c61