Prazosin for the treatment of behavioral symptoms in patients with Alzheimer disease with agitation and aggression.
OBJECTIVE
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.


METHODS
Double-blind, placebo controlled, parallel group study.


METHODS
A university AD center and a nursing home in Seattle, WA.


METHODS
Twenty-two nursing home and community-dwelling participants with agitation/aggression and probable or possible AD (mean age: 80.6 +/- 11.2).


METHODS
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.


METHODS
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, chi = 6.32, df = 1, p = 0.012) and BPRS (mean change: -9 +/- 9 versus -3 +/- 5, chi = 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.


CONCLUSIONS
Prazosin was well tolerated and improved behavioral symptoms in patients with agitation/aggression in AD.
Wang
Lucy Y
LY
VA Northwest Network Mental Illness Research, Education, and Clinical Center (MIRECC), Seattle, WA 98115, USA. wanglucy@u.washington.edu
Shofer
Jane B
JB
Rohde
Kirsten
K
Hart
Kim L
KL
Hoff
David J
DJ
McFall
Yun H
YH
Raskind
Murray A
MA
Peskind
Elaine R
ER
D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use*; D000368:Aged; D000369:Aged, 80 and over; D000374:Aggression / Q000187:drug effects / Q000523:psychology; D000544:Alzheimer Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D001526:Behavioral Symptoms / Q000188:drug therapy*; D010054:Brief Psychiatric Rating Scale; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D010865:Pilot Projects; D011224:Prazosin / Q000627:therapeutic use*; D011595:Psychomotor Agitation / Q000188:drug therapy / Q000523:psychology; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D014861:Washington
D000317:Adrenergic alpha-Antagonists; D011224:Prazosin
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