Divalproex sodium in nursing home residents with possible or probable Alzheimer Disease complicated by agitation: a randomized, controlled trial.
OBJECTIVE
Three placebo-controlled clinical trials have suggested the benefit of valproate for treatment of agitation associated with dementia; one was used as the basis for this multicenter trial, conducted by the Alzheimer's Disease (AD) Cooperative Study. It addresses the efficacy, safety, and tolerability of divalproex sodium for the treatment of agitation associated with dementia.


METHODS
This was a randomized, double-blind, placebo-controlled clinical trial in 153 nursing home residents with probable or possible AD complicated by agitation; 110 (72%) completed the trial. Participants were randomized to treatment with divalproex sodium at a target dose of 750 mg/day (N = 75) or placebo (N = 78) for 6 weeks. The primary outcome measure was change from baseline on the Brief Psychiatric Rating Scale (BPRS) Agitation factor. Secondary outcomes included total BPRS, Clinical Global Impression of Change, Cohen-Mansfield Agitation Inventory score, and measures of safety and tolerability.


RESULTS
Compliance averaged 88%. Participants receiving divalproex achieved a mean dose of 800 mg/day. Change in mean BPRS Agitation factor scores did not differ between patients treated with divalproex and placebo, nor did secondary behavioral measures. Measures of safety and tolerability did not reveal clinically important drug/placebo differences.


CONCLUSIONS
This multicenter trial showed no benefit of divalproex sodium for treatment for agitation in dementia at a mean dose of 800 mg/day over 6 weeks. The results do not support findings from previous trials indicating possible benefit.
Tariot
Pierre N
PN
Department of Psychiatry, The Center for Aging and Developmental Biology, Univ. of Rochester Medical Center, Rochester, NY, USA. pierre_tariot@urmc.rochester.edu
Raman
Rema
R
Jakimovich
Laura
L
Schneider
Lon
L
Porsteinsson
Anton
A
Thomas
Ronald
R
Mintzer
Jacobo
J
Brenner
Ronald
R
Schafer
Kim
K
Thal
Leon
L
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006707:Homes for the Aged; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D009735:Nursing Homes; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D011595:Psychomotor Agitation / Q000175:diagnosis / Q000188:drug therapy*; D016896:Treatment Outcome; D014635:Valproic Acid / Q000008:administration & dosage*
D014635:Valproic Acid