title: Divalproex sodium in nursing home residents with possible or probable Alzheimer Disease complicated by agitation: a randomized, controlled trial.
abstract: 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.
authors.affiliation: Department of Psychiatry, The Center for Aging and Developmental Biology, Univ. of Rochester Medical Center, Rochester, NY, USA. pierre_tariot@urmc.rochester.edu
authors.forename: Pierre N
authors.initials: PN
authors.lastname: Tariot
authors.forename: Rema
authors.initials: R
authors.lastname: Raman
authors.forename: Laura
authors.initials: L
authors.lastname: Jakimovich
authors.forename: Lon
authors.initials: L
authors.lastname: Schneider
authors.forename: Anton
authors.initials: A
authors.lastname: Porsteinsson
authors.forename: Ronald
authors.initials: R
authors.lastname: Thomas
authors.forename: Jacobo
authors.initials: J
authors.lastname: Mintzer
authors.forename: Ronald
authors.initials: R
authors.lastname: Brenner
authors.forename: Kim
authors.initials: K
authors.lastname: Schafer
authors.forename: Leon
authors.initials: L
authors.lastname: Thal
mesh_terms: 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*
chemical_list: D014635:Valproic Acid