Article

Divalproex Sodium in Nursing Home Residents With Possible or Probable Alzheimer Disease Complicated by Agitation

Department of Psychiatry, The Center for Aging and Developmental Biology, Univ. of Rochester Medical Center, Rochester, NY, USA.
American Journal of Geriatric Psychiatry (Impact Factor: 3.52). 12/2005; 13(11):942-9. DOI: 10.1176/appi.ajgp.13.11.942
Source: PubMed

ABSTRACT 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.
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.
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.
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.

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    • "One such treatment is the short-chain branched fatty acid, valproic acid (2- propylpentanoic acid, valproate; VPA), which is often administered to patients as the divalproex sodium formulation. Some studies suggest that VPA may afford symptomatic relief of agitation in people with dementia (Porsteinsson et al., 1997; Porsteinsson et al., 2003; Sival et al., 2002; Tariot et al., 2002), although the most recent study found no benefit (Tariot et al., 2005). A multicenter clinical trial is currently being conducted by the Alzheimer's Disease Cooperative Study (ADCS) that is investigating the potential for VPA to attenuate progression of the clinical features of AD (Tariot et al., 2002). "
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