Dementias are frequent in the nursing home, and in many cases are complicated by agitation. Treatment of agitation ideally entails identification and reversal of precipitants. Pharmacotherapy is considered when these steps fall. Although more than half of nursing home patients receive psychotropic medications, many of whom have dementia, few studies have examined their effectiveness. Antipsychotics are used, but their efficacy is limited and toxicity is common. Alternatives are needed urgently. Anticonvulsants have shown early promise as potentially safe, effective forms of treatment for this problem. Two preliminary studies with carbamazepine strongly indicate efficacy. Valproate is a different anticonvulsant with a potentially greater safety profile, recently reported in the literature to show efficacy for this problem. Its possible antiagitation effects may be attributable to its GABA-ergic properties. It is used by clinicians for agitation, but there is no empirical evidence of its efficacy. We propose a preliminary study of the efficacy and tolerability of valproate 375 mg/d and 750 mg/d compared to placebo in the treatment of agitation associated with probable or possible Alzheimer's disease in nursing home patients. This will be a randomized, 3 arm, 6-week, double-blind, placebo-controlled study of valproate, followed by a 3-week washout and then a 6-week period of open treatment with clinically optimal doses of valproate. Seventy-five patients with possible or probable Alzheimer's disease will be enrolled from 10 nursing homes. The primary outcome measure will be change in total Brief Psychiatric Rating Scale score (week 6-week 0), using analysis of covariance. The primary hypothesis is that valproate will be superior to placebo in relieving agitation. Secondary aims address: 1) whether valproate use is associated with global improvement; 2) whether other behavioral measures show change; 3) tolerability and safety; 4) predictors of good or poor response; 5) improved characterization of agitation; 6) field testing of new instruments to assess behavior in dementia; 7) further clarification of safety and dosing via a time- limited open trial.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project--Cooperative Agreements (U01)
Project #
3U01AG010483-08S2
Application #
6098399
Study Section
Project Start
1998-09-30
Project End
1999-06-30
Budget Start
Budget End
Support Year
8
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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