Valproate use in neuropsychiatric disorders in the elderly

The literature regarding the use of valproate in the elderly derives primarily from studies in patients with dementia who experience agitation. At this juncture, there are 5 case reports or case series in patients with mixed neuropsychiatric disorders and 18 in patients with dementia, while there are 3 placebo-controlled studies in patients with dementia. In the aggregate, the published reports point toward probable improvement in agitation in a substantial proportion of patients. The level of evidence is not sufficient to define clinical practice, however, which is also a limitation with some other commonly used therapies, nor is the behavioral target of persistent agitation recognized by the Food and Drug Administration. Basic and preclinical studies of mechanism of action suggest a possible effect of valproate on cellular survival which, in theory, could be beneficial in patients with Alzheimer's disease. This hypothesis will be addressed in a multicenter trial beginning in 2003.