Magazine article Clinical Psychiatry News

Valproate Does Not Delay Psychosis in AD

Magazine article Clinical Psychiatry News

Valproate Does Not Delay Psychosis in AD

Article excerpt

VIENNA -- Valproate treatment over 2 years does nothing to delay the onset of agitation or psychosis in patients with Alzheimer's disease, and patients taking the anticonvulsant showed significantly more brain volume loss on MRI at year 1 than did those taking placebo.

But because the changes in brain volume did not correlate with any clinical differences between the groups, it's difficult to know just what to make of the observed volume loss, Dr. Pierre Tariot said at the International Conference on Alzheimer's Disease.

"Interpretation of these results really isn't possible at this juncture," said Dr. Tariot of the Banner Alzheimer's Institute, Phoenix, in an interview. "It could theoretically represent damage to the brain, but that seems unlikely due to the absence of correlation with clinical decline that is seen in natural history studies. There are case reports of 'pseudoatrophy' associated with valproate use, which may be relevant here. We have an ongoing analysis, and the full details will be presented at a later time."

The trial randomized 313 patients with mild-moderate Alzheimer's disease who lacked agitation or psychosis at baseline to either placebo or an extended-release form of divalproex sodium (Depakote ER) at a dose of 10-12 mg/kg per day. The primary outcome was time until the emergence of agitation and/or psychosis. The symptoms had to last at least 2 weeks, and had to be clinically significant in the opinion of the site physician.

Secondary end points included changes in the Neuropsychiatric Inventory (NPI) score the Cohen-Mansfield Agitation Inventory (CMAI), Mini-Mental State Exam (MMSE), the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) domain, and the Alzheimer's Disease Cooperative Study activities of daily living (ADCS-ADL) domain. …

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