Authors: Profenno, Louis A.; Jakimovich, Laura; Holt, Connie J.; Porsteinsson, Anton; Tariot, Pierre N.

Source: Current Alzheimer Research, Volume 2, Number 5, December 2005 , pp. 553-558(6)

Publisher: Bentham Science Publishers

Abstract:

OBJECTIVE: The Alzheimer's Disease Cooperative Study (ADCS) is conducting a clinical trial to address whether chronic valproate treatment can delay emergence of behavioral symptoms in outpatients with AD. Since there were no data on the safety and tolerability of divalproex sodium in outpatients with dementia, we undertook a pilot study to inform the design of the ADCS study. METHODS: We recruited 20 outpatients with probable AD, MMSE 10-20, without history of agitation or psychosis. This was a 10-week randomized, double-blind, placebo-controlled study assessing the safety and tolerability of 1,000 mg/day and 1,500 mg/day of divalproex sodium delayed-release for 8 weeks followed by extended-release for 2 weeks. Other outcome measures addressed cognition, function, global status, side effects, and laboratory data. RESULTS: Participants assigned to active treatment ingested approximately 30% less of their prescribed study medication compared to those receiving placebo (p < .05 Wilcoxon Rank Sum test). The average tolerated dose for all participants at week 8 was 810 mg/day or 11.5 mg/kg/day, similar to the dose tolerated by nursing home patients. The most common side effects were sleepiness and tiredness, with worse cognitive performance in those assigned to 1500 mg/day. CONCLUSIONS: These results were used to design the multi-center ADCS trial. Doses of less than 1000 mg/day of divalproex sodium were the maximum tolerated by these outpatients with AD. A larger study of divalproex sodium dose tolerability is needed to define treatment in outpatients with Alzheimer's disease.

Keywords: Alzheimer's disease; valproic acid; divalproex; tolerability; neuroprotection

Document Type: Research article

DOI: http://dx.doi.org/10.2174/156720505774932205

Affiliations: 1: Program in Neurobehavioral Therapeutics, Monroe Community Hospital, University of Rochester Medical Center, 435 East Henrietta Road, Rochester, NY 14620, USA.

Publication date: 2005-12-01

More about this publication?

• Current Alzheimer Research publishes peer-reviewed frontier review and research articles on all areas of Alzheimer's disease. This multidisciplinary journal will help in understanding the neurobiology, genetics, pathogenesis, and treatment strategies of Alzheimer's disease. The journal publishes objective reviews written by experts and leaders actively engaged in research using cellular, molecular, and animal models. The journal also covers original articles on recent research in fast emerging areas of molecular diagnostics, brain imaging, drug development and discovery, and clinical aspects of Alzheimer's disease. Manuscripts are encouraged that relate to the synergistic mechanism of Alzheimer's disease with other dementia and neurodegenerative disorders. Book reviews, meeting reports and letters-to-the-editor are also published. The journal is essential reading for researchers, educators and physicians with interest in age-related dementia and Alzheimer's disease. Current Alzheimer Research provides a comprehensive 'bird's-eye view' of the current state of Alzheimer's research for neuroscientists, clinicians, health science planners, granting, caregivers and families of this devastating disease.

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