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Important Notice: The Forum does not endorse any medical
product or therapy. ALL medications and supplements
should be taken ONLY under the supervision of a physician,
due to the possibility of side-effects, drug interactions,
etc.
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Name:
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Valproate
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Other Names:
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Depakene (valproic acid or sodium valproate), Depakote (divalproex sodium)
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Development Status:
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investigational in U.S.
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FDA Phase:
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Phase III
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Primary Medical Role:
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For treatment of seizure disorders and as a mood stablizer
for Biopolar Disorder.
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Role in Alzheimer's Disease:
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Potential therapy for agitation in AD patient.
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Pharmacological Role:
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Valproate is a branch-chained carboxylic acid that is a
gamma aminobutyric acid (GABA)–enhancing agent. Valproic
acid is also found to protect cultured rat hippocampal
neurons against A beta- and glutamate-induced injury
possibily through the stablization of intracellular
calcium levels.
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Side Effects:
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Common side effects are nausea and vomiting. Drowsiness,
poor coordination, dizziness or double vision could occur
in higher dosage. Side effects usually are mild and
temporary.
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Evidence pro its efficacy:
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Valproate is found to be well tolerated with little side
effect in the treatment of aggression in AD patients.
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Notes:
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A Phase III clinical trial NCT00071721 is ongoing but not
recruiting participants (clinicalTrials.gov). This record
was last updated Dec 22, 2008.
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Kim AJ, Shi Y, Austin RC, Werstuck GH. Valproate protects
cells from ER stress-induced lipid accumulation and
apoptosis by inhibiting glycogen synthase kinase-3. J Cell
Sci. 2005 Jan 1;118(Pt 1):89-99. Abstract
Hao Y, Creson T, Zhang L, Li P, Du F, Yuan P, Gould TD,
Manji HK, Chen G. Mood stabilizer valproate promotes ERK
pathway-dependent cortical neuronal growth and
neurogenesis. J Neurosci. 2004 Jul 21;24(29):6590-9. Abstract
Loy R, Tariot PN. Neuroprotective properties of valproate:
potential benefit for AD and tauopathies. J Mol Neurosci.
2002 Dec ;19(3):303-7. Abstract
Porsteinsson AP, Tariot PN, Erb R, Cox C, Smith E,
Jakimovich L, Noviasky J, Kowalski N, Holt CJ, Irvine C.
Placebo-controlled study of divalproex sodium for
agitation in dementia. Am J Geriatr Psychiatry. 2001
Winter;9(1):58-66. Abstract
Davis LL, Ryan W, Adinoff B, Petty F. Comprehensive review
of the psychiatric uses of valproate. J Clin
Psychopharmacol. 2000 Feb;20(1 Suppl 1):1S-17S. Abstract
Lindenmayer JP, Kotsaftis A. Use of sodium valproate in
violent and aggressive behaviors: a critical review. J
Clin Psychiatry. 2000 Feb;61(2):123-8. Abstract
Kunik ME, Puryear L, Orengo CA, Molinari V, Workman RH Jr.
The efficacy and tolerability of divalproex sodium in
elderly demented patients with behavioral disturbances.
Int J Geriatr Psychiatry. 1998 Jan;13(1):29-34. Abstract
Mark RJ, Ashford JW, Goodman Y, Mattson MP.
Anticonvulsants attenuate amyloid beta-peptide
neurotoxicity, Ca2+ deregulation, and cytoskeletal
pathology. Neurobiol Aging. 1995 Mar-Apr;16(2):187-98. Abstract
Mellow AM, Solano-Lopez C, Davis S. Sodium valproate in
the treatment of behavioral disturbance in dementia. J
Geriatr Psychiatry Neurol. 1993 Oct-Dec;6(4):205-9. Abstract
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