The measurement of ammonia blood levels in patients taking valproic acid: Looking for problems where they do not exist?

Chicharro, Ada V.; Marinis, Alejandro J. de; Kanner, Andrés M.

doi:10.1016/j.yebeh.2007.06.015

Cited by 65 publications

(57 citation statements)

References 21 publications

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“…22,23 This is variably related to hepatotoxicity and hyperammonemia. 24,25 Even in the absence of frank valproate-induced hyperammonemic encephalopathy, there are reports of reversible cognitive deficits associated with VPA use. 7,10 One prospective study of 36 epilepsy patients (age ranging from 22 to 74) with VPA levels in the normal therapeutic range reported an 86% incidence of cognitive impairment, with degree of cognitive adverse effects highly associated with increased age.…”

Section: Discussionmentioning

confidence: 99%

Chronic divalproex sodium use and brain atrophy in Alzheimer disease

et al. 2011

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Objective:We evaluated the effect of the divalproex sodium formulation of valproic acid on brain volumes using MRI in people with mild to moderate Alzheimer disease (AD) and assessed for changes associated with behavioral and cognitive effects.Methods: Eighty-nine of 313 participants randomized to divalproex or placebo in a 24-month, parallel-group trial received MRI scans at baseline and 12 months. Interval MRI annual percent changes in whole brain, ventricular, and hippocampal volumes were the primary outcomes of interest. Change from baseline in clinical outcomes was assessed at 6-month intervals.Results: There were no baseline differences between active treatment and placebo groups in age, education, brain volumes, clinical rating scores, or APOE ⑀4 carrier status. The group treated with divalproex showed a greater rate of decline in left and right hippocampal and brain volumes (Ϫ10.9% and Ϫ12.4% vs Ϫ5.6% and Ϫ6.3%, and Ϫ3.5% vs Ϫ1.4%, respectively), and a greater rate of ventricular expansion (24.5% vs 9.9%) (p Ͻ 0.001). Mini-Mental State Examination scores showed a more rapid decline with divalproex through month 12 (placebo ϭ Ϫ2.0 Ϯ 4.3, divalproex ϭ Ϫ3.9 Ϯ 4.0) (p ϭ 0.037), although there were no changes on other cognitive, behavioral, or functional ratings at 12 and 24 months.

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Section: Discussionmentioning

confidence: 99%

Chronic divalproex sodium use and brain atrophy in Alzheimer disease

et al. 2011

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“…These include Reye's syndrome, liver diseases, organic acidemias (like propionic or isovaleric acidurias), fatty acid oxidation defects and treatment with several drugs [1,8,9]. In fact, hyperammonemia is a frequent side-effect of valproic acid (2-n-propylpentanoic acid, VPA) treatment, which can potentially evolve to encephalopathy [10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

“…(2) an indirect effect on CPS I, namely by an interference of the drug with the synthesis of NAG, the essential activator of this enzyme [12,[24][25][26][27]; (3) a VPA-induced inhibition of mitochondrial FAO, through several synergistic mechanisms: VPA or metabolites may induce secondary carnitine depletion and ultimately reduce the bioavailability of acetyl-CoA [10,20,28,29]. This latter metabolite is essential for energy production and is one of the substrates for NAGS activity [11,20,30].…”

Section: Introductionmentioning

confidence: 99%

New insights on the mechanisms of valproate-induced hyperammonemia: Inhibition of hepatic N-acetylglutamate synthase activity by valproyl-CoA

Aires

Cruchten

IJlst

et al. 2011

Journal of Hepatology

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“…There have been many reports about the risk factors for hyperammonemia [4]. Recently, we studied a large cohort of 2724 adult patients and 1753 pediatric patients on VPA therapy Electronic supplementary material The online version of this article (doi:10.1007/s00228-015-1939-3) contains supplementary material, which is available to authorized users.…”

Section: Introductionmentioning

confidence: 99%

Changing incidence of hyperammonemia in Japan from 2006 to 2013: expansion of new antiepileptic drugs reduces the risk of hyperammonemia

Yamamoto

Takahashi

Imai

et al. 2015

Eur J Clin Pharmacol

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Drug interactions caused by enzyme-inducing AEDs, especially phenytoin, are closely related to the development of hyperammonemia. This study demonstrated that introduction of new AEDs changed the co-prescribing pattern in patients receiving valproic acid, resulting in a marked decrease of hyperammonemia. Although their higher cost may be problematic, new AEDs are beneficial for reducing the risk of drug interactions.

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The measurement of ammonia blood levels in patients taking valproic acid: Looking for problems where they do not exist?

Cited by 65 publications

References 21 publications

Chronic divalproex sodium use and brain atrophy in Alzheimer disease

Chronic divalproex sodium use and brain atrophy in Alzheimer disease

New insights on the mechanisms of valproate-induced hyperammonemia: Inhibition of hepatic N-acetylglutamate synthase activity by valproyl-CoA

Changing incidence of hyperammonemia in Japan from 2006 to 2013: expansion of new antiepileptic drugs reduces the risk of hyperammonemia

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