Valproic acid chemical structure
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Valproic acid

Valproic acid or 2-Propylpentanoic acid, is a chemical compound that has found clinical use as an anticonvulsant and mood-stabilizing drug, primarily in the treatment of epilepsy and bipolar disorder; but also used to treat migraine headaches and schizophrenia. In epileptics, valproic acid is used to control absence seizures, tonic-clonic seizures (grand mal), complex partial seizures, and the seizures associated with Lennox-Gastaut syndrome. more...

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Related drugs include the sodium salt – Sodium valproate, and a combined formulation – Valproate semisodium.

Valproate is believed to affect the function of the neurotransmitter GABA (as a GABA transaminase inhibitor) in the human brain.This principle was used by Ashoka Jahnavi-Prasad when he suggested that sodium valproate could be a safer alternative to lithium salts in treatment of bipolar illness.

Valproic acid has also been shown to be an inhibitor of an enzyme called histone deacetylase 1 (HDAC1). HDAC1 is needed for HIV to remain in infected cells. A study published in August 2005 revealed that patients treated with valproic acid in addition to highly active antiretroviral therapy (HAART) showed a 75% reduction in latent HIV infection. This may one day lead to a cure for HIV and AIDS.

Another potential indication may be leukemia in juvenile patients. Studies conducted by several European centres are ongoing. Although it is too early to make a definitive statement, preleminary results are encouraging.

Side effects

Common side effects are dyspepsia and/or weight-gain. Less common are dizziness, drowsiness, hair-loss, headaches, nausea, sedation and tremors,

Valproic acid can also rarely cause blood dyscrasia, impaired liver function, jaundice, thrombocytopenia, and prolonged coagulation times. In ~5% of pregnant users, valproic acid will cross the placenta and cause congenital anomalies. Some users have reported growth of curly hair during long-term medication of Sodium Valproate. Note that due to these side effects most doctors will ask for blood test to be worked initially as much as once a week then once every 2 months. Temporary liver enzymes increase has been reported in 20 per cent of cases during the first few months of taking the drug. Inflammation of the liver (hepatitis) is found in rare cases. Your doctor should educate you about hepatitis and how to spot it as the major symptom is jaundice.

There have also been reports of cognitive dysfunction, Parkinsonian syndrome and even pseudoatrophic brain changes in long-term treatment with valproic acid.

Contraindications

Valproate is contraindicated in overweight patients because it causes weight gain as outlined above, and in pregnant women because it is teratogenic. Preexisting liver damage, bone marrow depression and coagulation disorders are additional contraindication.

Formulations

US

  • Capsules – Depakene® by Abbott Laboratories.

UK

  • Capsules – Convulex® by Pfizer.

South Africa

  • Capsules – Convulex® by Byk Madaus.

Read more at Wikipedia.org


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Carnitine levels in valproic acid-treated psychiatric patients: a cross-sectional study
From Alternative Medicine Review, 9/1/05 by F.A. Moreno

Carnitine levels in valproic acid-treated psychiatric patients: a cross-sectional study. Moreno FA, Macey H, Schreiber B. J Clin Psychiatry 2005;66:555-558.

BACKGROUND: Carnitine facilitates the transport of long-chain fatty acids across the mitochondria for beta oxidation, and the removal of potentially toxic acylcoenzyme-A metabolites from the inner aspect of mitochondrion as acylcarnitines. Previous studies suggest a significant decrease in carnitine concentrations and changes in the ratio of acylcarnitine to free carnitine in seizure-disoriented patients treated with valproic acid (VPA), which may lead to clinical manifestations of carnitine deficiency. This study sought to explore whether the same decrease in plasma free carnitine and increase in acylcarnitines are seen when VPA is used in the treatment of patients with psychiatric disease. METHOD: Thirty psychiatric patients treated with VPA for at least six months were selected for the study and granted informed consent for participation. Exclusion criteria included liver disorder or pancreatitis, metabolic defects known to affect plasma carnitine levels, or noncompliance with VPA regimen. Plasma free carnitine, total carnitine, VPA, and amylase levels were determined, and liver function tests (LFFs) were performed. Pearson correlations were conducted between VPA levels, levels and ratios of carnitines, as well as LFTs and amylase levels. RESULTS: Plasma free and total carnitine levels were lower than the reported normal range for the laboratory performing the assay, and the ratio of acylcarnitine to free carnitine was increased. There was a significant positive correlation of VPA levels and acylcarnitine-free carnitine ratio, a trend toward significance between VPA levels and acylcarnitine levels, and a marginal negative correlation between VPA levels and free carnitine levels. VPA levels correlated also with several LFTs and acylcarnitine levels. Octanoyl carnitine and acylcarnitine levels, as well as acylcarnitine-free carnitine and octanoyl-free carnitine ratios, correlated significantly with amylase levels. CONCLUSION: Although the study was limited by a cross-sectional design without direct control comparison, the findings suggest that patients with various psychiatric conditions treated with polypharmacy that includes VPA may have lower plasma carnitine levels than would be expected in healthy controls.

COPYRIGHT 2005 Thorne Research Inc.
COPYRIGHT 2005 Gale Group

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