Valproate (2-propylpentanoate) is available as valproic acid, sodium valproate and semisodium valproate. It has actions on dopamine, GABA and glutamate neurotransmission and intracellular signaling. Its main psychiatric use is to treat bipolar disorder. It has been used in other psychiatric disorders, including schizophrenia and borderline personality disorder, but data are insufficient to recommend this. In acute mania, valproate monotherapy has similar efficacy to antipsychotic drugs and lithium whereas the combination of valproate and an antipsychotic is more effective than either drug alone. In maintenance treatment of bipolar disorder, valproate monotherapy has comparable efficacy to olanzapine although placebo-controlled evidence is limited. Maintenance treatment with valproate and quetiapine or olanzapine is more efficacious than valproate alone when an acute episode responds to the combination. Common adverse effects of valproate include weight gain, gastrointestinal symptoms, sedation, tremor and mild elevation of hepatic enzymes. Serious hepatic toxicity is rare in adults. Many adverse effects are dose related and resolve with dose reduction. Valproate is teratogenic and specifically associated with neural tube defect. Preliminary evidence has linked in utero exposure to decreased verbal intelligence in the offspring. These effects, plus a probable increased risk of polycystic ovary syndrome, limit valproate's use in women of childbearing potential.
"Valproic acid (VPA) is one of the most frequently prescribed antiepileptic drugs (Löscher, 2002) and is also increasingly used for other indications, such as bipolar psychiatric disorder (Bowden and Singh, 2005), schizophrenia, borderline personality disorder (Haddad et al., 2009), and migraine prophylaxis (Mathew et al., 1995). Antiepileptic therapy often takes years and may even last the entire lifetime of a patient. "
"VPA also blocks the voltage-gated sodium channels and T-type calcium channels . These mechanisms make VPA a broad spectrum anticonvulsant drug and it is also prescribed for the treatment of bipolar disorder, schizoaffective disorder, social phobias, neuropathic pain, and for the prophylaxis and treatment of migraine headaches  . It is highly protein bound to albumin (87–95%) and extensively metabolized in liver. "
[Show abstract][Hide abstract] ABSTRACT: Valproic acid, a branched short-chain fatty acid, has numerous action mechanisms which turn it into a broad spectrum anticonvulsant drug and make its use possible in some other pathologies such as bipolar disorder. It is extensively metabolized in liver, representing β -oxidation in the mitochondria one of its main metabolic route (40%). Carnitine is responsible for its entry into the mitochondria as any other fatty acid. Long-term high-dose VPA therapy or acute VPA overdose induces carnitine depletion, resulting in high levels of ammonia in blood. As a high correlation between salivary valproic acid levels and plasma ultrafiltrate levels was found in humans, saliva becomes a promising monitoring fluid in order to study valproic acid pharmacokinetics and its toxic effect. Extended-release (twice daily) formulations of valproic acid or carnitine supplementation are the proposed two therapeutic strategies in order to reverse hyperammonemia.
BioMed Research International 04/2014; 2014:217269. DOI:10.1155/2014/217269 · 2.71 Impact Factor
"Valproic acid (VPA) has traditionally been prescribed for epilepsy, but is increasingly used for psychiatric condition, such as bipolar disease by its modulation on GABA neurotransmission . Furthermore, it has been also shown to be associated with an increased prevalence of autism. "
Recent Advances in Autism Spectrum Disorders - Volume I, Edited by Michael Fitzgerald, 03/2013: chapter Valproic Acid in Autism Spectrum Disorder: From an Environmental Risk Factor to a Reliable Animal Model: pages 143-163; INTECH.
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