valproate

Valproate refers to the salt forms and related derivatives of valproic acid, a short-chain fatty acid used as an antiepileptic and mood stabilizer. It is available as valproic acid, sodium valproate, valproate semisodium, and other salts. Valproate is used to treat a broad range of seizure types and is also prescribed for bipolar disorder and, in some countries, migraine prevention.

Medical uses include broad-spectrum management of epilepsy, effective for generalized tonic-clonic and myoclonic seizures and often used when other anticonvulsants are unsuitable. It is also approved for acute mania and maintenance therapy in bipolar disorder and is used off-label for certain headache disorders. Dosing and duration depend on indication, age, and comorbidities.

Mechanism of action is multifaceted. Valproate increases brain gamma-aminobutyric acid (GABA) levels by inhibiting GABA-degrading enzymes and enhancing GABA synthesis. It also modulates neuronal excitability by blocking voltage-gated sodium and T-type calcium channels and, at higher concentrations, can influence gene expression through histone deacetylase inhibition.

Pharmacokinetics and interactions: Valproate is rapidly absorbed orally and is highly protein-bound. It undergoes hepatic metabolism, primarily by glucuronidation and beta-oxidation. It can interact with many drugs, including agents that affect liver enzymes and protein binding, necessitating monitoring for interactions and adverse effects.

Safety and adverse effects: Notable risks include hepatotoxicity, pancreatitis, teratogenicity with neural tube defects, weight gain, tremor, alopecia, and thrombocytopenia. The risk of severe liver injury is higher in young children and in patients with certain metabolic disorders. Pregnancy is contraindicated unless clearly justified; effective counseling and monitoring are required. Common monitoring includes liver function tests and blood counts, and abrupt discontinuation should be avoided.

Regulatory status: Valproate is widely prescribed and marketed as valproic acid and various salts; it is listed on the WHO essential medicines list in appropriate indications.