Valproate
Valproate is an anticonvulsant and mood-stabilizing medication primarily used in the treatment of epilepsy, bipolar disorder, and migraine prophylaxis. It is considered effective for a wide range of seizure types and is commonly used for both focal and generalized seizures. Additionally, valproate is sometimes used for psychiatric conditions, particularly in the management of bipolar disorder.
Trade Name
Valproate is marketed under various trade names, including Depakote, Depakene, Ergenyl, Orfiril and Epival.
Chemical Properties
Chemical structure: Valproate is a fatty acid derivative, with the active ingredient being valproic acid, a branched-chain carboxylic acid.
Molecular formula: C₈H₁₈O₂
Molecular weight: 158.23 g/mol
Solubility: Valproate is soluble in water and ethanol, and is available in various formulations, including tablets, oral solutions, and extended-release capsules.
Biochemical Properties
Mechanism of action: The exact mechanism of action of valproate is not fully understood, but it is believed to work by increasing the availability of the neurotransmitter GABA (gamma-aminobutyric acid) in the brain, which has an inhibitory effect on neuronal activity. Valproate also inhibits voltage-gated sodium channels and enhances potassium channel activity, contributing to its anticonvulsant effects. Additionally, it may have an effect on neurotransmitter systems like glutamate, further stabilizing neuronal excitability.
Pharmacology
Administration: Valproate can be taken orally in the form of tablets, oral solutions, or extended-release formulations. It is also available as an intravenous solution in certain settings.
Bioavailability: The bioavailability of valproate is nearly 100% when taken orally.
Metabolism: Valproate is extensively metabolized in the liver, primarily through conjugation with glucuronic acid and through the cytochrome P450 enzyme system. It has a relatively complex pharmacokinetic profile, with both active and inactive metabolites.
Half-life: The half-life of valproate ranges from 9 to 16 hours, depending on the individual, which allows for twice-daily or once-daily dosing with extended-release formulations.
Clinical Indications
Epilepsy: It is effective in the management of focal, generalized tonic-clonic, absence seizures, and myoclonic seizures. It can be used as monotherapy or in combination with other anticonvulsants.
Bipolar disorder: Valproate is used as a mood stabilizer to treat manic episodes in bipolar disorder, particularly in patients who are resistant to other treatments.
Migraine prophylaxis: It is also used as a preventive treatment for migraines, although it is not first-line therapy.
Other uses: In certain cases, valproate is used for the management of certain psychiatric conditions or to treat conditions like schizophrenia and aggression in certain populations.
Side Effects
Gastrointestinal issues: Nausea, vomiting, abdominal pain, and indigestion are common, especially at the start of treatment.
Sedation and drowsiness: Valproate can cause sedation, particularly when the dose is being adjusted.
Weight gain: Long-term use of valproate can lead to significant weight gain.
Tremors: Fine tremors, particularly in the hands, are a frequent side effect.
Hepatotoxicity: Valproate can cause liver damage, especially in children under the age of 2 or in those with pre-existing liver conditions. Liver function should be monitored regularly.
Hair thinning: Some people experience hair loss or thinning while on valproate.
Teratogenicity: Valproate is known to be teratogenic and can cause birth defects, especially neural tube defects. It is contraindicated in pregnancy unless no alternatives are available, and women of childbearing age are advised to use contraception while taking valproate.
Pancreatitis: Rarely, valproate can cause inflammation of the pancreas (pancreatitis), which may be severe or life-threatening.
Cognitive effects: Some individuals may experience cognitive impairment or difficulty concentrating, particularly with high doses or prolonged use.
Valproate is a highly effective treatment for epilepsy and bipolar disorder, but its use is associated with several significant side effects, including potential liver damage and teratogenic effects. Regular monitoring of liver function and careful consideration of the risks during pregnancy are important when prescribing valproate. Despite these risks, it remains one of the most widely used anticonvulsants, especially for patients who have not responded to other treatments.
