valproate valproate valproate (vpa) and its valproic acid, sodium valproate, and valproate semisodium forms are medications primarily used to treat epilepsy and bipolar disorder and prevent migraine headaches. they are useful for the prevention of seizures in those with absence seizures, partial seizures, and generalized seizures. they can be given intravenously or by mouth, and the tablet forms exist in both long- and short-acting formulations. valproateinn: valproic acidclinical datatrade namesdepakote, epilim, convulex, othersother namesvalproic acid; sodium valproate (sodium); valproate semisodium (semisodium); 2-propylvaleric acidahfs/drugs.commonographmedlineplusa682412license data us dailymed: valproic_acid us fda: valproic%20acid pregnancycategory au: d routes ofadministrationby mouth, intravenousatc coden03ag01 (who) legal statuslegal status au: s4 (prescription only) ca: ℞-only uk: pom (prescription only) us: ℞-only pharmacokinetic databioavailabilityrapid absorptionprotein binding80–90%metabolismliver—glucuronide conjugation 30–50%, mitochondrial β-oxidation over 40%elimination half-life9–16 hoursexcretionurine (30–50%)identifiers iupac name 2-propylpentanoic acid cas number99-66-1 ypubchem cid3121iuphar/bps7009drugbankdb00313 ychemspider3009 yunii614oi1z5wikeggd00399 ychebichebi:39867 ychemblchembl109 yniaid chemdb057177comptox dashboard (epa)dtxsid6023733 echa infocard100.002.525 chemical and physical dataformulac8h16o2molar mass144.214 g·mol−13d model (jsmol)interactive image smiles o=c(o)c(ccc)ccc inchi inchi=1s/c8h16o2/c1-3-5-7(6-4-2)8(9)10/h7h,3-6h2,1-2h3,(h,9,10) ykey:nijjyaxoarwzee-uhfffaoysa-n y (verify) common side effects of valproate include nausea, vomiting, somnolence, and dry mouth. serious side effects can include liver failure, and regular monitoring of liver function tests is therefore recommended. other serious risks include pancreatitis and an increased suicide risk. valproate is known to cause serious abnormalities in fetuses if taken during pregnancy, and is contra-indicated for women of childbearing age unless the drug is essential to their medical condition. as of 2022 the drug was still prescribed in the uk to potentially pregnant women, but use declined by 51% from 2018–19 to 2020–21. valproate's precise mechanism of action is unclear. proposed mechanisms include affecting gaba levels, blocking voltage-gated sodium channels, and inhibiting histone deacetylases. valproic acid is a branched short-chain fatty acid (scfa) made from valeric acid. valproate was first made in 1881 and came into medical use in 1962. it is on the world health organization's list of essential medicines and is available as a generic medication. in 2020, it was the 109th most commonly prescribed medication in the united states, with more than 6 million prescriptions. terminology valproic acid (vpa) is an organic weak acid. the conjugate base is valproate. the sodium salt of the acid is sodium valproate and a coordination complex of the two is known as valproate semisodium. medical uses 500mg tablets of depakote extended-release it is used primarily to treat epilepsy and bipolar disorder. it is also used to prevent migraine headaches. epilepsy valproate has a broad spectrum of anticonvulsant activity, although it is primarily used as a first-line treatment for tonic–clonic seizures, absence seizures and myoclonic seizures and as a second-line treatment for partial seizures and infantile spasms. it has also been successfully given intravenously to treat status epilepticus. bipolar disorder valproate products are also used to treat manic or mixed episodes of bipolar disorder. schizophrenia a 2016 systematic review compared the efficacy of valproate as an add-on for people with schizophrenia: there is limited evidence that adding valproate to antipsychotics may be effective for overall response and also for specific symptoms, especially in terms of excitement and aggression. valproate was associated with a number of adverse events among which sedation and dizziness appeared more frequently than in the control groups. outcome findings in words findings in numbers quality of evidence global outcome clinically significant responsewhen added to antipsychotic drugs valproate probably increases the chance of improvement. data are based on moderate quality evidence. rr 1.31 (1.16 to 1.47)moderate leaving the study early for any reasonvalproate in combination with antipsychotics may slightly reduce the chance of leaving the study early, but the difference between the two treatments is not clear. data supporting this finding are based on moderate quality evidence. rr 0.76 (0.47 to 1.24)moderate use of additional medication for sedationthe combination of valproate and antipsychotic drugs may increase the chance of being given additional sedating medication, but, at present it is not possible to be confident about the difference between the two treatments and data supporting this finding are very limited. rr 3.65 (0.11 to 122.31)very low mental state average score (panss total, high = poor)on average, people receiving the valproate combination scored lower (better) than people treated with antipsychotics in combination with placebo or antipsychotic drugs alone. there was a clear difference between the groups, but the meaning of this in day-to-day care is unclear.md 5.85 lower (7.8 lower to 3.91 lower)moderate adverse events abnormal liver function (blood test changes)*adding valproate to antipsychotic drug treatment does not clearly cause liver problems. data supporting this finding are based on moderate quality evidence. rr 1.26 (0.72 to 2.22)moderate nauseaadding valproate to antipsychotic drugs probably causes little or no increase to the chance of feeling sick, but the difference between the two treatments is not clear. data supporting this finding are based on moderate quality evidence. rr 1.22 (0.80 to 1.86)moderate missing outcomes and notes quality of life outcomes were not reported in the included studies. *increase in alanine transaminase/gamma-glutamyl transpeptidase dopamine dysregulation syndrome based upon five case reports, valproic acid may have efficacy in controlling the symptoms of the dopamine dysregulation syndrome that arise from the treatment of parkinson's disease with levodopa. migraines valproate is also used to prevent migraine headaches. other the medication has been tested in the treatment of aids and cancer, owing to its histone-deacetylase-inhibiting effects. contraindications contraindications include: pre-existing acute or chronic liver dysfunction or family history of severe liver inflammation (hepatitis), particularly medicine related. known hypersensitivity to valproate or any of the ingredients used in the preparation urea cycle disorders hepatic porphyria hepatotoxicity mitochondrial disease pancreatitis porphyria pregnancy (except when no other treatments are available for the treatment of epilepsy) adverse effects