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Valproate

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Valproate
INN:valproic acid
Clinical data
Trade namesDepakote, Epilim, Convulex,others
Other namesVPA; valproic acid; sodium valproate (sodium); valproate semisodium (semisodium); 2-propylvaleric acid
AHFS/Drugs.comMonograph
MedlinePlusa682412
License data
Pregnancy
category
  • AU:D
Routes of
administration		By mouth,intravenous
ATC code
Legal status
Legal status
Pharmacokineticdata
BioavailabilityRapid absorption
Protein binding80–90%[6]
MetabolismLiver—glucuronide conjugation30–50%,mitochondrial β-oxidationover 40%
Eliminationhalf-life9–16 hours[6]
ExcretionUrine (30–50%)[6]
Identifiers
  • 2-propylpentanoic acid
CAS Number
PubChemCID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
NIAID ChemDB
CompTox Dashboard(EPA)
ECHA InfoCard100.002.525Edit this at Wikidata
Chemical and physical data
FormulaC8H16O2
Molar mass144.214g·mol−1
3D model (JSmol)
  • O=C(O)C(CCC)CCC
  • InChI=1S/C8H16O2/c1-3-5-7(6-4-2)8(9)10/h7H,3-6H2,1-2H3,(H,9,10)checkY
  • Key:NIJJYAXOARWZEE-UHFFFAOYSA-NcheckY
(verify)

Valproate(valproic acid,VPA,sodium valproate,andvalproate semisodiumforms) are medications primarily used to treatepilepsyandbipolar disorderand preventmigraine headaches.[7]They are useful for the prevention of seizures in those withabsence seizures,partial seizures,andgeneralized seizures.[7]They can be givenintravenouslyor by mouth, and the tablet forms exist in both long- and short-acting formulations.[7]

Common side effects of valproate include nausea, vomiting,somnolence,and dry mouth.[7]Serious side effects can includeliver failure,and regular monitoring ofliver function testsis therefore recommended.[7]Other serious risks includepancreatitisand an increasedsuiciderisk.[7]Valproate is known to cause serious abnormalities in fetuses if taken duringpregnancy,[7][8]and is contra-indicated for women of childbearing age unless the drug is essential to their medical condition and the recipient is also prescribed acontraceptive.[7][9][4]TheUnited States Food and Drug Administrationhas indicated ablack box warninggiven the frequency and severity of the side effects andteratogenicity.[4]Additionally, there is also a black box warning due to risk ofhepatotoxicityand pancreatitis.[10]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.[11]

Valproate's precise mechanism of action is unclear.[7][12]Proposed mechanisms include affectingGABAlevels, blockingvoltage-gated sodium channels,inhibitinghistone deacetylases,and increasingLEF1.[13][14][15]Valproic acid is a branchedshort-chain fatty acid(SCFA), aderivativeofvaleric acid.[13]

Valproate was originally synthesized in 1881 and came into medical use in 1962.[16]It is on theWorld Health Organization's List of Essential Medicines[17][18]and is available as ageneric medication.[7]In 2021, it was the 155th most commonly prescribed medication in the United States, with more than 3million prescriptions.[19][20]

Medical uses[edit]

500mg tablets of Depakote extended-release

It is used primarily to treatepilepsyandbipolar disorderand to preventmigraine headaches.[21]

Epilepsy[edit]

Valproate has a broad spectrum ofanticonvulsantactivity, although it is primarily used as a first-line treatment fortonic–clonic seizures,absence seizuresandmyoclonic seizuresand as a second-line treatment forpartial seizuresandinfantile spasms.[21][22]It has also been successfully givenintravenouslyto treatstatus epilepticus.[23][24]

In the US, valproic acid is an anti-epileptic drugindicatedfor the treatment of manic episodes associated with bipolar disorder; monotherapy and adjunctive therapy of complex partial seizures and simple and complex absence seizures; adjunctive therapy in people with multiple seizure types that include absence seizures.[4][5]

Mental illness[edit]

Valproate products are used to treat manic or mixed episodes ofbipolar disorder.[25][26]

A 2016systematic reviewcompared the efficacy of valproate as an add-on for people withschizophrenia:[27]

There is limited evidence that adding valproate toantipsychoticsmay 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.[27]

Other neurological indications[edit]

Based upon five case reports, valproic acid may have efficacy in controlling the symptoms of thedopamine dysregulation syndromethat arise from the treatment ofParkinson's diseasewithlevodopa.[28][29][30]

Valproate is also used to preventmigraine headaches.

Other[edit]

The medication has been tested in the treatment ofAIDSandcancer,owing to itshistone-deacetylase-inhibiting effects.It has cardioprotective, kidney protective, antiinflammatory, and antimicrobial effects.[31]

Contraindications[edit]

Contraindications include:

Adverse effects[edit]

See also:List of adverse effects of valproic acidandList of adverse effects of valproate semisodium

Most common adverse effects include:[4]

Serious adverse effects include:[4]

Valproic acid has ablack box warningforhepatotoxicity,pancreatitis,and fetal abnormalities.[4]

There is evidence that valproic acid may cause premature growth plateossificationin children and adolescents, resulting in decreased height.[34][35][36]Valproic acid can also causemydriasis,a dilation of the pupils.[37]There is evidence that shows valproic acid may increase the chance ofpolycystic ovary syndrome(PCOS) in women with epilepsy or bipolar disorder. Studies have shown this risk of PCOS is higher in women with epilepsy compared to those with bipolar disorder.[38]Weight gain is also possible.[39]

Pregnancy[edit]

Further information:Fetal valproate spectrum disorder

Valproate causesbirth defects;[40]exposure duringpregnancyis associated with about three times as many major abnormalities as usual, mainlyspina bifidawith the risks being related to the strength of medication used and use of more than one drug.[41][42]"Fetal Valproate Syndrome"(FVS) has been used to refer to the effects of valproate exposure in utero.[43]However, similar to the discussion about the adverse effect of exposure toalcoholin utero ( "fetal alcohol spectrum disorder"), a 2019 study proposed the term"Fetal valproate spectrum disorder"(FVSD) because valproate exposure can lead to a wide range of possible presentations, which can be influenced by various factors (including dosage and timing of exposure). Thedysmorphic featuresassociated with VPA exposure can be subtle and age-dependent, making it challenging to designate individuals as having the characteristic dysmorphism or not, especially for those with limited expertise in the area. While the presence of typical facial dysmorphism is suggestive of the condition, it is not required for diagnosis. This change in terminology to FVSD would benefit individuals affected by the neurodevelopmental effects of VPA exposure without significant malformations, since they can experience impairments in their everyday functioning similar to those with classical FVS.[44]Characteristics of valproate syndrome may include facial features that tend to evolve with age, including atriangle-shaped forehead,tall forehead with bifrontal narrowing,epicanthic folds,medial deficiency of eyebrows, flat nasal bridge, broadnasal root,anteverted nares, shallowphiltrum,long upper lip and thinvermillion borders,thick lower lip and small downturned mouth.[45]Whiledevelopmental delayis usually associated with altered physical characteristics (dysmorphic features), this is not always the case.[46]

Children of mothers taking valproate during pregnancy are at risk for lowerIQs.[47][48][49]Maternal valproate use during pregnancy increased the probability ofautismin the offspring compared to mothers not taking valproate from 1.5% to 4.4%.[50]A 2005 study found rates of autism among children exposed to sodium valproate before birth in the cohort studied were 8.9%.[51]The normal incidence for autism in the general population in 2018 was estimated at 1 in 44 (2.3%).[52]An updated March 2023 report estimates the number increased to 1 in 36 in 2020 (approximately 4% of boys and 1% of girls).[53]A 2009 study found that the 3-year-old children of pregnant women taking valproate had an IQ nine points lower than that of a well-matched control group. However, further research in older children and adults is needed.[54][55][56]

Sodium valproate has been associated withparoxysmal tonic upgazeof childhood, also known as Ouvrier–Billson syndrome, from childhood or fetal exposure. This condition resolved after discontinuing valproate therapy.[57][58]

Women who intend to become pregnant should switch to a different medication if possible or decrease their dose of valproate.[59]Women who become pregnant while taking valproate should be warned that it causes birth defects and cognitive impairment in the newborn, especially at high doses (although valproate is sometimes the only drug that can control seizures, and seizures in pregnancy could have worse outcomes for the fetus than exposure to valproate). Studies have shown that takingfolic acidsupplements can reduce the risk of congenitalneural tubedefects.[4]The use of valproate for migraine or bipolar disorder during pregnancy is contraindicated in theEuropean Unionand theUnited States,and the medicines are not recommended for epilepsy during pregnancy unless there is no other effective treatment available.[60]

Paternal exposure[edit]

A 2023 retrospective study of Norway Denmark and Sweden found a significantly increased risk of neurodevelopmental disabilities in the children of fathers exposed to valproate up to 3 months prior to conception, compared to offspring paternally exposed to lamotrigine/levetiracetam.[61]: 9  This led theEMAto recommend "the need to consider effective contraception, while using valproate and for at least 3 months after treatment discontinuation. Male patients should not donate sperm during treatment and for at least 3 months after treatment discontinuation."[61]: 26 

Elderly[edit]

Valproate may cause increased somnolence in the elderly. In a trial of valproate in elderly patients withdementia,a significantly higher portion of valproate patients had somnolence compared to placebo. In approximately one-half of such patients, there was associated reduced nutritional intake and weight loss.[4]

Overdose and toxicity[edit]

Therapeutic range of valproic acid
Form Lower limit Upper limit Unit
Total (including
protein bound) 		50[62] 125[62] μg/mL or mg/L
350[63] 700[63] μmol/L
Free 6[62] 22[62] μg/mL or mg/L
35[63] 70[63] μmol/L

Excessive amounts of valproic acid can result in somnolence,tremor,stupor,respiratory depression,coma,metabolic acidosis,and death. In general, serum or plasma valproic acid concentrations are in a range of 20–100 mg/L during controlled therapy, but may reach 150–1500 mg/L following acute poisoning. Monitoring of the serum level is often accomplished using commercial immunoassay techniques, although some laboratories employgas or liquid chromatography.[64] In contrast to otherantiepileptic drugs,at present there is little favorable evidence for salivary therapeutic drug monitoring. Salivary levels of valproic acid correlate poorly with serum levels, partly due to valproate's weak acid property (pKa of 4.9).[65]

In severe intoxication,hemoperfusionorhemofiltrationcan be an effective means of hastening elimination of the drug from the body.[66][67]Supportive therapy should be given to all patients experiencing an overdose and urine output should be monitored.[4]SupplementalL-carnitineis indicated in patients having an acute overdose[68][69]and alsoprophylactically[68]in high risk patients.Acetyl-L-carnitinelowershyperammonemialess markedly[70]thanL-carnitine.

Interactions[edit]

Valproate inhibitsCYP2C9,glucuronyl transferase,andepoxide hydrolaseand is highly protein bound and hence may interact with drugs that are substrates for any of these enzymes or are highly protein bound themselves.[32]It may also potentiate the CNS depressant effects of alcohol.[32]It should not be given in conjunction with other antiepileptics due to the potential for reduced clearance of other antiepileptics (includingcarbamazepine,lamotrigine,phenytoinandphenobarbitone) and itself.[32]It may also interact with:[4][32][71]

  • Aspirin:may increase valproate concentrations. May also interfere with valproate's metabolism.
  • Benzodiazepines:may cause CNS depression and there are possible pharmacokinetic interactions.
  • Carbapenemantibiotics: reduce valproate levels, potentially leading to seizures.
  • Cimetidine:inhibits valproate's metabolism in the liver, leading to increased valproate concentrations.
  • Erythromycin:inhibits valproate's metabolism in the liver, leading to increased valproate concentrations.
  • Ethosuximide:valproate may increase ethosuximide concentrations and lead to toxicity.
  • Felbamate:may increase plasma concentrations of valproate.
  • Mefloquine:may increase valproate metabolism combined with the direct epileptogenic effects of mefloquine.
  • Oral contraceptives:may reduce plasma concentrations of valproate.
  • Primidone:may accelerate metabolism of valproate, leading to a decline of serum levels and potentialbreakthrough seizure.
  • Rifampicin:increases the clearance of valproate, leading to decreased valproate concentrations
  • Warfarin:valproate may increase free warfarin concentration and prolong bleeding time.
  • Zidovudine:valproate may increase zidovudine serum concentration and lead to toxicity.

Pharmacology[edit]

Pharmacodynamics[edit]

Although the mechanism of action of valproate is not fully understood,[32]traditionally, its anticonvulsant effect has been attributed to the blockade ofvoltage-gated sodium channelsand increased brain levels of the inhibitory synaptic neurotransmittergamma-aminobutyric acid(GABA).[32]The GABAergic effect is also believed to contribute towards the anti-manic properties of valproate.[32]In animals, sodium valproate raises cerebral and cerebellar levels of GABA, possibly by inhibiting GABA degradative enzymes, such asGABA transaminase,succinate-semialdehyde dehydrogenaseand by inhibiting the re-uptake of GABA by neuronal cells.[32] Prevention of neurotransmitter-induced hyperexcitability of nerve cells viaKv7.2 channelandAKAP5may also contribute to its mechanism.[72]Valproate has been shown to protect against a seizure-induced reduction inphosphatidylinositol (3,4,5)-trisphosphate(PIP3) as a potential therapeutic mechanism.[73]

Valproate is ahistone deacetylase inhibitor.By inhibition ofhistone deacetylase,it promotes more transcriptionally active chromatin structures, that is it exerts an epigenetic effect. This has been proven in mice: Valproic acid induced histone hyperacetylation had brain function effects on the next generation of mice through changes in sperm DNA methylation.[74]Intermediate molecules includeVEGF,BDNF,andGDNF.[75][76]

Endocrine actions[edit]

Valproic acid has been found to be anantagonistof theandrogenandprogesterone receptors,and hence as anonsteroidalantiandrogenandantiprogestogen,at concentrations much lower than therapeutic serum levels.[77]In addition, the drug has been identified as a potentaromatase inhibitor,and suppressesestrogenconcentrations.[78]These actions are likely to be involved in the reproductive endocrine disturbances seen with valproic acid treatment.[77][78]

Valproic acid has been found to directly stimulate androgen biosynthesis in thegonadsvia inhibition of histone deacetylases and has been associated withhyperandrogenismin women and increased4-androstenedionelevels in men.[79][80]High rates ofpolycystic ovary syndromeandmenstrual disordershave also been observed in women treated with valproic acid.[80]

Pharmacokinetics[edit]

Somemetabolitesof valproic acid.Glucuronidationandβ-oxidationare the main metabolic pathways;ω-oxidationmetabolites are consideredhepatotoxic.[81][82]Details see text.

Taken by mouth, valproate is rapidly and virtually completely absorbed from the gut.[81]When in the bloodstream, 80–90% of the substance are bound toplasma proteins,mainlyalbumin.Protein binding is saturable: it decreases with increasing valproate concentration, low albumin concentrations, the patient's age, additional use of other drugs such asaspirin,as well as liver and kidney impairment.[83][84]Concentrations in thecerebrospinal fluidand in breast milk are 1 to 10% of blood plasma concentrations.[81]

The vast majority of valproatemetabolismoccurs in theliver.[85]Valproate is known to be metabolized by thecytochrome P450enzymesCYP2A6,CYP2B6,CYP2C9,andCYP3A5.[85]It is also known to be metabolized by theUDP-glucuronosyltransferaseenzymesUGT1A3,UGT1A4,UGT1A6,UGT1A8,UGT1A9,UGT1A10,UGT2B7,andUGT2B15.[85]Some of the known metabolites of valproate by these enzymes and uncharacterized enzymes include (see image):[85]

  • viaglucuronidation(30–50%): valproic acid β-O-glucuronide
  • viabeta oxidation(>40%): 2E-ene-valproic acid, 2Z-ene-valproic acid, 3-hydroxyvalproic acid, 3-oxovalproic acid
  • viaomega oxidation:5-hydroxyvalproic acid, 2-propyl-glutaric acid
  • some others: 3E-ene-valproic acid, 3Z-ene-valproic acid, 4-ene-valproic acid, 4-hydroxyvalproic acid

All in all, over 20 metabolites are known.[81]

In adult patients taking valproate alone, 30–50% of an administered dose is excreted inurineas the glucuronide conjugate.[85]The other major pathway in the metabolism of valproate ismitochondrialbeta oxidation, which typically accounts for over 40% of an administered dose.[85]Typically, less than 20% of an administered dose is eliminated by other oxidative mechanisms.[85]Less than 3% of an administered dose of valproate is excreted unchanged (i.e., as valproate) in urine.[85]Only a small amount is excreted via the faeces.[81]Elimination half-lifeis 16±3 hours and can decrease to 4–9 hours when combined withenzyme inducers.[81][84]

Chemistry[edit]

Valproic acid is a branchedshort-chain fatty acidand the 2-n-propylderivative ofvaleric acid.[13]

History[edit]

Valproic acid was first synthesized in 1882 byBeverly S. Burtonas ananalogueofvaleric acid,found naturally invalerian.[86]Valproic acid is acarboxylic acid,a clear liquid at room temperature. For many decades, its only use was in laboratories as a "metabolically inert" solvent for organic compounds. In 1962, the French researcher Pierre Eymard serendipitously discovered the anticonvulsant properties of valproic acid while using it as a vehicle for a number of other compounds that were being screened for antiseizure activity. He found it preventedpentylenetetrazol-induced convulsions inlaboratory rats.[87]It was approved as an antiepileptic drug in 1967 in France and has become the most widely prescribed antiepileptic drug worldwide.[88]Valproic acid has also been used for migraineprophylaxisand bipolar disorder.[89]

Society and culture[edit]

Valproate is available as ageneric medication.[7]

Approval status[edit]

Indications United States
FDA-labelled indication?[6] 		Australia
TGA-labelled indication?[21] 		United Kingdom
MHRA-labelled indication?[90] 		Literature support
Epilepsy Yes Yes Yes Limited (depends on the seizure type; it can help with certain kinds of seizures: drug-resistant epilepsy, partial and absence seizures, can be used againstglioblastomaand other tumors both to improve survival and treat seizures, and againsttonic–clonic seizuresand status epilepticus).[91][92][93][94]
Bipolar mania Yes Yes Yes Limited.[95][failed verification]
Bipolar depression No No No Moderate.[96]
Bipolar maintenance No No No Limited.[97]
Migraine prophylaxis Yes Yes (accepted) No Limited.
Acute migraine management No No No Only negative results.[98]
Schizophrenia No No No Weak evidence.[99]
Agitation in dementia No No No Weak evidence. Not recommended for agitation in people with dementia.[100]Increased rate of adverse effects, including a risk of serious adverse effects.[100]
Fragile X syndrome Yes (orphan) No No Limited.[76]
Familial adenomatous polyposis Yes (orphan) No No Limited.
Chronic pain & fibromyalgia No No No Limited.[101]
Alcohol hallucinosis No No No One randomised double-blind placebo-controlled trial.[102]
Intractable hiccups No No No Limited, five case reports support its efficacy, however.[103]
Non-epileptic myoclonus No No No Limited, three case reports support its efficacy, however.[104]
Cluster headaches No No No Limited, two case reports support its efficacy.[105]
West syndrome No No No A prospective clinical trial supported its efficacy in treating infantile spasms.[106]
HIV infection eradication No No No Double-blind placebo-controlled trials have been negative.[107][108][109]
Myelodysplastic syndrome No No No Several clinical trials have confirmed its efficacy as a monotherapy,[110]as an adjunct totretinoin[110]and as an adjunct to hydralazine.[111]
Acute myeloid leukaemia No No No Two clinical trials have confirmed its efficacy in this indication as both a monotherapy and as an adjunct totretinoin.[112][113][114]
Cervical cancer No No No One clinical trial supports its use here.[115]
Malignant melanoma No No No One phase II study has seemed to discount its efficacy.[116]
Breast cancer No No No A phase II study has supported its efficacy.[117]
Impulse control disorder No No No Limited.[118][119]

Off-label uses[edit]

In 2012, pharmaceutical companyAbbottpaid $1.6 billion in fines to US federal and state governments for illegal promotion of off-label uses for Depakote, including the sedation of elderly nursing home residents.[120][121]

Some studies have suggested that valproate may reopen thecritical periodfor learningabsolute pitchand possibly other skills such as language.[122][123]

Formulations[edit]

Sodium valproate
Clinical data
Other namesvalproate sodium (USANUS)
License data
Legal status
Legal status
Identifiers
  • sodium 2-propylpentanoate
CAS Number
PubChemCID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard(EPA)
ECHA InfoCard100.002.525Edit this at Wikidata
Chemical and physical data
FormulaC8H15NaO2
Molar mass166.196g·mol−1
3D model (JSmol)
  • CCCC(CCC)C(=O)[O-].[Na+]
  • InChI=1S/C8H16O2.Na/c1-3-5-7(6-4-2)8(9)10;/h7H,3-6H2,1-2H3,(H,9,10);/q;+1/p-1checkY
  • Key:AEQFSUDEHCCHBT-UHFFFAOYSA-McheckY
(verify)
Valproate semisodium
Clinical data
Trade namesDepakote, others
Other namessemisodium valproate, divalproex sodium (USANUS)
License data
Legal status
Legal status
Identifiers
  • sodium 2-propylpentanoate;2-propylpentanoic acid
CAS Number
PubChemCID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard(EPA)
ECHA InfoCard100.002.525Edit this at Wikidata
Chemical and physical data
FormulaC16H31NaO4
Molar mass310.410g·mol−1
3D model (JSmol)
  • CCCC(CCC)C(=O)O.CCCC(CCC)C(=O)[O-].[Na+]
  • InChI=1S/2C8H16O2.Na/c2*1-3-5-7(6-4-2)8(9)10;/h2*7H,3-6H2,1-2H3,(H,9,10);/q;;+1/p-1checkY
  • Key:MSRILKIQRXUYCT-UHFFFAOYSA-McheckY

Valproate exists in two main molecular variants:sodium valproateandvalproic acid without sodium(often implied by simplyvalproate). A mixture between these two is termedsemisodium valproate.It is unclear whether there is any difference in efficacy between these variants, except from the fact that about 10% more mass ofsodium valproateis needed thanvalproic acid without sodiumto compensate for the sodium itself.[126]

Terminology[edit]

Valproate is a negative ion. Theconjugate acidof valproate is valproic acid (VPA). Valproic acid is fully ionized into valproate at the physiologic pH of the human body, and valproate is the active form of the drug. Sodium valproate is the sodiumsaltof valproic acid. Divalproex sodium is acoordination complexcomposed of equal parts of valproic acid and sodium valproate.[127]

Brand names of valproic acid[edit]

Branded products include:

Brand names of sodium valproate[edit]

Portugal[edit]
  • Tablets – Diplexil-R byBial.
United States[edit]
  • Intravenous injection – Depacon by Abbott Laboratories.
  • Syrup – Depakene by Abbott Laboratories. (Note: Depakenecapsulesare valproic acid).
  • Depakote tablets are a mixture of sodium valproate and valproic acid.
  • Tablets – Eliaxim by Bial.
Australia[edit]
  • Epilim Crushable Tablets Sanofi[130]
  • Epilim Sugar Free Liquid Sanofi[130]
  • Epilim Syrup Sanofi[130]
  • Epilim Tablets Sanofi[130]
  • Sodium Valproate Sandoz Tablets Sanofi
  • Valpro Tablets Alphapharm
  • Valproate Winthrop Tablets Sanofi
  • Valprease tablets Sigma
New Zealand[edit]
  • Epilim by Sanofi-Aventis

All the above formulations arePharmac-subsidised.[131]

UK[edit]
  • Depakote Tablets (as in USA)
  • Tablets – Orlept by Wockhardt and Epilim by Sanofi
  • Oral solution – Orlept Sugar Free by Wockhardt and Epilim by Sanofi
  • Syrup – Epilim by Sanofi-Aventis
  • Intravenous injection – Epilim Intravenous by Sanofi
  • Extended release tablets – Epilim Chrono by Sanofi is a combination of sodium valproate and valproic acid in a 2.3:1 ratio.
  • Enteric-coated tablets – Epilim EC200 by Sanofi is a 200 mg sodium valproateenteric-coatedtablet.
UK only[edit]
  • Capsules – Episenta prolonged release by Beacon
  • Sachets – Episenta prolonged release by Beacon
  • Intravenous solution for injection – Episenta solution for injection by Beacon
Germany, Switzerland, Norway, Finland, Sweden[edit]
  • Tablets – Orfiril by Desitin Pharmaceuticals
  • Intravenous injection – Orfiril IV by Desitin Pharmaceuticals
South Africa[edit]
  • Syrup – Convulex by Byk Madaus[132]
  • Tablets – Epilim by Sanofi-synthelabo
Malaysia[edit]
  • Tablets – Epilim (200 ENTERIC COATED) by Sanofi-Aventis
  • Controlled release tablets – Epilim Chrono (500 CONTROLLED RELEASE) by Sanofi-Aventis[133]
Romania[edit]
  • Companies are SANOFI-AVENTIS FRANCE, GEROT PHARMAZEUTIKA GMBH and DESITIN ARZNEIMITTEL GMBH
  • Types are Syrup, Extended release mini tablets, Gastric resistant coated tablets, Gastric resistant soft capsules, Extended release capsules, Extended release tablets and Extended release coated tablets
Canada[edit]
Japan[edit]
  • Tablets – Depakene byKyowa Hakko Kirin
  • Extended release tablets – Depakene-R by Kyowa Hakko Kogyo and Selenica-R byKowa
  • Syrup – Depakene by Kyowa Hakko Kogyo
Europe[edit]

In much of Europe, Dépakine and Depakine Chrono (tablets) are equivalent to Epilim and Epilim Chrono above.

Taiwan[edit]
Iran[edit]
  • Tablets – Epival 200 (enteric coated tablet) and Epival 500 (extended release tablet) by Iran Najo
  • Slow release tablets – Depakine Chrono bySanofi Winthrop Industrie(France)
Israel[edit]

Depalept and Depalept Chrono (extended release tablets) are equivalent to Epilim and Epilim Chrono above. Manufactured and distributed bySanofi-Aventis.

India, Russia andCIScountries[edit]
  • Valparin Chrono by Sanofi India
  • Valprol CR by Intas Pharmaceutical (India)
  • Encorate Chrono by Sun Pharmaceutical (India)
  • Serven Chrono by Leeven APL Biotech (India)
Uruguay[edit]
  • Tablets – DI DPA by Megalabs

Brand names of valproate semisodium[edit]

  • Brazil – Depakote byAbbott Laboratoriesand Torval CR by Torrent do Brasil
  • Canada – Epival by Abbott Laboratories
  • Mexico – Epival and Epival ER (extended release) by Abbott Laboratories
  • United Kingdom – Depakote (for psychiatric conditions) and Epilim (for epilepsy) bySanofi-Aventisand generics
  • United States – Depakote and Depakote ER (extended release) by Abbott Laboratories and generics[4]
  • India – Valance and Valance OD by Abbott Healthcare Pvt Ltd, Divalid ER by Linux laboratories Pvt Ltd, Valex ER by Sigmund Promedica, Dicorate by Sun Pharma
  • Germany – Ergenyl Chrono by Sanofi-Aventis and generics
  • Chile – Valcote and Valcote ER by Abbott Laboratories
  • France and other European countries – Depakote
  • Peru – Divalprax by AC Farma Laboratories
  • China – Diprate OD

Research[edit]

A 2023 systematic review of the literature identified only one study in which valproate was evaluated in the treatment of seizures in infants aged 1 to 36 months. In a randomized control trial, valproate alone was found to show poorer outcomes for infants than valproate plus levetiracetam in terms of reduction of seizures, freedom from seizures, daily living ability, quality of life, and cognitive abilities.[134]

References[edit]

  1. ^abc"FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)".nctr-crs.fda.gov.FDA.Retrieved22 October2023.
  2. ^Anvisa(31 March 2023)."RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial"[Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese).Diário Oficial da União(published 4 April 2023).Archivedfrom the original on 3 August 2023.Retrieved3 August2023.
  3. ^"Product monograph brand safety updates".Health Canada.7 July 2016.Retrieved13 July2024.
  4. ^abcdefghijklmn"Depakote- divalproex sodium tablet, delayed release".Archivedfrom the original on 5 March 2016.Retrieved10 November2015.
  5. ^abcd"Depakote ER- divalproex sodium tablet, extended release".DailyMed.24 February 2023.Archivedfrom the original on 28 January 2023.Retrieved19 February2024.
  6. ^abcd"Depakene, Stavzor (valproic acid) dosing, indications, interactions, adverse effects, and more".Medscape Reference.WebMD.Archivedfrom the original on 21 February 2014.Retrieved13 February2014.
  7. ^abcdefghijk"Valproic Acid".The American Society of Health-System Pharmacists. 24 November 2020.Archivedfrom the original on 31 July 2017.
  8. ^"Valproate banned without the pregnancy prevention programme".GOV.UK.Archivedfrom the original on 24 April 2018.Retrieved26 April2018.
  9. ^"Drug Safety Update - Valproate medicines (Epilim, Depakote): contraindicated in women and girls of childbearing potential unless conditions of Pregnancy Prevention Programme are met".GOV.UK - Medicines and Healthcare products Regulatory Agency.24 April 2018.Archivedfrom the original on 7 January 2023.Retrieved17 April2022.
  10. ^"FDA Information on Valporate"(PDF).
  11. ^Davis N (17 April 2022)."Sodium valproate: what are dangers of epilepsy drug for unborn babies?".The Observer.Archivedfrom the original on 28 July 2022.Retrieved17 April2022.
  12. ^Owens MJ, Nemeroff CB (2003). "Pharmacology of valproate".Psychopharmacology Bulletin.37(Suppl 2): 17–24.PMID14624230.
  13. ^abcGhodke-Puranik Y, Thorn CF, Lamba JK, Leeder JS, Song W, Birnbaum AK, et al. (April 2013)."Valproic acid pathway: pharmacokinetics and pharmacodynamics".Pharmacogenetics and Genomics.23(4): 236–241.doi:10.1097/FPC.0b013e32835ea0b2.PMC3696515.PMID23407051.
  14. ^"Valproic acid".DrugBank.University of Alberta. 29 July 2017. Archived fromthe originalon 31 July 2017.Retrieved30 July2017.
  15. ^Santos R, Linker SB, Stern S, Mendes AP, Shokhirev MN, Erikson G, et al. (June 2021)."Deficient LEF1 expression is associated with lithium resistance and hyperexcitability in neurons derived from bipolar disorder patients".Molecular Psychiatry.26(6): 2440–2456.doi:10.1038/s41380-020-00981-3.PMC9129103.PMID33398088.
  16. ^Scott DF (1993).The history of epileptic therapy: an account of how medication was developed(1st ed.). Carnforth u.a.: Parthenon Publ. Group. p. 131.ISBN978-1-85070-391-4.Archivedfrom the original on 14 January 2023.Retrieved17 September2017.
  17. ^World Health Organization(2019).World Health Organization model list of essential medicines: 21st list 2019.Geneva: World Health Organization.hdl:10665/325771.WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  18. ^World Health Organization(2021).World Health Organization model list of essential medicines: 22nd list (2021).Geneva: World Health Organization.hdl:10665/345533.WHO/MHP/HPS/EML/2021.02.
  19. ^"The Top 300 of 2021".ClinCalc.Archivedfrom the original on 15 January 2024.Retrieved14 January2024.
  20. ^"Valproate - Drug Usage Statistics".ClinCalc.Archivedfrom the original on 6 October 2021.Retrieved14 January2024.
  21. ^abcRossi, S, ed. (2013).Australian Medicines Handbook(2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust.ISBN978-0-9805790-9-3.
  22. ^Löscher W (2002). "Basic pharmacology of valproate: a review after 35 years of clinical use for the treatment of epilepsy".CNS Drugs.16(10): 669–694.doi:10.2165/00023210-200216100-00003.PMID12269861.S2CID67999301.
  23. ^Olsen KB, Taubøll E, Gjerstad L (2007). "Valproate is an effective, well-tolerated drug for treatment of status epilepticus/serial attacks in adults".Acta Neurologica Scandinavica. Supplementum.187:51–54.doi:10.1111/j.1600-0404.2007.00847.x.PMID17419829.S2CID11159645.
  24. ^Kwan SY (June 2010)."The role of intravenous valproate in convulsive status epilepticus in the future"(PDF).Editorial.Acta Neurologica Taiwanica.19(2): 78–81.PMID20830628.Archived(PDF)from the original on 19 February 2024.Retrieved19 February2024.
  25. ^"Valproate Information".U.S.Food and Drug Administration(FDA).Archivedfrom the original on 3 May 2015.Retrieved24 April2015.
  26. ^Jochim J, Rifkin-Zybutz RP, Geddes J, Cipriani A (October 2019)."Valproate for acute mania".The Cochrane Database of Systematic Reviews.2019(10): CD004052.doi:10.1002/14651858.CD004052.pub2.PMC6797024.PMID31621892.
  27. ^abWang Y, Xia J, Helfer B, Li C, Leucht S (November 2016)."Valproate for schizophrenia".The Cochrane Database of Systematic Reviews.2016(11): CD004028.doi:10.1002/14651858.CD004028.pub4.PMC6734130.PMID27884042.Archived fromthe originalon 29 July 2017.Retrieved27 July2017.
  28. ^Pirritano D, Plastino M, Bosco D, Gallelli L, Siniscalchi A, De Sarro G (2014)."Gambling disorder during dopamine replacement treatment in Parkinson's disease: a comprehensive review".BioMed Research International.2014:728038.doi:10.1155/2014/728038.PMC4119624.PMID25114917.
  29. ^Connolly B, Fox SH (January 2014)."Treatment of cognitive, psychiatric, and affective disorders associated with Parkinson's disease".Neurotherapeutics.11(1): 78–91.doi:10.1007/s13311-013-0238-x.PMC3899484.PMID24288035.
  30. ^Averbeck BB, O'Sullivan SS, Djamshidian A (2014)."Impulsive and compulsive behaviors in Parkinson's disease".Annual Review of Clinical Psychology.10:553–580.doi:10.1146/annurev-clinpsy-032813-153705.PMC4197852.PMID24313567.
  31. ^Singh D, Gupta S, Verma I, Morsy MA, Nair AB, Ahmed AF (October 2021)."Hidden pharmacological activities of valproic acid: A new insight".Biomedicine & Pharmacotherapy.142:112021.doi:10.1016/j.biopha.2021.112021.PMID34463268.
  32. ^abcdefghijklmno"Valpro sodium valproate"(PDF).TGA eBusiness Services.Alphapharm Pty Limited. 16 December 2013.Archivedfrom the original on 27 August 2021.Retrieved14 February2014.
  33. ^"Depakote 250mg Tablets - Summary of Product Characteristics".electronic Medicines Compendium.Sanofi. 28 November 2013.Archivedfrom the original on 1 February 2014.Retrieved18 January2014.
  34. ^Wu S, Legido A, De Luca F (January 2004). "Effects of valproic acid on longitudinal bone growth".Journal of Child Neurology.19(1): 26–30.doi:10.1177/088307380401900105011.PMID15032379.S2CID19827846.
  35. ^Robinson PB, Harvey W, Belal MS (February 1988)."Inhibition of cartilage growth by the anticonvulsant drugs diphenylhydantoin and sodium valproate".British Journal of Experimental Pathology.69(1): 17–22.PMC2013195.PMID3126792.
  36. ^Guo CY, Ronen GM, Atkinson SA (September 2001). "Long-term valproate and lamotrigine treatment may be a marker for reduced growth and bone mass in children with epilepsy".Epilepsia.42(9): 1141–1147.doi:10.1046/j.1528-1157.2001.416800.x.PMID11580761.S2CID25499280.
  37. ^"Could Depakote cause Mydriasis".eHealthMe.com. 18 November 2014. Archived fromthe originalon 5 December 2014.Retrieved24 April2015.
  38. ^Bilo L, Meo R (October 2008). "Polycystic ovary syndrome in women using valproate: a review".Gynecological Endocrinology.24(10): 562–570.doi:10.1080/09513590802288259.PMID19012099.S2CID36426338.
  39. ^Chukwu J, Delanty N, Webb D, Cavalleri GL (January 2014). "Weight change, genetics and antiepileptic drugs".Expert Review of Clinical Pharmacology.7(1): 43–51.doi:10.1586/17512433.2014.857599.PMID24308788.S2CID33444886.
  40. ^New evidence in France of harm from epilepsy drug valproateArchived21 April 2017 at theWayback MachineBBC, 2017
  41. ^Koch S, Göpfert-Geyer I, Jäger-Roman E, Jakob S, Huth H, Hartmann A, et al. (February 1983). "[Anti-epileptic agents during pregnancy. A prospective study on the course of pregnancy, malformations and child development]".Deutsche Medizinische Wochenschrift(in German).108(7): 250–257.doi:10.1055/s-2008-1069536.PMID6402356.
  42. ^Moore SJ, Turnpenny P, Quinn A, Glover S, Lloyd DJ, Montgomery T, et al. (July 2000)."A clinical study of 57 children with fetal anticonvulsant syndromes".Journal of Medical Genetics.37(7): 489–497.doi:10.1136/jmg.37.7.489.PMC1734633.PMID10882750.
  43. ^Ornoy A (July 2009). "Valproic acid in pregnancy: how much are we endangering the embryo and fetus?".Reproductive Toxicology.28(1): 1–10.Bibcode:2009RepTx..28....1O.doi:10.1016/j.reprotox.2009.02.014.PMID19490988.
  44. ^Clayton-Smith J, Bromley R, Dean J, Journel H, Odent S, Wood A, et al. (July 2019)."Diagnosis and management of individuals with Fetal Valproate Spectrum Disorder; a consensus statement from the European Reference Network for Congenital Malformations and Intellectual Disability".Orphanet Journal of Rare Diseases.14(1): 180.doi:10.1186/s13023-019-1064-y.PMC6642533.PMID31324220.
  45. ^Kulkarni ML, Zaheeruddin M, Shenoy N, Vani HN (October 2006). "Fetal valproate syndrome".Indian Journal of Pediatrics.73(10): 937–939.doi:10.1007/bf02859291.PMID17090909.S2CID38371596.
  46. ^Adab N, Kini U, Vinten J, Ayres J, Baker G, Clayton-Smith J, et al. (November 2004)."The longer term outcome of children born to mothers with epilepsy".Journal of Neurology, Neurosurgery, and Psychiatry.75(11): 1575–1583.doi:10.1136/jnnp.2003.029132.PMC1738809.PMID15491979.This argues that the fetal valproate syndrome constitutes a real clinical entity that includes developmental delay and cognitive impairments, but that some children might exhibit some developmental delay without marked dysmorphism.
  47. ^Umur AS, Selcuki M, Bursali A, Umur N, Kara B, Vatansever HS, et al. (May 2012). "Simultaneous folate intake may prevent adverse effect of valproic acid on neurulating nervous system".Child's Nervous System.28(5): 729–737.doi:10.1007/s00381-011-1673-9.PMID22246336.S2CID20344828.
  48. ^Cassels C (8 December 2006)."NEAD: In Utero Exposure To Valproate Linked to Poor Cognitive Outcomes in Kids".Medscape.Archivedfrom the original on 31 July 2011.Retrieved23 May2007.
  49. ^Meador KJ, Baker GA, Finnell RH, Kalayjian LA, Liporace JD, Loring DW, et al. (August 2006)."In utero antiepileptic drug exposure: fetal death and malformations".Neurology.67(3): 407–412.doi:10.1212/01.wnl.0000227919.81208.b2.PMC1986655.PMID16894099.
  50. ^Christensen J, Grønborg TK, Sørensen MJ, Schendel D, Parner ET, Pedersen LH, et al. (April 2013)."Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism".JAMA.309(16): 1696–1703.doi:10.1001/jama.2013.2270.PMC4511955.PMID23613074.
  51. ^Rasalam AD, Hailey H, Williams JH, Moore SJ, Turnpenny PD, Lloyd DJ, et al. (August 2005). "Characteristics of fetal anticonvulsant syndrome associated autistic disorder".Developmental Medicine and Child Neurology.47(8): 551–555.doi:10.1017/S0012162205001076.PMID16108456.
  52. ^Maenner MJ, Shaw KA, Bakian AV, et al. Prevalence and Characteristics of Autism Spectrum Disorder Among Children Aged 8 Years — Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2018. MMWR Surveill Summ 2021;70(No. SS-11):1–16. DOI:http://dx.doi.org/10.15585/mmwr.ss7011a1
  53. ^Maenner MJ, Warren Z, Williams AR, et al. Prevalence and Characteristics of Autism Spectrum Disorder Among Children Aged 8 Years — Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2020. MMWR Surveill Summ 2023;72(No. SS-2):1–14. DOI:http://dx.doi.org/10.15585/mmwr.ss7202a1
  54. ^I.Q. Harmed by Epilepsy Drug in UteroArchived29 December 2015 at theWayback MachineBy RONI CARYN RABIN,New York Times,15 April 2009
  55. ^Meador KJ, Baker GA, Browning N, Clayton-Smith J, Combs-Cantrell DT, Cohen M, et al. (April 2009)."Cognitive function at 3 years of age after fetal exposure to antiepileptic drugs".The New England Journal of Medicine.360(16): 1597–1605.doi:10.1056/NEJMoa0803531.PMC2737185.PMID19369666.
  56. ^Valproate Products: Drug Safety Communication - Risk of Impaired Cognitive Development in Children Exposed In Utero (During Pregnancy)Archived2 September 2011 at theWayback Machine.FDA. June 2011
  57. ^Luat AF, Asano E, Chugani HT (September 2007). "Paroxysmal tonic upgaze of childhood with co-existent absence epilepsy".Epileptic Disorders.9(3): 332–336.doi:10.1684/epd.2007.0119.PMID17884759.
  58. ^Ouvrier RA, Billson F (July 1988). "Benign paroxysmal tonic upgaze of childhood".Journal of Child Neurology.3(3): 177–180.doi:10.1177/088307388800300305.PMID3209843.S2CID38127378.
  59. ^Valproate Not To Be Used for Migraine During Pregnancy, FDA WarnsArchived9 July 2013 at theWayback Machine
  60. ^"New measures to avoid valproate exposure in pregnancy endorsed".European Medicines Agency.31 May 2018.Archivedfrom the original on 16 October 2019.Retrieved16 October2019.
  61. ^ab"PRAC non-interventional imposed PASS final study report assessment report"(PDF).EMA.p. 34.
  62. ^abcdSuzanne B (11 December 2013)."Valproic Acid Level".Medscape.Archivedfrom the original on 4 May 2015.Retrieved5 June2015.
  63. ^abcd"Free Valproic Acid Assay (Reference – 2013.03.006) Notice of Assessment"(PDF).Canadian Agency for Drugs and Technologies in Health (CADTH) with INESSS's permission. April 2014. Archived fromthe original(PDF)on 3 March 2016.Retrieved5 June2015.
  64. ^Sztajnkrycer MD (2002). "Valproic acid toxicity: overview and management".Journal of Toxicology. Clinical Toxicology.40(6): 789–801.doi:10.1081/CLT-120014645.PMID12475192.S2CID23031095.
  65. ^Patsalos PN, Berry DJ (February 2013). "Therapeutic drug monitoring of antiepileptic drugs by use of saliva".Therapeutic Drug Monitoring.35(1): 4–29.doi:10.1097/FTD.0b013e31827c11e7.PMID23288091.S2CID15338188.
  66. ^Thanacoody RH (August 2009). "Extracorporeal elimination in acute valproic acid poisoning".Clinical Toxicology.47(7): 609–616.doi:10.1080/15563650903167772.PMID19656009.S2CID13592043.
  67. ^R. Baselt,Disposition of Toxic Drugs and Chemicals in Man,8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 1622–1626.
  68. ^abLheureux PE, Penaloza A, Zahir S, Gris M (October 2005)."Science review: carnitine in the treatment of valproic acid-induced toxicity - what is the evidence?".Critical Care.9(5): 431–440.doi:10.1186/cc3742.PMC1297603.PMID16277730.
  69. ^Mock CM, Schwetschenau KH (January 2012). "Levocarnitine for valproic-acid-induced hyperammonemic encephalopathy".American Journal of Health-System Pharmacy.69(1): 35–39.doi:10.2146/ajhp110049.PMID22180549.
  70. ^Matsuoka M, Igisu H (July 1993). "Comparison of the effects of L-carnitine, D-carnitine and acetyl-L-carnitine on the neurotoxicity of ammonia".Biochemical Pharmacology.46(1): 159–164.doi:10.1016/0006-2952(93)90360-9.PMID8347126.
  71. ^Herzog AG, Farina EL, Blum AS (June 2005)."Serum valproate levels with oral contraceptive use".Epilepsia.46(6): 970–971.doi:10.1111/j.1528-1167.2005.00605.x.PMID15946343.S2CID7696039.
  72. ^Kay HY, Greene DL, Kang S, Kosenko A, Hoshi N (October 2015)."M-current preservation contributes to anticonvulsant effects of valproic acid".The Journal of Clinical Investigation.125(10): 3904–3914.doi:10.1172/JCI79727.PMC4607138.PMID26348896.
  73. ^Chang P, Walker MC, Williams RS (February 2014)."Seizure-induced reduction in PIP3 levels contributes to seizure-activity and is rescued by valproic acid".Neurobiology of Disease.62:296–306.doi:10.1016/j.nbd.2013.10.017.PMC3898270.PMID24148856.
  74. ^Sakai K, Hara K, Tanemura K (3 September 2023)."Testicular histone hyperacetylation in mice by valproic acid administration affects the next generation by changes in sperm DNA methylation".PLOS ONE.18(3): e0282898.Bibcode:2023PLoSO..1882898S.doi:10.1371/journal.pone.0282898.PMC9997898.PMID36893188.
  75. ^Kostrouchová M, Kostrouch Z, Kostrouchová M (2007)."Valproic acid, a molecular lead to multiple regulatory pathways"(PDF).Folia Biologica.53(2): 37–49.PMID17448293.Archived fromthe original(PDF)on 21 February 2014.Retrieved13 February2014.
  76. ^abChiu CT, Wang Z, Hunsberger JG,Chuang DM(January 2013)."Therapeutic potential of mood stabilizers lithium and valproic acid: beyond bipolar disorder".Pharmacological Reviews.65(1): 105–142.doi:10.1124/pr.111.005512.PMC3565922.PMID23300133.
  77. ^abDeath AK, McGrath KC, Handelsman DJ (December 2005). "Valproate is an anti-androgen and anti-progestin".Steroids.70(14): 946–953.doi:10.1016/j.steroids.2005.07.003.hdl:10453/16875.PMID16165177.S2CID25958985.
  78. ^abWyllie E, Cascino GD, Gidal BE, Goodkin HP (17 February 2012).Wyllie's Treatment of Epilepsy: Principles and Practice.Lippincott Williams & Wilkins. pp. 288–.ISBN978-1-4511-5348-4.Archivedfrom the original on 6 June 2014.
  79. ^Uchida H, Maruyama T, Arase T, Ono M, Nagashima T, Masuda H, et al. (June 2005)."Histone acetylation in reproductive organs: Significance of histone deacetylase inhibitors in gene transcription".Reproductive Medicine and Biology.4(2): 115–122.doi:10.1111/j.1447-0578.2005.00101.x.PMC5891791.PMID29662388.
  80. ^abIsojärvi JI, Taubøll E, Herzog AG (2005). "Effect of antiepileptic drugs on reproductive endocrine function in individuals with epilepsy".CNS Drugs.19(3): 207–223.doi:10.2165/00023210-200519030-00003.PMID15740176.S2CID9893959.
  81. ^abcdefHaberfeld H, ed. (2021).Austria-Codex(in German). Vienna: Österreichischer Apothekerverlag. Depakine chrono retard 300 mg Filmtabletten.
  82. ^Kumar S, Wong H, Yeung SA, Riggs KW, Abbott FS, Rurak DW (July 2000). "Disposition of valproic acid in maternal, fetal, and newborn sheep. II: metabolism and renal elimination".Drug Metabolism and Disposition.28(7): 857–864.PMID10859160.
  83. ^Schneemann H, Young L, Koda-Kimble MA, eds. (2001).Angewandte Arzneimitteltherapie(in German). Springer. pp. 28–29.ISBN3-540-41356-1.
  84. ^abValproateFDA Professional Drug Information.Accessed 6 August 2021.
  85. ^abcdefgh"Valproic Acid".DrugBank.University of Alberta. 31 August 2017.Archivedfrom the original on 31 July 2017.Retrieved1 September2017.
  86. ^Burton BS (1882). "On the propyl derivatives and decomposition products of ethylacetoacetate".Am. Chem. J.3:385–395.
  87. ^Meunier H, Carraz G, Neunier Y, Eymard P, Aimard M (1963). "[Pharmacodynamic properties of N-dipropylacetic acid]" [Pharmacodynamic properties of N-dipropylacetic acid].Therapie(in French).18:435–438.PMID13935231.
  88. ^Perucca E (2002). "Pharmacological and therapeutic properties of valproate: a summary after 35 years of clinical experience".CNS Drugs.16(10): 695–714.doi:10.2165/00023210-200216100-00004.PMID12269862.S2CID803106.
  89. ^Henry TR (2003). "The history of valproate in clinical neuroscience".Psychopharmacology Bulletin.37(Suppl 2): 5–16.PMID14624229.
  90. ^Joint Formulary Committee (2013).British National Formulary (BNF)(65 ed.). London, UK: Pharmaceutical Press.ISBN978-0-85711-084-8.
  91. ^Rimmer EM, Richens A (May–June 1985). "An update on sodium valproate".Pharmacotherapy.5(3): 171–184.doi:10.1002/j.1875-9114.1985.tb03413.x.PMID3927267.S2CID7700266.
  92. ^Glauser TA, Cnaan A, Shinnar S, Hirtz DG, Dlugos D, Masur D, et al. (March 2010)."Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy".The New England Journal of Medicine.362(9): 790–799.doi:10.1056/NEJMoa0902014.PMC2924476.PMID20200383.
  93. ^Jiang M (6 April 2015)."Co-Administration of Valproic Acid and Lamotrigine in the Treatment of Refractory Epilepsy (P1.238)".Neurology.84(14 Supplement): P1.238.doi:10.1212/WNL.84.14_supplement.P1.238.S2CID74543829.Archivedfrom the original on 27 August 2021.Retrieved4 May2015– via www.neurology.org.
  94. ^Berendsen S, Kroonen J, Seute T, Snijders T, Broekman ML, Spliet WG, et al. (1 September 2014)."O9.06 * Prognostic Relevance and Oncogenic Correlates of Epilepsy in Glioblastoma Patients".Neuro-Oncology.16(suppl_2): ii21.doi:10.1093/neuonc/nou174.77.PMC4185847.
  95. ^Vasudev K, Mead A, Macritchie K, Young AH (2012). "Valproate in acute mania: is our practice evidence based?".International Journal of Health Care Quality Assurance.25(1): 41–52.doi:10.1108/09526861211192395.PMID22455007.
  96. ^Bond DJ, Lam RW, Yatham LN (August 2010). "Divalproex sodium versus placebo in the treatment of acute bipolar depression: a systematic review and meta-analysis".Journal of Affective Disorders.124(3): 228–234.doi:10.1016/j.jad.2009.11.008.PMID20044142.
  97. ^Haddad PM, Das A, Ashfaq M, Wieck A (May 2009). "A review of valproate in psychiatric practice".Expert Opinion on Drug Metabolism & Toxicology.5(5): 539–551.doi:10.1517/17425250902911455.PMID19409030.S2CID74028228.
  98. ^Frazee LA, Foraker KC (March 2008). "Use of intravenous valproic acid for acute migraine".The Annals of Pharmacotherapy.42(3): 403–407.doi:10.1345/aph.1K531.PMID18303140.S2CID207263036.
  99. ^Wang Y, Xia J, Helfer B, Li C, Leucht S (November 2016)."Valproate for schizophrenia".The Cochrane Database of Systematic Reviews.2016(11): CD004028.doi:10.1002/14651858.CD004028.pub4.PMC6734130.PMID27884042.
  100. ^abBaillon SF, Narayana U, Luxenberg JS, Clifton AV (October 2018)."Valproate preparations for agitation in dementia".The Cochrane Database of Systematic Reviews.2018(10): CD003945.doi:10.1002/14651858.CD003945.pub4.PMC6516950.PMID30293233.
  101. ^Gill D, Derry S, Wiffen PJ, Moore RA (October 2011)."Valproic acid and sodium valproate for neuropathic pain and fibromyalgia in adults".The Cochrane Database of Systematic Reviews.2011(10): CD009183.doi:10.1002/14651858.CD009183.pub2.PMC6540387.PMID21975791.
  102. ^Aliyev ZN, Aliyev NA (July–August 2008)."Valproate treatment of acute alcohol hallucinosis: a double-blind, placebo-controlled study".Alcohol and Alcoholism.43(4): 456–459.doi:10.1093/alcalc/agn043.PMID18495806.
  103. ^Jacobson PL, Messenheimer JA, Farmer TW (November 1981). "Treatment of intractable hiccups with valproic acid".Neurology.31(11): 1458–1460.doi:10.1212/WNL.31.11.1458.PMID6796902.S2CID1578958.
  104. ^Sotaniemi K (July 1982). "Valproic acid in the treatment of nonepileptic myoclonus".Archives of Neurology.39(7): 448–449.doi:10.1001/archneur.1982.00510190066025.PMID6808975.
  105. ^Wheeler SD (July–August 1998)."Significance of migrainous features in cluster headache: divalproex responsiveness".Headache.38(7): 547–551.doi:10.1046/j.1526-4610.1998.3807547.x.PMID15613172.S2CID27948702.
  106. ^Siemes H, Spohr HL, Michael T, Nau H (September–October 1988). "Therapy of infantile spasms with valproate: results of a prospective study".Epilepsia.29(5): 553–560.doi:10.1111/j.1528-1157.1988.tb03760.x.PMID2842127.S2CID23789333.
  107. ^Smith SM (September 2005)."Valproic acid and HIV-1 latency: beyond the sound bite".Retrovirology.2(1): 56.doi:10.1186/1742-4690-2-56.PMC1242254.PMID16168066.
  108. ^Routy JP, Tremblay CL, Angel JB, Trottier B, Rouleau D, Baril JG, et al. (May 2012)."Valproic acid in association with highly active antiretroviral therapy for reducing systemic HIV-1 reservoirs: results from a multicentre randomized clinical study".HIV Medicine.13(5): 291–296.doi:10.1111/j.1468-1293.2011.00975.x.PMID22276680.S2CID27571864.
  109. ^Archin NM, Cheema M, Parker D, Wiegand A, Bosch RJ, Coffin JM, et al. (February 2010)."Antiretroviral intensification and valproic acid lack sustained effect on residual HIV-1 viremia or resting CD4+ cell infection".PLOS ONE.5(2): e9390.Bibcode:2010PLoSO...5.9390A.doi:10.1371/journal.pone.0009390.PMC2826423.PMID20186346.
  110. ^abHardy JR, Rees EA, Gwilliam B, Ling J, Broadley K, A'Hern R (March 2001)."A phase II study to establish the efficacy and toxicity of sodium valproate in patients with cancer-related neuropathic pain".Journal of Pain and Symptom Management.21(3): 204–209.doi:10.1016/S0885-3924(00)00266-9.PMID11239739.[permanent dead link]
  111. ^Candelaria M, Herrera A, Labardini J, González-Fierro A, Trejo-Becerril C, Taja-Chayeb L, et al. (April 2011). "Hydralazine and magnesium valproate as epigenetic treatment for myelodysplastic syndrome. Preliminary results of a phase-II trial".Annals of Hematology.90(4): 379–387.doi:10.1007/s00277-010-1090-2.PMID20922525.S2CID13437134.
  112. ^Bug G, Ritter M, Wassmann B, Schoch C, Heinzel T, Schwarz K, et al. (December 2005). "Clinical trial of valproic acid and all-trans retinoic acid in patients with poor-risk acute myeloid leukemia".Cancer.104(12): 2717–2725.doi:10.1002/cncr.21589.PMID16294345.S2CID1802132.
  113. ^Kuendgen A, Schmid M, Schlenk R, Knipp S, Hildebrandt B, Steidl C, et al. (January 2006)."The histone deacetylase (HDAC) inhibitor valproic acid as monotherapy or in combination with all-trans retinoic acid in patients with acute myeloid leukemia".Cancer.106(1): 112–119.doi:10.1002/cncr.21552.PMID16323176.S2CID43747497.
  114. ^Fredly H, Gjertsen BT, Bruserud O (July 2013)."Histone deacetylase inhibition in the treatment of acute myeloid leukemia: the effects of valproic acid on leukemic cells, and the clinical and experimental evidence for combining valproic acid with other antileukemic agents".Clinical Epigenetics.5(1): 12.doi:10.1186/1868-7083-5-12.PMC3733883.PMID23898968.
  115. ^Coronel J, Cetina L, Pacheco I, Trejo-Becerril C, González-Fierro A, de la Cruz-Hernandez E, et al. (December 2011). "A double-blind, placebo-controlled, randomized phase III trial of chemotherapy plus epigenetic therapy with hydralazine valproate for advanced cervical cancer. Preliminary results".Medical Oncology.28(Suppl 1): S540–S546.doi:10.1007/s12032-010-9700-3.PMID20931299.S2CID207372333.
  116. ^Rocca A, Minucci S, Tosti G, Croci D, Contegno F, Ballarini M, et al. (January 2009)."A phase I-II study of the histone deacetylase inhibitor valproic acid plus chemoimmunotherapy in patients with advanced melanoma".British Journal of Cancer.100(1): 28–36.doi:10.1038/sj.bjc.6604817.PMC2634690.PMID19127265.
  117. ^Munster P, Marchion D, Bicaku E, Lacevic M, Kim J, Centeno B, et al. (April 2009). "Clinical and biological effects of valproic acid as a histone deacetylase inhibitor on tumor and surrogate tissues: phase I/II trial of valproic acid and epirubicin/FEC".Clinical Cancer Research.15(7): 2488–2496.doi:10.1158/1078-0432.CCR-08-1930.PMID19318486.S2CID3230087.
  118. ^Hicks CW, Pandya MM, Itin I, Fernandez HH (June 2011). "Valproate for the treatment of medication-induced impulse-control disorders in three patients with Parkinson's disease".Parkinsonism & Related Disorders.17(5): 379–381.doi:10.1016/j.parkreldis.2011.03.003.PMID21459656.
  119. ^Sriram A, Ward HE, Hassan A, Iyer S, Foote KD, Rodriguez RL, et al. (February 2013). "Valproate as a treatment for dopamine dysregulation syndrome (DDS) in Parkinson's disease".Journal of Neurology.260(2): 521–527.doi:10.1007/s00415-012-6669-1.PMID23007193.S2CID21544457.
  120. ^Aizenman NC (7 May 2012)."Abbott Laboratories to pay $1.6 billion over illegal marketing of Depakote".Washington Post.Archivedfrom the original on 28 June 2018.Retrieved27 June2018.
  121. ^Schmidt M, Thomas K (8 May 2012)."Abbott settles marketing lawsuit".New York Times.Archivedfrom the original on 28 June 2018.Retrieved27 June2018.
  122. ^Gervain J, Vines BW, Chen LM, Seo RJ, Hensch TK, Werker JF, et al. (2013)."Valproate reopens critical-period learning of absolute pitch".Frontiers in Systems Neuroscience.7:102.doi:10.3389/fnsys.2013.00102.PMC3848041.PMID24348349.
  123. ^Thomson H."Learning drugs reawaken grown-up brain's inner child".New Scientist.New Scientist Ltd.Archivedfrom the original on 8 May 2021.Retrieved8 May2021.
  124. ^"Valproate sodium injection".DailyMed.1 January 2021.Archivedfrom the original on 8 October 2022.Retrieved7 October2022.
  125. ^"Valproate sodium injection, solution".DailyMed.29 April 2021.Archivedfrom the original on 9 October 2022.Retrieved7 October2022.
  126. ^Taylor D, Paton C, Kapur S (2009).The Maudsley Prescribing Guidelines(Tenth ed.). CRC Press. p. 124.ISBN978-0-203-09283-5.Archivedfrom the original on 14 January 2023.Retrieved17 September2017.
  127. ^Brayfield A (ed.).Martindale: The Complete Drug Reference.London: Pharmaceutical Press.Archivedfrom the original on 27 August 2021.Retrieved3 March2018.
  128. ^"Depakene- valproic acid capsule, liquid filled".DailyMed.19 September 2019.Archivedfrom the original on 11 July 2020.Retrieved14 April2020.
  129. ^"Depakin - Banca Dati Farmaci dell'AIFA"[Depakin - The AIFA Medicines Database].farmaci.agenziafarmaco.gov.it(in Italian).Italian Medicines Agency.6 June 2023.Archivedfrom the original on 6 June 2023.Retrieved6 June2023.
  130. ^abcd"Australian product information epilim (sodium valproate) crushable tablets, enteric-coated tablets, syrup, liquid"(PDF).TGA eBS.15 April 2020.Archivedfrom the original on 15 March 2020.Retrieved15 April2020.
  131. ^"Sodium valproate -- Pharmaceutical Schedule".Pharmaceutical Management Agency. Archived fromthe originalon 4 March 2016.Retrieved22 June2014.
  132. ^"South African Electronic Package Inserts: Convulex".Archived fromthe originalon 12 August 2010.Retrieved2 January2006.
  133. ^"Malaysian Package Inserts: Epilim".Archivedfrom the original on 5 June 2023.Retrieved5 June2023.
  134. ^Treadwell JR, Wu M, Tsou AY (October 2022).Management of Infantile Epilepsies.effectivehealthcare.ahrq.gov(Report). Rockville (MD): Agency for Healthcare Research and Quality (US).doi:10.23970/ahrqepccer252.PMID36383706.Report No.: 22(23)-EHC004 Report No.: 2021-SR-01.Archivedfrom the original on 5 July 2023.Retrieved12 July2023.
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