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.[3] They are useful for the prevention of seizures in those with absence seizures, partial seizures, and generalized seizures.[3] They can be given intravenously or by mouth, and the tablet forms exist in both long- and short-acting formulations.[3]

Valproate
INN: valproic acid
Clinical data
Trade namesDepakote, Epilim, Convulex, others
Other namesValproic 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
Pharmacokinetic data
BioavailabilityRapid absorption
Protein binding80–90%[2]
MetabolismLiver—glucuronide conjugation 30–50%, mitochondrial β-oxidation over 40%
Elimination half-life9–16 hours[2]
ExcretionUrine (30–50%)[2]
Identifiers
  • 2-propylpentanoic acid
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
NIAID ChemDB
CompTox Dashboard (EPA)
ECHA InfoCard100.002.525
Chemical and physical data
FormulaC8H16O2
Molar mass144.214 g·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-N checkY
  (verify)

Common side effects of valproate include nausea, vomiting, somnolence, and dry mouth.[3] Serious side effects can include liver failure, and regular monitoring of liver function tests is therefore recommended.[3] Other serious risks include pancreatitis and an increased suicide risk.[3] Valproate is known to cause serious abnormalities in fetuses if taken during pregnancy,[3][4] and is contra-indicated for women of childbearing age unless the drug is essential to their medical condition.[3][5] 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.[6] Valproate's precise mechanism of action is unclear.[3][7] Proposed mechanisms include affecting GABA levels, blocking voltage-gated sodium channels, inhibiting histone deacetylases, and increasing LEF1.[8][9][10] Valproic acid is a branched short-chain fatty acid (SCFA), a derivative of valeric acid.[8]

Valproate was first made in 1881 and came into medical use in 1962.[11] It is on the World Health Organization's List of Essential Medicines[12][13] and is available as a generic medication.[3] In 2020, it was the 109th most commonly prescribed medication in the United States, with more than 6 million prescriptions.[14][15]

Terminology

Valproate is a negative ion. The conjugate acid of 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 sodium salt of valproic acid. Divalproex sodium is a coordination complex composed of equal parts of valproic acid and sodium valproate.[16]

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.[17]

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.[17][18] It has also been successfully given intravenously to treat status epilepticus.[19][20]

Bipolar disorder

Valproate products are also used to treat manic or mixed episodes of bipolar disorder.[21][22]

Schizophrenia

A 2016 systematic review compared the efficacy of valproate as an add-on for people with schizophrenia:[23]

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.[23]

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.[24][25][26]

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.[27]

Contraindications

Contraindications include:

Adverse effects
See also: List of adverse effects of valproic acid and List of adverse effects of valproate semisodium

Most common adverse effects include:[30]

Serious adverse effects include:[30]

Valproic acid has a black box warning for hepatotoxicity, pancreatitis, and fetal abnormalities.[30]

It is worthy of mentioning that some adverse effects related to valproic acid may be dose-dependent such as pancytopenia.[31]

There is evidence that valproic acid may cause premature growth plate ossification in children and adolescents, resulting in decreased height.[32][33][34] Valproic acid can also cause mydriasis, a dilation of the pupils.[35] There is evidence that shows valproic acid may increase the chance of polycystic 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.[36] Weight gain is also possible.[37]

Pregnancy

Valproate causes birth defects;[38] exposure during pregnancy is associated with about three times as many major abnormalities as usual, mainly spina bifida with the risks being related to the strength of medication used and use of more than one drug.[39][40] "Fetal valproate syndrome" (FVS) has been used to refer to the effects of valproate exposure in utero.[41] However, similar to the discussion about the adverse effect of exposure to alcohol in 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). The dysmorphic features associated 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 benefits 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.[42] Characteristics of valproate syndrome may include facial features that tend to evolve with age, including a triangle-shaped forehead, tall forehead with bifrontal narrowing, epicanthic folds, medial deficiency of eyebrows, flat nasal bridge, broad nasal root, anteverted nares, shallow philtrum, long upper lip and thin vermillion borders, thick lower lip and small downturned mouth.[43] While developmental delay is usually associated with altered physical characteristics (dysmorphic features), this is not always the case.[44]

Children of mothers taking valproate during pregnancy are at risk for lower IQs.[45][46][47] Maternal valproate use during pregnancy increased the probability of autism in the offspring compared to mothers not taking valproate from 1.5% to 4.4%.[48] A 2005 study found rates of autism among children exposed to sodium valproate before birth in the cohort studied were 8.9%.[49] The normal incidence for autism in the general population in 2018 was estimated at 1 in 44 (2.3%).[50] An updated March 2023 report estimates the number increased to 1 in 36 in 2020 (approximately 4% of boys and 1% of girls).[51] 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.[52][53][54]

Sodium valproate has been associated with paroxysmal tonic upgaze of childhood, also known as Ouvrier–Billson syndrome, from childhood or fetal exposure. This condition resolved after discontinuing valproate therapy.[55][56]

Women who intend to become pregnant should switch to a different medication if possible or decrease their dose of valproate.[57] 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 taking folic acid supplements can reduce the risk of congenital neural tube defects.[30] The use of valproate for migraine or bipolar disorder during pregnancy is contraindicated in the European Union and the United States, and the medicines are not recommended for epilepsy during pregnancy unless there is no other effective treatment available.[58]

Elderly

Valproate may cause increased somnolence in the elderly. In a trial of valproate in elderly patients with dementia, 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.[30]

Overdose and toxicity
Therapeutic range of valproic acid
Form Lower limit Upper limit Unit
Total (including
protein bound)		 50[59]125[59]µg/mL or mg/L
350[60]700[60]μmol/L
Free 6[59]22[59]µg/mL or mg/L
35[60]70[60]μmol/L

Excessive amounts of valproic acid can result in somnolence, tremor, stupor, respiratory depression, coma, metabolic acidosis, and death.[61] 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 employ gas or liquid chromatography.[62] In contrast to other antiepileptic 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).[63]

In severe intoxication, hemoperfusion or hemofiltration can be an effective means of hastening elimination of the drug from the body.[64][65] Supportive therapy should be given to all patients experiencing an overdose and urine output should be monitored.[30] Supplemental L-carnitine is indicated in patients having an acute overdose[66][67] and also prophylactically[66] in high risk patients. Acetyl-L-carnitine lowers hyperammonemia less markedly[68] than L-carnitine.

Interactions

Valproate inhibits CYP2C9, glucuronyl transferase, and epoxide hydrolase and is highly protein bound and hence may interact with drugs that are substrates for any of these enzymes or are highly protein bound themselves.[28] It may also potentiate the CNS depressant effects of alcohol.[28] It should not be given in conjunction with other antiepileptics due to the potential for reduced clearance of other antiepileptics (including carbamazepine, lamotrigine, phenytoin and phenobarbitone) and itself.[28] It may also interact with:[30][28][69]

  • Aspirin: may increase valproate concentrations. May also interfere with valproate's metabolism.
  • Benzodiazepines: may cause CNS depression and there are possible pharmacokinetic interactions.
  • Carbapenem antibiotics: 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 potential breakthrough 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

Pharmacodynamics

Although the mechanism of action of valproate is not fully understood,[28] traditionally, its anticonvulsant effect has been attributed to the blockade of voltage-gated sodium channels and increased brain levels of gamma-aminobutyric acid (GABA).[28] The GABAergic effect is also believed to contribute towards the anti-manic properties of valproate.[28] In animals, sodium valproate raises cerebral and cerebellar levels of the inhibitory synaptic neurotransmitter, GABA, possibly by inhibiting GABA degradative enzymes, such as GABA transaminase, succinate-semialdehyde dehydrogenase and by inhibiting the re-uptake of GABA by neuronal cells.[28]

Prevention of neurotransmitter-induced hyperexcitability of nerve cells, via Kv7.2 channel and AKAP5, may also contribute to its mechanism.[70] Also, it has been shown to protect against a seizure-induced reduction in phosphatidylinositol (3,4,5)-trisphosphate (PIP3) as a potential therapeutic mechanism.[71]

It also has histone-deacetylase-inhibiting effects. The inhibition of histone deacetylase, by promoting more transcriptionally active chromatin structures, likely presents the epigenetic mechanism for regulation of many of the neuroprotective effects attributed to valproic acid. Intermediate molecules mediating these effects include VEGF, BDNF, and GDNF.[72][73]

Endocrine actions

Valproic acid has been found to be an antagonist of the androgen and progesterone receptors, and hence as a nonsteroidal antiandrogen and antiprogestogen, at concentrations much lower than therapeutic serum levels.[74] In addition, the drug has been identified as a potent aromatase inhibitor, and suppresses estrogen concentrations.[75] These actions are likely to be involved in the reproductive endocrine disturbances seen with valproic acid treatment.[74][75]

Valproic acid has been found to directly stimulate androgen biosynthesis in the gonads via inhibition of histone deacetylases and has been associated with hyperandrogenism in women and increased 4-androstenedione levels in men.[76][77] High rates of polycystic ovary syndrome and menstrual disorders have also been observed in women treated with valproic acid.[77]

Pharmacokinetics
Some metabolites of valproic acid. Glucuronidation and β-oxidation are the main metabolic pathways; ω-oxidation metabolites are considered hepatotoxic.[78][79] Details see text.

Taken by mouth, valproate is rapidly and virtually completely absorbed from the gut.[78] When in the bloodstream, 80–90% of the substance are bound to plasma proteins, mainly albumin. Protein binding is saturable: it decreases with increasing valproate concentration, low albumin concentrations, the patient's age, additional use of other drugs such as aspirin, as well as liver and kidney impairment.[80][81] Concentrations in the cerebrospinal fluid and in breast milk are 1 to 10% of blood plasma concentrations.[78]

The vast majority of valproate metabolism occurs in the liver.[82] Valproate is known to be metabolized by the cytochrome P450 enzymes CYP2A6, CYP2B6, CYP2C9, and CYP3A5.[82] It is also known to be metabolized by the UDP-glucuronosyltransferase enzymes UGT1A3, UGT1A4, UGT1A6, UGT1A8, UGT1A9, UGT1A10, UGT2B7, and UGT2B15.[82] Some of the known metabolites of valproate by these enzymes and uncharacterized enzymes include (see image):[82]

  • via glucuronidation (30–50%): valproic acid β-O-glucuronide
  • via beta oxidation (>40%): 2E-ene-valproic acid, 2Z-ene-valproic acid, 3-hydroxyvalproic acid, 3-oxovalproic acid
  • via omega 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.[78]

In adult patients taking valproate alone, 30–50% of an administered dose is excreted in urine as the glucuronide conjugate.[82] The other major pathway in the metabolism of valproate is mitochondrial beta oxidation, which typically accounts for over 40% of an administered dose.[82] Typically, less than 20% of an administered dose is eliminated by other oxidative mechanisms.[82] Less than 3% of an administered dose of valproate is excreted unchanged (i.e., as valproate) in urine.[82] Only a small amount is excreted via the faeces.[78] Elimination half-life is 16±3 hours and can decrease to 4–9 hours when combined with enzyme inducers.[78][81]

Chemistry

Valproic acid is a branched short-chain fatty acid and the 2-n-propyl derivative of valeric acid.[8]

History

Valproic acid was first synthesized in 1882 by Beverly S. Burton as an analogue of valeric acid, found naturally in valerian.[83] Valproic acid is a carboxylic 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 prevented pentylenetetrazol-induced convulsions in laboratory rats.[84] It was approved as an antiepileptic drug in 1967 in France and has become the most widely prescribed antiepileptic drug worldwide.[85] Valproic acid has also been used for migraine prophylaxis and bipolar disorder.[86]

Society and culture

Valproate is available as a generic medication.[3]

Approval status
Indications United States
FDA-labelled indication?[2]		 Australia
TGA-labelled indication?[17]		 United Kingdom
MHRA-labelled indication?[87]		 Literature support
EpilepsyYesYesYesLimited (depends on the seizure type; it can help with certain kinds of seizures: drug-resistant epilepsy, partial and absence seizures, can be used against glioblastoma and other tumors both to improve survival and treat seizures, and against tonic–clonic seizures and status epilepticus).[88][89][90][91]
Bipolar maniaYesYesYesLimited.[92]
Bipolar depressionNoNoNoModerate.[93]
Bipolar maintenanceNoNoNoLimited.[94]
Migraine prophylaxisYesYes (accepted)NoLimited.
Acute migraine managementNoNoNoOnly negative results.[95]
SchizophreniaNoNoNoWeak evidence.[96]
Agitation in dementiaNoNoNoWeak evidence. Not recommended for agitation in people with dementia.[97] Increased rate of adverse effects, including a risk of serious adverse effects.[97]
Fragile X syndromeYes (orphan)NoNoLimited.[73]
Familial adenomatous polyposisYes (orphan)NoNoLimited.
Chronic pain & fibromyalgiaNoNoNoLimited.[98]
Alcohol hallucinosisNoNoNoOne randomised double-blind placebo-controlled trial.[99]
Intractable hiccupsNoNoNoLimited, five case reports support its efficacy, however.[100]
Non-epileptic myoclonusNoNoNoLimited, three case reports support its efficacy, however.[101]
Cluster headachesNoNoNoLimited, two case reports support its efficacy.[102]
West syndromeNoNoNoA prospective clinical trial supported its efficacy in treating infantile spasms.[103]
HIV infection eradicationNoNoNoDouble-blind placebo-controlled trials have been negative.[104][105][106]
Myelodysplastic syndromeNoNoNoSeveral clinical trials have confirmed its efficacy as a monotherapy,[107] as an adjunct to tretinoin[107] and as an adjunct to hydralazine.[108]
Acute myeloid leukaemiaNoNoNoTwo clinical trials have confirmed its efficacy in this indication as both a monotherapy and as an adjunct to tretinoin.[109][110][111]
Cervical cancerNoNoNoOne clinical trial supports its use here.[112]
Malignant melanomaNoNoNoOne phase II study has seemed to discount its efficacy.[113]
Breast cancerNoNoNoA phase II study has supported its efficacy.[114]
Impulse control disorderNoNoNoLimited.[115][116]

Off-label uses

In 2012, pharmaceutical company Abbott paid $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.[117][118]

Some studies have suggested that valproate may reopen the critical period for learning absolute pitch and possibly other skills such as language.[119][120]

Formulations
Sodium valproate
Clinical data
Other namesvalproate sodium (USAN US)
License data
Legal status
Legal status
Identifiers
  • sodium 2-propylpentanoate
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.002.525
Chemical and physical data
FormulaC8H15NaO2
Molar mass166.196 g·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-1 checkY
  • Key:AEQFSUDEHCCHBT-UHFFFAOYSA-M checkY
  (verify)
Valproate semisodium
Clinical data
Trade namesDepakote, others
Other namessemisodium valproate, divalproex sodium (USAN US)
License data
Identifiers
  • sodium 2-propylpentanoate;2-propylpentanoic acid
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.002.525
Chemical and physical data
FormulaC16H31NaO4
Molar mass310.410 g·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-1 checkY
  • Key:MSRILKIQRXUYCT-UHFFFAOYSA-M checkY

Valproate exists in two main molecular variants: sodium valproate and valproic acid without sodium (often implied by simply valproate). A mixture between these two is termed semisodium valproate. It is unclear whether there is any difference in efficacy between these variants, except from the fact that about 10% more mass of sodium valproate is needed than valproic acid without sodium to compensate for the sodium itself.[123]

Brand names of valproic acid

Branded products include:

Portugal
  • Tablets – Diplexil-R by Bial.
United States
  • Intravenous injection – Depacon by Abbott Laboratories.
  • Syrup – Depakene by Abbott Laboratories. (Note Depakene capsules are valproic acid).
  • Depakote tablets are a mixture of sodium valproate and valproic acid.
  • Tablets – Eliaxim by Bial.
Australia
  • Epilim Crushable Tablets Sanofi[126]
  • Epilim Sugar Free Liquid Sanofi[126]
  • Epilim Syrup Sanofi[126]
  • Epilim Tablets Sanofi[126]
  • Sodium Valproate Sandoz Tablets Sanofi
  • Valpro Tablets Alphapharm
  • Valproate Winthrop Tablets Sanofi
  • Valprease tablets Sigma
New Zealand
  • Epilim by Sanofi-Aventis

All the above formulations are Pharmac-subsidised.[127]

UK
  • 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 valproate enteric-coated tablet.
UK only
  • 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
  • Tablets – Orfiril by Desitin Pharmaceuticals
  • Intravenous injection – Orfiril IV by Desitin Pharmaceuticals
South Africa
  • Syrup – Convulex by Byk Madaus[128]
  • Tablets – Epilim by Sanofi-synthelabo
Malaysia
  • Tablets – Epilim (200 ENTERIC COATED) by Sanofi-Aventis
  • Controlled release tablets – Epilim Chrono (500 CONTROLLED RELEASE) by Sanofi-Aventis[129]
Romania
  • 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
Japan
  • Tablets – Depakene by Kyowa Hakko Kirin
  • Extended release tablets – Depakene-R by Kyowa Hakko Kogyo and Selenica-R by Kowa
  • Syrup – Depakene by Kyowa Hakko Kogyo
Europe

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

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

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

India, Russia and CIS countries
  • 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
  • Tablets - DI DPA by Megalabs

Brand names of valproate semisodium
  • Brazil – Depakote by Abbott Laboratories and 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) by Sanofi-Aventis and generics
  • United States – Depakote and Depakote ER (extended release) by Abbott Laboratories and generics[30]
  • 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

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.[130]

References
  1. 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). Archived from the original on 3 August 2023. Retrieved 3 August 2023.
  2. "Depakene, Stavzor (valproic acid) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 21 February 2014. Retrieved 13 February 2014.
  3. "Valproic Acid". The American Society of Health-System Pharmacists. 24 November 2020. Archived from the original on 31 July 2017.
  4. "Valproate banned without the pregnancy prevention programme". GOV.UK. Retrieved 26 April 2018.
  5. "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.
  6. Davis N (17 April 2022). "Sodium valproate: what are dangers of epilepsy drug for unborn babies?". The Observer.
  7. Owens MJ, Nemeroff CB (2003). "Pharmacology of valproate". Psychopharmacology Bulletin. 37 (Suppl 2): 17–24. PMID 14624230.
  8. Ghodke-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. PMC 3696515. PMID 23407051.
  9. "Valproic acid". DrugBank. University of Alberta. 29 July 2017. Archived from the original on 31 July 2017. Retrieved 30 July 2017.
  10. 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. PMC 9129103. PMID 33398088.
  11. 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. ISBN 9781850703914.
  12. 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.
  13. 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.
  14. "The Top 300 of 2020". ClinCalc. Retrieved 7 October 2022.
  15. "Valproate - Drug Usage Statistics". ClinCalc. Retrieved 7 October 2022.
  16. Brayfield A (ed.). Martindale: The Complete Drug Reference. London: Pharmaceutical Press. Retrieved 3 March 2018.
  17. Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.
  18. 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. PMID 12269861. S2CID 67999301.
  19. 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. PMID 17419829. S2CID 11159645.
  20. Kwan SY (June 2010). "The role of intravenous valproate in convulsive status epilepticus in the future" (PDF). Acta Neurologica Taiwanica. 19 (2): 78–81. PMID 20830628.
  21. "Valproate Information". Fda.gov. Archived from the original on 3 May 2015. Retrieved 24 April 2015.
  22. 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. PMC 6797024. PMID 31621892.
  23. 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. PMC 6734130. PMID 27884042. Archived from the original on 29 July 2017. Retrieved 27 July 2017.
  24. 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. PMC 4119624. PMID 25114917.
  25. 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. PMC 3899484. PMID 24288035.
  26. 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. PMC 4197852. PMID 24313567.
  27. Činčárová L, Zdráhal Z, Fajkus J (December 2013). "New perspectives of valproic acid in clinical practice". Expert Opinion on Investigational Drugs. 22 (12): 1535–1547. doi:10.1517/13543784.2013.853037. PMID 24160174. S2CID 11855893.
  28. "Valpro sodium valproate" (PDF). TGA eBusiness Services. Alphapharm Pty Limited. 16 December 2013. Retrieved 14 February 2014.
  29. "Depakote 250mg Tablets - Summary of Product Characteristics". electronic Medicines Compendium. Sanofi. 28 November 2013. Archived from the original on 1 February 2014. Retrieved 18 January 2014.
  30. "Depakote- divalproex sodium tablet, delayed release". Archived from the original on 5 March 2016. Retrieved 10 November 2015.
  31. Rissardo JP, Fornari Caprara AL, Freitas Silveira JO (30 September 2019). "Valproic acid-associated pancytopenia: A dose-dependent adverse effect". Romanian Journal of Neurology. 18 (3): 150–153. doi:10.37897/RJN.2019.3.9. S2CID 219250201.
  32. 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. PMID 15032379. S2CID 19827846.
  33. 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. PMC 2013195. PMID 3126792.
  34. 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. PMID 11580761. S2CID 25499280.
  35. "Could Depakote cause Mydriasis". eHealthMe.com. 18 November 2014. Archived from the original on 5 December 2014. Retrieved 24 April 2015.
  36. 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. PMID 19012099. S2CID 36426338.
  37. 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. PMID 24308788. S2CID 33444886.
  38. New evidence in France of harm from epilepsy drug valproate Archived 21 April 2017 at the Wayback Machine BBC, 2017
  39. 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. PMID 6402356.
  40. Moore SJ, Turnpenny P, Quinn A, Glover S, Lloyd DJ, Montgomery T, Dean JC (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. PMC 1734633. PMID 10882750.
  41. Ornoy A (July 2009). "Valproic acid in pregnancy: how much are we endangering the embryo and fetus?". Reproductive Toxicology. 28 (1): 1–10. doi:10.1016/j.reprotox.2009.02.014. PMID 19490988.
  42. 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. PMC 6642533. PMID 31324220.
  43. 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. PMID 17090909. S2CID 38371596.
  44. 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. PMC 1738809. PMID 15491979. 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.
  45. Umur AS, Selcuki M, Bursali A, Umur N, Kara B, Vatansever HS, Duransoy YK (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. PMID 22246336. S2CID 20344828.
  46. Cassels C (8 December 2006). "NEAD: In Utero Exposure To Valproate Linked to Poor Cognitive Outcomes in Kids". Medscape. Archived from the original on 31 July 2011. Retrieved 23 May 2007.
  47. 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. PMC 1986655. PMID 16894099.
  48. Christensen J, Grønborg TK, Sørensen MJ, Schendel D, Parner ET, Pedersen LH, Vestergaard M (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. PMC 4511955. PMID 23613074.
  49. Rasalam AD, Hailey H, Williams JH, Moore SJ, Turnpenny PD, Lloyd DJ, Dean JC (August 2005). "Characteristics of fetal anticonvulsant syndrome associated autistic disorder". Developmental Medicine and Child Neurology. 47 (8): 551–555. doi:10.1017/S0012162205001076. PMID 16108456.
  50. 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
  51. 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
  52. I.Q. Harmed by Epilepsy Drug in Utero Archived 29 December 2015 at the Wayback Machine By RONI CARYN RABIN, New York Times, 15 April 2009
  53. 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. PMC 2737185. PMID 19369666.
  54. Valproate Products: Drug Safety Communication - Risk of Impaired Cognitive Development in Children Exposed In Utero (During Pregnancy) Archived 2 September 2011 at the Wayback Machine. FDA. June 2011
  55. 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 (inactive 1 August 2023). PMID 17884759.{{cite journal}}: CS1 maint: DOI inactive as of August 2023 (link)
  56. Ouvrier RA, Billson F (July 1988). "Benign paroxysmal tonic upgaze of childhood". Journal of Child Neurology. 3 (3): 177–180. doi:10.1177/088307388800300305. PMID 3209843. S2CID 38127378.
  57. Valproate Not To Be Used for Migraine During Pregnancy, FDA Warns Archived 9 July 2013 at the Wayback Machine
  58. "New measures to avoid valproate exposure in pregnancy endorsed". European Medicines Agency. 31 May 2018.
  59. Suzanne B (11 December 2013). "Valproic Acid Level". Medscape. Archived from the original on 4 May 2015. Retrieved 5 June 2015.
  60. "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 from the original (PDF) on 3 March 2016. Retrieved 5 June 2015.
  61. Rissardo JP, Caprara AL, Durante Í (2021). "Valproate-associated Movement Disorder: A Literature Review". Prague Medical Report. 122 (3): 140–180. doi:10.14712/23362936.2021.14. PMID 34606429. S2CID 238356343.
  62. Sztajnkrycer MD (2002). "Valproic acid toxicity: overview and management". Journal of Toxicology. Clinical Toxicology. 40 (6): 789–801. doi:10.1081/CLT-120014645. PMID 12475192. S2CID 23031095.
  63. 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. PMID 23288091. S2CID 15338188.
  64. Thanacoody RH (August 2009). "Extracorporeal elimination in acute valproic acid poisoning". Clinical Toxicology. 47 (7): 609–616. doi:10.1080/15563650903167772. PMID 19656009. S2CID 13592043.
  65. R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 1622–1626.
  66. Lheureux 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. PMC 1297603. PMID 16277730.
  67. 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. PMID 22180549.
  68. 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. PMID 8347126.
  69. 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. PMID 15946343. S2CID 7696039.
  70. 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. PMC 4607138. PMID 26348896.
  71. 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. PMC 3898270. PMID 24148856.
  72. Kostrouchová M, Kostrouch Z, Kostrouchová M (2007). "Valproic acid, a molecular lead to multiple regulatory pathways" (PDF). Folia Biologica. 53 (2): 37–49. PMID 17448293. Archived from the original (PDF) on 21 February 2014. Retrieved 13 February 2014.
  73. Chiu 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. PMC 3565922. PMID 23300133.
  74. Death 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. PMID 16165177. S2CID 25958985.
  75. Wyllie E, Cascino GD, Gidal BE, Goodkin HP (17 February 2012). Wyllie's Treatment of Epilepsy: Principles and Practice. Lippincott Williams & Wilkins. pp. 288–. ISBN 978-1-4511-5348-4. Archived from the original on 6 June 2014.
  76. 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. PMC 5891791. PMID 29662388.
  77. Isojärvi 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. PMID 15740176. S2CID 9893959.
  78. Haberfeld H, ed. (2021). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. Depakine chrono retard 300 mg Filmtabletten.
  79. 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. PMID 10859160.
  80. Schneemann H, Young L, Koda-Kimble MA, eds. (2001). Angewandte Arzneimitteltherapie (in German). Springer. pp. 28–29. ISBN 3540413561.
  81. Valproate FDA Professional Drug Information. Accessed 6 August 2021.
  82. "Valproic Acid". DrugBank. University of Alberta. 31 August 2017.
  83. Burton BS (1882). "On the propyl derivatives and decomposition products of ethylacetoacetate". Am. Chem. J. 3: 385–395.
  84. 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. PMID 13935231.
  85. 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. PMID 12269862. S2CID 803106.
  86. Henry TR (2003). "The history of valproate in clinical neuroscience". Psychopharmacology Bulletin. 37 (Suppl 2): 5–16. PMID 14624229.
  87. Joint Formulary Committee (2013). British National Formulary (BNF) (65 ed.). London, UK: Pharmaceutical Press. ISBN 978-0-85711-084-8.
  88. 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. PMID 3927267. S2CID 7700266.
  89. 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. PMC 2924476. PMID 20200383.
  90. 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 – via www.neurology.org.
  91. 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. PMC 4185847.
  92. 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. PMID 22455007.
  93. 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. PMID 20044142.
  94. 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. PMID 19409030. S2CID 74028228.
  95. 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. PMID 18303140. S2CID 207263036.
  96. 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. PMC 6734130. PMID 27884042.
  97. Baillon 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. PMC 6516950. PMID 30293233.
  98. 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. PMC 6540387. PMID 21975791.
  99. 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. PMID 18495806.
  100. 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. PMID 6796902. S2CID 1578958.
  101. 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. PMID 6808975.
  102. 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. PMID 15613172. S2CID 27948702.
  103. 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. PMID 2842127. S2CID 23789333.
  104. 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. PMC 1242254. PMID 16168066.
  105. 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. PMID 22276680. S2CID 27571864.
  106. 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. PMC 2826423. PMID 20186346.
  107. Hardy 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. PMID 11239739.
  108. 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. PMID 20922525. S2CID 13437134.
  109. 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. PMID 16294345. S2CID 1802132.
  110. 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. PMID 16323176. S2CID 43747497.
  111. 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. PMC 3733883. PMID 23898968.
  112. 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. PMID 20931299. S2CID 207372333.
  113. 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. PMC 2634690. PMID 19127265.
  114. 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. PMID 19318486. S2CID 3230087.
  115. 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. PMID 21459656.
  116. 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. PMID 23007193. S2CID 21544457.
  117. Aizenman NC (7 May 2012). "Abbott Laboratories to pay $1.6 billion over illegal marketing of Depakote". Washington Post. Retrieved 27 June 2018.
  118. Schmidt M, Thomas K (8 May 2012). "Abbott settles marketing lawsuit". New York Times. Retrieved 27 June 2018.
  119. Gervain J, Vines BW, Chen LM, Seo RJ, Hensch TK, Werker JF, Young AH (2013). "Valproate reopens critical-period learning of absolute pitch". Frontiers in Systems Neuroscience. 7: 102. doi:10.3389/fnsys.2013.00102. PMC 3848041. PMID 24348349.
  120. Thomson H. "Learning drugs reawaken grown-up brain's inner child". New Scientist. New Scientist Ltd. Retrieved 8 May 2021.
  121. "Valproate sodium injection". DailyMed. 1 January 2021. Retrieved 7 October 2022.
  122. "Valproate sodium injection, solution". DailyMed. 29 April 2021. Retrieved 7 October 2022.
  123. Taylor D, Paton C, Kapur S (2009). The Maudsley Prescribing Guidelines (Tenth ed.). CRC Press. p. 124. ISBN 9780203092835.
  124. "Depakene- valproic acid capsule, liquid filled". DailyMed. 19 September 2019. Retrieved 14 April 2020.
  125. "Depakin - Banca Dati Farmaci dell'AIFA" [Depakin - The AIFA Medicines Database]. farmaci.agenziafarmaco.gov.it (in Italian). Italian Medicines Agency. 6 June 2023. Archived from the original on 6 June 2023. Retrieved 6 June 2023.
  126. "Australian product information epilim (sodium valproate) crushable tablets, enteric-coated tablets, syrup, liquid" (PDF). TGA eBS. 15 April 2020. Retrieved 15 April 2020.
  127. "Sodium valproate -- Pharmaceutical Schedule". Pharmaceutical Management Agency. Archived from the original on 4 March 2016. Retrieved 22 June 2014.
  128. "South African Electronic Package Inserts: Convulex". Archived from the original on 12 August 2010. Retrieved 2 January 2006.
  129. "Malaysian Package Inserts: Epilim". Retrieved 5 June 2023.
  130. 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. PMID 36383706. Report No.: 22(23)-EHC004 Report No.: 2021-SR-01. Retrieved 12 July 2023.
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.