Editing Valproate (section)

==Medical uses==
[[File:Depakote 500mg ER.jpg|thumb|250px|500mg tablets of Depakote extended-release]]

Valproate or valproic acid is used primarily to treat [[epilepsy]] and [[bipolar disorder]] and to prevent [[migraine headache]]s.<ref name = AMH/>

===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]].<ref name = AMH/><ref>{{cite journal | vauthors = Löscher W | title = Basic pharmacology of valproate: a review after 35 years of clinical use for the treatment of epilepsy | journal = CNS Drugs | volume = 16 | issue = 10 | pages = 669–694 | year = 2002 | pmid = 12269861 | doi = 10.2165/00023210-200216100-00003 | s2cid = 67999301 }}</ref> It has also been successfully given [[Intravenous therapy|intravenously]] to treat [[status epilepticus]].<ref>{{cite journal | vauthors = Olsen KB, Taubøll E, Gjerstad L | title = Valproate is an effective, well-tolerated drug for treatment of status epilepticus/serial attacks in adults | journal = Acta Neurologica Scandinavica. Supplementum | volume = 187 | pages = 51–54 | year = 2007 | pmid = 17419829 | doi = 10.1111/j.1600-0404.2007.00847.x | s2cid = 11159645 }}</ref><ref>{{cite journal | vauthors = Kwan SY | title = The role of intravenous valproate in convulsive status epilepticus in the future | journal = Acta Neurologica Taiwanica | volume = 19 | issue = 2 | pages = 78–81 | date = June 2010 | pmid = 20830628 | url = http://www.ant-tnsjournal.com/Mag_Files/19-2/N201072314227_192edi.pdf | department = Editorial | access-date = 19 February 2024 | archive-date = 19 February 2024 | archive-url = https://web.archive.org/web/20240219233048/http://www.ant-tnsjournal.com/Mag_Files/19-2/N201072314227_192edi.pdf | url-status = live }}</ref>

In the US, valproic acid is also prescribed as an anti-epileptic drug [[indicated]] for 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.<ref name="Depakote FDA label" /><ref name="Depakote ER FDA label">{{cite web | title=Depakote ER- divalproex sodium tablet, extended release | website=DailyMed | date=24 February 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0dc024ce-efc8-4690-7cb5-639c728fccac | access-date=19 February 2024 | archive-date=28 January 2023 | archive-url=https://web.archive.org/web/20230128143053/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0dc024ce-efc8-4690-7cb5-639c728fccac | url-status=live }}</ref>

===Mental illness===
Valproate products are used to treat manic or mixed episodes of [[bipolar disorder]].<ref name=":1">{{cite web |url=https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/valproate-information |title=Valproate Information |publisher=U.S. [[Food and Drug Administration]] (FDA) |access-date=24 April 2015 |url-status=dead |archive-url=https://web.archive.org/web/20150503091048/https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm192645.htm |archive-date=3 May 2015 }}</ref><ref>{{cite journal | vauthors = Jochim J, Rifkin-Zybutz RP, Geddes J, Cipriani A | title = Valproate for acute mania | journal = The Cochrane Database of Systematic Reviews | volume = 2019 | issue = 10 | pages = CD004052 | date = October 2019 | pmid = 31621892 | pmc = 6797024 | doi = 10.1002/14651858.CD004052.pub2 }}</ref>

A 2016 [[systematic review]] compared the efficacy of valproate as an add-on for people with [[schizophrenia]]:<ref name=Wan2016>{{cite journal | vauthors = Wang Y, Xia J, Helfer B, Li C, Leucht S | title = Valproate for schizophrenia | journal = The Cochrane Database of Systematic Reviews | volume = 2016 | issue = 11 | pages = CD004028 | date = November 2016 | pmid = 27884042 | pmc = 6734130 | doi = 10.1002/14651858.CD004028.pub4 | url = http://www.cochrane.org/CD004028/SCHIZ_valproate-schizophrenia | url-status = dead | access-date = 27 July 2017 | archive-url = https://web.archive.org/web/20170729002449/http://www.cochrane.org/CD004028/SCHIZ_valproate-schizophrenia | archive-date = 29 July 2017 }}</ref>
{| class="wikitable"
|-
| There is limited evidence that adding valproate to [[antipsychotic]]s 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.<ref name=Wan2016/>
|-
| style="padding:0;" |
{| class="wikitable collapsible collapsed" style="width:100%;"
|-
! scope="col" style="text-align: left;"| Outcome
! scope="col" style="text-align: left;"| Findings in words
! scope="col" style="text-align: left;"| Findings in numbers
! scope="col" style="text-align: left;"| Quality of evidence
|-
! colspan="4" style="text-align: left;"| Global outcome
|-
| Clinically significant response||When added to antipsychotic drugs valproate probably increases the chance of improvement. Data are based on moderate quality evidence.
 || [[Relative risk|RR]] 1.31 (1.16 to 1.47) || [[The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach|Moderate]]
|-
| Leaving the study early for any reason || Valproate in combination with antipsychotics may slightly reduce the chance of leaving the study early, but the difference between the two treatments is not clear. Data supporting this finding are based on moderate quality evidence.
 || RR 0.76 (0.47 to 1.24) || [[The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach|Moderate]]
|-
| Use of additional medication for sedation|| The combination of valproate and antipsychotic drugs may increase the chance of being given additional sedating medication, but, at present it is not possible to be confident about the difference between the two treatments and data supporting this finding are very limited.
 || RR 3.65 (0.11 to 122.31) || [[The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach|Very low]]
|-
! colspan="4" style="text-align: left;"| [[Mental health|Mental state]]
|-
| Average score ([[Positive and Negative Syndrome Scale|PANSS]] total, high = poor)|| On average, people receiving the valproate combination scored lower (better) than people treated with antipsychotics in combination with placebo or antipsychotic drugs alone. There was a clear difference between the groups, but the meaning of this in day-to-day care is unclear. || [[Mean absolute difference|MD]] 5.85 lower (7.8 lower to 3.91 lower) || [[The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach|Moderate]]
|-
! colspan="4" style="text-align: left;"| [[Adverse event]]s
|-
| Abnormal liver function (blood test changes)* || Adding valproate to antipsychotic drug treatment does not clearly cause liver problems. Data supporting this finding are based on moderate quality evidence.
 || RR 1.26 (0.72 to 2.22) || [[The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach|Moderate]]
|-
| Nausea || Adding valproate to antipsychotic drugs probably causes little or no increase to the chance of feeling sick, but the difference between the two treatments is not clear. Data supporting this finding are based on moderate quality evidence.
 || RR 1.22 (0.80 to 1.86) || [[The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach|Moderate]]
|-
! colspan="4" style="text-align: left;"| Missing outcomes and notes
|-
| || [[Quality of life]] outcomes were not reported in the included studies. <br />*Increase in alanine transaminase/gamma-glutamyl transpeptidase ||  ||
|-
|}
|}

===Other neurological indications===
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]].<ref name="pmid25114917">{{cite journal | vauthors = Pirritano D, Plastino M, Bosco D, Gallelli L, Siniscalchi A, De Sarro G | title = Gambling disorder during dopamine replacement treatment in Parkinson's disease: a comprehensive review | journal = BioMed Research International | volume = 2014 | pages = 728038 | year = 2014 | pmid = 25114917 | pmc = 4119624 | doi = 10.1155/2014/728038 | doi-access = free }}</ref><ref name="pmid24288035">{{cite journal | vauthors = Connolly B, Fox SH | title = Treatment of cognitive, psychiatric, and affective disorders associated with Parkinson's disease | journal = Neurotherapeutics | volume = 11 | issue = 1 | pages = 78–91 | date = January 2014 | pmid = 24288035 | pmc = 3899484 | doi = 10.1007/s13311-013-0238-x }}</ref><ref name="pmid24313567">{{cite journal | vauthors = Averbeck BB, O'Sullivan SS, Djamshidian A | title = Impulsive and compulsive behaviors in Parkinson's disease | journal = Annual Review of Clinical Psychology | volume = 10 | pages = 553–580 | year = 2014 | pmid = 24313567 | pmc = 4197852 | doi = 10.1146/annurev-clinpsy-032813-153705 }}</ref>

Valproate is not commonly used to prevent or treat [[Migraine|migraine headaches]], but it may be prescribed if other medications are not effective.<ref>{{Cite web |date=2018-09-27 |title=Valproic acid: medicine used for bipolar disorder, epilepsy and migraine |url=https://www.nhs.uk/medicines/valproic-acid/#:~:text=Valproic%20acid%20is%20not%20used,cannot%20take%20other%20migraine%20medicines. |access-date=2024-11-20 |website=nhs.uk |language=en}}</ref>

===Other===
The medication has been tested in the treatment of [[AIDS]] and [[cancer]], owing to its [[Histone deacetylase inhibitor|histone-deacetylase-inhibiting effects]].{{Citation needed|date=November 2024}} It has cardioprotective, kidney protective, antiinflammatory, and antimicrobial effects.<ref name="elsevier">{{cite journal | vauthors = Singh D, Gupta S, Verma I, Morsy MA, Nair AB, Ahmed AF | title = Hidden pharmacological activities of valproic acid: A new insight | journal = Biomedicine & Pharmacotherapy | volume = 142 | pages = 112021 | date = October 2021 | pmid = 34463268 | doi = 10.1016/j.biopha.2021.112021 | doi-access = free }}</ref>