Depakote

Raw research findings for this medication. Mostly single studies, not curated or confirmed robust.

About Depakote

What it is

Valproic acid (valproate) is a broad-spectrum anticonvulsant and mood stabiliser; it raises GABA levels, blocks sodium and T-type calcium channels, and affects gene expression. It is used for many types of epilepsy, for mania and bipolar disorder, and to prevent migraine. It can harm an unborn baby, so its use in women who could become pregnant is strictly controlled. It is sold as Depakote, Depakine and Epilim, among other names.

How genes come into it

Valproate is cleared mainly by UGT enzymes (UGT2B7, UGT1A6) and by mitochondrial beta-oxidation, with a smaller part by CYP2C9 and CYP2C19; studies have looked at all of these for blood levels. A notable gene is POLG: in people with mitochondrial disorders caused by POLG variants, valproate can cause severe liver failure, and the US label warns about this. There is no CPIC or DPWG guideline.

What research found

Every published finding on gene variants and Depakote. Upload your DNA file to see which of these rows apply to you.

Rated evidence (24 rated variants)

PharmGKB weighs all studies of a variant and rates how strong the evidence is, from 1A (strongest) to 4.

UGT2B7 rs7668258: Level 3. Metabolism/PK: Epilepsy. 3.

UGT1A10;UGT1A6;UGT1A7;UGT1A8;UGT1A9 rs2070959: Level 3. Dosage: Epilepsy. 2.

UGT1A6 rs1105879: Level 3. Dosage: Epilepsy. 2.

UGT1A10;UGT1A6;UGT1A7;UGT1A8;UGT1A9 rs6759892: Level 3. Dosage: Epilepsy. 2.

Metabolism (37 findings)

Studies of how quickly the body processes this medication.

ABAT rs1731017: Genotype GG is associated with increased exposure to valproic acid in people with Epilepsy as compared to genotype AA.

APEH rs3816877: Genotype CC is associated with increased concentrations of valproic acid in people with Epilepsy as compared to genotype CT.

CYP2A6 CYP2A6*1, CYP2A6*4: CYP2A6 *4 is associated with decreased metabolism of valproic acid in people with Epilepsy as compared to CYP2A6 *1/*1.

CYP2C19 CYP2C19 intermediate metabolizer: CYP2C19 intermediate metabolizer and poor metabolizer is associated with increased concentrations of valproic acid as compared to CYP2C19 normal metabolizer.

Response (49 findings)

Studies of how well it worked in people carrying a variant.

rs2769605: Genotype CC is associated with decreased response to lithium or valproic acid in people with Bipolar Disorder as compared to genotypes CT + TT.

ABCB1 rs1128503: Genotype AA is associated with decreased clinical benefit to valproic acid in children with Epilepsy as compared to genotypes AG + GG.

CACNA1H rs3751664: Allele T is associated with increased resistance to valproic acid in people with Epilepsy as compared to allele C.

CYP2C9 rs9332120: Allele C is associated with increased response to carbamazepine, lamotrigine, phenytoin, primidone or valproic acid in children with Epilepsy as compared to allele T.

Dosing (23 findings)

Studies of how much of the drug people needed or tolerated.

CYP2C19 rs4244285: Genotypes AA + AG are associated with increased dose of valproic acid in people with Myelodysplastic Syndromes as compared to genotype GG.

CYP2C9 CYP2C9*1, CYP2C9*2, CYP2C9*3: CYP2C9 *1/*2 + *1/*3 are associated with decreased dose of valproic acid in people with Bipolar Disorder and Psychotic Disorders as compared to CYP2C9 *1/*1.

GRIN2B rs1019385: Genotype AC is associated with decreased dose of valproic acid in people with Epilepsy as compared to genotype AA.

GRIN2B rs1019385: Genotype CC is associated with decreased dose of valproic acid in people with Epilepsy as compared to genotypes AA + AC.

Study findings and evidence levels: PharmGKB (CC BY-SA 4.0). Guidelines: CPIC and DPWG, as bundled in PharmCAT. Most studies were done mainly in people of European ancestry.

Related Drugs

More drugs from the same category

Antiepileptics (class) (Anticonvulsants)

Cerebyx (Anticonvulsants)

Dilantin (Anticonvulsants)

Not a prescribing recommendation. This page is educational information about pharmacogenomic research and clinical guidelines - it is not medical or dosing advice, and not a prediction of how any medication will work for you. Never start, stop, or change a medication or dose based on it; talk to your doctor or pharmacist, who can order clinical-grade testing if appropriate.

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Content updated September 2026.

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