Valproate
Depakote · Divalproex sodium
Anticonvulsant/Mood StabilizerGeneric availableTDM data
Divalproex sodium dissociates to the valproate ion in the gastrointestinal tract. The mechanisms by which valproate exerts its therapeutic effects have not been established. It has been suggested that its activity in epilepsy is related to increased brain concentrations of gamma-aminobutyric acid (GABA).
Compare Valproate →FDA-Approved Indications
- Acute manic or mixed episodes in Bipolar I (adults)
- Complex partial seizures — mono or adjunct (adults; pediatric 10+)
- Simple and complex absence seizures (adults; pediatric)
- Multiple seizure types including absence — adjunct (adults; pediatric)
- Migraine prophylaxis (adults)
Common Off-Label Uses
- Agitation in dementia
- Impulse control disorders
- Neuropathic pain
- Alcohol withdrawal
What Sets This Drug Apart
- Broadest-spectrum mood stabilizer: strongest evidence for acute mania and mixed states; more effective than lithium for rapid-cycling and mixed-feature presentations
- HIGHEST teratogenicity risk among mood stabilizers: Tomson 2018 EURAP 10.3% major congenital malformation rate (dose-dependent); essentially contraindicated in women of childbearing potential
- Three-component FDA BOXED WARNING: hepatotoxicity (especially <2 years old and POLG-mutation carriers), birth defects, and pancreatitis
- UGT-metabolized with moderate CYP2C9 inhibition; critically increases lamotrigine levels (halve lamotrigine dose with co-administration) and carbamazepine-epoxide levels
- Weight gain significant and cumulative; PCOS-like metabolic syndrome reported in young women
- Multiple formulations: divalproex DR/ER, valproic acid liquid — allows flexible dosing and administration routes including IV loading for acute mania
Boxed Warning
LIFE THREATENING ADVERSE REACTIONS