Overview
Valproic acid/sodium valproate is an anticonvulsant and mood stabilizer used primarily for epilepsy, bipolar disorder, and migraine prophylaxis. It works by increasing GABA levels and modulating sodium channels in the brain.
Mechanism of Action
Enhances GABAergic neurotransmission by inhibiting GABA transaminase and succinic semialdehyde dehydrogenase, increases GABA synthesis, and modulates voltage-gated sodium channels. May also affect NMDA receptors and histone deacetylase inhibition.
Indications
- Epilepsy (partial and generalized seizures)
- Bipolar disorder (acute mania, maintenance)
- Migraine prophylaxis
- Off-label: neuropathic pain, agitation in dementia
Dosage
Epilepsy: Adults: Start 10-15 mg/kg/day, increase weekly; max 60 mg/kg/day. Bipolar: 750-1500 mg/day. Migraine: 500-1000 mg/day. Pediatric dosing based on weight. Administer in divided doses with food to reduce GI upset.
Contraindications
- Hepatic disease or significant dysfunction
- Urea cycle disorders
- Known hypersensitivity to valproate
- Pregnancy for migraine prophylaxis
- Mitochondrial disorders caused by POLG mutations
Side Effects
- Nausea, vomiting, diarrhea
- Weight gain
- Tremor, sedation
- Alopecia
- Thrombocytopenia
- Hepatotoxicity
- Pancreatitis
- Hyperammonemia
Interactions
- Lamotrigine: increases lamotrigine toxicity
- Phenobarbital, phenytoin: decreases valproate levels
- Warfarin: increases anticoagulant effect
- Aspirin: increases valproate toxicity
- Carbapenem antibiotics: decreases valproate levels