Medicine & USMLE

Valproic Acid (Valproate)

  1. Valproic Acid (Valproate)
  2. Carbamazepine
  3. Ethosuximide
  4. Gabapentin
  5. Lamotrigine
  6. Levetiracetam
  7. Barbituates (Phenobarbital, Thiopental)
  8. Topiramate
  9. Vigabatrin


Valproic acid, also known as valproate, is a drug used to treat seizures and bipolar disorder. This drug works by a combination of two mechanisms: (1) blocking sodium channels and (2) increasing GABA availability in the brain. Both of these mechanisms prevent the generation and propagation of action potentials in neural impulses. Valproic acid is therefore useful as a broad-spectrum antiepileptic, treating a  wide variety of seizures, including myoclonic, generalized, focal, and absence seizures. Valproic acid can also be used as a mood-stabilizing drug to treat bipolar disorder. Notable side effects of valproic acid include hepatotoxicity.  Importantly, valproic acid is teratogenic and is contraindicated during pregnancy.

Key Points

  • Valproic acid (valproate)
    • Mechanism
      • Blocks Sodium (Na+) channels
        • Prolongs inactivation, preventing firing of next action potential
      • Increases GABA concentration
        • Via inhibition of GABA transaminase, which breaks down GABA
      • Also blocks NMDA channels, affecting potassium current
    • Clinical Use
      • Seizures (antiepileptic)
        • Broad-spectrum antiepileptic used 1st-line for generalized/tonic-clonic and myoclonic seizures
        • Also used for partial/focal seizures, absence seizures (2nd-line after ethosuximide)
      • Bipolar disorder
        • Mood stabilizer for BPD
      • Also used for migraine prophylaxis and trigeminal neuralgia
        • Think of the Na+, GABA, and NMDA effects as untargeted: like a sledgehammer for the brain (can be used for a lot of disorders)
    • Adverse Effects
      • Hepatotoxicity
        • Rare but fatal; monitor liver function tests
      • Teratogen
        • Neural tube defects
      • GI distress, pancreatitis, tremor, weight gain