UMEM Educational Pearls

Category: Toxicology

Title: Valproic Acid and the Antidote

Keywords: valproic acid, carnitine, ammonia (PubMed Search)

Posted: 7/15/2010 by Fermin Barrueto, MD (Updated: 9/25/2023)
Click here to contact Fermin Barrueto, MD

Valproic Acid (Depakote) is a drug that uniquely has the ability to raise serum ammonia concentrations. It is able to do this without raising liver er enzymes and it can occur in overdose or at therapeutic levels. Do not think of this in the context of hepatic encephalopathy. This a metabolic derangement caused by VPA.

  • Any patient with somnolence, lethargy, decreased responsiveness - order a serum ammonia level as well as Valproic acid level
  • If the serum ammonia is elevated in conjunction with altered mental status consider a trial of carnitine
  • L-carnitine is a safe drug that is used in nutritional supplementation. VPA and other anticonvulsants cause carnitine deficiency
  • Most effective dose is unknown but from a recent review: IV 100 mg/kg once, followed by infusions of 50 mg/kg (to a maximum of 3 g per dose) every 8 hours until patient improves, ammonia decreases



  Perrott J, Murphy NG, Zed PJ. L-carnitine for acute valproic Acid overdose: a   systematic review of published cases. Ann Pharmacother. 2010  Jul-Aug;44(7-8):1287-93. Epub 2010 Jun 29.