Altered Mental Status and Hyperammonemia after Overdose of Valproic Acid with Therapeutic Valproic Acid Concentrations
- 1 Division of Emergency Medicine, Washington University School of Medicine, St. Louis, USA
- 2 Department of Medicine, Washington University School of Medicine, St. Louis, USA
Abstract
Valproic acid is used in the treatment of multiple disorders. Adverse effects from valproic acid include hepatotoxicity, hypotension, metabolic acidosis, and decreased mental status. Valproic acid also causes hyperammonemia. Many physicians assume that this is due to a supratherapeutic valproic acid concentration; when in fact, it can occur with therapeutic valproic acid concentrations. This is because the hyperammonemia may be related to carnitine deficiency and disruption of the urea cycle, which can both occur with therapeutic valproic acid concentrations. We report a patient presented to the emergency department with alteration of mental status after ingesting valproic acid for recreational purposes, who developed hyperammonemia with a therapeutic valproic acid concentration.
- Sztajnkrycer, M.D. (2002) Valproic Acid Toxicity: Overview and Management. Journal of Toxicology—Clinical Toxicology, 40, 789-801. http://dx.doi.org/10.1081/CLT-120014645
- Lheureux, P.E. and Hantson, P. (2009) Carnitine in the Treatment of Valproic Acid-Induced Toxicity. Journal of Toxicology—Clinical Toxicology, 47, 101-111. http://dx.doi.org/10.1080/15563650902752376
- Dealberto, M.J. and Sarazin, F.F. (2008) Valproate-Induced Hyperammonemic Encephalopathy without Cognitive Sequelae: A Case Report in the Psychiatric Setting. The Journal of Neuropsychiatry and Clinical Neurosciences, 20, 369-371. http://dx.doi.org/10.1176/appi.neuropsych.20.3.369
- Verrotti, A., Trotta, D., Morgese, G., et al. (2002) Valproate-Induced Hyperammonemic Encephalopathy. Metabolic Brain Disease, 17, 367-373. http://dx.doi.org/10.1023/A:1021918104127
- Hamer, H.M., Knake, S., Schomburg, U., et al. (2000) Valproate-Induced Hyperammonemic Encephalopathy in the Presence of Topiramate. Neurology, 54, 230-232. http://dx.doi.org/10.1212/WNL.54.1.230
- Itoh, H., Suzuki, Y., Fujisaki, K., et al. (2012) Correlation between Plasma Ammonia Level and Serum Trough Concentration of Free Valproic Acid in Patients with Epilepsy. Biological and Pharmaceutical Bulletin, 35, 971-974. http://dx.doi.org/10.1248/bpb.35.971
- Laub, M.C. (1986) Hyperammonemia in Valproate Therapy in Children and Adolescents. Der Nervenarzt, 57, 314-318.
- Spiller, H.A., Krenzelok, E.P., Klein-Schwartz, W., et al. (2000) Multicenter Case Series of Valproic Acid Ingestion: Serum Concentrations and Toxicity. Journal of Toxicology—Clinical Toxicology, 38, 755-760. http://dx.doi.org/10.1081/CLT-100102388
- Raskind, J.Y. and El-Chaar, G.M. (2000) The Role of Carnitine Supplementation during Valproic Acid Therapy. Annals of Pharmacotherapy, 34, 630-638. http://dx.doi.org/10.1345/aph.19242
- Li, J., Norwood, D.L., Mao, L.F., et al. (1991) Mitochondrial Metabolism of Valproic Acid. Biochemistry, 30, 388-394. http://dx.doi.org/10.1021/bi00216a012
- Mackay, F.J., Wilton, L.V., Pearce, G.L., et al. (1997) Safety of Long-Term Lamotrigine in Epilepsy. Epilepsia, 38, 881-886. http://dx.doi.org/10.1111/j.1528-1157.1997.tb01252.x
- Shan, J.C., Hsieh, M.H., Liu, C.C., et al. (2010) Clinical Alertness to Valproic Acid-Induced Hyperammonemia—Two Case Reports. Journal of Psychopharmacology, 24, 943-945. http://dx.doi.org/10.1177/0269881109102635