The measurement of ammonia blood levels in patients taking valproic acid: looking for problems where they do not exist?

Epilepsy Behav. 2007 Nov;11(3):361-6. doi: 10.1016/j.yebeh.2007.06.015. Epub 2007 Sep 12.


Hyperammonemia (HA) commonly occurs with the use of valproic acid (VPA); while it has no clinical significance in most cases, the Physician Desk Reference recommends its discontinuation in the presence of HA. The purpose of this study is to review the literature in order to estimate the prevalence and magnitude of HA in VPA treated patients, to establish any association with hepatotoxicity and encephalopathy and to identify any factors associated with its occurrence. A search of MEDLINE and Cochrane Database of Systematic Reviews, between 1980 and 2005 was performed. Out of 183 studies, 24 met our inclusion criteria. The prevalence of HA in the prospective studies ranged between 70% and 100%, while in cross-sectional studies it varied between 16% and 100%. Ammonia (NH(3)) blood levels increased by a two-fold average relative to the baseline levels. There was no association between HA and clinical symptoms. Concomitant administration of other antiepileptic drugs (AEDs) was the factor most frequently associated with HA.

Publication types

  • Review

MeSH terms

  • Ammonia / blood*
  • Anticonvulsants / adverse effects*
  • Epilepsy / blood*
  • Epilepsy / drug therapy*
  • Epilepsy / epidemiology
  • Female
  • Humans
  • MEDLINE / statistics & numerical data
  • Male
  • Retrospective Studies
  • Valproic Acid / adverse effects*


  • Anticonvulsants
  • Valproic Acid
  • Ammonia