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Valproic Acid-Associated Hyperammonemia: A Systematic Review.

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Area of Science:

  • Neurology
  • Clinical Pharmacology
  • Toxicology

Background:

  • Hyperammonemia is a known adverse effect of valproic acid (VPA), but its prevalence and management remain unclear.
  • Variability exists in monitoring and treating VPA-induced hyperammonemia due to lack of established guidance.
  • This systematic review addresses the clinical uncertainty surrounding VPA-associated hyperammonemia.

Approach:

  • A systematic review was conducted using electronic databases: Ovid MEDLINE, Embase, Web of Science, and PsycINFO.
  • Search terms targeted hyperammonemia in patients receiving VPA.
  • Independent review by two researchers, with a third resolving discrepancies, ensured rigorous screening and selection.

Key Points:

  • 240 articles were included in the review.
  • Asymptomatic hyperammonemia (5%-73%) was more prevalent than symptomatic (0.7%-22.2%), occurring within therapeutic VPA levels.
  • Risk factors include other medications, liver injury, and carnitine metabolism defects; discontinuation of VPA typically resolves symptoms.

Conclusions:

  • Valproic acid-associated hyperammonemia is a common adverse effect, potentially occurring at therapeutic VPA concentrations.
  • Further research is necessary to establish the benefits of routine ammonia monitoring.
  • Additional studies are needed to guide the clinical management of VPA-induced hyperammonemia.