Adverse drug reactions induced by valproic acid

Clin Biochem. 2013 Oct;46(15):1323-38. doi: 10.1016/j.clinbiochem.2013.06.012. Epub 2013 Jun 20.


Valproic acid is a widely-used first-generation antiepileptic drug, prescribed predominantly in epilepsy and psychiatric disorders. VPA has good efficacy and pharmacoeconomic profiles, as well as a relatively favorable safety profile. However, adverse drug reactions have been reported in relation with valproic acid use, either as monotherapy or polytherapy with other antiepileptic drugs or antipsychotic drugs. This systematic review discusses valproic acid adverse drug reactions, in terms of hepatotoxicity, mitochondrial toxicity, hyperammonemic encephalopathy, hypersensitivity syndrome reactions, neurological toxicity, metabolic and endocrine adverse events, and teratogenicity.

Keywords: ADR; AED; AHS; ALP; ALT; AST; Adverse drug reactions; Alpers-Huttenlocher syndrome; CI; CYP; DRESS; Drug monitoring; HHV; Hepatocytotoxicity; IQ; MELAS; Mitochondrial toxicity; OR; POLG; SCAR; SJS; Stevens–Johnson syndrome; TEN; VPA; Valproic acid; adverse drug reaction; alanine aminotransferase; alkaline phosphatase; antiepileptic drug; aspartate aminotransferase; confidence interval; cytochrome p450; drug reaction with eosinophilia and systemic symptoms; human herpes virus; intelligence quotient; mitochondrial DNA polymerase γ; mitochondrial myopathy, encephalopathy, lactic acidosis and stroke; odds ratio; severe cutaneous adverse reaction; toxic epidermal necrolysis; valproic acid; γ-GTP; γ-glutamyl transpeptidase.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Anticonvulsants / adverse effects*
  • Antipsychotic Agents / adverse effects*
  • Drug Hypersensitivity / etiology
  • Endocrine System / drug effects
  • Epilepsy / drug therapy
  • Humans
  • Hyperammonemia / chemically induced
  • Liver / drug effects
  • Mitochondria / drug effects
  • Nervous System / drug effects
  • Psychotic Disorders / drug therapy
  • Teratogenesis / drug effects
  • Valproic Acid / adverse effects*


  • Anticonvulsants
  • Antipsychotic Agents
  • Valproic Acid