title: Mitochondrial toxicity of antiepileptic drugs and their tolerability in mitochondrial disorders.
abstract: BACKGROUND
  Epilepsy is a frequent CNS manifestation of mitochondrial disorders (MIDs). At present, patients with MID-related epilepsy are largely treated in the same way as any other epilepsy sufferer. The problem with this approach is that some antiepileptic drugs (AEDs) are mitochondrial toxic and care is, therefore, needed when administering these AEDs to patients with MIDs.
  
  
  METHODS
  This review summarizes and discusses the mitochondrial toxicity, tolerability and beneficial effects of AED in patients with MIDs. The literature for this article was retrieved through PubMed using the search terms: 'mitochondrial disorder', 'mitochondriopathy', 'mitochondrial', 'cytopathy', 'metabolic disease', 'epilepsy', 'seizures' and various AEDs alone or in combination.
  
  
  CONCLUSIONS
  Mitochondrial-toxic AEDs may trigger or worsen an MID or may be even fatal in single cases. The AED with the most well-known mitochondrial toxicity is valproic acid (VPA), which has been known to exhibit a deleterious effect in patients with POLG1 mutations and patients with myoclonic epilepsy with ragged red fibers syndrome and VPA should only be applied in MIDs in case of a drug-resistant status epilepticus. AEDs other than VPA, which may affect the mitochondrial metabolism, include phenobarbital, carbamazepine, phenytoin, oxcarbazepine, ethosuximide, zonisamide, topiramate, gabapentin and vigabatrin. AEDs which interfere with mitochondrial function should be avoided whenever justifiable to the patient's well-being. Collateral beneficial effects of AEDs should also influence their choice in MIDs.
authors.affiliation: Danube University Krems, Krankenanstalt Rudolfstiftung, Postfach 20, 1180 Vienna, Krems Austria, Europe. fifigs1@yahoo.de
authors.forename: Josef
authors.initials: J
authors.lastname: Finsterer
authors.forename: Sinda
authors.initials: S
authors.lastname: Zarrouk Mahjoub
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects* / Q000378:metabolism*; D004347:Drug Interactions / Q000502:physiology; D004827:Epilepsy / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D000927:Anticonvulsants