Document Detail

Valproic acid. A reappraisal of its pharmacological properties and clinical efficacy in epilepsy.
MedLine Citation:
PMID:  7512905     Owner:  NLM     Status:  MEDLINE    
Valproic acid is a branched-chained fatty acid, structurally unrelated to any other antiepileptic drug. Since publication of the original review in the Journal in 1977, several clinical trials have documented its efficacy and safety in adults and children for the treatment of generalised seizures (absence, tonic-clonic, myoclonic), partial seizures (simple, complex, secondarily generalised) and compound/combination seizures (including those refractory to treatment with other antiepileptic drugs). Valproic acid monotherapy has demonstrated efficacy equivalent to that of carbamazepine, phenytoin, and phenobarbital in the treatment of both generalised and partial seizures and ethosuximide in the treatment of absence seizures. Adverse effects associated with the drug are primarily gastrointestinal (nausea, vomiting, dyspepsia) in nature, although the use of enteric-coated formulations has reduced the incidence of abdominal discomfort. Weight gain, tremor and transient hair loss are commonly reported. Importantly, valproic acid has minimal neurological adverse effects (sedation, ataxia, impairment of cognitive function) compared with other antiepileptic drugs, a finding that may be of particular relevance in many patients with epilepsy. The incidence of rare, fatal liver failure has been greatly reduced by identifying and avoiding administration of valproic acid to high risk patient populations. An estimated risk of 1 to 2% for neural tube defects, predominantly spina bifida aperta, with maternal use of valproic acid therapy has been reported. Valproic acid inhibits hepatic drug metabolism and displaces other highly bound drugs from their plasma protein binding sites. Therefore, coadministered drugs which are highly protein bound or hepatically metabolised may require dosage adjustment. Enzyme-inducing antiepileptic drugs may increase valproic acid metabolism and necessitate increasing its dosage. Thus, comparative trials and extensive clinical experience have demonstrated the efficacy and tolerability of valproic acid and support its role as a valuable and well established first-line treatment for patients with a broad range of seizure types.
R Davis; D H Peters; D McTavish
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Drugs     Volume:  47     ISSN:  0012-6667     ISO Abbreviation:  Drugs     Publication Date:  1994 Feb 
Date Detail:
Created Date:  1994-05-24     Completed Date:  1994-05-24     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7600076     Medline TA:  Drugs     Country:  NEW ZEALAND    
Other Details:
Languages:  eng     Pagination:  332-72     Citation Subset:  IM    
Adis International Limited, Auckland, New Zealand.
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MeSH Terms
Anticonvulsants / pharmacokinetics,  pharmacology
Clinical Trials as Topic
Drug Interactions
Electroencephalography / drug effects
Epilepsy / drug therapy*
Valproic Acid / administration & dosage,  pharmacokinetics,  pharmacology,  therapeutic use*
Reg. No./Substance:
0/Anticonvulsants; 99-66-1/Valproic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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