ABSTRACT
Complete seizure control is the single most important determinant of good quality of life for patients with epilepsy and the chronic nature of the disorder requires that antiepileptic drugs (AEDs) be administered for many years, often for a lifetime. Therefore, long-term experience is of particular importance in evaluating the efficacy and safety of an AED. Valproic acid increases γ-aminobutyric acid (GABA) synthesis and release and potentiates GABAergic transmission in specific brain regions and it also has also been found to reduce the release of the excitatory amino acid β-hydroxybutyric acid and to attenuate neuronal excitation mediated by activation of N-methyl-D-aspartate (NMDA) glutamate receptors. In addition to these effects, valproic acid exerts direct actions on excitable membranes, including blockade of voltage-dependent sodium channels. Valproate is generally regarded as a first-choice agent for most forms of idiopathic and symptomatic generalised epilepsies. Many of these syndromes are associated with multiple seizure types, including tonic-clonic, myoclonic and absence seizures, and prescription of a broad-spectrum drug such as valproate has clear advantages in this situation. The elimination half-life is in the order of 9 to 18 hours, but shorter values (5 to 12 hours) are observed in patients comedicated with enzymeinducing agents such as phenytoin, carbamazepine and barbiturates. The most commonly reported adverse effects of valproate include gastrointestinal disturbances, tremor and bodyweight gain. Other notable adverse effects include encephalopathy symptoms (at times associated with hyperammonaemia), platelet disorders, pancreatitis, liver toxicity and teratogenicity. According to the some study results, endocrine manifestations of reproductive system disorders, including polycystic ovary syndrome, may be more common in women treated with valproate than in those treated with other AEDs.