[Tolerance to and unwanted effects of valproate sodium]

Sodium valproate (VPA) has been in clinical use for the treatment of epilepsy in Switzerland since 1967. A review of the literature associated with our personal experience since 1976 has shown VPA to be a remarkably safe and effective antiepileptic drug in a wide range of epileptic conditions in children and adults. Apparently, VPA is also a safe antiepileptic drug (AED) in old-age epilepsy due to good control of seizure frequency and fewer side effects when compared with other AEDs. Side effects can be minimized by initiating the drug slowly. VPA tended to be associated with fewer neurologic side effects than the other major AEDs. It had minimal impact on cognitive function and was associated with fewer cognitive and behavioral problems than phenytoin and phenobarbital. Sedation is most marked when patients take VPA in combination with other AEDs. The more common dose-related phenomena quite specific to VPA included weight gain, tremor and hair loss and did not usually abate with continued treatment but may respond to a lowering of the dosage or to a change in the dosing regimen. The incidence of gastrointestinal disturbances could be reduced considerably by using either enteric or 'chrono' VPA tablets. VPA chrono regimen in our studies demonstrated the equivalence or even superiority of a single daily dose over divided dosing schedules. There appeared to be no greater prevalence of toxicity, and administration as a single daily dose obviously improved compliance. Fatal hepatotoxicity is a rare, idiosyncratic, not dose-related adverse reaction that has been reported coincident with VPA therapy.(ABSTRACT TRUNCATED AT 250 WORDS)