Conventional and controlled release valproate in children with epilepsy: a cross-over study comparing plasma levels and cognitive performances

We studied plasma levels and behavioural effects of a newly developed controlled release formulation of valproate (VPA-CR) in children with epilepsy. Valproate plasma levels and performances in attention and vigilance tasks were monitored during a 12-h period (daytime), both during monotherapy of conventional valproate (VPA) and 4 weeks after switching to a similar dosage of VPA-CR taken once daily. There was no significant difference between the two formulations with respect to mean diurnal trough and peak valproate plasma levels, and to mean fluctuation. The significantly higher Cmax/Cmin ratio during VPA-CR seems mainly due to low valproate plasma levels early in the morning. Neuropsychological assessment showed no significant differences, either between patients and controls, or within patients and controls when comparing the results obtained on the VPA and VPA-CR day. During both VPA and VPA-CR treatment, no correlation was found between cognitive performance and valproate plasma levels. The advantage of VPA-CR is that the once daily regimen may increase compliance and is more convenient for schoolchildren.