Conventional vs controlled-release CBZ : A multicentre, double-blind, cross-over study

Efficacy of tolerability of a new controlled-release (CR) formulation of carbamazepine (CBZ) (Tegretol CR), were assessed in a formal multicentre, double-blind, cross-over trial, carried out in 48 epileptic patients (21 men, 27 women; mean age 34 years). Before entering the study, patietns (pts) had been taking conventional CBZ monotherapy, but without a complete seizure control (n = 22 pts), or with intermittent side-effects (n = 4 pts), or with seizures and intermittent side-effects (n = 22 pts). Eligible pts were given conventional CBZ and CR CBZ, in randomized sequence, at individualized daily doses, subdivided in the lowest number of administration. Each period of the cross-over consisted of a first phase of titration (lasting up to 2 months) and of a second phase of maintenance (lasting 1 month) used for evaluation. A 12-hour plasma CBZ and CBZ-epoxide profile concentrations, as well as efficacy and tolerability, were evaluated at the end of each period. The mean daily CBZ dose has been increased by 15% during administration of the CR formulation. Fluctuation indices of total CBZ and 10,11-epoxide plasma levels at steady-state were significantly (p < 0.02) lower during CR CBZ treatment, leading to a significant (p < 0.001) decrease of intermittent side-effects (6 pts on CR CBZ vs 36 on conventional CBZ). In addition, a complete seizure control was obtained in 4 pts when treated with CR CBZ; 38 pts on CR CBZ (vs 15 pts on conventional CBZ) were treated with a b.i.d. regimen.