COMBINATION VALPROATE CARBAMAZEPINE THERAPY IN PARTIAL EPILEPSIES RESISTANT TO CARBAMAZEPINE MONOTHERAPY

Eighteen patients with poorly controlled partial epilepsy on carbamazepine monotherapy at maximum tolerated doses were treated with valproate adjunctive therapy. Both medications were maintained for at least 3 months at the highest tolerated doses. Three patients had >50% decrease in seizure frequency on bitherapy; six patients were moderately improved, with a 22-44% decrease in seizure frequency; the remaining nine patients were unchanged or worsened, with up to a 49% increase in seizure frequency. Five of six patients with more than four seizures per month improved on bitherapy. Four patients had a shift of predominant seizure type from tonic-clonic to complex partial; two of these patients were moderately improved and two had an overall increase in seizures. Clinical toxicity was common on bitherapy, managed by a reduction in carbamazepine dose in most patients. We conclude that valproate-carbamazepine bitherapy may be beneficial in approximately half of patients who have failed high-dose carbamazepine monotherapy; however, marked improvement is infrequent. Valproate-carbamazepine bitherapy is also frequently associated with clinical anticonvulsant toxicity at the beginning of bitherapy, but this is generally easily managed with medication adjustment.