Safety and efficacy of divalproex sodium monotherapy in partial epilepsy: a double-blind, concentration-response design clinical trial. Depakote Monotherapy for Partial Seizures Study Group

Abstract

This is the first randomized, double-blind, parallel-group, multicenter trial that evaluated the efficacy of divalproex sodium monotherapy by comparing seizure frequency in 143 patients with poorly controlled partial epilepsy randomly assigned to high (80 to 150 micrograms/mL; 555 to 1,040 mumol/L) or low (25 to 50 micrograms/mL; 175 to 345 mumol/L) plasma valproate groups. There was a statistically significant reduction from baseline in the 8-week frequency of complex partial (p = 0.001) and secondarily generalized tonic-clonic seizures (p = 0.018) for patients in the high, compared with the low, plasma valproate group. Compared with baseline, there was a 30% median reduction in complex partial seizures for patients in the high group and a 19% increase for those in the low group. The median reduction for secondarily generalized tonic-clonic seizures was 70% for patients in the high group compared with a 22% increase in the low group. Adverse events that occurred significantly more frequently in the high group included tremors, thrombocytopenia, alopecia, asthenia, diarrhea, vomiting, and anorexia. This study demonstrates the efficacy of divalproex sodium as monotherapy for the treatment of partial-onset seizures and supports its role as one of the first-line antiepileptic drug treatments for patients with partial epilepsy.