Tonic-clonic seizures: a systematic review of antiepilepsy drug efficacy and safety

This systematic review of studies of patients with generalized tonic-clonic seizures is an effort to evaluate whether one therapeutic agent is superior to another in terms of reducing seizures and tolerability. Recognizing that assessing relative efficacy is dependent on controlling the specific type of seizure or epilepsy treated, we restricted our review to studies in which the seizure types were clearly identified. Overall, complete control of generalized tonic-clonic seizures was achieved in 53% of treated patients. The percentage of patients who became seizure free was not significantly different with carbamazepine, phenytoin, or valproate. When patients who had a partial onset of their generalized tonic-clonic seizures were grouped, complete control was achieved in 48% with carbamazepine, 49% with phenytoin, and 52% with valproate. Overall, carbamazepine, phenytoin, and valproate appear to have similar efficacy in the treatment of tonic-clonic seizures, with complete control reported in 51%, 50%, and 55% of patients, respectively. The best response in primary generalized seizures was with valproate, with 61% reported as seizure free. Acute and dose-related central nervous system side effects occurred with equal frequency with carbamazepine, phenytoin, and valproate treatment. These side effects diminished after chronic exposure. Overall, 9.9% of patients discontinued treatment due to adverse effects. The lowest incidences of clinically important side effects and rash were reported in patients treated with valproate.