A double-blind controlled clinical trial of oxcarbazepine versus phenytoin in adults with previously untreated epilepsy. A double-blind controlled clinical trial of oxcarbazepine versus phenytoin in children and adolescents with epilepsy. Phenobarbitone, phenytoin, carbamazepine, or sodium valproate for newly diagnosed adult epilepsy: a randomised comparative monotherapy trial.
In the last 5 years oxcarbazepine (OXC) has been registered in many countries for use as first-line and add-on treatment for partial seizures with or without secondarily generalized seizures (PS) and generalized tonic-clonic seizures without partial onset (GTCS). Its use as monotherapy in adults with newly diagnosed epilepsy was investigated in this double-blind, randomized, parallel-group comparison with phenytoin (PHT). A total of 287 adult patients, with either PS or GTCS, were randomized. After retrospective baseline assessment, patients were randomized to OXC or PHT in a 1:1 ratio. The double-blind treatment phase was divided into two periods: a flexible titration period of 8 weeks, followed by 48 weeks of maintenance treatment. In the efficacy analyses, no statistically significant differences were found between the treatment groups. Seventy patients (59.3%) in the OXC group and 69 (58.0%) in the PHT group were seizure-free during the maintenance period. A total of 56 of the patients in the OXC group discontinued treatment prematurely (five because of tolerability reasons) compared to 61 in the PHT group (16 for tolerability reasons). The number of premature discontinuations due to adverse experiences showed a statistically significant difference in favour of OXC. There was no statistically significant difference between the groups with respect to the total number of premature discontinuations. This trial provides further support for the efficacy and safety of OXC as first-line treatment in adults with PS and GTCS. In addition, the results show that OXC has significant advantages over PHT in terms of tolerability. In many countries oxcarbazepine (OXC) has been registered for use as first-line and add-on treatment for patients with partial seizures with or without secondarily generalized seizures (PS) and generalized tonic-clonic seizures without partial onset (GTCS). Its use as monotherapy in children and adolescents with newly diagnosed epilepsy was investigated in this double-blind, randomized, parallel-group comparison with phenytoin (PHT). A total of 193 patients aged 5-18 years with either PS or GTCS were enrolled. After a retrospective baseline assessment, patients were randomized to OXC or PHT in a 1:1 ratio. The double-blind treatment phase comprised two periods: an 8-week flexible titration period; followed by 48 weeks maintenance treatment. In the efficacy analyses, there were no statistically significant differences between OXC and PHT. Forty-nine (61%) patients in the OXC group and 46 (60%) in the PHT group were seizure-free during the maintenance period. In total, 24 patients in the OXC group discontinued treatment prematurely (two for tolerability reasons) compared with 34 in the PHT group (14 for tolerability reasons). The number of premature discontinuations due to adverse experiences was statistically significantly lower in the OXC group than in the PHT group. Moreover, the odds of an individual discontinuing prematurely (regardless of reason) were almost twice as high in the PHT group. This trial provides further support for the efficacy and safety of OXC as first-line treatment in children and adolescents with PS and GTCS. In addition, the results show that OXC in these patients has significant advantages over PHT in terms of tolerability and treatment retention. Recent studies have shown that most newly diagnosed epileptic patients can be satisfactorily treated with a single antiepileptic drug. We therefore undertook a prospective randomised pragmatic trial of the comparative efficacy and toxicity of four major antiepileptic drugs, utilised as monotherapy in newly diagnosed epileptic patients. Between 1981 and 1987 243 adult patients aged 16 years or over, newly referred to two district general hospitals with a minimum of two previously untreated tonic-clonic or partial with or without secondary generalised seizures were randomly allocated to treatment with phenobarbitone, phenytoin, carbamazepine, or sodium valproate. The protocol was designed to conform with standard clinical practice. Efficacy was assessed by time to first seizure after the start of treatment and time to enter one year remission. The overall outcome with all of the four drugs was good with 27% remaining seizure free and 75% entering one year of remission by three years of follow up. No significant differences between the four drugs were found for either measure of efficacy at one, two, or three years of follow up. The overall incidence of unacceptable side effects, necessitating withdrawal of the randomised drug, was 10%. For the individual drugs phenobarbitone (22%) was more likely to be withdrawn than phenytoin (3%), carbamazepine (11%), and sodium valproate (5%). In patients with newly diagnosed tonic-clonic or partial with or without secondary generalised seizures, the choice of drug will be more influenced by considerations of toxicity and costs.
For participants with partial onset seizures oxcarbazepine is significantly less likely to be withdrawn, but current data do not allow a statement as to whether oxcarbazepine is equivalent, superior or inferior to phenytoin in terms of seizure control. However, the design of the studies may have biased seizure outcomes and misclassification of epilepsy type may have biased withdrawal rates.