Multiple treatment comparisons in epilepsy monotherapy trials

Multiple treatment comparisons from epilepsy monotherapy trials were synthesized in a single stratified Cox regression model adjusted for treatment by epilepsy type interactions and making use of direct and indirect evidence. Primary outcomes were time to treatment failure and time to 12 month remission from seizures. A secondary outcome was time to first seizure.Individual patient data for 6418 patients from 20 randomised trials comparing eight antiepileptic drugs were synthesized. For partial onset seizures (4628 (72%) patients), lamotrigine, carbamazepine and oxcarbazepine provide the best combination of seizure control and treatment failure. Lamotrigine is clinically superior to all other drugs for treatment failure but estimates suggest a disadvantage compared to carbamazepine for time to 12 month remission [Hazard Ratio (95% Confidence Interval) = 0.87(0.73 to 1.04)] and time to first seizure [1.29(1.13 to 1.48)]. Phenobarbitone may delay time to first seizure [0.77(0.61 to 0.96)] but at the expense of increased treatment failure [1.60(1.22 to 2.10)]. For generalized onset tonic clonic seizures (1790 (28%) patients) estimates suggest valproate or phenytoin may provide the best combination of seizure control and treatment failure but some uncertainty remains about the relative effectiveness of other drugs.For patients with partial onset seizures, results favour carbamazepine, oxcarbazepine and lamotrigine. For generalized onset tonic clonic seizures, results favour valproate and phenytoin.Epilepsy is a common neurological condition with a prevalence of around 0.5% and a life time incidence of around 3% [1]. The majority of people with epilepsy are treated with a single (monotherapy) antiepileptic drug (AED), and 60–70% of patients will enter a remission from seizures soon after starting treatment, often on a first AED [2,3]. Current guidelines recommend valproate (VPA) as a treatment of first choice for patients with generalized onset seizures whilst carbamazep