Anti-seizure medications (ASMs) remain the mainstay of the treatment of epilepsy and the majority of patients with epilepsy (60–70%) will achieve a sustained remission from seizures. The number of ASMs has increased dramatically in recent years and there are now over 20 ASMs licensed and available [1]. Given that epilepsy is a chronic condition, often requiring years of treatment, a choice among these drugs requires evidence about longer-term clinical and cost effectiveness, which will come largely from randomized controlled trials (RCTs), in which treatments are compared head to head. Much of this evidence comes from publically funded trials rather than those sponsored by the pharmaceutical industry, whose trials are designed to meet regulatory requirements rather than to inform clinical decision-making. In the EU this currently results in non-inferiority trials assessing six-month remission rate [2,3], whilst in the USA this resulted in short-term trials using a historical control design [4]. More recently, the US FDA has allowed extrapolation of adjunctive therapy RCT data. Approval requires pharmacokinetic studies and recommendations for dosing to achieve levels similar to those obtained in adjunctive therapy. This approach has resulted in approvals for monotherapy for perampanel, eslicarbazepine and brivaracetam, without the need for a separate efficacy trial.