Antiepileptic drug monotherapy versus polytherapy: pursuing seizure freedom and tolerability in adults

Abstract

Despite the availability of many new antiepileptic drugs (AEDs), only around 50% of people with epilepsy will become seizure free on their first drug. This article explores treatment options and issues influencing whether AEDs should be substituted or combined in the remainder of the patient population.

Prior to the introduction of novel AEDs, it was generally opined that combining traditional agents did not necessarily lead to an improvement in seizure control and might increase the propensity for side effects. Newer AEDs, many with different mechanisms of action, have increased the potential for polytherapy regimens, although robust data to support or refute this therapeutic strategy are sparse. It seems sensible to substitute rather than combine when the first AED produces an idiosyncratic reaction, is poorly tolerated at a low/moderate dose or shows no efficacy. Polytherapy may be preferred if the patient tolerates their first or second AED well, but with a suboptimal response, particularly when there is an identifiable anatomical substrate for the seizures. AED selection requires consideration of many factors some of which are discussed in this study.

There are no definitive answers on whether to combine or substitute AEDs. Different strategies are required for different scenarios in different patients.