Truly "rational" polytherapy: maximizing efficacy and minimizing drug interactions, drug load, and adverse effects

Abstract

While several newer AEDs have study data that support monotherapy usage, most possess FDA indications for adjunctive treatment of partial onset seizures, leading to their initial (and often persistent) clinical use as adjunctive polytherapy for patients with refractory epilepsy. This review considers a practical approach to the appropriate role for polytherapy in epilepsy, presents the evidence for AED polytherapy, reviews the mythic but practically reasonable concept of "rational polytherapy," and concludes with practical strategies for avoiding and employing polytherapy in clinical practice. The appropriate indications for AED polytherapy include transitional polytherapy during titration of a new adjunctive AED toward monotherapy or long-term maintenance AED polytherapy in medically refractory epilepsy.

Keywords: Epilepsy; antiepileptic drugs; drug interactions.; drug load; polytherapy.

Fig. (1)

Therapeutic Triage in Epilepsy Care. Newly diagnosed epilepsy patients are most appropriately treated with antiepileptic drug monotherapy. Following failure of a second monotherapy, clinicians should implement courses of sequential chronic maintenance polytherapy and intensive evaluation to ensure correct epilepsy syndrome diagnosis and exclusion of nonepileptic spells. Pre-surgical evaluation with seizure-protocol magnetic resonance imaging (MRI) of the brain and ictal video-EEG recording of the patient’s habitual clinical spells should also be strongly considered to evaluate the patient’s potential to benefit from non-pharmacologic treatment options such as epilepsy surgery and VNS.