title: What are the arguments for and against rational therapy for epilepsy?
abstract: Although more than a dozen new anti-seizure drugs (ASDs) have entered the market since 1993, a substantial proportion of patients (~30 %) remain refractory to current treatments. Thus, a concerted effort to identify and develop new therapies that will help these patients continues. Until this effort succeeds, it is reasonable to re-assess the use of currently available therapies and to consider how these therapies might be utilized in a more efficacious manner. This applies to the selection of monotherapies in newly-diagnosed epilepsy, but perhaps, more importantly, to the choice of combination treatments in otherwise drug-refractory epilepsy. Rational polytherapy is a concept that is predicated on the combination of drugs with complementary mechanisms of action (MoAs) that work synergistically to maximize efficacy and minimize the potential for adverse events. Furthermore, rational polytherapy requires a detailed understanding of the MoA subclasses amongst available ASDs and an appreciation of the empirical evidence that supports the use of specific combinations. The majority of ASDs can be loosely categorized into those that target neurotransmission and network hyperexcitability, modulate intrinsic neuronal properties through ion channels, or possess broad-spectrum efficacy as a result of multiple mechanisms. Within each of these categories, there are discrete pharmacological profiles that differentiate individual ASDs. This chapter will consider how knowledge of MoA can help guide therapy in a rational manner, both in the selection of monotherapies for specific seizure types and syndromes, but also in the choice of drug combinations for patients whose epilepsy is not optimally controlled with a single ASD.
authors.affiliation: Anticonvulsant Drug Development Program, Department of Pharmacology and Toxicology, University of Utah, 417 Wakara Way, Suite 3211, Salt Lake City, UT, 84108, USA, melissa.barker@utah.edu.
authors.forename: Melissa
authors.initials: M
authors.lastname: Barker-Haliski
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Sills
authors.forename: H Steve
authors.initials: HS
authors.lastname: White
mesh_terms: D000927:Anticonvulsants / Q000627:therapeutic use*; D004827:Epilepsy / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D009435:Synaptic Transmission
chemical_list: D000927:Anticonvulsants