Scoping review of rational polytherapy in patients with drug‐resistant epilepsy

There is a paucity of literature regarding the optimal selection of combination antiseizure medications (ASMs) for drug‐resistant epilepsy (DRE). The aim of this scoping review is to evaluate current evidence related to “rational polytherapy” among adults with DRE. Using the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses for Scoping Reviews (PRISMA‐SCr) guidelines, PubMed, ProQuest, CINAHL, and Cochrane databases were searched using DRE‐ and polytherapy‐related keywords. The exclusion criteria applied included: non‐English; non‐human studies; non‐research studies; participants less than 18 years; status epilepticus; ASM monotherapy; and certain ASMs. In Covidence, two researchers independently reviewed articles for inclusion at each phase, with a third resolving conflicts. Data were extracted, with quality appraisal using the Mixed Methods Appraisal Tool (MMAT). Of the 6477 studies imported for screening, 33 studies were included. Clinical, humanistic, and economic outcomes were reported by 26, 12, and one study, respectively. Common efficacy‐related clinical outcomes included ≥50% reduction in seizure frequency (n = 14), seizure freedom (n = 14), and percent reduction in seizure frequency (n = 8). Common humanistic outcomes included quality of life (n = 4), medication adherence (n = 2), sleep‐related outcomes (n = 2), and physician and patient global assessments (n = 2). The economic study reported quality‐adjusted life years. The median MMAT score was 80 (range: 60–100). Two studies referenced the standard definition of DRE, whereas five studies did not specifically define DRE. Gaps in the literature include limited generalizability, minimal reports in pregnancy, and lack of optimal ASM combinations, among others. Strengths of the evidence include addressing a variety of outcomes. Inconsistent definitions of DRE, small sample sizes, and heterogeneity among studies limit the ability to draw meaningful conclusions. Optimal combinations of ASMs for rational polytherapy for DRE is unclear.