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

Abstract

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.

Drug-Resistant Epilepsy: Experience From a Tertiary Care Center in Saudi Arabia

“…The most common ASM combinations used in our cohort were LEV and CBZ, LEV and valproic acid (VPA), and LEV and lamotrigine (LTG). According to a 2023 scoping review of rational polytherapy in patients with DRE [ 34 ], the combination of VPA and LTG is promising, despite the known drug interaction that requires slow titration of the latter. However, the optimal combinations of ASMs for DRE remain unclear and are largely determined on a case-by-case basis.…”

Determinants of quality of life in adults with epilepsy: a multicenter, cross-sectional study from Germany

“…The number of ASMs was not significantly correlated with QoL. There is a lack of consensus in the literature about the roles of monotherapy and polytherapy [ 39 ]. Our data suggest that poor QoL related to pharmacotherapy is due to the side effects of the medications, regardless of the number of ASMs, and patients receiving polytherapy have a higher risk of adverse events.…”

The Purinergic P2X7 Receptor as a Target for Adjunctive Treatment for Drug-Refractory Epilepsy

“…While monotherapy, referring to the use of a single medication for the treatment of a condition, is effective for most people with epilepsy, adjunctive therapy may be needed to obtain better seizure control, in particular, in patients not responding to commonly used ASMs [148]. Epilepsy is a complex disease associated with large-scale changes in gene expression, protein translation, and pathological processes, such as selective neuronal loss, gliosis, and synaptic remodelling [9,[149][150][151].…”