ReviewNeurology and therapy2026
Narrative Review: Efficacy, Safety, and Tolerability of Newer Third-Generation Antiseizure Medications for Focal Epilepsy: A New Benchmark in Treatment Outcomes?
Review in Neurology and therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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4 authors.
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Abstract
introductionFocal seizures are the most common form of epilepsy. This narrative review analyzes the efficacy, safety, and tolerability of five newer third-generation antiseizure medications (ASMs) approved for treatment of focal seizures: lacosamide, perampanel, eslicarbazepine acetate, brivaracetam, and cenobamate.
methodsA search of PubMed and ClinicalTrials.gov identified phase 2/3 randomized controlled trials and long-term open-label extension (OLE) studies for the five most recently approved ASMs for focal seizures. Efficacy data were summarized, including median percent reduction in seizure frequency, ≥ 50% responder rates, ≥ 75% responder rates (when reported), and seizure freedom rates. Safety and tolerability were assessed based on treatment-emergent adverse events (TEAEs), serious adverse events, and discontinuation rates. Long-term efficacy, safety, and treatment retention rates were also summarized.
resultsAll five ASMs had statistically significant efficacy vs. placebo in short-term trials, with cenobamate demonstrating higher median percent seizure reduction (35.5-100%), ≥ 50% responder rates (40-81.6%), and seizure freedom rates (up to 52.4%) compared to the other four third-generation ASMs. In long-term OLEs, cenobamate had ≥ 50% responder rates > 70% and the highest estimated treatment retention rates at 3 years (61-65%) compared to lacosamide (51-53%), perampanel (46%), and brivaracetam (48%). Common TEAEs across all ASMs included dizziness, somnolence, fatigue, and headache. Brivaracetam and lacosamide had favorable profiles in multiple network meta-analyses. Specific safety considerations include psychiatric adverse events for perampanel and brivaracetam, and a risk of drug reaction with eosinophilia and systemic symptoms (DRESS) for cenobamate (significant risk reduction achieved using a gradual titration schedule).
conclusionAll third-generation ASMs were effective adjunctive therapies. Cenobamate was associated with higher responder and seizure freedom rates and higher long-term retention rates. Brivaracetam and lacosamide had favorable tolerability profiles. The notable seizure freedom rates with cenobamate suggest a potential new benchmark in focal seizure treatment. Comparator trials are needed to confirm possible efficacy and tolerability differences among third-generation ASMs.
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