Effectiveness and safety of perampanel in patients with lennox-gastaut syndrome: a single-arm meta-analysis with meta-regression and sensitivity analyses

BACKGROUND: Lennox-Gastaut syndrome (LGS) is characterized by multiple types of drug-resistant seizures that usually begin during early childhood and typically include tonic seizures with elevated risks of severe injuries, and are commonly associated with cognitive and behavioral impairments. Perampanel blocks glutamate activity at postsynaptic AMPA receptors and has emerged as a potential therapeutic strategy to disrupt the underlying excitatory mechanisms of this syndrome. OBJECTIVES: To evaluate the effectiveness and safety of perampanel in patients with LGS. METHODS: We conducted a systematic review and meta-analysis following Cochrane guidelines. PubMed, Embase, and Cochrane databases were searched for randomized controlled trials (RCTs) or observational studies. Pooled analyses used single-proportion meta-analysis with 95% confidence intervals (CI). RESULTS: Fourteen studies comprising 330 patients were included. The pooled ≥50% responder rate was 46.5% (95% CI 34-59.2), ≥75% responder rate 21.7% (8.2-38.4), seizure freedom 4.9% (0-15.2), and seizure aggravation 4.4% (0-13). Reported adverse events included somnolence (14.0%), irritability (12%), aggression (10.8%), dizziness (5.2%), agitation (3.9%), and psychiatric symptoms (15.1%). Heterogeneity was substantial. CONCLUSION: Perampanel demonstrates clinically meaningful seizure reduction in LGS with modest seizure-freedom and a behaviorally skewed safety profile. Despite heterogeneity and mostly retrospective data, findings support adjunctive use and highlight the need for larger, high-quality RCTs.