Clinical Efficacy and Safety of Perampanel Monotherapy for the Treatment of Epilepsy: A Systematic Review and Meta-Analysis
Abstract number :
1.395
Submission category :
7. Anti-seizure Medications / 7E. Other
Year :
2025
Submission ID :
837
Source :
www.aesnet.org
Presentation date :
12/6/2025 12:00:00 AM
Published date :
Authors :
Presenting Author: Hemanth Dhananjaya, MBBS – M. S. Ramaiah Medical College, Bengaluru, Karnataka, India
Himanshu Jog, MBBS – M.S Ramaiah Medical College, Bangalore, India
Josh Zhong, MD – St. George’s University School of Medicine
Andrea Ballena Gil, MD – Universidad San Martin de Porres
Laura Saldanha Fontes, MD – Universidade do Sul de Santa Catarina, Santa Catarina, Brazi
Francisco Ribeiro Dias Filho, MD – Universidade Federal de Roraima, Roraima, Brazil
Leite Enzo Lima Maia, MD – Faculdade Pernambucana de Saúde, Recife, Brazil
Rationale: Perampanel (PER) is a selective non-competitive AMPA receptor antagonist approved for focal seizures (with or without secondary generalization) and primary generalized tonic-clonic seizures. While most studies have focused on adjunctive use, PER is increasingly used as monotherapy in pediatric and adult populations due to its once-daily dosing, broad-spectrum efficacy and distinctive mechanism of action. However, evidence on its use as monotherapy remains scattered across heterogeneous studies. This study aimed to synthesize the available evidence on the efficacy and safety of PER monotherapy across diverse geographic and demographic settings.
Methods: We systematically searched PubMed, Embase and Cochrane databases through May 2025. Studies reporting outcomes in ≥ 5 patients receiving PER monotherapy were included. Outcomes assessed were 50% responder rate, seizure-free rate, treatment retention, incidence of adverse event (AE) and discontinuation due to AEs. Pooled estimates were calculated using an inverse variance-weighted random-effects model. Mixed-effects meta-regression was performed to explore heterogeneity, with age group (pediatric vs. mixed/adult) as a moderator. All analyses were conducted using R software (v4.4.1).
Results: Of 625 screened studies, 21 met inclusion criteria, comprising 1,156 patients treated with either primary or secondary PER monotherapy. Studies included a broad age range (mean 24 years), seizure types (focal and generalized), and diverse global regions. Maintenance doses ranged from 2-20 mg/day, with 4 mg/day most commonly reported.
The pooled 50% responder rate at 3, 6, and 12 months were 84.0%, 79.5%, and 74.5%, respectively. Seizure freedom rate at 3, 6, 12, and 24 months were 67.9%, 64%, 65.7%, and 55.23%, respectively. Treatment retention rate at 3, 6, and 12 months were 91.1%, 82.9%, and 72.0%. Treatment-emergent AEs were reported in 28.2% (95% CI: 20.7-37.1), most commonly dizziness, somnolence, and irritability. Most AEs were mild to moderate. Discontinuation due to AEs occurred in 6.7% (95% CI: 4.7-9.5) of patients. Substantial heterogeneity was observed for most outcomes (Figure 1). Meta-regression revealed that pediatric-only studies had higher 12-month responder rates (β=0.805, p=0.0018), seizure-free rates (β=0.65, p=0.022), and retention (β=0.78, p=0.0197), accounting for 24-72% of observed heterogeneity. A trend toward lower AE rates in pediatric populations (β=-0.61, p=0.125) was noted but was not statistically significant. Residual heterogeneity could likely be due to differences in study design, PER dosing, and epilepsy subtype distributions.
Conclusions: PER monotherapy appears to be an effective and well-tolerated treatment option for both focal and generalized epilepsy. Efficacy and retention are particularly favorable in pediatric populations. These findings support the role of PER monotherapy as a viable treatment option in routine clinical practice and underscore the need for further comparative studies across age groups and against other first-line antiseizure medications.
Funding: None
Anti-seizure Medications