Abstract
Objective
Perampanel (PER) is a novel antiepileptic drug. The efficacy, tolerability and safety
of PER in children and adolescents with epilepsy are still unclear. We aimed to study
the efficacy and safety of PER in children and adolescents with epilepsy.
Methods
We searched PubMed, Embase and Cochrane Library for relevant literature up to November
2022. Then we extracted the relevant data from eligible literature for systematic
review and meta-analysis.
Result
Twenty-one studies involving 1968 children and adolescent patients were included.
A reduction in seizure frequency of at least 50 percent occurred in 51.5% (95% confidence
interval [CI] [47.1%, 55.9%]) of patients. Complete seizure cessation occurred in
20.6% (95%CI [16.7%, 25.4%]). The incidence of adverse events was 40.8% (95%CI [33.8%,
48.2%]). The most common adverse events were drowsiness 15.3% (95% CI [13.7%, 16.9%]),
irritability 9.3% (95%CI [8.0%, 10.6%]), dizziness 8.4% (95% CI [7.2%, 9.7%]). The
incidence of drug discontinuation due to adverse events was 9.2% (95% CI [7.0%, 11.5%]).
Conclusion
PER is generally well tolerated and effective in the treatment of epilepsy in children
and adolescents. Larger studies are still needed to explore the application of PER
in children and adolescents.
Risk of bias and limitation
The funnel plot suggests that there may be publication bias in our meta-analysis, and most of the included studies were Asian, so there may be some racial
differences.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Brain and DevelopmentAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Epilepsy in adults.Lancet. 2019; 393: 689-701
- The Epidemiology of Epilepsy.Neuroepidemiology. 2020; 54: 185-191
- An update for epilepsy research and antiepileptic drug development: Toward precise circuit therapy.Pharmacol Ther. 2019; 201: 77-93
- Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies.Epilepsia. 2010; 51: 1069-1077
- Perampanel: a novel, orally active, noncompetitive AMPA-receptor antagonist that reduces seizure activity in rodent models of epilepsy.Epilepsia. 2011; 52: 1331-1340
Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al. (editors).Cochrane handbook for systematic reviews of interventions version 6.3 (updated February 2022). Cochrane; 2022. Available from www.training.cochrane.org/handbook.
- Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses.Eur J Epidemiol. 2010; 25: 603-605
Rostom A, Dubé C, Cranney A, Saloojee N, Sy R, Garritty C, et al. Celiac Disease. Rockville(MD): Agency for Healthcare Research and Quality(US); 2004 Sep. (Evidence Reports/Technology Assessments, No.104.) Appendix D. Quality Assessment Forms. http://www.ncbi.nlm.nih.gov/books/NBK35156.
Quality Assessment Tool for Case Series Studies. National Heart, Lung, and Blood Institute. https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools. Accessed October 21, 2022.
- Effectiveness and Tolerability of Perampanel in Children and Adolescents with Refractory Epilepsies: First Experiences.Neuropediatrics. 2015; 46: 110-116
- Open-label study to investigate the safety and efficacy of adjunctive perampanel in pediatric patients (4 to <12 years) with inadequately controlled focal seizures or generalized tonic-clonic seizures.Epilepsia. 2020; 61: 125-137
- Clinical experience on the use of perampanel in epilepsy among child neurologists in the Philippines.Brain Dev. 2021; 43: 411-418
- Tolerability and efficacy of perampanel in children with refractory epilepsy.Dev Med Child Neurol. 2017; 59: 441-444
- Perampanel and childhood absence epilepsy: A real life experience.Front Neurol. 2022; 13952900
- The efficacy of perampanel in young children with drug-resistant epilepsy.Seizure. 2020; 75: 82-86
- Efficacy and tolerability of perampanel in children and adolescents with pharmacoresistant epilepsy: The first real-world evaluation in Asian pediatric neurology clinics.Epilepsy Behav. 2018; 85: 188-194
- Adjunctive perampanel in adolescents with inadequately controlled partial-onset seizures: A randomized study evaluating behavior, efficacy, and safety.Epilepsia. 2016; 57: 1120-1129
- Effectiveness and tolerability of perampanel in children and adolescents with refractory epilepsies -An Italian multicenter study.Epilepsy Res. 2016; 127: 93-100
- Perampanel as adjunctive therapy in drug resistant epilepsy in adolescents and children waiting for epilepsy surgery: A multicenter observational study in Thailand.Seizure. 2022; 100: 103-108
- Efficacy and tolerability of perampanel in pediatric patients with Dravet syndrome.Epilepsy Res. 2019; 154: 34-38
- Real-life effectiveness and tolerability of perampanel in pediatric patients aged 4 years or older with epilepsy: A korean national multicenter study.J Clin Neurol. 2020; 16: 53-59
- Efficacy and tolerability of adjunctive perampanel treatment in children under 12 years of age with refractory epilepsy.Korean J Pediatr. 2019; 62: 269-273
- Real-world evaluation of perampanel effectiveness in Japanese adolescents with epilepsy.Epileptic Disord. 2022; 24: 813-821
- Efficacy and adverse reactions of perampanel in the treatment of epilepsy in children.Front Neurol. 2022; 13 (924057)
- Utility and Safety of Perampanel in Pediatric FIRES and Other Drug-Resistant Epilepsies.Child Neurol Open. 2021; 8 (2329048X211055335)
- Effectiveness and tolerability of adjunctive perampanel in the treatment of pediatric patients with uncontrolled epilepsy: A retrospective, single-center, real-world study.Epilepsy Behav. 2022; 137108961
- Use of perampanel in children with refractory epilepsy of genetic aetiology.Epileptic Disord. 2022; 24: 687-695
- Effectiveness and safety of perampanel in Chinese paediatric patients (2–14 years) with refractory epilepsy: a retrospective, observational study.Epileptic Disord. 2021; 23: 854-864
- Effectiveness and tolerability of adjunctive perampanel in pediatric patients (aged 4–12 years) with refractory epilepsy: An observational study.Medicine (Baltimore). 2022; 101: e31408
- Therapeutic drug monitoring of perampanel in children diagnosed with epilepsy: Focus on influencing factors on the plasma concentration-to-dose ratio.Epilepsia Open. 2022; 7: 737-746
- Pharmacokinetics, exposure–cognition, and exposure–efficacy relationships of perampanel in adolescents with inadequately controlled partial-onset seizures.Epilepsy Res. 2016; 127: 126-134
- Cognitive effects of adjunctive perampanel for partial-onset seizures: A randomized trial.Epilepsia. 2016; 57: 243-251
- Long-term effects of adjunctive perampanel on cognition in adolescents with partial seizures.Epilepsy Behav. 2018; 83: 50-58
- Perampanel and Visuospatial Skills in Children With Epilepsy.Front Neurol. 2021; 12696946
- Effects of perampanel on secondary bilateral synchrony and behavioral problems in adolescents with epilepsy showing insufficient response with levetiracetam.Seizure. 2020; 80: 131-137
- Usefulness of perampanel with concomitant levetiracetam for patients with drug-resistant epilepsy.Eur J Paediatr Neurol. 2019; 23: 197-203
- Real-world analysis of hospitalizations in patients with epilepsy and treated with perampanel.Epilepsia Open. 2021; 6: 645-652
- Efficacy and safety of perampanel in adolescent patients with drug-resistant partial seizures in three double-blind, placebo-controlled, phase III randomized clinical studies and a combined extension study.Eur J Paediatr Neurol. 2015; 19: 435-445
- Efficacy, tolerability and safety of perampanel in population with pharmacoresistant focal seizures: A systematic review and meta-analysis.Epilepsy Res. 2022; 182106895
- Adjunctive Perampanel Oral Suspension in Pediatric Patients From ≥2 to <12 Years of Age With Epilepsy: Pharmacokinetics, Safety, Tolerability, and Efficacy.J Child Neurol. 2019; 34: 284-294
- Systematic review and meta-analysis of the efficacy and safety of perampanel in the treatment of partial-onset epilepsy.CNS Drugs. 2013; 27: 817-827
- The efficacy and safety of adjunctive perampanel for the treatment of refractory focal-onset seizures in patients with epilepsy: A meta-analysis.Epilepsia Open. 2022; 7: 271-279
- Clinical profiles associated with serum perampanel concentrations in children with refractory epilepsy.Epilepsy Behav. 2019; 94: 82-86
- Exploring the Evidence for Broad-Spectrum Effectiveness of Perampanel: A Systematic Review of Clinical Data in Generalised Seizures.CNS Drugs. 2021; 35: 821-837
- Safety of lamotrigine in paediatrics: a systematic review.BMJ Open. 2015; 5: e007711
- Safety of Levetiracetam in Paediatrics: A Systematic Review.PLoS One. 2016; 11: e0149686
- Efficacy and safety of lacosamide in pediatric patients with epilepsy: A systematic review and meta-analysis.Epilepsy Behav. 2022; 134108781
- Efficacy, tolerability, and safety of zonisamide in children with epileptic spasms: A systematic review and meta-analysis.Seizure. 2021; 91: 374-383
Article info
Publication history
Published online: March 04, 2023
Accepted:
February 13,
2023
Received in revised form:
February 9,
2023
Received:
November 21,
2022
Publication stage
In Press Corrected ProofIdentification
Copyright
© 2023 Published by Elsevier B.V. on behalf of The Japanese Society of Child Neurology. All rights reserved.
