Effectiveness and tolerability of perampanel in children and adolescents with refractory epilepsies-An Italian observational multicenter study

P De Liso; F Vigevano; N Specchio; L De Palma; P Bonanni; E Osanni; G Coppola; P Parisi; S Grosso; A Verrotti; A Spalice; F Nicita; N Zamponi; S Siliquini; L Giordano; P Martelli; R Guerrini; A Rosati; L Ilvento; V Belcastro; P Striano; M S Vari; G Capovilla; F Beccaria; O Bruni; A Luchetti; G Gobbi; A Russo; D Pruna; A E Tozzi; R Cusmai

doi:10.1016/j.eplepsyres.2016.08.021

Effectiveness and tolerability of perampanel in children and adolescents with refractory epilepsies-An Italian observational multicenter study

Epilepsy Res. 2016 Nov:127:93-100. doi: 10.1016/j.eplepsyres.2016.08.021. Epub 2016 Aug 18.

Authors

P De Liso¹, F Vigevano², N Specchio², L De Palma², P Bonanni³, E Osanni³, G Coppola⁴, P Parisi⁵, S Grosso⁶, A Verrotti⁷, A Spalice⁸, F Nicita⁸, N Zamponi⁹, S Siliquini⁹, L Giordano¹⁰, P Martelli¹⁰, R Guerrini¹¹, A Rosati¹¹, L Ilvento¹¹, V Belcastro¹², P Striano¹³, M S Vari¹³, G Capovilla¹⁴, F Beccaria¹⁴, O Bruni¹⁵, A Luchetti¹⁵, G Gobbi¹⁶, A Russo¹⁶, D Pruna¹⁷, A E Tozzi¹⁸, R Cusmai²

Affiliations

¹ Department of Neurosciences, Neurology Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy; Department of Paediatrics, Child Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy. Electronic address: [email protected].
² Department of Neurosciences, Neurology Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
³ Epilepsy and Clinical Neurophysiology Unit, Scientific Institute, IRCCS Eugenio Medea, Conegliano, Treviso, Italy.
⁴ Child and Adolescent Neuropsychiatry, Medical School, University of Salerno, Salerno, Italy.
⁵ NESMOS Department, Faculty of Medicine and Psychology, Sant'Andrea Hospital, Sapienza University, Rome, Italy.
⁶ Paediatric Neurology-Immunology and Endocrinology Unit, University of Siena, Siena, Italy.
⁷ Department of Paediatrics, University of L'Aquila, L'Aquila, Italy.
⁸ Department of Paediatrics, Child Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy.
⁹ Child Neuropsychiatry Unit, Polytechnic University of the Marche, Ancona, Italy.
¹⁰ Paediatric Neuropsychiatric Division, Spedali Civili, Brescia, Italy.
¹¹ Paediatric Neurology Unit, Children's Hospital A. Meyer, University of Firenze, Florence, Italy.
¹² Neurology Unit, Department of Neuroscience, Sant'Anna Hospital, Como, Italy.
¹³ Paediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, G. Gaslini Institute, Genoa, Italy.
¹⁴ Department of Child Neuropsychiatry, Epilepsy Centre, C. Poma Hospital, Mantova, Italy.
¹⁵ Child Neuropsychiatry Unit, S. Andrea Hospital, Rome, Italy.
¹⁶ Child Neurology Unit, IRCCS Institute of Neurological Sciences, Bologna, Italy.
¹⁷ Epilepsy Unit, Child Neuropsychiatry Department, University Hospital, Cagliari, Italy.
¹⁸ Multifactorial and Complex Diseases Research Area, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

PMID: 27568598
DOI: 10.1016/j.eplepsyres.2016.08.021

Abstract

Purpose: To evaluate the efficacy and tolerability of Perampanel (PER) in children and adolescents with refractory epilepsies in daily clinical practice conditions.

Patients and methods: This Italian multicenter retrospective observational study was performed in 16 paediatric epilepsy centres. Inclusion criteria were: (i) ≤18 years of age, (ii) history of refractory epilepsy, (iii) a follow-up ≥5 months of PER add-on therapy. Exclusion criteria were: (i) a diagnosis of primary idiopathic generalized epilepsy, (ii) variation of concomitant AEDs during the previous 4 weeks. Response was defined as a ≥50% reduction in monthly seizure frequency compared with the baseline.

Results: 62 patients suffering from various refractory epilepsies were included in this study: 53% were males, the mean age was 14.2 years (range 6-18 years), 8 patients aged <12 years. Mean age at epilepsy onset was 3.4 years and the mean duration of epilepsy was 10.8 years (range 1-16), which ranged from 2 seizures per-month up to several seizures per-day (mean number=96.5). Symptomatic focal epilepsy was reported in 62.9% of cases. Mean number of AEDs used in the past was 7.1; mean number of concomitant AEDs was 2.48, with carbamazepine used in 43.5% of patients. Mean PER daily dose was 7.1mg (2-12mg). After an average of 6.6 months of follow-up (5-13 months), the retention rate was 77.4% (48/62). The response rate was 50%; 16% of patients achieved ≥75% seizure frequency reduction and 5% became completely seizure free. Seizure aggravation was observed in 9.7% of patients. Adverse events were reported in 19 patients (30.6%) and led to PER discontinuation in 4 patients (6.5%). The most common adverse events were behaviour disturbance (irritability and aggressiveness), dizziness, sedation and fatigue.

Conclusion: PER was found to be a safe and effective treatment when used as adjunctive therapy in paediatric patients with uncontrolled epilepsy.

Keywords: Adolescents; Antiepileptic drug; Children; Perampanel; Refractory epilepsy; Treatment outcome.

Publication types

Multicenter Study
Observational Study

MeSH terms

Adolescent
Anticonvulsants / adverse effects
Anticonvulsants / therapeutic use*
Child
Drug Resistant Epilepsy / drug therapy*
Female
Follow-Up Studies
Humans
Italy
Male
Nitriles
Pyridones / adverse effects
Pyridones / therapeutic use*
Retrospective Studies
Seizures / drug therapy
Treatment Outcome

Substances

Anticonvulsants
Nitriles
Pyridones
perampanel