Efficacy and tolerability of adjunctive perampanel treatment in children under 12 years of age with refractory epilepsy

Abstract

Purpose There is limited data on the use of perampanel in children under 12 years of age. We evaluated the efficacy and tolerability of adjunctive perampanel treatment in children under 12 years of age with refractory epilepsy. Methods This retrospective observational study was performed in Kyungpook National University Hospital from July 2016 to March 2018. A responder was defined as a patient with ≥50% reduction in monthly seizure frequency compared with the baseline. Adverse events and discontinuation data were obtained to evaluate tolerability. Results Twenty-two patients (8 males, 14 females) aged 3.1–11.4 years (mean, 8.0±2.5 years) were included in this study. After an average of 9.2 months (range, 0.5–19 months) of follow-up, 15 patients (68%) showed a reduction in seizure frequency, including 5 patients (23%) with seizure freedom. The age at epilepsy onset was significantly lower ( P =0.048), and the duration of epilepsy was significantly longer ( P =0.019) in responders than in nonresponders. Nine patients (41%) experienced adverse events, including somnolence (23%), respiratory depression (9%), violence (4.5%), and seizure aggravation (4.5%). The most serious adverse event was respiratory depression, which required mechanical ventilation in 2 patients (9%). Eight patients (36%) discontinued perampanel due to lack of efficacy or adverse events. Three out of 4 patients (75%) who discontinued perampanel due to adverse events had an underlying medical condition. Conclusion Perampanel offers a treatment option for refractory epilepsy in children. Adjunctive treatment with perampanel requires special consideration in those with underlying medical conditions to prevent serious adverse events.

The efficacy of perampanel in young children with drug-resistant epilepsy

“…The results were compatible with previous studies in children over 12 years. According to previous studies, the responder rates were 31%-68% in children with refractory epilepsy under 18 years, whereas the rate of seizure freedom ranged from 9 % to 23 % [7,10,11]. Therefore, the efficacy of PER as adjunctive therapy for young children with intractable epilepsy was good.…”

Perampanel markedly improved clinical seizures in a patient with a Rett‐like phenotype and 960‐kb deletion on chromosome 9q34.11 including the STXBP1

“…PER is a novel antiepileptic drug that selectively inhibits the postsynaptic AMPA receptor and is effective for treating drug-resistant epilepsy. [21][22][23][24][25][26] PER efficacy has been demonstrated in focal epilepsy and, more recently, in primary generalized tonic-clonic seizures. 23,24 A recent open-label study indicated that PER treatment was effective in adults with Lennox-Gastaut syndrome.…”

“…26 Recently, two studies reported the efficacy of PER for treating refractory epilepsy complications in various neurodevelopmental disorders. 21,22 However, the previous two reports did not report genotypic data for RTT-P, such as mutations of MECP2, FOXG1, and CDKL5.…”

“…Antagonism of AMPA receptors has been associated with antiseizure effects. PER is a novel antiepileptic drug that selectively inhibits the postsynaptic AMPA receptor and is effective for treating drug‐resistant epilepsy 21–26 . PER efficacy has been demonstrated in focal epilepsy and, more recently, in primary generalized tonic‐clonic seizures 23,24 .…”

Perampanel is also a useful adjunctive treatment option in refractory epilepsy in children

“…Yun et al [6] investigated the efficacy and tolerability of adjunctive PER treatment in children under 12 years of age with refractory epilepsy. A total 22 patients, aged 3.1–11.4 years showed responder rate of 68% (≥50% seizure reduction), wherein 23% showed seizure freedom.…”