Perampanel and childhood absence epilepsy: A real life experience

Abstract

ObjectivesThe aim of our study was to evaluate the effectiveness and tolerability of perampanel (PER) as first add-on and as second line monotherapy in subjects with childhood absence epilepsy.MethodsOur sample consisted of 20 patients with childhood absence epilepsy, aged between 8 and 10, already in therapy with a first antiseizure medication with incomplete seizure control. PER was added as first add-on in a dose ranging from 3 to 8 mg/die with 1- 2 mg/week increments. The patients that were seizure-free were shifted to a PER monotherapy. All patients underwent a standardized neuropsychological evaluation in order to assess non-verbal intelligence and executive functions before adding PER and after 6 months of drug therapy. All parents completed two questionnaires, in order to assess the emotional-behavioral problems and parental stress.Results15/20 patients responded to add-on PER and were seizure-free, in 3/20 patients we observed a reduction of seizure frequency <50%, and in the 2 remaining patients the add-on therapy with PER did not lead to a reduction in seizures frequency from baseline. The patients who were seizure-free were switched to PER monotherapy. 9/15 patients remained seizure-free in monotherapy with PER. In the first month of therapy with PER 2/20 patients (10%) reported mild, transient side effects of irritability, headache and dizziness, which did not lead to discontinuation of therapy. Adjunctive treatment with PER did not negatively affect non-verbal intelligence, executive functions, emotional/behavioral symptoms of children and parental stress levels.SignificanceOur clinical experience in real life showed that PER appears to be effective in the control of absence seizures in childhood absence epilepsy, with a favorable tolerability profile. PER would seem effective on absence seizures even in monotherapy. Further studies with larger samples, longer follow-up and controlled vs. placebo (or other first choice antiseizure medications) are needed to confirm our data.

The broad-spectrum activity of perampanel: state of the art and future perspective of AMPA antagonism beyond epilepsy

“…Results regarding absence seizure are supported by another study that evaluated PER as the first add-on and second-line monotherapy in 20 subjects with CAE (16). Overall, 75% of patients were seizurefree with add-on therapy, and 60% remained seizure-free with PER monotherapy.…”

“…Mild, transient side effects were reported only by two and did not lead to PER discontinuation. Moreover, PER did not negatively affect non-verbal intelligence, executive functions, emotional and behavioral symptoms, and parental stress (16).…”

“…As these were the first studies, the enrolled population comprised patients with highly pharmaco-resistant epilepsy, and PER was being used in combination with ≥3 antiseizure medications (ASMs). Subsequent studies suggest that PER is even more effective when used as an earlier rather than late ASM (13)(14)(15)(16)(17)(18)(19)(20).…”

Perampanel for the treatment of people with idiopathic generalized epilepsy in clinical practice

“…In the IGE group, the responder and seizure freedom rates were substantially lower than those observed in the current study; however, this is likely to reflect that PWE in the study were more refractory to treatment than those included in PERMIT, because 56.7% were being treated with ≥3 concomitant ASMs at baseline 25 (compared with 25.3% in the current study). The fifth study was an Italian, single‐center, retrospective, observational study, which demonstrated that PER was effective and well tolerated as first add‐on and second‐line monotherapy in 20 PWE with childhood absence epilepsy over a mean follow‐up duration of 10.2 months 26 . The final study was an Italian, multicenter, observational, retrospective study, in which PER was shown to be effective and well tolerated as only add‐on therapy in 503 PWE with focal, generalized, or undetermined epilepsy treated for up to 12 months, although outcomes were not reported separately for PWE with generalized epilepsy 27 …”

“…Approval of PER for the treatment of GTCS in IGE was based on the results of one phase 3, randomized, double‐blind, placebo‐controlled trial 17,18 . Clinical practice studies provide evidence on how a drug performs when used outside the relative restrictions of clinical trials, 19–21 but real‐world evidence on the use of PER to specifically treat IGE is currently limited 22–27 …”