Perampanel as adjuvant treatment in epileptic encephalopathies: A multicenter study in routine clinical practice

Alonso-Singer, Pablo; Prior, M.J. Aguilar-Amat; Oliva-Navarro, Javier; Massot‐Tarrús, Andreu; Giráldez, Beatriz G.; Bermejo, Pedro Emilio; DeToledo-Heras, María; Aledo‐Serrano, Ángel; Martinez-Cayuelas, Elena; Tirado-Requero, Pilar; Velazquez-Fragua, R.; López-Sobrino, Gloria; Ojeda, Joaquín

doi:10.1016/j.yebeh.2022.108836

Cited by 6 publications

(11 citation statements)

References 45 publications

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“…In this cohort, approximately 20% of the patients experienced irritability and aggression, particularly in association with rapid titration, duration of epilepsy, and numerous previous treatments. This percentage is consistent with that already reported by other real‐world studies assessing people with epilepsy and epileptic encephalopathies 12–15 . Psychiatric AEs were experienced more often by patients with previous psychiatric comorbidity and intellectual disability 15 …”

Section: Discussionsupporting

confidence: 90%

“…This percentage is consistent with that already reported by other real-world studies assessing people with epilepsy and epileptic encephalopathies. [12][13][14][15] Psychiatric AEs were experienced more often by patients with previous psychiatric comorbidity and intellectual disability. 15 PER has recently been investigated in a phase 3, multicenter, double-blind, randomized controlled trial as adjunctive therapy in patients with inadequately controlled seizures associated with LGS (NCT02834793).…”

Section: Discussionmentioning

confidence: 99%

“…Only a few reports about the use of PER in patients with LGS have been published so far, and they included a limited number of LGS subjects in mixed cohorts of patients with drug-resistant epilepsies. [12][13][14][17][18][19][20][21] Two realworld studies specifically investigated PER use in LGS patients, providing weak evidence that it may be efficacious and generally well tolerated. 12,13 This study provides the largest cohort exploring the long-term effectiveness of PER in LGS patients.…”

Section: Discussionmentioning

confidence: 99%

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Long‐term effectiveness of add‐on perampanel in patients with Lennox–Gastaut syndrome: A multicenter retrospective study

et al. 2023

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This retrospective study assessed long‐term effectiveness of add‐on perampanel (PER) in patients with Lennox–Gastaut syndrome (LGS). Outcomes included time to PER failure and time to seizure relapse in responders. PER failure was defined as either discontinuation of PER or initiation of another treatment. Seizure relapse in responders was defined as occurrence of a seizure in seizure‐free patients and increase of at least 50% in average monthly seizure frequency for those who were responders. Eighty‐seven patients were included. Treatment failure occurred in 52 (59.8%) subjects at a median time of 12 months. Treatment failure was due to lack of efficacy in 27 (52.0%) patients, lack of tolerability in 14 (27.0%), and both reasons in 11 (21.0%). A slower titration was associated with a lower risk of PER failure compared to faster titration schedules, and the occurrence of adverse events increased the risk of treatment failure. Thirty‐six patients (41.4%) were responders during a median follow‐up of 11 months. Seizure relapse occurred in 13 of 36 (36.1%) patients after a median time of 21 months. The overall rate of seizure responders was 23 of 87 (26.4%) at the end of follow‐up. This study provides real‐world evidence on the effectiveness of PER as adjunctive treatment in LGS patients.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Long‐term effectiveness of add‐on perampanel in patients with Lennox–Gastaut syndrome: A multicenter retrospective study

et al. 2023

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“…Future studies need large samples to confirm the effectiveness of PER monotherapy for focal epilepsy in children. Other epilepsy syndromes shown in previous studies, such as Dravet syndrome (8,12,13), Lennox-Gastaut syndrome (18)(19)(20), and focal epilepsy combined with ESES (10), presented good effectiveness with PER treatment.…”

Section: Discussionmentioning

confidence: 74%

Effectiveness and tolerability of perampanel monotherapy in children with newly diagnosed focal epilepsy

et al. 2023

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ObjectiveTo examine the clinical effectiveness and tolerability of perampanel (PER) as initial monotherapy in pediatric patients with newly diagnosed focal epilepsy.MethodsA retrospective analysis was conducted on 62 children with newly diagnosed focal epilepsy who were treated with PER at the Epilepsy Center of Jinan Children's Hospital from July 2021 to July 2022. The treatment status, prognosis, and adverse reactions were followed up for a minimum of 6 months after the initiation of PER monotherapy. The effectiveness of the patients was estimated by the PER effective rate at 3-, 6-, and 12-month follow-up evaluations and adverse reactions were also recorded. The effective rates of PER in different etiologies and epilepsy syndromes were also statistically analyzed.ResultsThe effective rates of PER treatment at the different time points of evaluation were 88.7% (3 months), 79.1% (6 months), and 80.4% (12 months). With PER treatment, seizure freedom varied over time, with 61.3%, 71.0%, and 71.7% of patients at the 3-, 6-, and 12-month follow-ups, respectively. Among the etiologies of epilepsy, the effective rates of genetic etiology, structural etiology, and unknown etiology were generally above 50% at the 3-, 6-, and 12-month follow-ups. Among the epilepsy syndromes, the categories with higher treatment efficacy were self-limiting epilepsy with centrotemporal spikes (SeLECTs), self-limited epilepsy with autonomic seizures (SeLEAS), and childhood occipital visual epilepsy (COVE), with an effective rate of above 80%. Adverse events were documented in 22 patients (35.5%), but they were mild and tolerable. The most common adverse events comprised irritability, drowsiness, dizziness, and increased appetite.ConclusionPER has favorable effectiveness and tolerability as initial monotherapy for children with newly diagnosed focal epilepsy, which could be a potential option for long-term medication in the treatment of focal epilepsy in children. The current study provided potential evidence for PER as initial monotherapy in children with focal epilepsy in clinical practice.

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“…Perampanel is indicated for focal seizures and primary generalised tonic-clonic seizures [173,174]. Perampanel has been evaluated in observational studies in cohorts of patients with DEEs that included LGS, DS and TSC [175][176][177][178][179][180][181][182], while other studies have been performed exclusively in patients with LGS [183,184] and DS [185]. Perampanel was being evaluated in a phase III RCT; however, the study was terminated by the sponsor because of challenges with recruitment that were exacerbated because of the coronavirus disease 2019 pandemic (NCT02834793).…”

Section: Perampanel (Per)mentioning

confidence: 99%

Psychobehavioural and Cognitive Adverse Events of Anti-Seizure Medications for the Treatment of Developmental and Epileptic Encephalopathies

Strzelczyk

Schubert‐Bast

2022

CNS Drugs

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The developmental and epileptic encephalopathies encompass a group of rare syndromes characterised by severe drug-resistant epilepsy with onset in childhood and significant neurodevelopmental comorbidities. The latter include intellectual disability, developmental delay, behavioural problems including attention-deficit hyperactivity disorder and autism spectrum disorder, psychiatric problems including anxiety and depression, speech impairment and sleep problems. Classical examples of developmental and epileptic encephalopathies include Dravet syndrome, Lennox–Gastaut syndrome and tuberous sclerosis complex. The mainstay of treatment is with multiple anti-seizure medications (ASMs); however, the ASMs themselves can be associated with psychobehavioural adverse events, and effects (negative or positive) on cognition and sleep. We have performed a targeted literature review of ASMs commonly used in the treatment of developmental and epileptic encephalopathies to discuss the latest evidence on their effects on behaviour, mood, cognition, sedation and sleep. The ASMs include valproate (VPA), clobazam, topiramate (TPM), cannabidiol (CBD), fenfluramine (FFA), levetiracetam (LEV), brivaracetam (BRV), zonisamide (ZNS), perampanel (PER), ethosuximide, stiripentol, lamotrigine (LTG), rufinamide, vigabatrin, lacosamide (LCM) and everolimus. Bromide, felbamate and other sodium channel ASMs are discussed briefly. Overall, the current evidence suggest that LEV, PER and to a lesser extent BRV are associated with psychobehavioural adverse events including aggressiveness and irritability; TPM and to a lesser extent ZNS are associated with language impairment and cognitive dulling/memory problems. Patients with a history of behavioural and psychiatric comorbidities may be more at risk of developing psychobehavioural adverse events. Topiramate and ZNS may be associated with negative effects in some aspects of cognition; CBD, FFA, LEV, BRV and LTG may have some positive effects, while the remaining ASMs do not appear to have a detrimental effect. All the ASMs are associated with sedation to a certain extent, which is pronounced during uptitration. Cannabidiol, PER and pregabalin may be associated with improvements in sleep, LTG is associated with insomnia, while VPA, TPM, LEV, ZNS and LCM do not appear to have detrimental effects. There was variability in the extent of evidence for each ASM: for many first-generation and some second-generation ASMs, there is scant documented evidence; however, their extensive use suggests favourable tolerability and safety (e.g. VPA); second-generation and some third-generation ASMs tend to have the most robust evidence documented over several years of use (TPM, LEV, PER, ZNS, BRV), while evidence is still being generated for newer ASMs such as CBD and FFA. Finally, we discuss how a variety of factors can affect mood, behaviour and cognition, and untangling the associations between the effects of the underlying syndrome and those of the ASMs can be challenging. In particular, there is enormous h...

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Perampanel as adjuvant treatment in epileptic encephalopathies: A multicenter study in routine clinical practice

Cited by 6 publications

References 45 publications

Long‐term effectiveness of add‐on perampanel in patients with Lennox–Gastaut syndrome: A multicenter retrospective study

Long‐term effectiveness of add‐on perampanel in patients with Lennox–Gastaut syndrome: A multicenter retrospective study

Effectiveness and tolerability of perampanel monotherapy in children with newly diagnosed focal epilepsy

Psychobehavioural and Cognitive Adverse Events of Anti-Seizure Medications for the Treatment of Developmental and Epileptic Encephalopathies

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