Safety and Efficacy of Brivaracetam in Pediatric Refractory Epilepsy: A Single-Center Clinical Experience

McGuire, Sara; Silva, Gustavo; Lal, Darshan; Khurana, Divya S.; Legido, Agustín; Hasbani, Daphne M.; Carvalho, Karen S.; Melvin, Joseph J.; Valencia, Ignacio

doi:10.1177/0883073819879276

Cited by 16 publications

(9 citation statements)

References 23 publications

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“…In the McGuire et al retrospective study, 28 BRV was effective in 7 of the 11 patients with a history of focal seizures, representing the majority of the responders in the cohort (8 responders in a cohort of 20 patients). Three patients had mixed epilepsy, and one of those responded to BRV.…”

Section: Comparative Efficacymentioning

confidence: 96%

“…The first data on the potential effect of BRV for the treatment of generalized seizures in pediatric patients were extrapolated from Strzelczyk et al 32 These authors reported a failure response to BRV in 70% of the 10 children studied, although the remaining 30% were seizure‐free for longer than 6 months. McGuire et al 28 also showed that BRV efficacy for generalized seizures was poor, with none of the treated patients reaching at least 50% of seizure reduction. However, the number of concurrent ASMs used in the non‐responder cohort was considerably higher compared to that of the responders (1.74 in a range of 1 to 4, compared to 2.5 ranging from 1 to 6), suggesting a more refractory epileptic phenotype.…”

Section: Comparative Efficacymentioning

confidence: 99%

“…One patient in Nissenkorn's study 29 developed psychosis after discontinuing treatment but was already affected by depression and used to develop the same AE when treated with LEV. Also, in McGuire's cohort, all the patients that experienced behavioral concerns had psychiatric issues before the start of BRV, with 3 of the 17 children having previously discontinued LEV for the same reason; however, none of them had TEAEs when treated with BRV 28 . This strengthens what was previously published in a small open‐label study in a cohort of adults, in which the majority of the patients reported improvement (93%) or the complete resolution (62%) of their symptoms after the switch from LEV to BRV 39 .…”

Section: Safety and Tolerabilitymentioning

confidence: 99%

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Potential role of brivaracetam in pediatric epilepsy

et al. 2020

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Brivaracetam (BRV), which is considered to be the second generation of the drug of levetiracetam (LEV), 1 is a new antiseizure medication (ASM). It is a 2S)-2-[(4R)-2-oxo-4-propylpyrrolidin-1-yl] butanamide with four different diastereomers 2 capable of binding to SV2A vesicles with high affinity. 3 It was discovered as part of a program established by UCB Pharma to identify selective, high-affinity SV2A ligands that have higher antiepileptic properties than LEV. 2,4,5 Brivaracetam has a 10-30 times greater affinity and selectivity than LEV 6,7 and, compared to the latter, shows greater permeability of the blood-brain barrier in rodent models. 8 In recent years, it has been tested as an ASM in adult and pediatric patients. Most of the studies on the tolerability and efficacy of BRV concern the adult population; the data on the pediatric population are still sparse. The purpose of this review is to provide a comprehensive overview of the available data published about its efficacy and tolerability at the pediatric age.

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Section: Comparative Efficacymentioning

confidence: 96%

Section: Comparative Efficacymentioning

confidence: 99%

Section: Safety and Tolerabilitymentioning

confidence: 99%

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Potential role of brivaracetam in pediatric epilepsy

et al. 2020

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“…Brivaracetam is a third-generation ASM that is indicated as adjunctive therapy in the treatment of focal seizures (with or without secondary generalisation in the EU) [137,138]. A Cochrane analysis identified six trials evaluating add-on BRV for DREs (Table S1 of the ESM) [139], while BRV has also been analysed in a large number of observational studies in patients with DEEs/DREs [140][141][142][143][144][145][146][147][148]. Brivaracetam is an analogue of LEV that has 15-30 times greater affinity for SV2A and higher brain permeability compared with LEV [149].…”

Section: Brivaracetam (Brv)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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“…A study by McGuire et al showed that brivaracetam was safe and efficacious in the reduction of pediatric refractory epilepsy. 54 Perampanel is also another molecule used in the treatment of DS. In a report by Chang et al, perampanel was found to be a safe and effective adjuvant therapy to treat drug resistant epilepsy in young children.…”

Section: New Molecules In Epilepsymentioning

confidence: 99%

A Review of the Prevalence, Etiology, Diagnosis, and Management of Pediatric Epilepsies in India

Kalra

Venkataraman

Shah

2022

Journal of Pediatric Neurology

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Pediatric seizures are one of the most common neurological manifestations seen in pediatrics. Unravelling the etiology, timely and appropriate investigations followed by suitable therapies are essential for improving quality of life. During the pandemic, focused group discussions were conducted among 50 pediatric neurologists across five cities in India to gather insights on treatment practices in pediatric epilepsy and to optimize therapeutic strategies and alternative approaches for rational use of antiepileptic medications. These discussions were mainly aimed at reviewing current literature on prevalence, etiology, diagnosis, and management of epilepsy in children and subsequently rationalizing diagnostic and treatment approaches in routine clinical practice. Epileptic encephalopathies comprise of childhood epilepsy with progressive cerebral dysfunction. Genomics plays a vital role in identifying the underlying genetic associations, empowering precision therapy. Currently, the ketogenic diet has become a well-recognized modality for reducing severity of seizures. To overcome the high incidence of adverse effects due to older antiepileptic drugs, newer drugs are being developed to improve ease of use, diminish drug interactions, decrease adverse effects, and identify drugs with unique mechanisms of action. Common lacunae in practice include information gaps, educating parents, or caregivers about rational drug use and ensuring compliance to antiepileptic medications. This article discussed the consensus clinical viewpoint of expert clinicians, as well as insights on optimized treatment of pediatric epilepsies in both infancy and childhood. It also discusses aspects, like reducing drug burden, emerging therapies in the identification of the genetic basis of epilepsies, and targeted therapy alternatives, for pediatric populations in the Indian scenario.

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Safety and Efficacy of Brivaracetam in Pediatric Refractory Epilepsy: A Single-Center Clinical Experience

Cited by 16 publications

References 23 publications

Potential role of brivaracetam in pediatric epilepsy

Potential role of brivaracetam in pediatric epilepsy

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

A Review of the Prevalence, Etiology, Diagnosis, and Management of Pediatric Epilepsies in India

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