Efficacy and safety of Levetiracetam as adjunctive treatment in children with focal onset seizures: A systematic review and meta-analysis

Cao, Yaohua; He, Xin; Zhao, Lina; He, Yuwen; Wang, Sen; Zhang, Tiantian; Jiang, Jie

doi:10.1016/j.eplepsyres.2019.04.001

Cited by 15 publications

(9 citation statements)

References 55 publications

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“…Levetiracetam is a broad-spectrum ASM that is recommended as a first-line add-on agent for focal seizures, with a favorable profile of efficacy and safety for both children and adults. It is one of the most-prescribed new-generation ASMs 12 .…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of levetiracetam as adjunctive therapy for refractory focal epilepsy

Manreza

Pan

Carbone

et al. 2021

Arq. Neuro-Psiquiatr.

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Background: Epilepsy affects about 50 million people worldwide and around 30% of these patients have refractory epilepsy, with potential consequences regarding quality of life, morbidity and premature mortality. Objective: The aim of treatment with antiseizure medications (ASMs) is to allow patients to remain without seizures, with good tolerability. Levetiracetam is a broad-spectrum ASM with a unique mechanism of action that differs it from other ASMs. It has been shown to be effective and safe for treating adults and children with epilepsy. Methods: This was a phase III, multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of levetiracetam in children and adults (4-65 years) as an adjuvant treatment for focal-onset seizures. It was conducted among 114 patients undergoing treatment with up to three ASMs. The primary efficacy analysis was based on the proportion of patients who achieved a reduction of ≥ 50% in the mean number of focal seizures per week, over a 16-week treatment period. The patients were randomized to receive placebo or levetiracetam, titrated every two weeks from 20 mg/kg/day or 1,000 mg/day up to 60 mg/kg/day or 3,000 mg/day. Results: Levetiracetam was significantly superior to placebo (p = 0.0031); 38.7% of the participants in the levetiracetam group and 14.3% in the control group shows reductions in focal seizures. Levetiracetam was seen to have a favorable safety profile and an adverse event rate similar to that of placebo. Conclusion: Corroborating the results in the literature, levetiracetam was shown to be effective and safe for children and adults with refractory focal-onset epilepsy.

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Section: Discussionmentioning

confidence: 99%

Efficacy and safety of levetiracetam as adjunctive therapy for refractory focal epilepsy

Manreza

Pan

Carbone

et al. 2021

Arq. Neuro-Psiquiatr.

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“…6 Levetiracetam is the most widely used antiepileptic drug in the United States, in large part because of its efficacy and generally favorable safety profile. 11 A recent meta-analysis by Cao et al 12 showed a positive response, with greater than 50% reduction in seizure or seizure freedom in children who use levetiracetam as adjunctive therapy for focal epilepsy compared to placebo. However, a Cochrane Review by Mbizvo et al 10 found the rate of behavioral side effects in children treated with levetiracetam to be as high as 23%.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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Brivaracetam is a new antiepileptic drug with limited data in children. The objective of this study was to assess the efficacy/tolerability of brivaracetam. This is a retrospective chart review of children/adolescents with refractory epilepsy treated with brivaracetam from 2016 to 2018. The primary outcome was seizure reduction (decrease in seizure frequency >50%). Twenty-three patients were identified. Mean age at initiation was 12.5 years. Fourteen were females. Epilepsy was focal in 11, generalized in 6, and mixed in 3. Average dose was 3.9 mg/kg/d. The mean duration of treatment was 8.2 months. Eight had greater than 50% decrease in seizure frequency, of which 7 had focal epilepsy, and 1 had Lennox-Gastaut/mixed epilepsy. Two had drowsiness and 3 behavioral complaints. One experienced tingling and dizziness. Our retrospective review suggests that brivaracetam is an effective therapy for refractory focal epilepsy in children older than 4 years of age.

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“…However, the SmPC and PI for LEV contain a warning for PBAEs including psychotic symptoms, suicidal ideation, irritability and aggressive behaviours [115,116]. Furthermore, a number of pooled analyses and meta-analyses of RCTs and observational studies have confirmed the association with PBAEs, particularly hostility, aggression, irritability, nervousness and anxiety [120,[123][124][125][126][127][128], with a higher rate of PBAEs compared with many other ASMs (Table S1 of the ESM) [36,37,127], which can lead to treatment discontinuations in a small proportion of patients [126,127] (Table S1 of the ESM).…”

Section: Levetiracetam (Lev)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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Efficacy and safety of Levetiracetam as adjunctive treatment in children with focal onset seizures: A systematic review and meta-analysis

Cited by 15 publications

References 55 publications

Efficacy and safety of levetiracetam as adjunctive therapy for refractory focal epilepsy

Efficacy and safety of levetiracetam as adjunctive therapy for refractory focal epilepsy

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

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

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