Comparative efficacy of antiepileptic drugs in children and adolescents: A network meta‐analysis

Rosati, Anna; Ilvento, Lucrezia; Lucenteforte, Ersilia; Pugi, Alessandra; Crescioli, Giada; McGreevy, Kathleen S.; Virgili, Gianni; Mugelli, Alessandro; Masi, Salvatore; Guerrini, Renzo

doi:10.1111/epi.13981

Cited by 40 publications

(37 citation statements)

References 68 publications

(111 reference statements)

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“…Finally, even in areas where RCTs exist, there are still important deficiencies in the quality of the information available. As eloquently stated in a recent metanalysis of pediatric RCTs in epilepsy, “the quality of studies should be improved through the use of comparative designs, relevant outcomes, appropriate follow‐up length, and more reliable inclusion criteria.”…”

Section: From Clinical Trials To Clinical Practicementioning

confidence: 99%

From clinical trials of antiepileptic drugs to treatment

Perucca

2018

Epilepsia Open

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SummaryRational prescribing should be based on the assessment of high‐quality evidence about the benefits and risks of available treatment options. Because clinical trials, particularly randomized controlled trials (RCTs), provide the best source of evidence, their design and results need to be carefully scrutinized. The majority of RCTs of antiepileptic drugs (AEDs) have been designed to address regulatory requirements, and generally they involve restrictive eligibility criteria, rigid dosing schemes, short duration of follow‐up, and comparison with placebo rather than standard treatments. Although these studies have high internal validity, they are conducted in a setting that is distant from routine clinical practice and therefore their usefulness in guiding treatment decisions is limited. Information more directly applicable to clinical practice can be derived from a relatively small number of comparative effectiveness monotherapy RCTs, although the design of some of these studies was probably biased in favor of the sponsor's product. Alarmingly, there is a paucity of well‐designed trials in epilepsy syndromes other than focal epilepsies, and no RCTs at all in most of the less common epileptic syndromes of infancy and childhood. In the light of these shortcomings, there is scope for re‐assessing regulatory requirements to facilitate generation of data more directly applicable to the routine clinical setting. Likewise, research‐funding organizations should be sensitized about the lack of adequate evidence to guide therapeutic practice in epilepsy, and the need to promote high‐quality comparative effectiveness trials. Future prospective pragmatic trials may benefit from the increasingly widespread availability of electronic health records.

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Section: From Clinical Trials To Clinical Practicementioning

confidence: 99%

From clinical trials of antiepileptic drugs to treatment

Perucca

2018

Epilepsia Open

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“…Approximately 1% of the general population suffers from epilepsy, which is a chronic disorder characterized by spontaneous recurrent seizures and an increased risk of comorbid conditions, particularly cognitive impairment, anxiety, depression, and sudden unexpected death (Hauser et al, ; Tellez‐Zenteno, Patten, Jette, Williams, & Wiebe, ). Up to 40% of all patients with epilepsy continue to experience seizures and comorbid features despite optimal pharmacological treatment, and many antiepileptic drugs have significant side effects that limit their use (Berg, ; Hu et al, ; Reynolds, ; Rosati et al, ). More effective and specific antiepileptic interventions are therefore urgently needed.…”

Section: Introductionmentioning

confidence: 99%

Astrocytes and Glutamine Synthetase in Epileptogenesis

Eid

Lee

Patrylo

et al. 2018

J of Neuroscience Research

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The cellular, molecular, and metabolic mechanisms that underlie the development of mesial temporal lobe epilepsy are incompletely understood. Here we review the role of astrocytes in epilepsy development (a.k.a. epileptogenesis), particularly astrocyte pathologies related to: aquaporin 4, the inwardly rectifying potassium channel Kir4.1, monocarboxylate transporters MCT1 and MCT2, excitatory amino acid transporters EAAT1 and EAAT2, and glutamine synthetase. We propose that inhibition, dysfunction or loss of astrocytic glutamine synthetase is an important causative factor for some epilepsies, particularly mesial temporal lobe epilepsy and glioblastoma-associated epilepsy. We postulate that the regulatory mechanisms of glutamine synthetase as well as the downstream effects of glutamine synthetase dysfunction, represent attractive, new targets for antiepileptogenic interventions. Currently, no antiepileptogenic therapies are available for human use. The discovery of such interventions is important as it will fundamentally change the way we approach epilepsy by preventing the disease from ever becoming manifest after an epileptogenic insult to the brain.

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“…In a meta-analysis, LTG was superior in terms of tolerability, but carbamazepine monotherapy showed a superior trend for seizure control [7]. However, other metaanalyses have reported that the best option for seizure outcome and tolerability was LTG in focal epilepsy [1,8]. LTG showed better tolerability than carbamazepine in two randomized controlled studies, although the studies were limited by the small sample size of pediatric patients [5,9].…”

Section: Discussionmentioning

confidence: 99%

“…This study was limited because it was an observational study and therefore had less impact than a randomized controlled study. A randomized controlled study that directly compares the effects of LTG and OXC is needed, although studies have evaluated comparable antiepileptic drugs in pediatric focal epilepsy patients by meta-analysis [8].…”

Section: Discussionmentioning

confidence: 99%