Which antiseizure medications are effective for absence seizure in children and adolescents? A Cochrane Review summary with commentary.

Abstract

The aim of this commentary is to discuss the published Cochrane Review ‘Ethosuximide, sodium valproate or lamotrigine for absence seizures in children and adolescents’ by Brigo et al.,a under the direct supervision of the Cochrane Epilepsy Group. This Cochrane Corner is produced in agreement with Developmental Medicine & Child Neurology by Cochrane Rehabilitation. Absence seizures account for 10% to 17% of all seizures in children and adolescents.2 Absence seizures present as short sudden episodes of loss of awareness and can be divided into typical absence seizure, atypical absence seizure, and absence seizures with special features.3, 4 Sodium valproate, ethosuximide, and lamotrigine are three antiseizure medications commonly used to treat absence seizures. Ethosuximide is indicated only for the treatment of generalized absence seizure, whilst valproate and lamotrigine are used in other types of seizures. Non-systematic reviews have suggested that ethosuximide and sodium valproate are equally effective, while lamotrigine is considered as a second-line drug, reserved for intractable absence seizure.5 Accidental injury is a common complication of absence seizure; around 20% of adolescents with absence seizure were reported to suffer an injury during an absence seizure.6 This could impact their rehabilitation process and thus prescribing antiseizure medication based on evidence is important. The aim of this Cochrane Review was to determine the best choice of antiseizure medication for children and adolescents with typical absence seizure between ethosuximide, valproate, and lamotrigine compared with placebo and each other. The population addressed in this review were children and adolescents up to 16 years of age with typical absence seizure. The interventions studied were sodium valproate, ethosuximide, or lamotrigine as monotherapy or add-on treatment. The intervention was compared with placebo or with one another. The primary study outcomes were proportion of seizure-free participants at 1 month, 3 months, 6 months, 12 months, and 18 months after randomization; 50% or greater reduction in the frequency of seizures; and incidence of adverse effects. Secondary study outcomes included normalization of electroencephalogram (EEG) and/or negative hyperventilation test. The review authors searched the Cochrane Register of Studies (CRS) and MEDLINE (OVID) up to September 2020. The CRS Web included randomized or quasi-randomized, controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialized Registers of Cochrane Review Groups. The authors also contacted Sanofi Winthrop, Glaxo Wellcome (now GlaxoSmithKline), and Parke Davis (now Pfizer), manufacturers of sodium valproate, lamotrigine, and ethosuximide respectively. They also reviewed references of identified studies and retrieved relevant studies. The review authors did not include any new studies in the present review. The review authors assessed five full-text reports for possible inclusion. However, the studies were excluded for the following reasons: three studies were commentaries; one a review; and another one not relevant to the current review. This current review is based on the eight studies (691 participants) from the 2019 review. The review authors did not perform meta-analysis due to the different methodologies used in the included studies. The authors concluded that ethosuximide represents the optimal initial empirical monotherapy for children and adolescents with absence seizure with regards to both efficacy and tolerability. If absence and generalized tonic–clonic seizures coexist, valproate should be preferred, as ethosuximide is inefficacious on tonic–clonic seizures. The conclusions remain the same as the previous update as there was no new study found since the last version of the review was published. The review would influence the choice of antiseizure medication that should be prescribed for children and adolescents with typical absence seizure. Children with absence seizure are also at risk of having behaviour/psychiatric status, and psychosocial and cognitive function issues including attention, memory, and learning disability.7-9 This group of patients will often require multidisciplinary rehabilitation management. Selecting the best treatment for absence seizure is very important to optimize the outcome and improve the quality of life in patients with absence seizure. Poorly controlled absence seizure will lead to accidental injury and may influence the outcome of coordinated multidisciplinary rehabilitation management. Another issue to consider relates to females of child-bearing age, as a proportion of the adolescents will require antiseizure medication beyond the age group studied.10 There is a need to improve the design of randomized controlled trial research in this area to provide more concrete evidence to guide decision-making as most of the trials included in the systematic review are of poor methodological quality. The authors thank Cochrane Rehabilitation and Cochrane Epilepsy Group for reviewing the contents of the Cochrane Corner. The authors have stated that they had no interests that could be perceived as posing a conflict or bias.