The Challenges of Epilepsy in Children (original) (raw)
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Antiepileptic Drug Treatment in Children with Epilepsy
CNS drugs, 2015
Most children with new-onset epilepsy achieve seizure freedom with appropriate antiepileptic drugs (AEDs). However, nearly 20 % will continue to have seizures despite AEDs, as either monotherapy or in combination. Despite the growing market of new molecules over the last 20 years, the proportion of drug-resistant epilepsies has not changed. In this review, we report the evidence of efficacy and safety based on phase III randomized controlled clinical trials (RCTs) of AEDs currently used in the paediatric population. We conducted a literature search using the PubMed database and the Cochrane Database of Systematic Reviews. We also analysed the RCTs of newer AEDs whose efficacy in adolescents and adults might suggest possible use in children. Most of the phase III trials on AEDs in children have major methodological limitations that considerably limit meaningful conclusions about comparative efficacy between old and new molecules. Since the efficacy of new drugs has only been reported...
Antiepileptic drug development in children: considerations for a revisited strategy
Drugs, 2008
The European Commission and the European Parliament have acknowledged the specific need for a proper evaluation of new drugs in children. The evaluation of the antiepileptic drugs (AEDs) available on the market illustrates the deficit in therapeutic trials for childhood epilepsy syndromes. Currently, the development of AEDs is mainly performed in children with focal epilepsy, whereas infants and the specific age-related epilepsy syndromes, particularly epileptic encephalopathies, are neglected. Infantile epilepsies remain 'therapeutic orphans', although they are the most frequent and deleterious disorders in the area of epilepsy. In order to circumvent the difficulties faced when conducting AED trials in children, we addressed the question of improving feasibility without decreasing quality, while optimally taking into account paediatric ethical requirements. For this review, we first raise the issues of paediatric epilepsies that require special considerations for randomize...
Safety and Tolerability of Antiepileptic Drug Treatment in Children with Epilepsy
2012
The aim of treating epilepsy is to control or at least decrease seizures without producing unacceptable adverse effects that impair quality of life. Antiepileptic drugs (AEDs) have been considered amongst the drugs most frequently associated with fatal suspected adverse drug reactions. Physicians must therefore be as familiar with safety and tolerability data of AEDs as they are with the expected therapeutic effects. AEDs may cause dose-related adverse effects (i.e. drowsiness, fatigue, dizziness, blurry vision and incoordination) that, in most cases, may be obviated by lowering the dosage, reducing the number of drugs or switching to a better tolerated AED. AEDs also have the potential of precipitating idiosyncratic adverse effects (i.e. serious cutaneous, haematological and hepatic events), which are more common in children and usually require
Antiepileptic Drug Development in Children
Drugs, 2008
the specific need for a proper evaluation of new drugs in children. The evaluation of the antiepileptic drugs (AEDs) available on the market illustrates the deficit in therapeutic trials for childhood epilepsy syndromes. Currently, the development of AEDs is mainly performed in children with focal epilepsy, whereas infants and the specific age-related epilepsy syndromes, particularly epileptic encephalopathies, are neglected. Infantile epilepsies remain 'therapeutic orphans', although they are the most frequent and deleterious disorders in the area of epilepsy. In order to circumvent the difficulties faced when conducting AED trials in children, we addressed the question of improving feasibility without decreasing quality, while optimally taking into account paediatric ethical requirements.
Seizure, 2014
Epilepsy is the most common chronic neurologic disorder that requires long-term medication in children. Its prevalence has been estimated at 0.5-1% in children. 1,2 Prior to 1993, the choice of AEDs was limited to old antiepileptic drugs (AEDs) (phenobarbital, primidone, phenytoin, carbamazepine, valproate and ethosuximide). Among them, valproate, carbamazepine and phenobarbital are effective and more widely used medications for the treatment of many types of epilepsy. 3 Since 1993, 11 new AEDs (felbamate, oxcarbazepine, gabapentin, lamotrigine, topiramate, levetiracetam, tiagabine, vigabatrin,pregabalin, rufinamide, zonisamide, and lacosamide) have been introduced to the market. Because of the lack of data on the efficacy and safety of the new AEDs, their applications depend on the clinicians' own experiences. Levetiracetam and oxcarbazepine are the new generation AEDs, that are increasingly used as monotherapy as well as add-on therapy in children. 4,5 However, treatment failure due to lack of seizure control or intolerable adverse effects remains the major consequences in children suffering from epilepsy. The pharmacokinetics of AEDs in pediatric population differ considerably from those of adults. 6 Although it has been suggested that the efficacy of AEDs in adults could be used to predict the efficacy of AEDs in the pediatric population, 7 effectiveness of old and new AEDs in everyday child neurology practice has not been
New Versus Classic Antiepileptic Drug Therapy In Pediatric Epilepsy
2013
The current study was designed to compare the efficacy and safety between new and classic antiepileptic drugs (AEDs). Children diagnosed with epilepsy from birth to 12 years old were included in the present study. All data were collected retrospectively and twenty six children were enrolled in the analysis. Predominant seizure types were generalized tonic-clonic and the classical drugs were the most commonly prescribed drugs. Five patients (19%) among those who were treated with classic drugs become seizure free compared to 1 patient only (4%) who became seizure free from those who were treated with new antiepileptics. No side effects were reported except for 2 patients receiving the classic drug, carbamazepine, who developed skin rashes and dizziness. In conclusion, the results of the current study showed that the classic AEDs remain essential and still considered as the first line treatment in pediatric epilepsy. (Ahmed A. Elberry, Hala E. Alnazzawi, Afaf G. Almalki, Asma'a A....
Clinical Development of Antiepileptic Drugs for Children
2007
A clinical development plan specific to children is a necessary component of every development plan for a new antiepileptic drug (AED). In the last decade, considerable discussion has occurred in the medical and regulatory communities, resulting in specific pediatric drug development legislation. Ethical issues are a foremost consideration in the design and conduct of studies. The timing of clinical studies differs between adults and children. In general, studies in children will not be performed until efficacy and safety has been demonstrated in adults. Exceptions include development of AEDs for seizure types seen only in children. Formulation preparation and dosing selection are often more challenging in children. Clinical trials including pharmacokinetic studies will be conducted in patients. A relatively small number of children, given subdivision into age groups and seizure types, are available for study. Clinical trials must be designed with children in mind, adjusting the length of the trials and the choice of controls. Efficacy extrapolation from adults may be considered for partial seizures in children, but not in infants. Seizure counts remain an appropriate efficacy endpoint; however, ascertainment in infants and younger children may require EEG monitoring. Safety specific to growing and developing children must be evaluated and long-term effects monitored.
Antiepileptic Drug Development for “Therapeutic Orphans”
Epilepsia, 2003
Epilepsy is the most common serious neurological disorder among children. Excluding the elderly, the incidence of epilepsy is highest among children. About half of children with epilepsy have epilepsy syndromes that have unique onset in childhood. Clinical drug trials of antiepileptic drugs (AEDs) among children have been primarily performed using drugs developed for the larger adult partial epilepsy market. The current AED drug development system essentially renders children with epilepsy "therapeutic orphans" who can only benefit from AED development if a drug developed for adult partial epilepsy happens to also be effective for a pediatric epilepsy syndrome. The rapid evolution of different seizure types and childhood epilepsy syndromes, and rapid changes in baseline neurolog-ical status, make distinguishing clinical changes due to study drugs in clinical trials and the natural history of the epilepsy syndrome difficult. Unique ethical issues (e.g., informed consent), practical and logistical issues (e.g., serum AED level monitoring with microassay methods), as well as major financial and regulatory disincentives for the pharmaceutical industry are additional barriers to need-based AED development for children. A government-funded pediatric epilepsy group or consortium to conduct clinical trials similar to the successful Children's Oncology Group (COG) and regulations plus financial incentives that encourage the pharmaceutical industry to develop AEDs specifically for children are needed.
The Safety and Tolerability of Newer Antiepileptic Drugs in Children and Adolescents
CNS Drugs, 2010
Childhood epilepsy continues to be intractable in more than 25% of patients diagnosed with epilepsy. The introduction of new anti-epileptic drugs (AEDs) provides more options for treatment of children with epilepsy. We review the safety and tolerability of seven new AEDs (levetiracetam, lamotrigine, oxcarbazepine, ruinamide, topiramate, vigabatrin and zonisamide) focusing on their side effect proiles and safety in children and adolescents. Many considerations that are speciic for children such as the impact of AEDs on the developing brain are not addressed during the development of new AEDs. They are usually approved as adjunctive therapies based upon clinical trials involving adult patients with partial epilepsy. However, 2 of the AEDs reviewed here (ruinamide and vigabatrin) have FDA approval in the U.S. for speciic Pediatric epilepsy syndromes, which are discussed below. The Pediatrician or Neurologists decision on the use of a new AED is an evolutionary process largely dependent on the patient characteristics, personal/peer experiences and literature about eficacy and safety proiles of these medications. Evidence based guidelines are limited due to a lack of randomized controlled trials involving pediatric patients for many of these new AEDs.