The choice of antiepileptic drugs (AEDs) entails a number of considerations detailed later. All these considerations cannot be fully or adequately addressed by controlled studies alone, and are thus grounds for individualization of therapy. Although evidence-based data from randomized controlled trials (RCTs) on drug efficacy are a critical part of the choice, as they provide an objective method to compare efficacy, they often do not address many other aspects that are important in such choices such as comparative efficacy, comorbidity, and ease of use.
FACTORS AFFECTING AED INITIATION
During the process of patient evaluation and medication decision, several considerations affect treatment choices. These include:
Comparative efficacy: This refers to the ability of medication to control seizures and is usually best determined by RCTs. However, efficacy of drugs in specific epilepsy syndromes and long-term efficacy over years, even for common seizure types, are difficult to determine using RCTs, and data are limited. Furthermore, the phenomenon of seizure aggravation from AEDs has not been studied adequately but will affect the choice of an AED.
Relative tolerability: This refers to the medication adverse effect profile, which varies for each patient. A prominent example is the increased risk of liver toxicity for valproate (VPA) therapy in children under the age of 2 years with metabolic disorders. Relative tolerability also applies to lifestyle side effects including weight gain, gingival hyperplasia, alopecia, hyperactivity, and others. Children with behavior problems and/or with attention deficit disorder are particularly hyperactive with GABA-ergic drugs such as benzodiazepines barbiturates or VPA.
Cost and availability: The cost of the newer AEDs may prevent their use, particularly in developing countries. Furthermore, many drugs are available only in some countries either because they are too expensive or because, paradoxically, they are too inexpensive (with little financial incentive for their importation), or for regulatory reasons.
Ease of initiation of the antiepileptic drug: Medications that are titrated gradually such as lamotrigine (LTG) and topiramate (TPM) may not be chosen if rapid therapeutic levels are required. In these situations, medications with intravenous preparations or rapid oral titration schedules such as VPA, phenytoin (PHT), or levetiracetam (LEV) are alternative choices.
Preexisiting medications and the potential for pharmacokinetic drug interactions: An example is the reciprocal ability of VPA to increase the epoxide level of carbamazpine (CBZ) and CBZ lowering the level of VPA.
Availability of syndrome-specific and age-specific efficacy and tolerability data: Many AEDs are only proven to be effective in adult symptomatic and cryptogenic partial epilepsy, but have not been fully studied in children. In addition, some unique epilepsy syndromes and seizure types in childhood including neonatal seizures, West syndrome, early myoclonic encephalopathy, Ohtahara syndrome, and several other syndromes do not occur in adults. Furthermore, many of these disorders are relatively uncommon or rare and controlled studies are not available. This is also the case in more common pediatric epilepsy syndromes such as benign occipital epilepsy of childhood.
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