Chapter 562

Although other treatment modalities, such as the ketogenic diet, epilepsy surgery, and the vagus nerve stimulator, are appropriate options at some point for certain patients, antiepileptic drugs (AEDs) represent almost invariably the first and, in the great majority of patients, the only treatment in patients diagnosed with epilepsy. Until 1993, 4 AEDs represented more than 90% of all prescriptions for epilepsy: phenobarbital, phenytoin, carbamazepine, and valproate. These drugs are now referred to as the “older” AEDs. Adrenocorticotropic hormone (ACTH) was available but was used only for limited specific indications. Since 1993, many “newer” AEDs have become available. As a group, most of these newer drugs offer welcome alternatives with less or different side effects, fewer or no pharmacokinetic interactions, and a spectrum of efficacy that covers a wider range of different seizure types. However, despite the availability of these newer drugs, the percentage of patients whose seizures can never be fully controlled by medication has not been reduced and remains around 25% to 30% of all patients diagnosed with epilepsy. With so many AEDs to choose from, the challenge of matching the best possible drug to a given patient has grown substantially. The first goal of therapy is to find as rapidly as possible the AED that will provide the best possible seizure control while maximizing tolerability and safety. The currently available evidence-based guidelines address only a small proportion of the seizure types and syndromes, and selecting the most appropriate drug will also involve clinical experience and art.1,2 Often the choice will have to be tailored for a given patient, and in addition to seizure type and epilepsy syndrome, personal characteristics of the patient will have to be taken into account, such as gender, age, comorbid conditions, other medications, and lifestyle.

### How Does Epilepsy Differ in Children?

Compared to practice in adults, the drug treatment of epilepsy in children differs in many ways. Children have seizure types, epilepsy syndromes, and underlying etiologies that cover a much broader spectrum. As the brain matures, seizures in children may evolve over time. The decision to initiate treatment after a first or even second seizure may differ in children, due to factors such as prognosis and impact of seizures on lifestyle. Antiepileptic therapy in children occurs in a context of growing, learning, and developing. Children may receive therapies that are only exceptionally used in adults, such as adrenocorticotropic hormone (ACTH), steroids, or the ketogenic diet. Often, antiepileptic drugs (AEDs) are used off label in children, either based on age or based on seizure type. Certain side effects of medications are more likely to occur in the pediatric age range, whereas others are more likely to occur in adults. Because children need to develop and learn, possible cognitive side effects of AEDs are a particular concern in this age group.3 Children’s pharmacokinetics differ, because they have invariably shorter drug elimination half-lives and higher clearances, which translate into substantially higher dosage requirements ...

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