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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.
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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 ...