When choosing initial antiepileptic drug (AED) therapy for a patient with epilepsy, assess whether the suspected diagnosis is a focal or generalized epilepsy. In focal epilepsies, there is felt to be a discrete seizure focus within a local network, typically in a single hemisphere. Progression to a bilateral tonic-clonic seizure may ensue. The majority of AEDs are effective for focal epilepsy. In contrast, generalized epilepsies are characterized by seizures that rapidly engage diffuse bilateral networks; in addition to generalized-onset tonic-clonic seizures, common examples include absence and generalized myoclonic seizures. A smaller group of AEDs are considered effective for generalized epilepsy, and some commonly used drugs, such as carbamazepine, oxcarbazepine, and gabapentin, may actually worsen the condition. These drugs should be avoided in generalized epilepsy or in cases where the diagnosis is uncertain. In some situations, there may be a need for an AED to treat another condition in addition to epilepsy. Common examples include comorbid migraine headaches or neuropathic pain. This should be considered when choosing initial therapy (see Chapter 73 ).
In generalized epilepsies, commonly used drugs including levetiracetam, lamotrigine, valproate, zonisamide, and topiramate. Clobazam and perampanel are also reasonable choices, and ethosuximide is appropriate if absence seizures are the only seizure type (not shown). Of these, levetiracetam is frequently chosen first due to its rapid titration, absence of drug interactions, and excellent safety profile. However, it does have the potential to worsen mood or cause irritability. In fact, most so-called “broad spectrum” AEDs appropriate for generalized epilepsy have frequent adverse psychiatric effects, the main exceptions being lamotrigine and valproate. Lamotrigine is very well tolerated but requires a several-week titration and is often ineffective against myoclonus, and is therefore a poor choice if rapid seizure control is needed or if myoclonus is common. Initial treatment with levetiracetam with early consideration of transition to lamotrigine is a reasonable approach in the common situation where mood is a concern and rapid treatment is needed. Valproic acid has adverse effects including weight gain, hair loss, tremor, and decreased bone density, but is considered the most effective drug for generalized epilepsy. However, it must be avoided if pregnancy is a possibility, as it has a high risk of teratogenesis ( Table 71.1 ).
Initial Treatment of Epilepsy
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