Partial Epilepsies Medication

Antiepileptic drugs (AEDs) are the first-line treatment for partial epilepsy. All AEDs are effective, but all have potential adverse effects.

Classic (old) agents include phenobarbital, primidone, phenytoin, carbamazepine, and valproate. After a 15-year hiatus in drug approvals, many new AEDs became available, starting in the early 1990s. The new drugs approved in the United States are felbamate (Felbatol), gabapentin (Neurontin), lamotrigine (Lamictal), topiramate (Topamax), tiagabine (Gabitril), levetiracetam (Keppra), zonisamide (Zonegran), and oxcarbazepine (Trileptal).

Class Summary

These agents prevent seizure recurrence and terminate clinical and electrical seizure activity.

Phenytoin (Dilantin, Phenytek)

Phenytoin may act in the motor cortex, where it may inhibit spread of seizure activity. Dose should be individualized. Administer larger dose before retiring if dose cannot be divided equally.

Carbamazepine (Tegretol, Carbatrol, Equetro, Epitol)

Carbamazepine may block posttetanic potentiation by reducing summation of temporal stimulation.

Valproic acid (Depakote, Depakene, Depacon, Stavzor)

Valproic acid is chemically unrelated to other drugs that treat seizure disorders. Although its mechanism of action not established, its activity may be related to increased brain levels of gamma-aminobutyric acid (GABA) or enhanced GABA action. It also may potentiate postsynaptic GABA responses, affect potassium channels, or have a direct membrane-stabilizing effect.

For conversion to monotherapy, concomitant AED dosage ordinarily can be reduced by approximately 25% every 2 weeks. This reduction may start at initiation of therapy or be delayed by 1-2 weeks if concern that seizures may occur with reduction. Monitor patients closely during this period for increased seizure frequency.

As adjunctive therapy, divalproex sodium may be added to patient's regimen at 10-15 mg/kg/d. The dose may be increased by 5-10 mg/kg/wk to achieve optimal clinical response. Ordinarily, optimal clinical response is achieved at daily doses of less than 60 mg/kg/d.

Gabapentin (Neurontin)

Gabapentin is structurally related to GABA, but does not interact with GABA receptors; it is not converted metabolically into GABA or a GABA agonist, and is not an inhibitor of GABA uptake or degradation. Nor does it exhibit affinity for other common receptor sites.

Titration to effect can take place over several days (300 mg on day 1, 300 mg bid on day 2, 300 mg tid on day 3).

Topiramate (Topamax)

Topiramate is a sulfamate-substituted monosaccharide with a broad spectrum of antiepileptic activity that may have a state-dependent sodium channel-blocking action. This agent potentiates the inhibitory activity of GABA and may block glutamate activity. Monitoring of plasma concentrations is not necessary to optimize therapy. On occasions, the addition of topiramate to phenytoin may require adjustment of the dose of phenytoin to achieve optimal clinical outcome.

Lamotrigine (Lamictal, Lamictal ODT, Lamictal XR)

A triazine derivative used in neuralgia, lamotrigine inhibits release of glutamate and inhibits voltage-sensitive sodium channels, leading to stabilization of neuronal membrane.

Felbamate (Felbatol)

An oral AED with weak inhibitory effects on GABA-receptor binding and benzodiazepine-receptor binding, felbamate has little activity at the MK-801 receptor-binding site of the N-Methyl-D-aspartate (NMDA) receptor-ionophore complex. However, felbamate is an antagonist at the strychnine-insensitive glycine recognition site of the NMDA receptor-ionophore complex. Felbamate is not indicated as first-line antiepileptic treatment.

Oxcarbazepine (Trileptal)

Oxcarbazepine has pharmacologic activity primarily through its 10-monohydroxy metabolite (MHD). This agent may block voltage-sensitive sodium channels, inhibit repetitive neuronal firing, and impair synaptic impulse propagation. Its anticonvulsant effect may also occur by affecting potassium conductance and high-voltage activated calcium channels. Drug pharmacokinetics are similar in older children (>8 y) and adults. Young children (< 8 y) have 30-40% greater clearance than older children and adults. Children younger than 2 years have not been studied in controlled clinical trials.

Primidone (Mysoline)

This agent decreases neuron excitability and increases seizure threshold.

Tiagabine (Gabitril)

Tiagabine's mechanism of action against seizures is unknown, but is believed to be related to the ability to enhance activity of GABA, which is a major inhibitory neurotransmitter in the CNS.

Tiagabine may block GABA uptake into presynaptic neurons, permitting more GABA to be available for receptor binding on surfaces of postsynaptic cells; it also may prevent propagation of neural impulses that contribute to seizures by GABAergic action.

When adding tiagabine to the antiepileptic regimen, modification of concomitant AEDs is not necessary unless clinically indicated.

Zonisamide (Zonegran)

Zonisamide is indicated for adjunct treatment of partial seizures with or without secondary generalization. Evidence suggests that it is also effective in myoclonic and other generalized seizure types.

Levetiracetam (Keppra)

Levetiracetam is used as add-on therapy for partial seizures. Its mechanism of action is unknown. It has a favorable adverse effect profile, with no life-threatening toxicity reported.

Pregabalin (Lyrica)

Pregabalin is a structural derivative of GABA. Its mechanism of action is unknown. It binds with high affinity to alpha2-delta site (a calcium channel subunit). In vitro, it reduces calcium-dependent release of several neurotransmitters, possibly by modulating calcium channel function. Pregabalin is FDA approved for neuropathic pain associated with diabetic peripheral neuropathy or postherpetic neuralgia and as adjunctive therapy in partial-onset seizures.

Lacosamide (Vimpat)

Lacosamide selectively enhances slow inactivation of voltage-gated sodium channels, resulting in stabilization of hyperexcitable neuronal membranes and inhibition of repetitive neuronal firing. It is indicated for adjunctive therapy for partial-onset seizures.

Vigabatrin (Sabril)

The precise mechanism of action of vigabatrin is unknown. It is an irreversible inhibitor of GABA transaminase (GABA-T). GABA-T metabolizes GABA, an inhibitory neurotransmitter, thereby increasing CNS GABA levels. The use of vigabatrin must be weighed against the risk of permanent vision loss with this agent, which is available only from restricted access program.

Vigabatrin is indicated for adjunctive treatment for complex partial seizures in adults who have had inadequate response to first-line therapy.

Ethotoin (Peganone)

Ethotoin may act in the motor cortex, where it may inhibit the spread of seizure activity. The activity of brain stem centers responsible for the tonic phase of grand mal seizures may also be inhibited.