Complex Partial Seizures Medication

Updated: Nov 27, 2017
  • Author: Elizabeth Carroll, DO; Chief Editor: Selim R Benbadis, MD  more...
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Medication

Medication Summary

Numerous different anticonvulsants may be used in the treatment of focal impaired awareness seizures. These agents tend to share certain properties but may have differing (or, in some cases, unknown) mechanisms of action.

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Anticonvulsants

Class Summary

All current antiepileptic drugs (AEDs), with the exception of ethosuximide, can be used in the treatment of complex partial seizures. The choice of an AED should be guided by certain general principles. The best-tolerated AED should be selected for the patient on the basis of side effects and drug interactions. Certain medications may offer favorable side effects (eg, topiramate and weight loss), whereas others may be chosen solely on the basis of route of excretion (eg, levetiracetam and renal excretion).

Monotherapy is always initially preferred over polytherapy for treating seizures. High dosages of a single agent may be required to achieve seizure control before adding a second agent.

Carbamazepine (Carbatrol, Tegretol, Tegretol XR, Epitol, Equetro)

Carbamazepine is effective for treatment of complex partial seizures. It appears to act by reducing polysynaptic responses and blocking posttetanic potentiation. Its major mechanism of action is reducing sustained, high-frequency, repetitive neural firing.

Phenytoin (Dilantin, Phenytek)

The primary site of action of hydantoins appears to be the motor cortex, where they may inhibit spread of seizure activity. Phenytoin may reduce maximal activity of the brainstem centers responsible for the tonic phase of grand mal seizures. Individualize the dose. If the daily dose cannot be divided equally, a large dose should be taken at bedtime. A phosphorylated formulation (fosphenytoin) is available for parenteral use and may be given intramuscularly (IM) or intravenously (IV).

Valproic acid (Depakene, Depacon)

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

For conversion to monotherapy, concomitant AED dosage is ordinarily reduced by approximately 25% every 2 weeks. Reduction may be started at the beginning of therapy or may be delayed 1-2 weeks if seizures are likely to occur with reduction. Monitor patients closely during this period for increased seizure frequency.

As adjunctive therapy, divalproex sodium 10-15 mg/kg/d may be added to the regimen; the dosage may be increased 5-10 mg/kg/d every week to the optimal clinical response (usually with < 60 mg/kg/d).

Gabapentin (Neurontin)

Gabapentin has properties in common with other anticonvulsants, but its exact mechanism of action is unknown. It is structurally related to GABA but does not interact with GABA receptors.

Lamotrigine (Lamictal, Lamictal XR, Lamictal ODT)

Lamotrigine is a triazine derivative that is useful in treatment of seizures and neuralgic pain. It inhibits release of glutamate and inhibits voltage-sensitive sodium channels, which stabilizes the neuronal membrane. Follow the manufacturer's recommendations for dose adjustments.

Topiramate (Topamax)

Topiramate is a sulfamate-substituted monosaccharide with a broad spectrum of antiepileptic activity; it may have state-dependent sodium channel blocking action; it potentiates the inhibitory activity of GABA. It may block glutamate activity. Monitoring of plasma concentrations is not necessary to optimize therapy. If topiramate is added to phenytoin, the phenytoin dose may have to be adjusted to achieve optimal clinical outcome.

Tiagabine (Gabitril)

Tiagabine's mechanism of action in the antiseizure effect is unknown but is thought to be related to its ability to enhance activity of GABA, the major inhibitory neurotransmitter in the central nervous system (CNS). It may block GABA uptake into presynaptic neurons, increasing GABA for receptor binding on surfaces of postsynaptic cells and possibly preventing propagation of neural impulses that contribute to seizures by GABAergic action. Modification of concomitant AED doses is not necessary unless clinically indicated.

Felbamate (Felbatol)

Felbamate is an oral AED that has weak inhibitory effects on GABA receptor binding and benzodiazepine receptor binding but interacts as antagonist at strychnine-insensitive glycine recognition site of N-methyl-D-aspartate (NMDA) receptor-ionophore complex. It is not indicated as first-line antiepileptic treatment. It is recommended only in those patients whose epilepsy is so severe that the benefits outweigh the risks of aplastic anemia or liver failure.

Phenobarbital

Phenobarbital has anticonvulsant activity at anesthetic doses and can be administered orally. If the IM route is chosen, the drug should be injected into a large muscle (eg, gluteus maximus or vastus lateralis) or other areas with little risk of encountering a nerve trunk or major artery. Injection into or near peripheral nerves may result in permanent neurologic deficit.

Restrict IV use to conditions in which other routes are not feasible because the patient is unconscious (eg, cerebral hemorrhage, eclampsia, status epilepticus) or in which prompt action is imperative.

Oxcarbazepine (Trileptal)

Oxcarbazepine exerts its pharmacologic activity primarily via 10-monohydroxy derivative (MHD). It may block voltage-sensitive sodium channels, inhibit repetitive neuronal firing, and impair synaptic impulse propagation. The anticonvulsant effect may occur by affecting potassium conductance and high-voltage activated calcium channels. Pharmacokinetics are similar in children older than 8 years and in adults. Children younger than 8 years have 30-40% increased clearance. Use in children younger than 2 years has not been studied in controlled clinical trials.

Eslicarbazepine (Aptiom)

Eslicarbazepine acetate is a prodrug that is activated to eslicarbazepine (S-licarbazepine), the major active metabolite of oxcarbazepine. It stabilizes neuronal membranes by blocking sodium channels. This action may inhibit repetitive firing and may decrease the propagation of synaptic impulses. It may also increase potassium conductance and modulate the activity of high-voltage activated calcium channels. It is indicated as adjunctive treatment or monotherapy for partial-onset seizures in adults.

Levetiracetam (Keppra)

Levetiracetam is used for adjunctive treatment of partial seizures. It binds to presynaptic vesicle protein (SV2A). It blocks high-voltage calcium currents and suppresses several negative modulators of GABA and glycine-gated currents.

Brivaracetam (Briviact)

Precise mechanism of action is unknown. Brivaracetam displays a high and selective affinity for synaptic vesicle protein 2A (SV2A) in the brain, which may contribute to the anticonvulsant effect. It is indicated as adjunctive therapy for partial-onset seizures in adults and children aged 16 y or older.

Pregabalin (Lyrica)

Pregabalin binds to the alpha2-delta subunit site of voltage-gated calcium channels in CNS tissues. It modulates calcium channel function and reduces release of multiple neurotransmitters.

Zonisamide (Zonegran)

Zonisamide may block sodium channels and reduce voltage-dependent, T-type Ca2+ currents and transient inward currents. It binds to the allosteric GABA/benzodiazepine receptor ionophore. It has weak carbonic anhydrase inhibiting activity.

Vigabatrin (Sabril)

Vigabatrin's precise mechanism is unknown. It is an irreversible inhibitor of GABA transaminase (GABA-T). GABA-T metabolizes GABA, an inhibitory neurotransmitter, thereby increasing CNS GABA levels. Use of vigabatrin must be weighed against the risk of permanent vision loss. Vigabatrin is available only from a restricted access program. It is indicated for adjunctive treatment of complex partial seizures in adults and children aged 10 y or older who have had inadequate response to first-line therapy.

Ethotoin (Peganone)

Ethotoin shares the actions of the hydantoin-derivative anticonvulsants; however, the drug apparently does not have the antiarrhythmic properties demonstrated by phenytoin.

Lacosamide (Vimpat)

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

Methsuximide (Celontin)

Methsuximide shares the actions of the succinimide-derivative anticonvulsants. It is indicated for the control of absence (petit mal) seizures refractory to other medications.

Ezogabine (Potiga)

Neuronal potassium channel opener. Stabilizes neuronal KCNQ (Kv7) channels in the open position, increasing the stabilizing membrane current and preventing bursts of action potentials during the sustained depolarizations associated with seizures. Indicated as adjunctive therapy in partial-onset seizures uncontrolled by current medications.

Perampanel (Fycompa)

Perampanel is a noncompetitive antagonist of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor. It is indicated as adjunct treatment for partial-onset seizures with or without secondary generalized seizures in adults and children aged 12 years or older.

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