Epileptic and Epileptiform Encephalopathies Medication

Updated: Jul 26, 2022
  • Author: Masanori Takeoka, MD; Chief Editor: Stephen L Nelson, Jr, MD, PhD, FAACPDM, FAAN, FAAP, FANA  more...
  • Print

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and to prevent complications. The agents used in the treatment of epilepsy include anticonvulsants and adrenocorticotropic hormones.


Adrenocorticotropic hormones

Class Summary

These agents stimulate the adrenal cortex to release of corticosteroids.

Corticotropin (ACTH, Acthar)

Efficacy in epileptic encephalopathies is variable. However, ACTH is associated with serious, potentially life-threatening side effects. ACTH gel preparation is used in epilepsy and is the only anticonvulsant medication that must be administered by IM injection.

Prednisone (Deltasone, Meticorten, Orasone)

Prednisone may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear neutrophil (PMN) activity.


Anticonvulsant agents

Class Summary

These agents prevent seizure recurrence and terminate clinical and electrical seizure activity. If absence seizures are present, ethosuximide is the appropriate medication. This may be the case for patients with chronic absence epilepsy. These agents may be used in conjunction with an anticonvulsive AED, such as phenytoin (Dilantin), for patients at risk of tonic-clonic seizures in whom valproic acid is contraindicated.

Vigabatrin (Sabril)

Vigabatrin inhibits gamma-aminobutyric acid transaminase (GABA-T), increasing the levels of the inhibitory compound GABA within the brain.

Carbamazepine (Tegretol)

Carbamazepine appears to act by reducing polysynaptic responses and blocking posttetanic potentiation. Its major mechanism of action is to reduce sustained high-frequency repetitive neural firing.

Diazepam (Valium)

A long-acting benzodiazepine, diazepam has anxiolytic and anticonvulsant properties. Diazepam is effective for multiple seizure types, but is usually used for control of intermittent episodes of increased seizure activity in epilepsy patients on stable anticonvulsant regimens.

Diazepam's mechanism of action is based on inhibition of neuronal excitation through binding to gamma-aminobutyric acid (GABA) and more specifically to GABA-A receptors.

This agent is available in oral solution (5 mg/5 mL or 5 mg/mL), tablets (Valium) 2 mg, 5 mg, 10 mg, rectal gel (Diastat or Diastat AcuDial delivery system and injection), and solution (5 mg/mL).

Valproic acid (Depakote, Depakene, Depacon)

Valproic acid is chemically unrelated to other drugs used to treat seizure disorders.

Although its mechanism of action is not established, the activity of valproic acid may be related to increased brain levels of GABA or enhanced GABA action. This agent may also potentiate postsynaptic GABA responses, affect potassium channels, or have direct membrane-stabilizing effect.

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

As adjunctive therapy, valproic acid may be added to the patient's regimen at a dosage of 10-15 mg/kg/d. The dosage 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.

Ethosuximide (Zarontin)

A succinimide AED, ethosuximide is effective only against absence seizures. It has no effect on generalized tonic-clonic, myoclonic, atonic, or partial seizures.

The mechanism of action of ethosuximide is based on reducing current in T-type calcium channels found on thalamic neurons. The spike-and-wave pattern during petit mal seizures is thought to be initiated in thalamocortical relays by activation of these channels.

Ethosuximide is available in large 250-mg capsules, which may be difficult for some children to swallow, and as syrup (250 mg/5 mL).

Zonisamide (Zonegran)

Zonisamide may stabilize neuronal membranes and suppress neuronal hypersynchronization through action at sodium and calcium channels. It does not affect GABA activity.

Lamotrigine (Lamictal, Lamictal ODT, Lamictal XR)

Lamotrigine is a thiazine derivative that inhibits the release of glutamate (an excitatory amino acid) and inhibits voltage-sensitive sodium channels

Levetiracetam (Keppra, Keppra XR, Spritam)

Levetiracetam has a mechanism of action that may involve inhibition of voltage-dependent, N-type calcium channels; facilitation of GABA-ergic inhibitory transmission through displacement of negative modulators; and reduction of the delayed rectifier potassium current.

Felbamate (Felbatol)

Felbamate is an oral antiepileptic agent with weak inhibitory effects on GABA-receptor binding and benzodiazepine receptor binding. It has little activity at the MK-801 receptor-binding site of the NMDA receptor-ionophore complex. However, felbamate is an antagonist at the strychnine-insensitive glycine recognition site of the NMDA receptor-ionophore complex.

Tiagabine (Gabitril)

The mechanism of action of tiagabine in antiseizure effects is unknown. It is believed to be related to its ability to enhance the activity of GABA, the major inhibitory neurotransmitter in the CNS.

Rufinamide (Banzel)

Rufinamide prolongs the inactive state of the sodium channels, thereby limiting repetitive firing of sodium-dependent action potentials, mediating anticonvulsant effects.

Clobazam (ONFI, Sympazan)

Benzodiazepine indicated for adjunctive treatment of seizures associated with Lennox-Gastaut syndrome in children aged 2 years or older.

Stiripentol (Diacomit)

Allylic alcohol that is unrelated to other anticonvulsants. The precise anticonvulsant effect in humans is unknown. Possible mechanisms of action include direct effects mediated through the GABA-A receptor and indirect effects involving inhibition of cytochrome P450 activity with resulting increase in blood levels of clobazam and its active metabolite. It is indicated for treatment of seizures associated with Dravet syndrome in patients aged 6 months and older who are taking clobazam. There are no clinical data to support the use of stiripentol as monotherapy in Dravet syndrome. 

Topiramate (Eprontia, Qudexy XR, Topamax)

Indicated as adjunctive therapy for treatment of seizures associated with Lennox-Gastaut syndrome in patients aged 2 years and older. Available as extended-release capsules that may be swallowed whole or opened and sprinkled on a spoonful of soft food.