Which medications in the drug class Anticonvulsants, Other are used in the treatment of Epilepsy and Seizures?

Updated: May 30, 2019
  • Author: David Y Ko, MD; Chief Editor: Selim R Benbadis, MD  more...
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Anticonvulsants, Other

These agents prevent seizure recurrence and terminate clinical and electrical seizure activity. Anticonvulsants are normally reserved for patients who are at increased risk for recurrent seizures.

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

Carbamazepine is indicated for the management of partial seizures and generalized tonic-clonic seizures. It has an active metabolite, 10-11 epoxide, which has anticonvulsant activity and can be measured in the serum. This agent works by binding to voltage-dependent sodium channels and inhibiting the generation of action potentials. Serum carbamazepine levels should be measured frequently when initially starting this medication, with a goal of being seizure free. Like phenytoin, carbamazepine has been associated with osteopenia.

Felbamate (Felbatol)

Felbamate is approved by the FDA for medically refractory partial seizures and Lennox-Gastaut syndrome. This agent has multiple mechanisms of action, including (1) inhibition of N-methyl-D-aspartate (NMDA)–associated sodium channels, (2) potentiation of GABAergic activity, and (3) inhibition of voltage-sensitive sodium channels. Felbamate is used only as a drug of last resort in medically refractory cases because of the risk of aplastic anemia and hepatic toxicity, which necessitates regular blood tests.

Lamotrigine (Lamictal, Lamictal ODT, Lamictal XR)

Lamotrigine, a triazine derivative, is an antiepileptic drug with a very broad spectrum of activity, like valproate. It is approved by the FDA for primary generalized and partial-onset epilepsy. Other indications include adjunctive therapy in the treatment of generalized seizures of Lennox-Gastaut syndrome, treatment of juvenile myoclonic epilepsy (JME) and maintenance treatment of bipolar I disorder. The mechanism of action is based on inhibiting the release of glutamate and voltage-sensitive sodium channels, leading to stabilization of the neuronal membrane.

Lamotrigine is quickly absorbed when given orally, and 55% is bound to plasma proteins. The therapeutic serum levels have not been definitively established.

Side effects of lamotrigine include rash and nausea. The dose has to be increased very slowly over several weeks to minimize the chance of rash, especially if the patient is on valproic acid. The risk of developing Stevens-Johnson syndrome, toxic epidermal necrolysis, and angioedema is 1 in 1000 adults and higher in children, but this risk is decreased with slower titration.

Levetiracetam (Keppra, Keppra XR)

Levetiracetam is indicated for adjunctive therapy in the treatment of primary generalized tonic-clonic seizures, JME, and partial-onset seizures in adults and children. The mechanism of action is thought to be through modulation of synaptic vesicle proteins. The metabolism of this drug is independent of the CYP450 system, which limits the potential for interaction with other antiepileptic drugs.

Levetiracetam has a rapid onset of action and is well tolerated. Common side effects include fatigue, somnolence, dizziness, and irritability. This medication is available in oral (including extended-release) and intravenous formulations.

Rufinamide (Banzel)

Rufinamide modulates sodium channel activity, particularly prolongation of the channel's inactive state. It significantly slows sodium channel recovery and limits sustained, repetitive firing of sodium-dependent action potentials. Rufinamide is indicated for adjunctive treatment of seizures associated with Lennox-Gastaut syndrome. It is well tolerated, with the most common side effects being somnolence and vomiting.

Topiramate (Topamax)

Topiramate is an AED with a broad spectrum of antiepileptic activity. This agent is approved for generalized, primary generalized, tonic-clonic, and partial-onset seizures. Topiramate has multiple mechanisms of action, including state-dependent sodium channel ̶ blocking action, enhancement of the inhibitory activity of the neurotransmitter GABA, and antagonism of the NMDA-glutamate receptor. It may block glutamate activity and is a weak carbonic anhydrase inhibitor. Weight loss, impaired cognition, and mood problems are common side effects of topiramate. The drug is also approved for migraine prevention.

Valproic acid (Depacon, Depakene, Stavzor)

Valproate, a broad-spectrum AED, is effective against most seizure types, including myoclonic seizures. It can also be used alone or in combination for the treatment of generalized or partial seizures. Valproate has multiple mechanisms of anticonvulsant action, including increasing GABA levels in the brain, as well as T-type calcium channel activity.

Divalproex sodium (Depakote, Depakote ER, Depakote Sprinkles)

Indicated for complex partial seizures and also for simple and complex absence seizures. May be used as monotherapy or adjunctive therapy. Valproate has multiple mechanisms of anticonvulsant action, including increasing GABA levels in the brain, as well as T-type calcium channel activity. The extended-release (ER) formulation allows for once-a-day administration.

Zonisamide (Zonegran)

Zonisamide is indicated for partial seizures. It blocks T-type calcium channels, prolongs sodium channel inactivation, and is a carbonic anhydrase inhibitor.

Dose adjustments may be required when zonisamide is given with other anticonvulsants, such as carbamazepine, phenytoin, and phenobarbital. The most common side effects of this drug include ataxia, anorexia, and fatigue.

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) and for primary generalized tonic-clonic seizures in adults and children aged 12 years or older.

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 as monotherapy or adjunctive therapy for partial-onset seizures.

Cannabidiol (Epidiolex)

Purified formulation of cannabidiol indicated for treatment of seizures associated with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) in patients aged 2 years or older. Cannabidiol is a structurally novel anticonvulsant and the exact mechanism by which it produces anticonvulsant effects is unknown. It does not appear to exert its anticonvulsant effects through CB1 receptors, nor through voltage-gated sodium channels.

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 2 years or older who are taking clobazam. There are no clinical data to support the use of stiripentol as monotherapy in Dravet syndrome.

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