Epilepsy and Seizures Medication
- Author: Jose E Cavazos, MD, PhD, FAAN; Chief Editor: Selim R Benbadis, MD more...
Medication Summary
The goals of pharmacotherapy are to reduce morbidity and prevent complications. The agents used for tonic-clonic seizures include anticonvulsants such as valproate, lamotrigine, phenytoin, felbamate, topiramate, and carbamazepine.
Anticonvulsant Agents
Class Summary
These agents prevent seizure recurrence and terminate clinical and electrical seizure activity.
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.
Valproic acid (Depakote, Depakote ER, Depakene, Depacon, Stavzor)
Considered the drug of first choice for primary generalized epilepsy, valproate has a very wide spectrum and is effective in most seizure types, including myoclonic seizures. It has multiple mechanisms of anticonvulsant effects, including increasing gamma-aminobutyric acid (GABA) levels in brain as well as T-type calcium channel activity. The extended-release (ER) formulation allows for once-a-day administration.
Phenytoin (Dilantin, Phenytek)
Phenytoin works for tonic-clonic seizures and is often used because it can be administered once a day. Long-term adverse effects of osteopenia and cerebellar ataxia now temper its use by neurologists. This agent is one of the most difficult antiepileptic drugs (AEDs) to use, due to its zero-order kinetics and narrow therapeutic index. In addition, it can have significant bidirectional drug interactions.
Carbamazepine (Tegretol, Tegretol XR, Carbatrol, Epitol, Equetro)
This older antiepileptic drug is used as a second-choice agent along with phenytoin. It has active metabolite 10-11 epoxide. Like phenytoin, carbamazepine has been associated with osteopenia.
Lamotrigine (Lamictal, Lamictal ODT, Lamictal XR)
Lamotrigine is a newer antiepileptic drug with a very broad spectrum of activity, like valproate. It is FDA approved for both primary generalized and partial-onset epilepsy.
Lamotrigine has several mechanisms of action that may account for its effectiveness. A major disadvantage is that 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.
Zonisamide (Zonegran)
One of newer antiepileptics recently introduced in the US market, zonisamide has been studied extensively in Japan and Korea and seems to have broad-spectrum properties. It blocks T-type calcium channels, prolongs sodium channel inactivation, and is a carbonic anhydrase inhibitor.
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 NMDA-associated sodium channels, (2) potentiation of GABA-ergic activity, and (3) inhibition of voltage-sensitive sodium channels. It is used only as drug of last resort in medically refractory cases because of the risk of aplastic anemia and hepatic toxicity, which necessitates regular blood tests.
Topiramate (Topamax)
An AED with a broad spectrum of antiepileptic activity, topiramate is approved for generalized tonic-clonic seizures. It has multiple mechanisms of action, including state-dependent sodium channel blocking action; it also potentiates inhibitory activity of the neurotransmitter GABA. It may block glutamate activity and is a carbonic anhydrase inhibitor.
Levetiracetam (Keppra, Keppra XR)
Levetiracetam is indicated for primary generalized tonic-clonic seizures in adults and children aged 6 years or older, as well as for use in juvenile myoclonic epilepsy and for partial seizures.
Rufinamide (Banzel)
An AED that is structurally unrelated to current antiepileptics, 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.
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.
Primidone (Mysoline)
Primidone decreases neuron excitability and increases the seizure threshold.
Ethosuximide (Zarontin)
Ethosuximide is a succinimide AED that is effective only against absence seizures. It has no effect on generalized tonic-clonic, myoclonic, atonic, or partial seizures. The mechanism of action is based on reducing current in T-type calcium channels 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. It is available in large 250-mg capsules, which may be difficult for some children to swallow, and as a syrup (250 mg/5 mL).
Lamotrigine (Lamictal, Lamictal ODT, Lamictal XR)
Lamotrigine is a triazine derivative used in neuralgia. It inhibits the release of glutamate and inhibits voltage-sensitive sodium channels, leading to stabilization of the neuronal membrane.
Methsuximide (Celontin)
Methsuximide shares the actions of the succinimide-derivative anticonvulsants. It increases the seizure threshold and suppresses the paroxysmal spike-and-wave pattern in absence seizures. It depresses nerve transmission in the motor cortex.
Phenobarbital
Phenobarbital works at CNS GABA receptors to potentiate CNS inhibition. It exhibits anticonvulsant activity in anesthetic doses. Phenobarbital is the best-studied barbiturate in treatment of status epilepticus.
In status epilepticus, achieving therapeutic levels as quickly as possible is important. Intravenous dosing may require approximately 15 minutes to attain peak levels in the brain. To terminate generalized convulsive status epilepticus, administer up to 15-20 mg/kg. If the patient has received a benzodiazepine, the potential for respiratory suppression significantly increases. Ventilation and intubation may be necessary. Hypotension may require treatment.
Phenobarbital is generally used after phenytoin or fosphenytoin fails. However, it can be used in lieu of phenytoin in certain circumstances.
If the intramuscular route is chosen, administer this agent into a large muscle such as the gluteus maximus or vastus lateralis or other areas where the risk of encountering a nerve trunk or major artery is low. Permanent neurologic deficit may result from injection into or near peripheral nerves.
Restrict intravenous use to conditions in which other routes are not possible, either because patient is unconscious or because prompt action is required.
A trend is to recommend agents other than phenobarbital (propofol, midazolam, other barbiturates) for refractory status epilepticus.
Clobazam (ONFI)
1,5-benzodiazepine that possesses potent anticonvulsant properties. Exact mechanism of action is not fully understood; thought to potentiate GABAergic neurotransmission resulting from binding to GABA-A receptor. The active metabolite, N-demethylclobazam, is largely responsible for its long duration of action. It is indicated for adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients older than 2 years.
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