Generalized Tonic-Clonic Seizures Medication
- Author: David Y Ko, MD; Chief Editor: Selim R Benbadis, MD more...
The goals of pharmacotherapy are to reduce morbidity and prevent complications. The agents used for tonic-clonic seizures include anticonvulsants such as valproate, lamotrigine, levetiracetam, phenytoin, felbamate, topiramate, and carbamazepine.
These agents prevent seizure recurrence and terminate clinical and electrical seizure activity.
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.
Ethotoin may act in the motor cortex, where it may the inhibit spread of seizure activity. The activity of the brain stem centers responsible for the tonic phase of grand mal seizures may also be inhibited.
Phenytoin works for tonic-clonic seizures and is often used because it can be administered once a day. Long-term side 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.
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 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.
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 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.
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 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.
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.
Primidone decreases neuron excitability and increases the seizure threshold.
Perampanel is a noncompetitive antagonist of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor. It is indicated as adjunctive treatment for primary generalized tonic-clonic seizures and for partial-onset seizures (with or without secondary generalized seizures) in adults and children aged 12 years or older.
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