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Temporal Lobe Epilepsy Medication

  • Author: David Y Ko, MD; Chief Editor: Selim R Benbadis, MD  more...
 
Updated: Apr 29, 2014
 

Medication Summary

Until a few years ago, 4 principal medications were used for partial seizures: phenytoin, carbamazepine, valproate, and phenobarbital. However, a number of newer medications have been approved by the FDA. Some of these newer AEDs are approved as monotherapy, but how they compare with the older AEDs is not known.

The initial choice of medication depends on many factors, including side-effect profile, dosage schedule, and comorbid conditions. The major VA trials did not show any significant difference in seizure control among the 4 older AEDs. Adverse effects were greater with phenobarbital and with primidone.

Single-drug therapy is the goal, and the dosage of each medication prescribed should be increased until either seizures are controlled or adverse effects occur.

The new AEDs have a class-wide warning about suicidal ideation mandated by the FDA, which arose from 4 suicides amongst 40,000 patients exposed to AEDs. The patient should be evaluated for mood changes, which may need treatment.

The anticonvulsant rufinamide (Banzel) was approved as an adjunctive therapy for seizures associated with Lennox-Gastaut syndrome.

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Anticonvulsants

Class Summary

These agents prevent seizure recurrence and terminate clinical and electrical seizure activity.

Carbamazepine (Tegretol, Carbatrol, Epitol, Equetro)

 

Carbamazepine affects sodium channels during sustained, rapid, repetitive firing. The extended release form is preferred (Tegretol XR or Carbatrol) because of twice-daily dosing, which improves compliance and leads to more stable blood levels. No intravenous (IV) formulation is available.

Phenytoin (Dilantin, Phenytek)

 

Phenytoin is one of oldest drugs known for treatment of seizures. In young women, it can coarsen facial features and can cause hirsutism and gingival hyperplasia. In addition, frequent blood-level determinations are required in patients taking the drug, because of nonlinear pharmacokinetics. Long-term use has been associated with peripheral neuropathy and osteopenia.

Valproate (Depacon, Depakene, Depakote, Depakote ER, Stavzor)

 

This anticonvulsant is effective for a broad spectrum of seizure types; it is believed to exert its anticonvulsant effect by increasing gamma-aminobutyric acid (GABA) levels in the brain. Valproate is approved for monotherapy or adjunctive therapy for partial seizures and generalized tonic-clonic seizures. Depakene is available as a capsule or syrup, and Depakote is available as a tablet or sprinkle.

Lamotrigine (Lamictal, Lamictal ODT, Lamictal XR)

 

Lamotrigine is a newer AED; it was approved as an adjunctive therapy and a crossover monotherapy for partial seizures. It also blocks sodium channels during sustained, rapid, repetitive neuronal firing. The drug is FDA approved for children younger than age 16 years only for Lennox-Gastaut syndrome; it is not FDA approved for children with partial seizures, because of an increased incidence of rash.

Gabapentin (Neurontin)

 

Gabapentin is approved by the FDA as an adjunctive therapy for partial seizures. It is structurally related to GABA but does not affect GABA directly, although it is thought to modulate the calcium channel.

Topiramate (Topamax)

 

Topiramate is approved by the FDA as a monotherapy or an adjunctive therapy for partial seizures and symptomatic generalized seizures. It exerts action by 4 mechanisms: sodium-channel blockade, enhancement of GABA activity, antagonism of AMPA/kainate-type glutamate excitatory receptors, and weak inhibition of carbonic anhydrase.

Tiagabine (Gabitril)

 

This drug enhances GABA activity by inhibiting uptake in neurons and astrocytes. Tiagabine can be used as an add-on therapy for partial seizures. It has been known to exacerbate seizures with spike-wave stupor. Some patients who were receiving off label and never had seizures had seizures induced with tiagabine when it was used with another medication, which lowers the seizure threshold.

Zonisamide (Zonegran)

 

Zonisamide is approved in the United States for adjunctive use in the treatment of partial seizures. It has been studied extensively in Japanese and European trials for primary generalized seizures. The drug blocks T-type calcium currents and prolongs sodium-channel inactivation. It is also a weak carbonic anhydrase inhibitor. In monotherapy, it has a long half-life (70 h).

Oxcarbazepine (Trileptal)

 

Oxcarbazepine is approved by the FDA as a monotherapy and as an adjunctive therapy for partial epilepsy in adults and children aged 2-16 years. It blocks sodium-activated channels during sustained, rapid, repetitive firing. Oxcarbazepine has antiepileptic activity, but its monohydroxy (MHD) metabolite is the most active compound. Oxcarbazepine is different from carbamazepine, which generates a 10-11 epoxide metabolite.

Levetiracetam (Keppra)

 

This drug was approved by the FDA in 1999 as an add-on therapy for partial seizures. It is also FDA approved as an add-on therapy for juvenile myoclonic epilepsy and primary generalized tonic-clonic seizures. The drug's mechanism of action is thought to be related to the binding of levetiracetam to presynaptic vesicle protein. The medication has a favorable adverse effect profile overall, except for behavioral changes.

Felbamate (Felbatol)

 

Felbamate is approved for medically refractory partial seizures and Lennox-Gastaut syndrome. It has multiple mechanisms of action, including blockade of the glycine site of the N-methyl-D-aspartate (NMDA) receptor, potentiation of GABAergic activity, and inhibition of voltage-sensitive sodium channels. However, felbamate has a high rate of life-threatening side effects, so the benefits and risks of the drug need to be carefully addressed.

Pregabalin (Lyrica)

 

Pregabalin was approved in 2005 for adjunctive use in partial seizures in adults. Its mechanism of action (calcium-channel modulation) is similar to that of gabapentin, but it is more potent and has linear pharmacokinetics.

Rufinamide (Banzel)

 

Rufinamide is structurally unrelated to other current antiepileptics. It modulates sodium-channel activity, particularly through prolongation of the channel's inactive state. The drug significantly slows sodium-channel recovery and limits sustained, repetitive firing of sodium-dependent action potentials. Rufinamide is indicated for the 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 the brain stem centers responsible for the tonic phase of grand mal seizures may also be inhibited.

Vigabatrin (Sabril)

 

Vigabatrin is a structural derivative of GABA. Its mechanism of action is unknown. Vigabatrin binds with high affinity to the alpha2-delta site (a calcium channel subunit). In vitro, it reduces the calcium-dependent release of several neurotransmitters, possibly by modulating calcium channel function. It is FDA approved for neuropathic pain associated with diabetic peripheral neuropathy or postherpetic neuralgia and as adjunctive therapy in partial-onset seizures.

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 for adjunctive therapy for partial-onset seizures.

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Contributor Information and Disclosures
Author

David Y Ko, MD Associate Professor of Clinical Neurology, Associate Director, USC Adult Epilepsy Program, Keck School of Medicine of the University of Southern California

David Y Ko, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, American Headache Society, American Clinical Neurophysiology Society

Disclosure: Received honoraria from UCB for speaking and teaching; Received consulting fee from Lundbeck for consulting; Received consulting fee from Westward for consulting; Received consulting fee from Esai for consulting; Received consulting fee from Supernus for consulting; Received consulting fee from Sunovion for speaking and teaching.

Coauthor(s)

Soma Sahai-Srivastava, MD Director of Neurology Ambulatory Care Services, LAC and USC Medical Center; Assistant Professor, Department of Neurology, Keck School of Medicine of the University of Southern California

Soma Sahai-Srivastava, MD is a member of the following medical societies: American Academy of Neurology, American Medical Association, American Headache Society

Disclosure: Nothing to disclose.

Chief Editor

Selim R Benbadis, MD Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida College of Medicine

Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Medical Association, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cyberonics; Eisai; Lundbeck; Sunovion; UCB; Upsher-Smith<br/>Serve(d) as a speaker or a member of a speakers bureau for: Cyberonics; Eisai; Glaxo Smith Kline; Lundbeck; Sunovion; UCB<br/>Received research grant from: Cyberonics; Lundbeck; Sepracor; Sunovion; UCB; Upsher-Smith.

Acknowledgements

Jose E Cavazos, MD, PhD, FAAN Associate Professor with Tenure, Departments of Neurology, Pharmacology, and Physiology, Program Director of the Clinical Neurophysiology Fellowship, University of Texas School of Medicine at San Antonio; Co-Director, South Texas Comprehensive Epilepsy Center, University Hospital System; Director of the San Antonio Veterans Affairs Epilepsy Center of Excellence and Neurodiagnostic Centers, Audie L Murphy Veterans Affairs Medical Center

Jose E Cavazos, MD, PhD, FAAN is a member of the following medical societies: American Academy of Neurology, American Clinical Neurophysiology Society, American Epilepsy Society, and American Neurological Association

Disclosure: GXC Global, Inc. Intellectual property rights Medical Director - company is to develop a seizure detecting device. No conflict with any of the Medscape Reference articles that I wrote or edited.

Erasmo A Passaro, MD, FAAN Director, Comprehensive Epilepsy Program/Clinical Neurophysiology Lab, Bayfront Medical Center, Florida Center for Neurology

Erasmo A Passaro, MD, FAAN is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, American Medical Association, and American Society of Neuroimaging

Disclosure: Glaxo Smith Kline Honoraria Speaking and teaching; UCB Honoraria Speaking and teaching; Pfizer Honoraria Speaking and teaching; Forest Honoraria Speaking and teaching

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

References
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