Juvenile Myoclonic Epilepsy Medication

  • Author: Elizabeth Carroll, DO; Chief Editor: Selim R Benbadis, MD   more...
 
Updated: Jun 8, 2011
 

Medication Summary

The goal of pharmacotherapy is to reduce morbidity and prevent complications.

The US Food and Drug Administration (FDA) has not approved any anticonvulsant solely for the treatment of juvenile myoclonic epilepsy (JME). In 2006, the FDA approved the adjunctive use of levetiracetam for the treatment of JME. Divalproex sodium has been approved as adjunctive therapy for patients with multiple seizure types that include absence seizures. However, many patients with JME do not have absence seizures.

In most patients with JME, seizures are well controlled with monotherapy. Valproic acid has been considered the treatment of choice for JME for many years, but epileptologists are increasingly using other choices as first-line therapies. Approximately 80% of patients with JME become seizure free with valproate monotherapy.

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Anticonvulsants

Class Summary

Anticonvulsants are the mainstay of therapy for JME. These agents are given to prevent myoclonic jerks or seizures, generalized tonic-clonic seizures (GTCSs), and absence seizures.

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Valproic acid and derivatives (Depakote, Depakene, Stavzor)

 

Divalproex sodium is indicated for monotherapy or adjunctive therapy in simple and complex absence seizures and adjunctively in many seizure types, including absence. In clinical practice, it is often a first-line anticonvulsant in JME. It is metabolized to valproic acid.

Valproic acid (Depakene), in a rapid-release formulation, is available as a cap and syrup; Depacon is an intravenous (IV) formulation. Stavzor is available as a 125-, 250-, or 500-mg delayed-release tablet.

Studies of combination therapy suggest that in practice, patients starting divalproex monotherapy need a low starting dose and target doses close to about 10 mg/kg/d. In the elderly, clearance of unbound drug is decreased; lowered doses are needed. Children often require higher doses per weight than adults do; some children given combination therapy (with enzyme-inducing antiepileptic drugs [EIAEDs]) may need doses as high as 60 mg/kg/d.

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Lamotrigine (Lamictal)

 

Lamotrigine is FDA-approved as add-on therapy in patients older than 16 years with partial seizures; it is recommended as adjunctive therapy in generalized seizures of Lennox-Gastaut syndrome in adults and children; it is also indicated for conversion to monotherapy after failure of at least 1 EIAED (eg, carbamazepine, phenytoin, phenobarbital). Several reports suggest that it is efficacious in JME and some of its seizure types; the present authors found benefit in some patients.

Lamotrigine is a well-tolerated anticonvulsant; it requires slow up-titration because of the risk of rash. It probably has fewer cognitive (ie, sedative) effects than most anticonvulsants do; some patients with JME have worsening of myoclonic jerks at low doses. In most patients, increasing the dose results in clinically significant improvement.

Serum concentrations of lamotrigine are useful in monitoring compliance and adjusting the dose; a few months into treatment, serum concentrations may decrease slightly because of enzymatic inducement in the liver. Conversion from EIAEDs can be faster than recommended. Conversion from (or add-on therapy with) valproic acid requires slow titration because valproic acid inhibits metabolism of lamotrigine. Starting at high doses may increase the incidence of rash.

No IV formulation is available.

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Topiramate (Topamax)

 

Topiramate is indicated and FDA-approved as adjunctive therapy for adults and children with partial-onset seizures and primary GTCSs. It is approved for monotherapy in primary GTCSs. Some patients with JME have primary GTCSs but may also have myoclonic and absence seizures. Topiramate is available as a 25-, 100-, or 200-mg tablet and as a 15- or 25-mg sprinkle capsule.

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Zonisamide (Zonegran)

 

Zonisamide is indicated for adjunctive treatment of partial seizures with or without secondary generalization. Evidence suggests effectiveness in myoclonic and other generalized seizure types as well.

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Levetiracetam (Keppra)

 

Levetiracetam is indicated as adjunctive therapy for myoclonic seizures in adults and adolescents and in primary GTCSs. The mechanism of action is unknown but is presumed to involve binding to the SV2A site in synaptic terminals.

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Contributor Information and Disclosures
Author

Elizabeth Carroll, DO  Resident Physician, Department of Neurology, University of South Florida College of Medicine

Elizabeth Carroll, DO is a member of the following medical societies: American Academy of Neurology, American Osteopathic Association, and Florida Osteopathic Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

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 eMedicine articles that I wrote or edited.

Mark Spitz, MD  Professor, Department of Neurology, University of Colorado Health Sciences Center

Mark Spitz, MD is a member of the following medical societies: American Academy of Neurology, American Clinical Neurophysiology Society, and American Epilepsy Society

Disclosure: pfizer Honoraria Speaking and teaching; ucb Honoraria Speaking and teaching; lumdbeck Honoraria Consulting

Specialty Editor Board

Ramon Diaz-Arrastia, MD, PhD  Professor, Department of Neurology, University of Texas Southwestern Medical Center at Dallas, Southwestern Medical School; Director, North Texas TBI Research Center, Comprehensive Epilepsy Center, Parkland Memorial Hospital

Ramon Diaz-Arrastia, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, New York Academy of Sciences, and Phi Beta Kappa

Disclosure: Nothing to disclose.

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

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 Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association

Disclosure: UCB Pharma Honoraria Speaking, consulting; Lundbeck Honoraria Speaking, consulting; Cyberonics Honoraria Speaking, consulting; Glaxo Smith Kline Honoraria Speaking, consulting; Pfizer Honoraria Speaking, consulting; Sleepmed/DigiTrace Honoraria Speaking, consulting

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Findings in a man with a history of generalized tonic-clonic seizures (mostly nocturnal) and myoclonic jerks (mostly in the morning) since the age of 14 years. Carbamazepine exacerbated his myoclonic seizures. Sleep-deprived EEG was digitally recorded and then plotted by using an analog paper machine. The patient was getting drowsy when this burst of polyspike and slow wave was recorded.
 
 
 
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