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Lennox-Gastaut Syndrome Medication

  • Author: Koshi A Cherian, MD; Chief Editor: Amy Kao, MD  more...
 
Updated: Apr 15, 2016
 

Medication Summary

The goals of pharmacotherapy in Lennox-Gastaut syndrome (LGS) are to reduce morbidity and prevent complications. Pharmacotherapeutic agents used in such patients include anticonvulsants and benzodiazepines.

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Anticonvulsants

Class Summary

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

Valproate (Depakote, Depakene, Depacon, Stavzor)

 

Valproate has been considered the first-line treatment option for children with LGS for the past 2 decades. It is reported to be more effective in patients with cryptogenic LGS than in those with symptomatic LGS.

Lamotrigine (Lamictal, Lamictal ODT, Lamictal XR)

 

Lamotrigine is valuable for patients with LGS despite risk of idiosyncratic dermatologic reactions. Consider it for use as soon as the diagnosis of LGS is made. Proper attention to concomitant medications, a low starting dose, and very slow titration can minimize the risk of dermatologic reactions. The initial dose, maintenance dose, titration intervals, and titration increments depend on concomitant medications.

Topiramate (Topamax)

 

Topiramate has been found to be safe and effective as adjunctive therapy (target dose 6 mg/kg/d) for patients with LGS.

Felbamate (Felbatol)

 

Felbamate has been found to be safe and effective in patients with LGS. However the significant risk of idiosyncratic reactions associated with its use make it a third-line or fourth-line drug for LGS.

Zonisamide (Zonegran)

 

Zonisamide is effective as long-term adjunctive therapy in children with LGS.

Vigabatrin (Sabril)

 

Vigabatrin was approved by US Food and Drug Administration (FDA) in 2009 as monotherapy for patients with infantile spasms aged 1 month to 2 years and as adjunctive therapy for adults with refractory complex partial seizures.

Levetiracetam (Keppra, Keppra XR)

 

Levetiracetam is approved by FDA for partial seizures, but may have efficacy against a range of seizure types in LGS.

Rufinamide (Banzel)

 

An antiepileptic agent 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. It is indicated for adjunctive therapy in adults and children aged 1 year or older with seizures associated with LGS.

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Benzodiazepines

Class Summary

By binding to specific receptor-sites, these agents appear to potentiate the effects of gamma-aminobutyrate (GABA) and facilitate inhibitory GABA neurotransmission and other inhibitory transmitters.

Clonazepam (Klonopin)

 

Clonazepam is considered an effective first-line AED therapy for seizures associated with LGS. Adverse effects and development of tolerance limit usefulness over time; dosing on an every-other-day schedule or alternating 2 benzodiazepines daily may slow development of tolerance. The benzodiazepine nitrazepam (Mogadon) is not approved by FDA but is available in many countries. The combination of valproic acid and a benzodiazepine may be better than either drug alone.

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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Contributor Information and Disclosures
Author

Koshi A Cherian, MD Assistant Professor, Department of Neurology and Pediatrics, Albert Einstein College of Medicine; Attending Physician, Department of Neurology, Division of Child Neurology and Epilepsy, Montefiore Medical Center; Attending Physician, Department of Pediatrics, Division of Child Neurology, Jacobi Medical Center; Staff Physician (Courtesy), Department of Pediatrics, Division of Child Neurology, St Barnabas Hospital

Koshi A Cherian, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, American Medical Association, Child Neurology Society, Medical Society of the State of New York

Disclosure: Nothing to disclose.

Coauthor(s)

Tracy A Glauser, MD Professor, Departments of Pediatrics and Neurology, University of Cincinnati College of Medicine; Director, Comprehensive Epilepsy Center, Co-Director, Genetic Pharmacology Service, Cincinnati Children's Hospital Medical Center

Tracy A Glauser, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, Child Neurology Society

Disclosure: Received consulting fee from Eisai for consulting; Received consulting fee from Lundbeck for consulting; Received consulting fee from Questcor for consulting; Received consulting fee from ucb Pharma for consulting; Received consulting fee from Supernus for consulting; Received honoraria from Supernus for speaking and teaching; Received consulting fee from Sunovion for consulting; Received royalty from AssureRx for license; Received consulting fee from Upsher-Smith for consulting; Received consul.

Diego A Morita, MD Assistant Professor of Pediatrics and Neurology, Department of Pediatrics, Division of Neurology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine

Diego A Morita, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, American Medical Association

Disclosure: Nothing to disclose.

Karen Mary Stannard, MD FRCPC

Karen Mary Stannard, MD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Chief Editor

Amy Kao, MD Attending Neurologist, Children's National Medical Center

Amy Kao, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, Child Neurology Society

Disclosure: Have stock from Cellectar Biosciences; have stock from Varian medical systems; have stock from Express Scripts.

Acknowledgements

David A Griesemer, MD Professor, Departments of Neuroscience and Pediatrics, Medical University of South Carolina

David A Griesemer, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Neurology, American Epilepsy Society, Child Neurology Society, and Society for Neuroscience

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

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Patient with Lennox-Gastaut syndrome wearing a helmet with face guard to protect against facial injury from atonic seizures
Slow spike wave pattern in a 24-year-old awake male with Lennox-Gastaut syndrome. The slow posterior background rhythm has frequent periods of 2- to 2.5-Hz discharges, maximal in the bifrontocentral areas, occurring in trains as long as 8 seconds without any clinical accompaniment.
 
 
 
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