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.
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 other 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.
Cannabidiol (Epidiolex)
Purified formulation of cannabidiol indicated for treatment of seizures associated with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), or tuberous sclerosis complex (TSC) in patients aged 1 year or older. Cannabidiol is a structurally novel anticonvulsant and the exact mechanism by which it produces anticonvulsant effects is unknown. It does not appear to exert its anticonvulsant effects through CB1 receptors, nor through voltage-gated sodium channels.
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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Patient with Lennox-Gastaut syndrome wearing a helmet with face guard to protect against facial injury from atonic seizures
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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.
