Based on clinical experience or conventional wisdom

Valproic acid

In recent decades, valproic acid has been considered as a first-line treatment option for children with Lennox-Gastaut syndrome (LGS).25,49,50 Valproic acid may be more effective for cryptogenic than for symptomatic LGS.51

Other commonly used antiepileptic drugs such as carbamazepine, phenytoin, ethosuximide, and phenobarbital are not considered first-line therapy for LGS. Carbamazepine may exacerbate atypical absence seizures. Phenytoin and ethosuximide are effective against only some seizures associated with LGS. Phenobarbital can exacerbate hyperactivity and aggressiveness or produce sedation and drowsiness (which may exacerbate tonic seizures).25,48,51,57–59

Benzodiazepines

Certain benzodiazepines—specifically clonazepam, nitrazepam, and clobazam—are also first-line therapeutic options.25,52 All are considered effective against seizures associated with LGS, but side effects and tolerance limit their usefulness over time25 The side effects of clonazepam and nitrazepam include hyperactivity, sedation, drooling, and incoordination, which can significantly affect the quality of life for patients with LGS.25 Nitrazepam is not available in the United States.25 Clobazam is considered the least sedating benzodiazepine and boasts the longest time to the development of tolerance. As of 2004, however, it also is unavailable in the United States.52

Some recommendations for slowing the development of tolerance include dosing on an every-other-day schedule or using two different benzodiazepines on an alternate-day basis.53,54

Not all benzodiazepines are beneficial for LGS: intravenous diazepam and lorazepam may induce tonic static epilepticus in some patients.55,56

Pyridoxine (vitamin B6)

Because patients with pyridoxine dependency may experience seizures and demonstrate a slow spike and wave pattern on EEG, some clinician-investigators have suggested trials of vitamin B6 in all children younger than 5 years who have treatment-resistant epilepsy.50 In one study of the efficacy of high-dose vitamin B6 in five patients with LGS, three patients had no response but the others exhibited a more noticeable response.60

It is reasonable and appropriate to conduct a vitamin B6 trial early in the treatment of a child with LGS, given the lack of serious side effects and the ease of performing such a therapeutic trial.61 Doses and duration of vitamin B6 therapy vary widely. In the clinical trial just mentioned, 50–100 mg vitamin B6 was given intramuscularly each day for the first 5 days, followed by 200–300 mg per day orally.60 Some clinicians (mainly in Japan) will administer high doses of pyridoxal phosphate (30–40 mg/kg per day).50 Wheless and Constantinou50 prescribe 100 mg of vitamin B6 three times daily for 2 weeks, stopping if there is no response to therapy after that period.

Adapted from: Glauser TA and Morita DA. Lennox-Gastaut syndrome. In: Devinsky O and Westbrook LE, eds. Epilepsy and Developmental Disabilities. Boston: Butterworth-Heinemann; 2001;65–78.
With permission from Elsevier (www.elsevier.com).
Reviewed and revised May 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.

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