Lennox-Gastaut syndrome and other symptomatic generalised epilepsies

Symptomatic (structural, metabolic, immune, infectious) generalised epilepsies occur in patients with generalised or multifocal brain disorders that also usually cause intellectual disability. Typically, these epilepsies start in childhood and persist in adult life. The seizures are often difficult to control.

Lennox-Gastaut syndrome is a symptomatic generalised epilepsy that is characterised by:

  • significant intellectual disability
  • slow spike-wave pattern on electroencephalogram
  • multiple seizure types (including tonic [especially nocturnal], myoclonic, atypical absence and tonic-clonic seizures).

First-line therapy for symptomatic generalised epilepsy is sodium valproate monotherapy.

If sodium valproate is needed in females of childbearing potential, have an informed discussion with the patient (and parents or carers of patients) about its harms and benefits before starting therapy; see Planning for pregnancy in patients with epilepsy and Teratogenic and neurodevelopmental effects of antiepileptic drugs.

If considering starting sodium valproate in males of reproductive potential, see Sodium valproate use in males of reproductive potential; a discussion about the potential risk of neurodevelopmental disorders in children born to males taking sodium valproate may be appropriate.

For a child, use:

sodium valproate , child older than 2 years, 5 mg/kg orally, twice daily for 5 days, then increase to 10 mg/kg twice daily; usual maintenance dose is 10 to 20 mg/kg twice daily; maximum 2500 mg daily. epilepsy, Lennox-Gastaut syndrome sodium valproate    

For females of childbearing potential who do not have reliable contraception, consider the relative harms and benefits of sodium valproate therapy, and the probability of pregnancy. If appropriate, use:

sodium valproate 400 mg orally, once daily for 1 week, then increase to initial target dose of 600 mg daily, taken as 200 mg in the morning and 400 mg at night. If needed, increase up to 1500 mg twice daily, but see teratogenic and neurodevelopmental effects. epilepsy, symptomatic generalised sodium valproate    

For adult females who have reliable contraception or cannot have children, or for adult males, use:

sodium valproate 500 mg orally, once daily for 1 week, then increase to initial target dose of 500 mg twice daily. If needed, increase up to 1500 mg twice daily. sodium valproate    

If the maximum dose of sodium valproate is not effective or adverse effects are intolerable, refer for expert advice—other antiepileptic drugs may need to be added or substituted. Second-line therapy is combination therapy with lamotrigine and sodium valproate. Sodium valproate inhibits lamotrigine clearance—reduce the rate of introduction and target dose of lamotrigine to lower the risk of serious skin reactions and dose-related toxicity. Other useful drugs include clobazam and topiramate.