Lamotrigine for generalized seizures associated with the Lennox-Gastaut syndrome. Lamictal Lennox-Gastaut Study Group

N Engl J Med. 1997 Dec 18;337(25):1807-12. doi: 10.1056/NEJM199712183372504.


Background: The Lennox-Gastaut syndrome, a severe form of epilepsy that usually begins in early childhood, is difficult to treat. Dose-related drug toxicity is common.

Methods: We conducted a double-blind, placebo-controlled trial of the antiepileptic drug lamotrigine in patients with the Lennox-Gastaut syndrome. Eligible patients had more than one type of predominantly generalized seizure, including tonic-clonic, atonic, tonic, and major myoclonic, and had seizures on average at least every other day. After a 4-week base-line period in which all participants received placebo, we randomly assigned 169 patients (age range, 3 to 25 years) to 16 weeks of lamotrigine (n= 79) or placebo (n=90) in addition to their other antiepileptic drugs.

Results: The median frequency of all major seizures changed from base-line levels of 16.4 and 13.5 per week in the lamotrigine and placebo groups, respectively, to 9.9 and 14.2 per week after 16 weeks of treatment (P=0.002). Thirty-three percent of the patients in the lamotrigine group and 16 percent of those in the placebo group had a reduction of at least 50 percent in the frequency of seizures (P= 0.01). There were no significant differences between groups in the incidence of adverse events, except for colds or viral illnesses, which was more common in the lamotrigine group (P=0.05).

Conclusions: Lamotrigine was an effective and well-tolerated treatment for seizures associated with the Lennox-Gastaut syndrome.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anticonvulsants / adverse effects
  • Anticonvulsants / therapeutic use*
  • Child
  • Child, Preschool
  • Double-Blind Method
  • Epilepsy / drug therapy*
  • Female
  • Humans
  • Intellectual Disability
  • Lamotrigine
  • Male
  • Seizures / drug therapy
  • Syndrome
  • Treatment Outcome
  • Triazines / adverse effects
  • Triazines / therapeutic use*


  • Anticonvulsants
  • Triazines
  • Lamotrigine