Double-blind, placebo-controlled, crossover study of lamotrigine in treatment-resistant generalised epilepsy

Epilepsia. 1998 Dec;39(12):1329-33. doi: 10.1111/j.1528-1157.1998.tb01332.x.


Purpose: Lamotrigine (LTG) is recognised as effective add-on therapy for focal epilepsies, but this is the first double-blind, placebo-controlled, crossover study in treatment-resistant generalised epilepsy.

Methods: The study consisted of 2 x 8-week treatment periods followed by a 4-week washout period. Patients received doses of either 75 or 150 mg daily, depending on their concomitant antiepileptic drugs (AEDs). Long-term continuation was offered at the end of the study with open-label LTG.

Results: Five centres in Australia recruited 26 patients who were having absence, myoclonic, or generalized tonic-clonic seizures or a combination of these. Twenty-two patients completed the study. There was a significant reduction in frequency of both tonic-clonic and absence seizure types with LTG. A 350% decrease in seizures was observed for tonic-clonic seizures in 50% of cases and for absence seizures in 33% of evaluable cases. Rash was the only adverse effect causing discontinuation. Twenty-three of 26 opted for open-label LTG, with 20 still receiving LTG for a mean of 26 months. In these 20, 80% had > or =50% seizure reduction and five (25%) were seizure free.

Conclusions: This study shows that LTG is effective add-on therapy in patients with refractory generalised epilepsies. Statistically significant reduction in seizures in both absence and tonic-clonic seizure types was seen even with low doses of LTG.

Publication types

  • Case Reports
  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Ambulatory Care
  • Anticonvulsants / administration & dosage
  • Anticonvulsants / therapeutic use*
  • Cross-Over Studies
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Epilepsy, Generalized / drug therapy*
  • Female
  • Humans
  • Lamotrigine
  • Male
  • Middle Aged
  • Placebos
  • Treatment Outcome
  • Triazines / administration & dosage
  • Triazines / therapeutic use*


  • Anticonvulsants
  • Placebos
  • Triazines
  • Lamotrigine