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

Purpose: Lamotrigine (LTG) is recognised as effective add-on therapy for fo cal epilepsies, but this is the first double-blind, placebo-controlled, cro ssover 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 cont inuation was offered at the end of the study with open-label LTG. Results: Five centres in Australia recruited 26 patients who were having ab sence, myoclonic, or generalized tonic-clonic seizures or a combination of these. Twenty-two patients completed the study. There was a significant red uction in frequency of both tonic-clonic and absence seizure types with LTG . A greater than or equal to 50% decrease in seizures was observed for toni c-clonic seizures in 50% of cases and for absence seizures in 33% of evalua ble 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 me an of 26 months. In these 20, 80% had greater than or equal to 50% seizure reduction and five (25%) were seizure free. Conclusions: This study shows that LTG is effective add-on therapy in patie nts with refractory generalised epilepsies. Statistically significant reduc tion in seizures in both absence and tonic-clonic seizure types was seen ev en with low doses of LTG.