Substitution of Carbamazepine by Lamotrigine and Sodium Valproate Combination in Medically Refractory Partial Epilepsies

Background: To evaluate the efficacy of lamotrigine (LTG) and sodium vaiproate (VPA) combination therapy in patients with partial epilepsies resistant to the maximally tolerable carbamazepine (CBZ) therapy Methods: Patients with partial epilepsies taking maximlly tolerable dose of CBZ with or without other antiepileptic drugs (AEDS) should have one or more episodes of complex partial seizures or secondarily generalized tonic-clonic seizures (2°GTC) per every 4 week period during 12 weeks of baseline phase. LTG and VPA were introduced with gradual tapering off of CBZ over 12 to 16 weeks. Seizure frequencies measured during the 12 week period starting from the 5th week of complete withdrawal of CBZ were compared with that of the baseline phase. Results: Complete substitution of CBZ by LTG and VPA in maximally tolerable doses was achieved in 32 of 35 patients included to the study. Mean number of seizures decreased from 6.0±10.7 episodes/4weeks to 2.2±3.5 episodes/4 weeks (p= 0.009). Complete freedom of seizures was achieved in 7 patients (21.9%). with the responder rate (> 50% seizure frequency reduction) of 65.6%. The first 4 weeks after complete withdrawal of CBZ were the most vulnerable period for the acute exacerbation of seizures or development of adverse experiences, which required a cereful clinical observation and dose adjustment. Conclusion: Complete substitution of CBZ by LTG and VPA combination therapy was worthwhile to try in patients resistant to maximally tolerable CBZ therapy.ope