226 EPIRES 00368 Epilepsy Res., 7 (1990) 226-229 Elsevier The efficacy and long-term tolerability of lamotrigine in the treatment of severe epilepsy J.W.A.S. Sander, P.C. Trevisol-Bittencourt, Y.M. Hart, P.N. Patsalos and S.D. Shorvon INS E G - Epilepsy Research Group, Institute of Neurology, Queen Square, London WCI N 3 BG ( U. K. ), and National Hospital- Chalfont Centre for Epilepsy, Chalfont St. Peter, Gerrards Cross, Bucks. SL9 0RJ (U. K.) (Received 8 May 1990; revision received 12 July 1990; accepted 20 July 1990) Key words: Lamotrigine; New antiepileptic drug; Refractory epilepsy; Long-term evaluation We report the effects of the addition of lamotrigine, a novel antiepileptic drug, to the therapy of 125 patients with severe refractory epilepsy. Forty-five patients (36%) reported adverse experiences and in 19 (15%), the drug was withdrawn. The commonest adverse experiences were diplopia, headache, ataxia, drowsiness, skin rash and deterioration in seizure control. Two patients were withdrawn for other reasons, The remaining 104 patients were followed for a mean of 11 moaths (range 3-27): 26 (25%) of these showed a marked improvement in seizure frequency (a 50% or more reduction when compared with the pre-trial period), but no patient was rendered seizure-free. Tolerance to the effects of the drug was not seen. INTRODUCTION Lamotrigine (LTG), a new antiepileptic drug (AED), is currently undergoing clinical evalu- ation. LTG is completely bioavailable and exhibits linear kinetics 6. In normal volunteers the mean elimination half-life is approximately 24 h, but in patients taking enzyme-inducing AEDs this is re- duced to a mean of 15 h, and when co-medication consists of sodium valproate only, the half-life is increased to approximately 59 h consequent upon sodium valproate inhibition of LTG metabolism 6. The antiepileptic activity of LTG is thought to be linked to its action on voltage-sensitive sodium channels resulting in the stabilisation of neuronal membranes and inhibition of excitatory amino acids, mainly glutamate 4. In animal models it has been shown to have an antiepileptic profile similar to that of phenytoin (PHT) and carbamazepine (CBZ) 7 and in controlled clinical studies it has been shown to reduce partial and generalised tonic- clonic seizures. We report here our experience with LTG used in an open fashion, in the management of patients with severe intractable epilepsy in a tertiary referral service. PATIENTS AND METHODS Correspondence to: Dr. J.W.A.S. Sander, National Hospital - Chalfont Centre for Epilepsy, Chalfont St. Peter, Gerrards Cross, Bucks. SL9 0RJ, U.K. LTG was evaluated in 125 patients (67 males; 58 females) using an add-on open label study design. All had severe refractory epilepsy and were evalu- 0920-1211/90/$03.50© 1990 Elsevier Science Publishers B.V. (Biomedical Division)