VIGABATRIN AND LAMOTRIGINE IN REFRACTORY EPILEPSY

Epilepsy arises from an imbalance of inhibitory and excitatory influen ces in the brain. Vigabatrin (VIG) decreases the breakdown of the inhi bitory neurotransmitter gamma-aminobutyric acid, whereas lamotrigine ( LTG) reduces presynaptic excitatory amino acid release. 22 patients wi th refractory epilepsy, treated with an anticonvulsant regimen contain ing VIG, entered a balanced, double blind, placebo controlled, crossov er trial of additional LTG. Treatment periods of 12 weeks (25 mg, 50 m g, 100 mg LTG twice daily for four weeks at each dose, and matched pla cebo) were followed by wash out intervals of four weeks. 14 of the 20 patients completing the study improved, resulting in a significant fal l in seizure days and numbers. Analysis of seizure type confirmed a be neficial effect on partial and secondary generalised tonic-clonic seiz ures. At the highest LTG dose (200 mg daily) there was a median fall o f 37% in seizure count with nine (45%) patients reporting >50% reducti on. Three of these patients were seizure free during this month of tre atment. Side effects were minimal throughout the study. Concentrations of other antiepileptic drugs, including those of carbamazepine 10,11- epoxide, were not modified by LTG. This study suggests a substantial e fficacy for a regimen containing VIG and LTG. Combinations of drugs wi th complementary modes of action may provide a rational pharmacologica l approach to the management of refractory epilepsy.