LAMOTRIGINE - A NEW ANTIEPILEPTIC DRUG FO R ADD-ON THERAPY OF HITHERTO REFRACTORY EPILEPSIES

Lamotrigine (Lamictal(R)) is a new antiepileptic drug for add-on thera py of drug resistant focal seizures with or without secondary generali zation. It probably acts by inhibiting the release of the excitatory n eurotransmitter glutamate. According to clinical studies a reduction o f seizure frequency of at least 50 % is achieved in about one of four patients. As it is expected, only rarely seizure freedom is achieved. However, in addition to reduced seizure frequency a reduction of seizu re severity is often observed. According to long term studies developm ent of tolerance to the drug with loss of efficacy seems to be very ra re. The recommended median daily dose for children is 5-15 mg/kg body weight and 100-400 mg for adults, divided in one to three dosages. Rel evant drug interactions are shortening of the elimination half-life of lamotrigine in combination with enzyme inducing other anticonvulsants and pronounced half-life prolongation in combination with valproate. In patients with valproate monotherapy lamotrigine has to be introduce d very slowly and carefully. Most often reported side effects are cuta neous allergies, which occur less frequently when lamotrigine is start ed with low and slowly increasing (every second week) dosages. In rega rd of neurotoxic disturbances in double blind studies no significant d ifferences between lamotrigine and placebo were documented. Blood leve ls and control of other laboratory values are not as important as with most conventional anticonvulsants. Efficacy seems to be at least as g ood in primary generalized seizures as in focal seizures with or witho ut secondary generalization according to uncontrolled studies and expe rience. Lamotrigine monotherapy may be effective in newly diagnosed ep ilepsies. However, up to now these clinical applications are not appro ved and have to be confirmed in double-blind studies.