LAMOTRIGINE SUBSTITUTION STUDY - EVIDENCE FOR SYNERGISM WITH SODIUM VALPROATE

Three hundred and forty seven patients with epilepsy from 54 centres a cross Europe not fully controlled with sodium valproate (VPA, n = 117) , carbamazepine (CBZ, n = 129), phenytoin (PHT, n = 92) or phenobarbit al (PB, n = 9) monotherapy were recruited into a lamotrigine (LTG) sub stitution study. If 50% or more seizure reduction occurred (responders ) on addition of LTG, an attempt was made to withdraw the original ant iepileptic drug (AED). IF successful, this was followed by a 12 week p eriod of LTG monotherapy. Overall, 73% patients completed the add-on p hase (47% responders), 41% attempted AED withdrawal and 23% achieved L TG monotherapy. In the 60 patients (17%) completing the trial by remai ning on LTG monotherapy, median monthly seizure frequency was reduced from 6 during baseline to 1.7. Sixteen percent of patients were withdr awn due to adverse effects, mostly during the add-on phase. Dizziness and diplopia occurred most frequently in the CBZ group, nervousness an d ataxia in the PHT group, and rash and tremor in the VPA group. Slowe r LTG dose escalation resulted in fewer withdrawals due to rash in the VPA-treated patients (38% to 8%, P < 0.01). The responder rate was hi gher (P < 0.01) in patients with idiopathic tonic-clonic seizures (61% ) than in those with partial seizures (43%). The addition of LTG to VP A (64% responders) produced a significantly better response (P < 0.001 ) than adding it to CBZ (41% responders) or PI-IT (38% responders). Th is effect was seen for partial (VPA, 57%; CBZ, 39%; PHT, 39%; P < 0.02 ) as well as tonic-clonic seizures (VPA, 70%; CBZ, 53%; PI-IT, 50%; NS ). These data lend credence to the suggestion of therapeutic synergy b etween LTG and VPA. (C) 1997 Elsevier Science B.V.