Antagonistic interaction of lacosamide with carbamazepine and valproate in the mouse tonic-clonic seizure model

Background
It is estimated that approximately 1% of people worldwide suffer from epilepsy. Currently available antiepileptic drugs (AEDs) are able to control epileptic seizures in about 70% of cases. In the remaining patients (30%), the application of two or three AEDs in combination is necessary for effective seizure management. The goal of this work was to characterize the interaction of three AEDs: lacosamide (LCM), carbamazepine (CBZ) and valproate (VPA) at the fixed-ratio of 1:1:1 in the mouse tonic-clonic seizure model.

Material and methods
Male albino Swiss mice, after receiving a combination of LCM, CBZ and VPA, were challenged with electric current to evoke tonic hind limb extension (seizure activity). Protection of the mice from tonic-clonic seizures was assessed by isobolographic analysis to determine the type of interaction occurring between these drugs.

Results
Type I isobolographic analysis revealed that the combination of LCM, CBZ and VPA produced infra-additive (antagonistic) interaction in the mouse tonic-clonic seizure model.

Conclusions
Since the three-drug mixture of LCM, CBZ and VPA exerted an antagonistic interaction in the tonic-clonic seizure test in mice, we would caution physicians against treating epilepsy patients with this unfavorable combination.