Additive interaction for three-drug combination of carbamazepine, lacosamide and lamotrigine against maximal electroshock-induced seizures – a type I isobolographic analysis

Introduction. Treatment of epilepsy patients with one antiepileptic drug often fails and then the insufficiently medicated patients need two or three antiepileptic drugs combined together to stop their seizures. However, polytherapy is always associated with drug-drug interactions whose nature may or may not be favorable for epilepsy patients. Preclinical studies on animals can help to select beneficial combinations of antiepileptic drugs that could be used in further clinical settings. Aim. To isobolographically characterize anticonvulsant effects of a combination of three antiepileptic drugs (carbamazepine, lacosamide and lamotrigine) at the fixed drug dose ratio of 1:1:1 in the mouse maximal electroshock-induced seizure test. Material and methods. Maximal electroconvulsions were evoked in male Swiss mice by a current (25 mA, 500 V, 0.2 s stimulus duration) delivered via auricular electrodes. Type I isobolographic analysis was applied to assess the interaction among carbamazepine, lacosamide and lamotrigine. Results. Isobolographic analysis revealed that the combination of carbamazepine, lacosamide and lamotrigine produced additive interaction in the mouse maximal electroshock-induced seizure test. Conclusions. Additivity among carbamazepine, lacosamide and lamotrigine in this preclinical study can be translated to clinical settings and this three-drug combination can be recommended as a treatment option for epilepsy patients who are resistant to standard treatment regimens.