Abstract
Combination therapy with two or three antiseizure medications (ASMs) is sometimes a preferred method of treatment in epilepsy patients. (1) Background: To detect the most beneficial combination among three ASMs, a screen test evaluating in vivo interactions with respect to their anticonvulsant properties, was conducted on albino Swiss mice; (2) Methods: Classification of interactions among lacosamide (LCM) and selected second-generation ASMs (lamotrigine (LTG), pregabalin (PGB), oxcarbazepine (OXC), and topiramate (TPM)) was based on the isobolographic analysis in the mouse maximal electroshock-induced seizure (MES) model. Interactions among LCM and second-generation ASMs were visualized using a polygonogram; (3) Results: In the mouse MES model, synergy was observed for the combinations of LCM + TPM + PGB and LCM + OXC + PGB. Additivity was reported for the other combinations tested i.e., LCM + LTG + TPM, LCM + LTG + PGB, LCM + LTG + OXC, and LCM + OXC + TPM in this seizure model. No adverse effects associated with triple ASM combinations, containing LCM and second-generation ASMs were observed in mice; (4) Conclusions: The combination of LCM + TPM + PGB was the most beneficial combination among the tested in this study, offering synergistic suppression of tonic-clonic seizures in mice subjected to the MES model. Both the isobolographic analysis and polygonogram method can be recommended for experimental epileptology when classifying interactions among the ASMs.
Highlights
Patients with epilepsy require efficacious treatment with current frontline antiseizure medications (ASMs)
We aimed to classify the interactions for three-drug combinations among 5 ASMs (namely, lacosamide (LCM), lamotrigine (LTG), oxcarbazepine (OXC), pregabalin (PGB), and topiramate (TPM)), so as to select the most beneficial combinations of ASMs, offering synergistic suppression of tonic-clonic seizures in the mouse maximal electroshock-induced seizure (MES) model by means of the isobolographic analysis of interactions accompanied with a polygonogram method
All the tested ASMs had their dose–response lines collateral to each other (Supplementary Figure S1)
Summary
Patients with epilepsy require efficacious treatment with current frontline antiseizure medications (ASMs). 70% of epilepsy patients are sufficiently treated with one drug, but the rest of the patients need polytherapy with two or three ASMs [1]. For these patients, physicians try to combine various ASMs so as to provide them with a significant reduction of seizure activity and/or seizure frequency [2]. Patients with refractory epilepsy need effective polytherapy with ASMs, but each polytherapy is usually associated with interactions among drugs, whose nature may be pharmacodynamic, pharmacokinetic, or mixed [9]. Physicians can prescribe their patients more than 25 ASMs, they still have no unanimous recommendations on which of these drugs preferentially combine to offer the epileptic patients the best treatment options [10]
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