# The Concomitant Effect of the Antiepileptic Drug Lacosamide and rTMS on an SH-SY5Y Model of Neuronal Excitability

## TL;DR

This study explores how combining a seizure medication and brain stimulation reduces overactive neuron signals in a lab model, which could help treat hard-to-manage epilepsy.

## Contribution

The novel contribution is demonstrating the synergistic effect of lacosamide and rTMS in reducing neuronal hyperexcitability in vitro.

## Key findings

- Combining lacosamide and rTMS significantly reduced KCl-induced calcium elevation compared to individual treatments.
- The combination treatment showed enhanced suppression of neuronal excitability in SH-SY5Y cells.
- Lacosamide and rTMS individually also reduced excitability but less effectively than the combination.

## Abstract

Background/Objectives: Epilepsy is identified by irregular neuronal hyperexcitability, generating recurrent seizures. Despite many available pharmacological treatments, certain patients with drug-resistant epilepsy may require novel therapeutic approaches. In the present study, we aimed to evaluate the effects of lacosamide, low-frequency repetitive transcranial magnetic stimulation, and their combination on intracellular calcium dynamics in an in vitro model of neuronal excitability, hypothesizing that these interventions could mitigate potassium chloride-induced neuronal excitation. Methods: We utilized differentiated SH-SY5Y human neuroblastoma cells as an in vitro model of neuronal excitability. Neuronal excitability was induced with 50 mM KCl, and cells were treated with lacosamide (300 µM), rTMS (1 Hz), or their combination. Intracellular calcium levels were quantified using fluo-4 AM fluorescence calcium imaging, with changes expressed as percentage change in fluorescence intensity (%ΔF/F) relative to baseline. Results: The combination of lacosamide and rTMS was the most effective, significantly reducing KCl-induced calcium elevation (ΔF/F = 9.15) compared to lacosamide alone (ΔF/F = 17.11), rTMS alone (ΔF/F = 23.70), and the untreated cells serving as controls (ΔF/F = 66.70). The combination showed a statistically significant effect, with enhanced suppression of neuronal excitability compared to individual treatments. Conclusions: Lacosamide and low-frequency rTMS (1 Hz) effectively attenuated KCl-induced changes in intracellular calcium levels in vitro, with their combination demonstrating the highest efficacy. These findings suggest a promising foundation in the management of drug-resistant epilepsy. Future studies are necessitated to validate these results and benefit clinical translation.