Effect of Vortioxetine on Pilocarpine Induced Status Epilepticus in Sprague Dawley Rats

Background:Status epilepticus (SE) is a frequently encountered medical emergency that may not respond to existing antiepileptic medications, underscoring the urgency for exploring alternative treatment options. Vortioxetine, a novel multimodal antidepressant, modulates several serotonin receptors and has shown anticonvulsant potential in other seizure models. However, its role in SE remains unexplored. Objective: The study assessed the impact of vortioxetine on seizure severity, onset latency, and 24-hour survival in a rodent model of status epilepticus using lithium-pilocarpine. Methods: Twenty-four male Sprague Dawley rats were randomized into four groups: (1) disease control (distilled water), (2) standard treatment (diazepam, 5 mg/kg), (3) vortioxetine 10 mg/kg, and (4) vortioxetine 20 mg/kg. All groups received lithium chloride and pilocarpine to induce SE. Modified Racine scale was used to score the seizure severity. Latency to stage 4 seizures and SE, seizure scores, and 24-hour survival rates were assessed. The mean differences between groups was analyzed by one-way ANOVA. This was followed by Tukey’s post hoc test to see the intergroup differences. Results: All animals in the disease control and low-dose vortioxetine groups progressed to stage 5 seizures and SE, with 33.3% and 16.7% mortality, respectively. In the high-dose vortioxetine group, 83.3% developed SE with no mortality. Diazepam significantly delayed seizure onset, reduced severity, and prevented SE. Vortioxetine at both doses showed only marginal increases in seizure latency and no significant reduction in seizure severity or SE incidence compared to control. Conclusion: Vortioxetine did not exhibit significant protective effects against lithium-pilocarpine-induced SE in Sprague Dawley rats at the doses tested. Its limited efficacy may be due to the complex pathophysiology of SE and the acute nature of the model. Further studies are warranted to explore its role in chronic epilepsy models or as adjunctive therapy.