Effect of Antidepressants (Sertraline, Escitalopram) in Combination with Antiepileptic Drugs (Sodium Valproate, Levetiracetam) on Seizures, Cognitive Impairment, and Oxidative Stress in Rats

Objectives: Depression is a major comorbidity in persons with epilepsy (pWE). The effect of antidepressants sertraline (SRT) and escitalopram (ESC) in combination with sodium valproate (SV) and levetiracetam (LEV) on seizure and cognitive impairment in rats was studied.

Methods: The male Wistar rats (200–250 g) were trained for Morris water maze (MWM), passive avoidance (pA) and elevated plus maze (EPM) test and baseline trials conducted before subjecting to pentylenetetrazole (pTZ)-induced kindling. SV and LEV were used in combination with SRT and ESC to evaluate effect on seizure development, cognition, and biochemical parameters. SRT (25 mg/kg), ESC (15 mg/kg), SV (150 mg/kg), and LEV (300 mg/kg) were injected daily at the same time and seizure stimuli given every alternate day 4-h,1-h, and 30 minutes, respectively, after dosing with above drugs. On day 49, retention trials performed, rats sacrificed, and blood and brains collected for malondialdehyde (MDA) and glutathione (GSH) estimation.

Results: SRT 25 mg/kg per se showed no protective effect, with SRT and LEV 12.5% and ESC and SV group none of the rats were kindled. In EPM, kindling increased transfer latency and drug treatments were ineffective. In PA, kindling did not alter transfer latency but SRT alone and SRT + LEV treatment decreased it as compared with baseline (p < 0.001). On combining SRT with LEV, opposite effects in MWM and PA were observed. There was a significant decrease in level of MDA in SRT as well as ESC + SV group as compared with normal control on day 49.

Conclusion: Use of antidepressants in PWE has to be done cautiously as their effect on seizure and cognitive impairment may vary.