Ferulic Acid Supplementation for Management of Depression in Epilepsy

Neuroinflammation driven altered neurochemical milieu have been reported to play a significant role in pathogenesis of comorbid depression in epilepsy. Most of the antiepileptic drugs (AEDs) such as levetiracetam, taigabine, topiramate have not been reported any significant effect in alleviating neuroinflammation, which may explain their ineffectiveness in ameliorating depression associated with epilepsy. The supplementation of antidepressants (ADs) attracts various pharmacokinetic and pharmacodynamic interactions with AEDs and was considered unsafe in epilepsy. This scenario pushes us to search therapies beyond ADs by critically exploring the disease mechanism. Thus, as suggested by our previous findings, anti-inflammatory phytotherapy (Ferulic acid) appears a promising adjuvant therapy with levetiracetam for effective and safe management of depression associated with epilepsy. Pentylenetetrazole kindling induced epileptic animals were treated with vehicle, levetiracetam (40 mg/kg/day i.p.) and levetiracetam in combination with two doses of ferulic acid (40, 80 mg/kg)/day/p.o. for 15 days. Every 5th day during the treatment, depression was evaluated and animals were administered pentylenetetrazole to evaluate the effect of different pharmacological interventions on seizure severity. The epileptic animals were reported decreased seizure threshold associated with comorbid depression. The treatment with levetiracetam was found ineffective in ameliorating the associated depression. However ferulic acid supplementation with levetiracetam ameliorated comorbid depression supported with restored circulating corticosterone levels, decreased proinflammatory cytokines (IL-1 beta, TNF-alpha) and indoleamine 2,3-dioxygenase activity in mice brain. Thus, suggesting supplementation of anti-inflammatory phytomolecules such as ferulic acid as safe and effective adjuvant therapy for the management of comorbid depression in epilepsy.