Your new experience awaits. Try the new design now and help us make it even better

REVIEW article

Front. Neurosci.

Sec. Neuropharmacology

Volume 19 - 2025 | doi: 10.3389/fnins.2025.1614297

This article is part of the Research TopicNovel Pharmacological Interventions in Emotional and Neuropsychiatric DisordersView all articles

Inflammatory Links between Epilepsy and Depression: A Review of Mechanisms and Therapeutic Strategies

Provisionally accepted
Yu-Qian ShiYu-Qian Shi1*He-Cai YangHe-Cai Yang1Cong HeCong He2Yu-Hao WangYu-Hao Wang1Jia ZhengJia Zheng1Xing-Yi WangXing-Yi Wang1Fang-Yi HaoFang-Yi Hao1Chu-Wen FengChu-Wen Feng3Lin MaLin Ma3Yue-hui ZhangYue-hui Zhang3Zheng LiuZheng Liu3
  • 1Heilongjiang University of Chinese Medicine, Harbin, China
  • 2Second Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang Province, China
  • 3First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang Province, China

The final, formatted version of the article will be published soon.

Select one of your emails

You have multiple emails registered with Frontiers:

Notify me on publication

Please enter your email address:

If you already have an account, please login

You don't have a Frontiers account ? You can register here

Depression is the most common psychiatric comorbidity of epilepsy. While antiseizure medications (ASMs) can exacerbate depressive symptoms, depression itself may increase both the frequency and duration of epileptic seizures. The pathophysiological mechanisms underlying epilepsy-depression comorbidity (EDC) involve neurotransmitter imbalance, inflammatory responses, oxidative stress (OS), gut microbiota dysbiosis, and neuroendocrine abnormalities. Recent studies highlight that inflammation contributes to EDC via multiple interconnected mechanisms, including glial cell activation, cytokine release, pyroptosis, and oxidative damage, ultimately leading to synaptic dysfunction and neuroimmune imbalance. Drawing from representative and recent evidence, this review summarizes the role of inflammation in the pathogenesis and progression of EDC. It also outlines current inflammation-targeted therapeutic strategies, such as anti-inflammatory drugs, antioxidants, herbal medicine, acupuncture, probiotic modulation, and precision therapies. This review provides a conceptual framework for understanding inflammation-mediated EDC and offers insights into targeted treatment approaches.

Keywords: Epilepsy-Depression Comorbidity, Neuroinflammation, gut-brain axis, Natural Anti-inflammatory Agents, Aging-Related Inflammation 1

Received: 09 May 2025; Accepted: 16 Jun 2025.

Copyright: © 2025 Shi, Yang, He, Wang, Zheng, Wang, Hao, Feng, Ma, Zhang and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Yu-Qian Shi, Heilongjiang University of Chinese Medicine, Harbin, China

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material