REVIEW article
Front. Neurol.
Sec. Epilepsy
Volume 16 - 2025 | doi: 10.3389/fneur.2025.1615079
Benzodiazepine-Resistant Epilepsy: Unraveling Molecular Mechanisms and Developing Multimodal Therapeutic Strategies
Provisionally accepted
- 1University of Electronic Science and Technology of China, Chengdu, Sichuan Province, China
- 2Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan Province, China
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Epilepsy is one of the most common nervous system diseases, which is characterized by recurrent seizures caused by abnormal neuronal discharges in the brain. Drug-resistant epilepsy (DRE) brings great challenges to clinical treatment. Benzodiazepines (BZDs), as the first-line treatment for acute seizures and Status Epilepticus (SE), are widely used because of their potent inhibitory neuromodulation by regulating γ-aminobutyric acid-A(GABA A ) receptors. However, long-term use of BZDs may induce drug resistance, leading to a significant decrease in efficacy and increasing the difficulty of treatment. This study begins with the definition of BZDsresistant epilepsy. It explores the underlying resistance mechanisms, including the down-regulation, decreased activity, and structural changes of GABA A receptors, synapse and neural network remodeling, genetic variation in drug metabolism, and the effects of drug efflux mechanisms. In addition, combined with clinical practice and research progress, this study evaluates the effectiveness and potential of drug combination therapies, personalized treatments, and new treatment methods, highlighting the advantages of simultaneous multi-drug therapy in controlling drug-resistant epilepsy. Further research on the mechanisms of BZDs resistance and optimization of treatment strategies can not only improve the therapeutic effect of drugresistant epilepsy but also provide a scientific basis for the development of antiepileptic drugs in the future.
Keywords: Benzodiazepines, Drug Resistance, treatment strategies, Epilepsy, seizure
Received: 20 Apr 2025; Accepted: 23 May 2025.
Copyright: © 2025 Huang, Zhang and Liang. 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: Yi Liang, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, 611731, Sichuan Province, China
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