Depression in Epilepsy: Drug and Non-Drug Interventions Based on Multimodal Pathogenesis

Depression is a common comorbidity in patients with epilepsy, significantly impacting their quality of life. However, the precise mechanisms underlying depression in epilepsy remain unclear. This review synthesizes the latest research on the pathogenesis of depression in epilepsy, focusing on abnormalities in monoamine neurotransmitters, neuroinflammation, HypothalamicPituitary-Adrenal (HPA) axis dysfunction, neurotrophic factors, mitochondrial dysfunction, and oxidative stress. The article explores the dual roles of antidepressants and antiepileptic drugs (AEDs) in the treatment of depression in epilepsy, highlighting drugs that may exacerbate either depression or seizure activity. The need for more nuanced treatment strategies, including the careful selection of antidepressants and AEDs, is emphasized. Additionally, non-drug interventions, such as Cognitive-Behavioral Therapy (CBT), neuromodulation techniques, and dietary modifications (anti-inflammatory and antioxidant foods), are reviewed as vital adjuncts to pharmacological treatments. This article aims to guide clinicians in choosing optimal treatment strategies and underscores the importance of timely depression screening, long-term management, and personalized therapy for patients with epilepsy and comorbid depression.