Transcranial Stimulation Methods in the Treatment of MDD Patients—The Role of the Neurotrophin System

Major depressive disorder (MDD) continues to be a primary cause of disability globally, with a significant number of patients exhibiting resistance to standard pharmacological and psychotherapeutic interventions. In recent years, non-invasive brain stimulation techniques, especially transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), have emerged as promising therapies for treatment-resistant MDD. A comprehensive search was performed in PubMed, which included all studies published over the last ten years. Eligible studies encompassed both animal models and clinical investigations. This review provides a comparative overview of transcranial electrical stimulation modalities, with a focus on their mechanisms of action, clinical efficacy, and underlying neurobiological mechanisms. We pay particular attention to the role of the neurotrophin system, specifically brain-derived neurotrophic factor (BDNF), in mediating the treatment effects of transcranial stimulation. Recent findings indicate that neuromodulation could improve neuroplasticity by increasing BDNF levels and associated signaling pathways, which may help stabilize mood and enhance the improvement of individuals with MDD. A more profound understanding of these mechanisms could lead to more precise, biomarker-driven interventions. Further research is essential to elucidating the long-term effects of brain stimulation on neurotrophin levels and to creating more individualized treatment strategies.