The improvement effects and mechanisms of virtual reality training on depression: a systematic review from a neurotransmitter-plasticity dual-pathway perspective

Background: Depression is a common mental disorder and a leading cause of disability, affecting approximately 280 million people worldwide. Its pathological mechanisms are closely linked to neurotransmitter homeostasis imbalance and neuroplasticity impairment. We aimed to systematically evaluate the clinical efficacy of virtual reality (VR) training in improving depression and to elucidate its dual-pathway regulatory mechanism involving neurotransmitter-plasticity interactions. Methods: We systematically searched PubMed, Web of Science, CNKI, and ScienceDirect databases from their formation to May 2025 to identify randomised controlled trials (RCTs) assessing VR-based interventions. Given the significant heterogeneity across protocols, we conducted a narrative synthesis in accordance with the Synthesis Without Meta-analysis (SWiM) reporting guidelines rather than a quantitative meta-analysis. We assessed the quality of the included studies using the Physiotherapy Evidence Database (PEDro) scale. Results: Based on 16 studies, we found that VR training can significantly alleviate depressive symptoms through multimodal sensory stimulation and immersive interactions, as the included RCTs generally reported reductions in depression scale scores. Preliminary evidence from several studies also suggests a positive correlation between clinical efficacy and biomarkers of neural structure recovery and functional network synchronisation. However, due to high heterogeneity in intervention protocols, control group designs, and outcome measures, we were unable to provide a unified estimate of the VR training efficacy. Conclusions: Evidence suggests that VR training may reverse the pathological cycle of depression through a synergistic dual pathway of neurotransmitter regulation and neuroplasticity enhancement, offering a novel strategy for precision intervention. Future research should optimise VR intervention protocols, explore synergistic effects with traditional therapies, and validate its long-term efficacy and safety in special populations. Registration: PROSPERO: CRD420261300373.