Comparative effectiveness of transcutaneous auricular vagus nerve stimulation and escitalopram for depressive symptoms in major depressive disorder

Major depressive disorder (MDD) is a prevalent psychiatric illness with substantial treatment challenges. This study compared the effectiveness of transcutaneous auricular vagus nerve stimulation (taVNS) and escitalopram in patients with severe MDD. This retrospective cohort study enrolled patients treated at our hospital between September 2021 and September 2025. Patients were allocated to either the escitalopram group or the taVNS group. Outcome assessments were performed at baseline and week 8, covering depressive symptoms (MADRS and HAMD-17), anxiety (HAMA), sleep quality (PSQI), cognitive function (MoCA), anhedonia (SHAPS), and heart rate variability indices (SDNN, RMSSD, and LF/HF ratio). Adverse events were documented throughout treatment. After propensity score matching was conducted, 120 patients were included in each group. Compared with escitalopram, taVNS produced greater improvements in sleep quality (PSQI P < 0.001), cognitive function (MoCA P = 0.024), anhedonia (SHAPS P = 0.040), and autonomic regulation (SDNN P = 0.006; RMSSD P = 0.016; LF/HF P < 0.001). Safety profiles differed: escitalopram caused more nausea, somnolence, and dry mouth, whereas taVNS mainly produced mild local skin reactions. No statistically significant between-group difference was observed between taVNS and escitalopram for core depressive symptoms. It offers additional benefits in sleep, cognition, anhedonia, and autonomic function, with a more favorable systemic safety profile.