Ear Nerve Stimulation Matches Escitalopram on Depression, With Extra Gains in Sleep

A retrospective cohort study from a single hospital has compared transcutaneous auricular vagus nerve stimulation (taVNS) with the antidepressant escitalopram in patients with severe major depressive disorder, and reports that the two approaches performed similarly on core depressive symptoms while differing on secondary outcomes.

The study enrolled patients treated between September 2021 and September 2025, allocating them to either an escitalopram group or a taVNS group. After propensity score matching, 120 patients were included in each group, allowing the researchers to compare the two treatments in balanced cohorts.

Outcome assessments were performed at baseline and at week 8. They covered depressive symptoms measured with the MADRS and HAMD-17 scales, anxiety with the HAMA, sleep quality with the PSQI, cognitive function with the MoCA, anhedonia with the SHAPS, and heart rate variability indices including SDNN, RMSSD and the LF/HF ratio. Adverse events were documented throughout treatment.

The central finding was negative on the primary comparison: no statistically significant between-group difference was observed between taVNS and escitalopram for core depressive symptoms. This suggests that, in this matched retrospective cohort, the non-invasive nerve stimulation approach was not distinguishable from the standard antidepressant on the main symptom measures.

However, taVNS showed advantages on several secondary measures. Compared with escitalopram, it produced greater improvements in sleep quality (PSQI, P < 0.001), cognitive function (MoCA, P = 0.024), and anhedonia (SHAPS, P = 0.040).

The stimulation group also showed greater improvements in autonomic regulation, reflected in heart rate variability: SDNN improved more (P = 0.006), as did RMSSD (P = 0.016) and the LF/HF ratio (P < 0.001). These indices capture different aspects of autonomic function, and the authors interpret the pattern as additional benefit beyond mood symptoms alone.

Safety profiles differed between the treatments. Escitalopram caused more nausea, somnolence and dry mouth, whereas taVNS mainly produced mild local skin reactions at the stimulation site. The study therefore describes a more favorable systemic safety profile for the device-based approach in this cohort.

Several limitations should temper interpretation. The study was retrospective and conducted at a single hospital, and patients were allocated to groups rather than randomly assigned, even after propensity score matching. Unmeasured differences between groups cannot be excluded, and the findings should be viewed as observational rather than as evidence from a randomized trial.

The article was published open access in BMC Psychiatry on 22 October 2026 and was shared early as a peer-reviewed, accepted version of record in progress, meaning it remains subject to further edits before the final version replaces it.

Within those constraints, the study adds to the evidence base for taVNS as a treatment option in severe major depressive disorder, indicating comparable effects on depressive symptoms in this cohort, with reported additional benefits in sleep, cognition, anhedonia and autonomic function, and a different side-effect profile dominated by mild local skin reactions rather than systemic antidepressant-type effects.

Subject of Research: Comparative effectiveness of transcutaneous auricular vagus nerve stimulation versus escitalopram in severe major depressive disorder

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

Article References: Wu, Y.-L., Ding, L., Yu, C.-Y., Wang, Y.-F., Zhang, Z.-H., Chai, G.-D., Fu, X.-Q., & Tuo, Y. (2026). Comparative effectiveness of transcutaneous auricular vagus nerve stimulation and escitalopram for depressive symptoms in major depressive disorder. BMC Psychiatry. https://doi.org/10.1186/s12888-026-08785-5

Image Credits: AI Generated

DOI: 10.1186/s12888-026-08785-5

Keywords: major depressive disorder, taVNS, escitalopram, vagus nerve stimulation, propensity score matching, heart rate variability, anhedonia, sleep quality, adverse events, BMC Psychiatry, retrospective cohort study, Comparative