Effects of vagus nerve stimulation on daily function and quality of life in markedly treatment-resistant major depression

March 10, 2025

Written by Joao L. de Quevedo, MD, PhD

Introduction

Depression is a devastating illness, but for those with treatment-resistant depression (TRD)—a form of depression that does not respond to multiple treatment attempts—finding relief can feel nearly impossible. Traditional antidepressants, therapy, and even advanced treatments like electroconvulsive therapy (ECT) often fail to provide lasting improvements.

A recent study published in Brain Stimulation explores a promising new approach: Vagus Nerve Stimulation (VNS). This one-year, randomized, sham-controlled trial investigated whether VNS could improve quality of life (QoL) and daily function in patients with severe TRD. 

What is Vagus Nerve Stimulation?

VNS is a neuromodulation therapy that involves implanting a small device under the skin, which sends electrical impulses to the vagus nerve, a crucial pathway between the brain and various organs. Initially approved for epilepsy, VNS has been studied for its potential in treating chronic depression when other treatments fail.

Study Overview

The study, known as the RECOVER trial, included 493 adults diagnosed with TRD who had previously undergone at least four unsuccessful antidepressant treatments. The participants were divided into two groups:

  • Active VNS Group (249 patients): Received real VNS therapy in addition to their usual treatment.
  • Sham VNS Group (244 patients): Underwent the implantation procedure but did not receive active stimulation.

Researchers followed these participants for 12 months, evaluating their quality of life, work productivity, and daily functioning at quarterly intervals using validated measurement tools.

Key Findings

  1. Improved Quality of Life (QoL)
    • The Mini-Q-LES-Q (a questionnaire assessing life satisfaction) showed significant improvements in the VNS group compared to the sham group (P = 0.050).
    • The Q-LES-Q (another QoL measure) showed a similar trend (P = 0.061).
  1. Better Daily Functioning
    • The Work Productivity and Activity Impairment Questionnaire (WPAI) revealed that VNS led to better ability to perform daily activities compared to the sham group (P = 0.050).
  1. Sustained Benefits Over Time
    • Patients in the active VNS group spent significantly more time in a state of clinically meaningful improvement in QoL and function compared to those in the sham group.
  1. No Significant Differences in Disability and General Health Measures
    • The WHODAS 2.0 (which measures disability) and the EQ-5D health scale did not show major differences between the two groups.

What Does This Mean for People with TRD?

The study suggests that VNS therapy offers more than just symptom relief—it enhances overall quality of life and day-to-day functioning. Unlike conventional treatments that focus on reducing depressive symptoms, VNS appears to help patients feel and function better in their daily lives.

Limitations and Considerations

While the results are promising, the study had some limitations:

  • The trial only measured outcomes for one year, so long-term effects remain unclear.
  • Some quality-of-life improvements may have been influenced by placebo effects.
  • The cost and surgical nature of VNS make it a more complex treatment than standard antidepressants.

Final Thoughts

For patients with severe TRD, VNS represents a potential breakthrough—one that goes beyond managing symptoms to improving overall well-being. While more research is needed, this study provides hope that neuromodulation therapies like VNS could be life-changing for those who have exhausted other options.

Reference

Rush, A. J., Conway, C. R., Aaronson, S. T., George, M. S., Riva-Posse, P., Dunner, D. L., Zajecka, J., Bunker, M. T., Quevedo, J., Allen, R. M., Alva, G., Luing, H., Nahas, Z., Manu, L., Bennett, J. I., Mickey, B. J., Becker, J., Sheline, Y., Cusin, C., Murrough, J. W., Reeves, K., Rosenquist, P. B., Lee, Y.-C., Majewski, S., Way, J., Olin, B., & Sackeim, H. A. (2024). Effects of vagus nerve stimulation on daily function and quality of life in markedly treatment-resistant major depression: Findings from a one-year, randomized, sham-controlled trial. Brain Stimulation. https://doi.org/10.1016/j.brs.2024.12.1187

How do you refer a patient or request an appointment to the UTHealth Houston Center for Interventional Psychiatry?

Second Opinion Intake Form – https://Go.uth.edu/CIPIntake.

Phone – (713) 486-2621

Fax – (713) 500-2728

E-mail – [email protected]