Vagus Nerve Stimulation: Emerging Success in Treating-Resistant Depression

The RECOVER trial shows a durable, two-year clinical benefit from implanted vagus nerve stimulation (VNS) for adults with severe, treatment‑resistant depression—sustained symptom reduction, improved function, and better quality of life in a cohort that had exhausted multiple prior therapies. These results position VNS as a viable therapeutic option for selected refractory cases.

The trial tested an implantable neurostimulator in nearly 500 adults with markedly treatment‑resistant depression across multiple U.S. sites; prespecified endpoints included standardized symptom scales (notably the MADRS), remission rates, quality-of-life measures, and functional outcomes. The blinded first year did not show a significant difference on the primary MADRS score between activated and inactive devices, yet later analyses identified durable improvements among patients who received active VNS and among early responders, with many maintaining or increasing benefit through 24 months.

Durability was clinically notable: a majority of early responders sustained benefit at two years, more than 20% of treated patients achieved full remission, and relapse rates were low among the strongest responders. By comparison, long-term remission and relapse profiles after medication or electroconvulsive therapy in markedly treatment‑resistant cohorts are typically less favorable, making these sustained VNS outcomes distinctive. For long-term management, the data support VNS as a maintenance option for appropriately selected patients.

Putative mechanisms include autonomic modulation, downstream effects on limbic networks, and reduction of proinflammatory signaling—combined actions that plausibly restore network stability and affect regulation. Practical selection criteria center on prolonged illness duration and multiple failed pharmacologic and brain‑stimulation trials (often a decade or more of chronicity), absence of contraindicated cardiac devices or unstable cardiac disease, and substantial functional impairment. Baseline evaluation should emphasize a comprehensive psychiatric history, assessment of current suicidality, prior neuromodulation exposure, and targeted cardiac assessment. In practice, the prototypical VNS candidate is a person with chronic, disabling depression who has not benefited from standard therapies and is medically suitable for implantation.

Integrating VNS into care requires referral to a multidisciplinary neuromodulation center, preoperative medical and cardiac clearance, coordinated implantation and device-programming pathways, and attention to reimbursement and device access. Safety and tolerability in the trial were acceptable, with predictable stimulation-related effects and no new safety signals; ongoing monitoring is required for mood response, device function, and adjustment of concomitant treatments. These results should prompt consideration of VNS as a defined option within treatment algorithms for refractory depression where resources and expertise permit.

Key Takeaways:

• RECOVER shows durable two-year benefits of VNS for severe treatment-resistant depression, with sustained symptom reduction and improved function.
• More than 20% of treated patients reached remission and relapse rates were low among strong responders, supporting VNS as a maintenance option.
• Optimal candidates are chronically ill, treatment-exhausted patients without contraindicated cardiac conditions; multidisciplinary evaluation and monitoring are essential.