New long-term data show sustained symptom improvement and functional gains in patients with highly treatment-resistant major depression receiving ongoing vagus nerve stimulation.
Why Vagus Nerve Stimulation Matters in Resistant Depression
Major depressive disorder becomes increasingly difficult to treat as treatment resistance accumulates. Patients who fail multiple antidepressants face lower response rates and higher relapse risk, even with advanced interventions. Vagus nerve stimulation has emerged as an adjunctive option for this population, delivering chronic neuromodulation through an implanted device to influence mood-regulating brain circuits. However, durability of benefit has remained a critical unanswered question, particularly beyond the first year of therapy.
The RECOVER trial extension was designed to address this gap by examining whether benefits achieved with vagus nerve stimulation persist, diminish, or continue to accrue over time in a real-world outpatient setting.
RECOVER Trial Tracks Long-Term Outcomes
The prospective, open-label RECOVER extension followed 214 adults with moderate to severe major depressive disorder who had experienced at least four failed antidepressant trials in the current episode. All participants had already completed 12 months of adjunctive vagus nerve stimulation and continued treatment for an additional 12 months.
Across five outcome measures, 78.8% of participants with substantial benefit at 12 months maintained this improvement at 18 months, rising slightly to 79.0% at 24 months. Among those with at least meaningful benefit at 12 months, maintenance rates reached 83.1% at 18 months and 81.3% at 24 months across seven measures. Importantly, benefit was not static. Among participants without meaningful benefit at 12 months, 30.6% achieved it by 18 months and 37.8% by 24 months. These outcomes were not explained by changes in medications or other interventional psychiatric treatments.
Implications For Clinical Practice
The findings suggest that vagus nerve stimulation offers more than short-term symptom relief in markedly treatment-resistant depression. Equally notable is the delayed response seen in a substantial minority, reinforcing the need for patience and continued therapy beyond the first year. For clinicians managing severe, refractory depression, these results support considering vagus nerve stimulation earlier in long-term treatment planning and counselling patients about realistic timelines for benefit emergence and durability.
Reference
Conway CR et al. Durability of the benefit of vagus nerve stimulation in markedly treatment-resistant major depression: a RECOVER trial report. International Journal of Neuropsychopharmacology. 2026;29(1):pyaf080.
