The extent and durability of improvement in depressive symptoms, quality of life, and daily function with three years of vagus nerve stimulation in markedly treatment-resistant depression: A RECOVER study report
- 1Department of Psychiatry, Washington University in St Louis, St Louis, MO, United States
Abstract
BackgroundIn markedly treatment-resistant depression, the RECOVER trial compared the time course, extent, and durability of benefits in groups randomized to three years of active VNS (Early-Active) or one year of sham VNS followed by two years of active VNS (Delayed-Active).
MethodsFor 436 participants completing month-12 (M12) assessments (Early-Active N=221; Delayed-Active N=215), longitudinal mixed-effects models characterized trajectories of benefit over 36 months in categorical outcomes pooled across blinded depressive symptom and global improvement measures. Additional analyses examined the proportions benefiting and the degree and durability of benefits.
ResultsThe Early-Active group had greater odds of improvement during the RCT phase (OR=1.66; 95% CI=1.17-2.35; P=0.005). This between-group difference increased until M12 and then progressively narrowed upon VNS activation in the Delayed-Active group, approaching parity by M36. Across both groups, emergence of new beneficiaries plateaued after 24 months of active VNS, but with participants progressively achieving higher degrees of benefit thereafter. Following activation, the Delayed-Active group had significant improvement in all six categorical outcome measures. Durability was strong across depressive symptoms, function, and quality-of-life outcomes. For participants receiving active VNS throughout, durability of response was 70% from M12 to M36.
ConclusionsActive VNS was associated with improved benefits for both treatment groups over years 2 and 3. New beneficiaries emerged during the first two years of active VNS with continued progression to higher levels of benefit in the third year. These clinical benefits were highly durable. ClinicalTrials.gov identifier: NCT03887715.
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BibTeX
@misc{conway2026extent,
title = {{The extent and durability of improvement in depressive symptoms, quality of life, and daily function with three years of vagus nerve stimulation in markedly treatment-resistant depression: A RECOVER study report}},
author = {C. R. Conway and S. T. Aaronson and A. J. Rush and Y.-C. Lee and C. Gordon and O. Shy and M. T. Bunker and P. Riva-Posse and M. S. George and J. Zajecka and Z. Nahas and D. L. Dunner and J. L. de Quevedo and M. Figee and B. J. Mickey and R. M. Allen and K. Reeves and D. Bohnenkamp and C. L. Kriedt and V. C. Hristidis and C. F. Zorumski and M. Macaluso and W. Duffy and Y. Sheline and G. Alva and C. Cusin and J. I. Bennett and Q. Tran and R. S. McIntyre and R. H. McAllister-Williams and H. A. Sackeim},
howpublished = {medRxiv},
year = {2026},
month = jul,
doi = {10.64898/2026.07.31.26358854},
url = {https://www.medrxiv.org/content/10.64898/2026.07.31.26358854v2},
note = {CC BY},
}
RIS
TY - UNPB
TI - The extent and durability of improvement in depressive symptoms, quality of life, and daily function with three years of vagus nerve stimulation in markedly treatment-resistant depression: A RECOVER study report
AU - C. R. Conway
AU - S. T. Aaronson
AU - A. J. Rush
AU - Y.-C. Lee
AU - C. Gordon
AU - O. Shy
AU - M. T. Bunker
AU - P. Riva-Posse
AU - M. S. George
AU - J. Zajecka
AU - Z. Nahas
AU - D. L. Dunner
AU - J. L. de Quevedo
AU - M. Figee
AU - B. J. Mickey
AU - R. M. Allen
AU - K. Reeves
AU - D. Bohnenkamp
AU - C. L. Kriedt
AU - V. C. Hristidis
AU - C. F. Zorumski
AU - M. Macaluso
AU - W. Duffy
AU - Y. Sheline
AU - G. Alva
AU - C. Cusin
AU - J. I. Bennett
AU - Q. Tran
AU - R. S. McIntyre
AU - R. H. McAllister-Williams
AU - H. A. Sackeim
PY - 2026
DA - 2026/07/31
PB - medRxiv
DO - 10.64898/2026.07.31.26358854
UR - https://www.medrxiv.org/content/10.64898/2026.07.31.26358854v2
AB - BackgroundIn markedly treatment-resistant depression, the RECOVER trial compared the time course, extent, and durability of benefits in groups randomized to three years of active VNS (Early-Active) or one year of sham VNS followed by two years of active VNS (Delayed-Active). MethodsFor 436 participants completing month-12 (M12) assessments (Early-Active N=221; Delayed-Active N=215), longitudinal mixed-effects models characterized trajectories of benefit over 36 months in categorical outcomes pooled across blinded depressive symptom and global improvement measures. Additional analyses examined the proportions benefiting and the degree and durability of benefits. ResultsThe Early-Active group had greater odds of improvement during the RCT phase (OR=1.66; 95% CI=1.17-2.35; P=0.005). This between-group difference increased until M12 and then progressively narrowed upon VNS activation in the Delayed-Active group, approaching parity by M36. Across both groups, emergence of new beneficiaries plateaued after 24 months of active VNS, but with participants progressively achieving higher degrees of benefit thereafter. Following activation, the Delayed-Active group had significant improvement in all six categorical outcome measures. Durability was strong across depressive symptoms, function, and quality-of-life outcomes. For participants receiving active VNS throughout, durability of response was 70% from M12 to M36. ConclusionsActive VNS was associated with improved benefits for both treatment groups over years 2 and 3. New beneficiaries emerged during the first two years of active VNS with continued progression to higher levels of benefit in the third year. These clinical benefits were highly durable. ClinicalTrials.gov identifier: NCT03887715.
ER -