New Clinical Trial Conducted at Sheppard Pratt Identifies Predictors of Response to Vagus Nerve Stimulation for Treatment-Resistant Depression

BALTIMORE, Oct. 13, 2025 /PRNewswire/ -- The Journal of Clinical Psychiatry recently published results from the RECOVER trial, a landmark study examining vagus nerve stimulation (VNS) therapy in individuals with treatment-resistant depression. The analysis, led by Scott T. Aaronson, MD, chief science officer of the Institute for Advanced Diagnostics and Therapeutics at Sheppard Pratt, provides new insight into which patients may be most likely to benefit from this innovative therapy.

The RECOVER trial enrolled 493 adults with markedly treatment-resistant major depressive disorder. On average participants had failed over 13 different treatments in their current episode of depression. All participants were implanted with a vagus nerve stimulation device and were randomized to either having the device turned on (active VNS) or not (sham VNS) in the first year of the study. At the end of the first year, all devices were turned on. Outcomes were evaluated across depressive symptoms, psychosocial functioning, and quality of life using well-established clinical measures.

Findings showed that intensity of baseline treatment history—particularly prior exposure to electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS)—served as important prognostic predictors of overall outcomes. Overall individuals who had not previously received these therapies higher response rates, than those who had. While these characteristics were generally associated with poorer prognosis, this subgroup of patients experienced greater benefit from active VNS compared to sham treatment and was a prescriptive predictor of improved outcome..

The study marks one of the first large-scale efforts to identify both prognostic and prescriptive predictors of response in treatment-resistant depression.

"By moving beyond symptoms alone and also looking at functioning and quality of life, we were able to better capture the full impact of treatment," said Dr. Aaronson. "These results highlight how clinicians may be able to personalize care and guide VNS therapy to the patients who stand to gain the most. For individuals who have faced years of unsuccessful treatments, this represents an important step forward."

The RECOVER trial underscores the role of VNS therapy as an option for patients living with chronic, treatment-resistant depression and highlights the importance of precision medicine in psychiatry.

The Institute for Advanced Diagnostics and Therapeutics at Sheppard Pratt is dedicated to caring for individuals with the most difficult-to-treat mental illnesses while advancing research into groundbreaking new therapies. Patients of the Institute have access to leading neuromodulation treatments, advanced psychopharmacology, and participation in cutting-edge clinical trials. For more information on the Institute for Advance Diagnostics and Therapeutics, visit www.sheppardpratt.org/the-institute-for-advanced-diagnostics-and-therapeutics

About Sheppard Pratt

Sheppard Pratt is the largest private, nonprofit provider of mental health, substance use, developmental disability, special education, and social services in the country. A nationwide resource, Sheppard Pratt provides services across a comprehensive continuum of care, spanning both hospital- and community-based resources. Since its founding in 1853, Sheppard Pratt has been innovating the field through research, best practice implementation, and a focus on improving the quality of mental health care on a global level. Sheppard Pratt has been consistently recognized as a top national psychiatric hospital by U.S. News & World Report for more than 30 years.

SOURCE Sheppard Pratt