Vagus Nerve Stimulation for Treatment-Resistant Depression: A Randomized, Controlled Acute Phase Trial

Authors

A. John Rush, University of Texas Southwestern Medical CenterFollow
Lauren B. Marangell, Baylor College of Medicine
Harold A. Sackeim, New York State Psychiatric InstituteFollow
Mark S. George, Medical University of South CarolinaFollow
Stephen K. Brannan, Cyberonics Inc.
Sonia M. Davis, Quintiles Inc.Follow
Robert Howland, University of Pittsburgh School of Medicine
Mitchel A. Kling, University of Maryland School of MedicineFollow
Barry Rittberg, University of Minnesota Medical SchoolFollow
William J. Burke, University of Nebraska Medical CenterFollow
Mark H. Rapaport, University of California - San Diego
John Zajecka, Rush-Presbyterian-St. Luke’s Medical Center
Andrew A. Nierenberg, Massachusetts General Hospital, Boston
Mustafa M. Husain, University of Texas Southwestern Medical CenterFollow
David Ginsberg, New York University School of MedicineFollow
Robert G. Cooke, University of TorontoFollow

Date of this Version

9-2005

Document Type

Article

Citation

Biological Psychiatry, Volume 58, Issue 5, 1 September 2005, Pages 347-354; doi:10.1016/j.biopsych.2005.05.025

Abstract

Background: Vagus nerve stimulation (VNS) alters both concentrations of neurotransmitters or their metabolites and functional activity of central nervous system regions dysregulated in mood disorders. An open trial has suggested efficacy.

Methods: This 10-week, acute, randomized, controlled, masked trial compared adjunctive VNS with sham treatment in 235 outpatients with nonpsychotic major depressive disorder (n = 210) or nonpsychotic, depressed phase, bipolar disorder (n = 25). In the current episode, participants had not responded adequately to between two and six research-qualified medication trials. A two-week, single-blind recovery period (no stimulation) and then 10 weeks of masked active or sham VNS followed implantation. Medications were kept stable. Primary efficacy outcome among 222 evaluable participants was based on response rates (≥ 50% reduction from baseline on the 24-item Hamilton Rating Scale for Depression [HRSD₂₄]).

Results: At 10-weeks, HRSD₂₄ response rates were 15.2% for the active (n = 112) and 10.0% for the sham (n = 110) groups (p = .251, last observation carried forward [LOCF]). Response rates with a secondary outcome, the Inventory of Depressive Symptomatology – Self-Report (IDS-SR₃₀), were 17.0% (active) and 7.3% (sham) (p = .032, LOCF). VNS was well tolerated; 1% (3/235) left the study because of adverse events.

Conclusions: This study did not yield definitive evidence of short-term efficacy for adjunctive VNS in treatment-resistant depression.