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 [HRSD 24]). Results: At 10-weeks, HRSD 24 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-SR 30), 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.
Bibliographical noteFunding Information:
This study was supported by Cyberonics, Inc., through contracts to investigating sites. Statistical analyses were conducted by Quintiles Inc. and reviewed by the senior authors. The following principal investigators and sites participated in this study (the approving IRBs are in parentheses): J. Barry, M.D., Stanford University School of Medicine (Stanford University/Human Subjects in Medical Research); M. Burke, M.D., Psychiatric Research Institute (Via Christi Regional Medical Center Institutional Review Board); W. Burke, University of Nebraska Medical Center (University of Nebraska Institutional Review Board); L. Carpenter, M.D., Brown University/Butler Hospital (Butler Hospital IRB); C. Conway, M.D., St. Louis University Health Science Center (St. Louis University IRB); R. Cooke, M.D., University of Toronto/Centre for Addiction and Mental Health (Centre for Addiction and Mental Health Research Ethics Board); R.A. Dominguez, M.D., University of Miami School of Medicine (University of Miami School of Medicine/Human Subjects Research Office); D. Dunner, M.D., University of Washington Center for Anxiety and Depression (Human Subjects Division, University of Washington); M.S. George, M.D., Medical University of South Carolina (Office of Research Integrity IRB #3); D. Ginsberg, M.D., New York University Medical Center (NYU Medical Center Institutional Board of Research Associates); R. Howland, M.D., University of Pittsburgh School of Medicine (University of Pittsburgh Institutional Review Board); M. Husain, M.D., The University of Texas Southwestern Medical Center (Office of Institutional Review Board UT Southwestern Medical Center); M. Kling, M.D., University of Maryland (University of Maryland Baltimore Institutional Review Board); L.B. Marangell, M.D., Baylor College of Medicine (Baylor College of Medicine IRB); F. Moreno, M.D., University of Arizona Health Science Center (Human Subjects Protection Program); A. Nierenberg, M.D., Massachusetts General Hospital (Massachusetts General Hospital IRB); P. Ninan, M.D., Emory University School of Medicine (Emory University Institutional Review Board); B. Rittberg, M.D., University of Minnesota Medical School (Research Subjects’ Protection Program IRB); T. Schwartz, M.D., SUNY Upstate Medical University at Syracuse (State University of New York Upstate Medical University Institutional Review Board); M. Soliman, M.D., University of California San Diego Department of Psychiatry (UCSD Human Research Protection Program); J. Zajecka, M.D., Rush Presbyterian-St. Luke’s Medical Center (Rush University Medical Center IRB).
- Bipolar disorder
- Clinical trial
- Major depressive disorder
- Side effects
- Treatment-resistant depression (TRD)
- Vagus nerve stimulation (VNS)