Background: The need for effective, long-term treatment for recurrent or chronic, treatment-resistant depression is well established. Methods: This naturalistic follow-up describes outpatients with nonpsychotic major depressive (n = 185) or bipolar (I or II) disorder, depressed phase (n = 20) who initially received 10 weeks of active (n = 110) or sham vagus nerve stimulation (VNS) (n = 95). The initial active group received another 9 months, while the initial sham group received 12 months of VNS. Participants received antidepressant treatments and VNS, both of which could be adjusted. Results: The primary analysis (repeated measures linear regression) revealed a significant reduction in 24-item Hamilton Rating Scale for Depression (HRSD 24) scores (average improvement, .45 points [SE = .05] per month (p < .001). At exit, HRSD 24 response rate was 27.2% (55/202); remission rate (HRSD 24 ≤ 9) was 15.8% (32/202). Montgomery Äsberg Depression Rating Scale (28.2% [57/202]) and Clinical Global Impression-Improvement (34.0% [68/200]) showed similar response rates. Voice alteration, dyspnea, and neck pain were the most frequently reported adverse events. Conclusions: These 1-year open trial data found VNS to be well tolerated, suggesting a potential long-term, growing benefit in treatment-resistant depression, albeit in the context of changes in depression treatments. Comparative long-term data are needed to determine whether these benefits can be attributed to VNS.
Bibliographical noteFunding Information:
This study was supported by Cyberonics, Inc, through contracts to investigational 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) (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 U.T. 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).
- Clinical trial
- Major depressive disorder, Bipolar disorder
- Side effects
- Treatment-resistant depression (TRD)
- Vagus nerve stimulation (VNS)