Treatment-Resistant Depression Registry

A Long-term, Prospective, Observational, Multi-center Patient Outcome Registry to Collect Data in Patients With Treatment-resistant Depression (TRD) Who Are Currently in a Major Depressive Episode.

This registry will collect information about patients with treatment-resistant depression (TRD) who are currently in a major depressive episode. For the purposes of this study, TRD is defined as an ongoing depression lasting at least 2 years or that has recurred at least 3 times, to include the current episode, during the patient's lifetime AND has not adequately responded to 4 or more adequate antidepressive treatments. The registry will follow the clinical course and outcomes for patients with TRD who are treated with and without adjunctive (used along with other treatments for depression) vagus nerve stimulation (VNS) therapy.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder

Detailed Description

Enrollment of TRD patients treated with VNS Therapy will consist of patients originally enrolled in the registry as well as patients who have completed the D-21 Dosing Study and are enrolled in the Registry for Long-Term Follow-up. Sites will maintain a screening log of all patients who have been screened for original TRD Registry patients.

Please note that because this is a post-approval registry, Cyberonics does not cover the cost of VNS Therapy implantation.

• Study Type: Observational
• Enrollment (Actual): 795

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona
  • California
    • Beverly Hills, California, United States
      • Cedars-Sinai Hospital
    • Garden Grove, California, United States, 92840
      • Mark Zetin, MD - Private Practice
    • Loma Linda, California, United States
      • Loma Linda University
    • Sacramento, California, United States, 95816
      • Sutter Institute for Medical Research
    • Sacramento, California, United States
      • Fair Oaks Psychiatric Associates
  • Connecticut
    • Farmington, Connecticut, United States, 06030-1410
      • University of Connecticut Health Center
  • Florida
    • Boca Raton, Florida, United States, 33431
      • Florida Atlantic University
    • Gainesville, Florida, United States, 32610-0256
      • University of Florida
  • Georgia
    • Brunswick, Georgia, United States, 31520
      • MG Martelli, MD, PC and Associates
    • Columbus, Georgia, United States
      • Arthur Holt, Private Practice
    • Decatur, Georgia, United States, 30030
      • Pact Atlanta, LLC
    • Macon, Georgia, United States, 31201
      • Private Practice
    • Marietta, Georgia, United States, 30060
      • Northwest Behavioral Research Center
    • Valdosta, Georgia, United States, 31602
      • Valdosta Psychiatric Associates LLC
  • Illinois
    • Evanston, Illinois, United States, 60201
      • Northshore University Health System
    • Evergreen Park, Illinois, United States
      • McGrath Clinic
    • Hoffman Estates, Illinois, United States
      • Alexian Brothers Behavioral Health Hospital
    • Skokie, Illinois, United States, 60076
      • Psychiatric Medicine Associates, LLC
    • Wheaton, Illinois, United States, 60187
      • Dupage Mental Health Services
  • Indiana
    • Indianapolis, Indiana, United States
      • 3c Methodist Hospital
  • Kansas
    • Wichita, Kansas, United States
      • Clinical Research Institute
  • Louisiana
    • Shreveport, Louisiana, United States, 71115
      • Louisiana Clinical Research, LLC
  • Maryland
    • Baltimore, Maryland, United States, 21208
      • Pharmasite Research Inc.
    • Baltimore, Maryland, United States, 21285
      • Sheppard Pratt Health Systems, Inc.
    • Glen Burnie, Maryland, United States, 21061
      • Clinical Insights
  • Massachusetts
    • Charlestown, Massachusetts, United States, 02129
      • Massachusetts General Hospital
    • Worcester, Massachusetts, United States, 01605
      • University of Massachusetts Medical School
  • Michigan
    • Rochester Hills, Michigan, United States, 48307
      • Rochester Center for Behavioral Medicine
  • Minnesota
    • St. Paul, Minnesota, United States, 55114
      • Psychiatric Recovery
  • Mississippi
    • Flowood, Mississippi, United States
      • Precise Research Centers
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University in St. Louis
    • St. Louis, Missouri, United States, 63128
      • Psych Care Consultants Research
  • New York
    • Amherst, New York, United States, 14226
      • Dent Neurologic Institute
    • Amherst, New York, United States, 14228
      • Suburban Psychiatric Associates
    • Jamaica, New York, United States, 11418
      • Jamaica Hospital Medical Center
    • New York, New York, United States, 10032
      • Columbia University
    • Syracuse, New York, United States, 13210
      • SUNY UMU at Syracuse
  • North Carolina
    • Winston Salem, North Carolina, United States, 27157
      • Wake Forest University - Health Sciences
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Case Medical Center
    • Findlay, Ohio, United States, 45840
      • Century Health
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Western Psychiatric Institute & Clinic (WPIC)
  • South Carolina
    • Charleston, South Carolina, United States, 29403
      • Medical University of South Carolina
  • Texas
    • Dallas, Texas, United States, 75390-8898
      • UT Southwestern Medical Center at Dallas
    • Houston, Texas, United States
      • Baylor College of Medicine
    • Houston, Texas, United States, 77008
      • Claghorn-Lesem Reserach Clinic, Ltd.
    • Plano, Texas, United States
      • The Mech Center
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center at San Antonio
    • San Antonio, Texas, United States
      • Alamo Superior Research
  • Utah
    • Salt Lake City, Utah, United States, 84105
      • Psychiatric & Behavioral Solutions
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University
  • Washington
    • Mercer Island, Washington, United States, 98040
      • Center For Anxiety and Depression
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with chronic depression that is at least two years in duration or a recurrent depression that includes at least three lifetime episodes including the current major depressive episode (MDE); and an inadequate response to four or more adequate antidepressant treatments.

Description

Inclusion Criteria:

• Patient diagnosed with a current major depressive episode according to DSM-IV-TR criteria.
• For D-21 patients only who have completed the D-21 dosing Study without any D-21 inclusion and exclusion protocol deviation.
• Patient has been in the current depressive episode for 2 years or longer, or has had at least 3 lifetime episodes including the current MDE.
• Patient has had an inadequate response to 4 or more adequate antidepressive treatments.
• The patient has a CGI severity of illness score of moderately ill (score of 4) or greater.
• The patient must be able to provide informed consent and complete all forms.

Exclusion Criteria:

• Patient has a history of schizophrenia, schizoaffective disorder, any other psychotic disorder, or a current major depressive episode that includes psychotic features; or is currently psychotic.
• Patient is currently enrolled in a double blind investigational study; patients who have completed the double-blind D-21 study will be allowed to enter the Registry for Long Term Follow-up
• Other than those patients who were enrolled in the D-21 study, patient has previously received VNS therapy.
• Patient has a history of rapid cycling bipolar disorder.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
1. 500 VNS Patients; VNS Patients - Treatment-resistant depression patients treated with VNS Therapy.
2. 300 Non-VNS Patients; Non-VNS Patients - Treatment-resistant depression patients not receiving VNS Therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Montgomery Asberg Depression Rating Scale (MADRS)% Responders (>/= 50% Improvement From Baseline)	Response Rate was computed and summarized as the proportion of patients that achieved ≥ 50% reduction from baseline in MADRS total score at each post-baseline visit. The MADRS is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60. The lower a score the less symptom severity is seen. A patient was considered a "Responder" (Yes = 1) if achieved ≥ 50% reduction from baseline in MADRS total score at visit month assessment post-baseline. A "Non-Responder" (No = 0) was any patient who did not achieve ≥ 50% reduction from baseline in MADRS score at visit month assessment post-baseline. Total number of patients in each group may be lower than ITT in a case of missing assessment data.	3-Month Through 60-Month (Post Baseline)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time Until Recurrence (TUR) for Patients That Achieved Remission, Based on Montgomery Asberg Depression Rating Scale (MADRS)	Recurrence based on MADRS is defined as first time attained MADRS total score ≥ 20 after achieving remission. Remission is a binary outcome response variable (Yes/No in-remission) defined as MADRS total score </= 9 at visit month assessment post-baseline. Duration of remission Computed as recorded date of the first recurrence/relapse (MADRS score >/= 20) minus the recorded date of first achieved remission (MADRS score </=9). Only a subpopulation that achieved remission will be included in the summary. Time-to-event analyses were summarized using Kaplan-Meier curves. Patients who did not achieve recurrence at the end of the study were censored on the last visit date recorded. Additionally, patients who discontinued early were censored on last date of contact. Censored observations and confidence intervals for the estimated median times were calculated.	3-Month Through 60-Month (Post Baseline)
Montgomery Asberg Depression Rating Scale (MADRS)% Remitters (MADRS Total Score ≤9 at Visit Month Assessment Post-Baseline)	Remission is a binary outcome response variable (Yes/No Inremission) defined as MADRS total score < 9 at visit month assessment post-baseline. The MADRS is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60. The lower a score the less symptom severity is seen and in general it is accepted that a score between 0-6 is indicative of a normal/symptom-free individual; 7-19 is indicative of a patient with mild depression; 20-34 is indicative of a patient with moderate depression; and >34 is indicative of a patient with severe depression. Total number of patients in each group may be lower than ITT in a case of missing assessment data.	3-Month Through 60-Month (Post Baseline)
Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Baseline MADRS Item 10 Suicidal Ideation	This assessment was completed telephonically by a third party rater (Central Rater Group). The rating was based on a clinical interview moving from broadly phrased questions about symptoms to more detailed ones, which allowed a precise rating of severity. The rater decided whether the rating lied on the defined scale steps (0, 2, 4, 6) or between them (1, 3, 5) and then checked the appropriate selection on the MADRS Item 10 Suicidal Thoughts (Ideation). Total number of patients analyzed may be lower than ITT in a case of missing assessment data.	1 Week Pre-Baseline
Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Medical Threat to Life of Most Recent Suicidal Gesture	This assessment was completed by the physician at the baseline visit in a clinical interview. The physician decided which category (as shown in outcome measure data table) best characterized the patient's medical threat to life of their most recent suicidal gesture or attempt. Total number of patients analyzed may be lower than ITT in a case of missing assessment data.	Baseline
Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Intent of Most Recent Suicidal Gesture	This assessment was completed by the physician at the baseline visit in a clinical interview. The physician decided which category (as shown in outcome measure data table) best characterized the patient's intent of their most recent suicidal gesture or attempt. Total number of patients analyzed may be lower than ITT in a case of missing assessment data.	Baseline
Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Primary Diagnosis of MDE	This assessment was completed by the physician at the screening visit. The physician decided which DSM-IV Diagnosis (as shown in outcome measure data table) best characterized the patient's primary diagnosis of MDE.	Screening

Collaborators and Investigators

• Sponsor: Cyberonics, Inc.
• Investigators: Principal Investigator: Anthony Rothschild, MD, University of Massachusetts, Worcester; Principal Investigator: Mark George, MD, Medical University of South Carolina; Principal Investigator: Herbert Ward, MD, University of Florida; Principal Investigator: Adam K. Ashton, MD, Suburban Psychiatric Associates; Principal Investigator: Thomas Schwartz, MD, SUNY UMU at Syracuse; Principal Investigator: Mark Zetin, MD, Private Practice; Principal Investigator: Darin D. Dougherty, MD, Massachusetts General Hospital; Principal Investigator: George Keepers, MD, Oregon Health and Science University; Principal Investigator: Mustafa M. Husain, MD, UT Southwestern Medical Center at Dallas; Principal Investigator: Leighton Y. Huey, MD, UConn Health; Principal Investigator: James Kimball, MD, Wake Forest University Health Sciences; Principal Investigator: Peter J. Holland, MD, Florida Atlantic University; Principal Investigator: Robert Howland, MD, Western Psychiatric Institute & Clinic (WPIC); Principal Investigator: Craig J Vine, MD, Psychiatric Recovery; Principal Investigator: Joel Young, MD, Rochester Center for Behavioral Science; Principal Investigator: Lawrence W Adler, MD, Clinical Insights; Principal Investigator: Harold Harsch, MD, Medical College of Wisconsin; Principal Investigator: Syed Ali, MD, Dupage Mental Health Services; Principal Investigator: Keming Gao, MD, University Hospitals Cleveland Medical Center; Principal Investigator: Todd M. Antin, M.D., DFAPA, Pact Atlanta, LLC; Principal Investigator: Basanti Basu, M.D., Century Health; Principal Investigator: Dwight Bearden, MD, Private Practice; Principal Investigator: David L. Dunner, MD, Center For Anxiety and Depression; Principal Investigator: Azfar Malik, MD, Psych Care Consultants Research; Principal Investigator: Joel Morgan, MD, Valdosta Psychiatric Associates LLC; Principal Investigator: Frederick W. Reimherr, MD, Psychiatric & Behavorial Solutions; Principal Investigator: John Zajecka, MD, Psychiatric Medicine Associates, LLC; Principal Investigator: Michael Banov, MD, Northwest Behavioral Research Center; Principal Investigator: Robert Lehman, MD, Pharmasite Research, Inc.; Principal Investigator: Scott Aaronson, MD, Sheppard Pratt Health Systems, Inc.; Principal Investigator: Jaishree Narayanan, MD, NorthShore University HealthSystem; Principal Investigator: Greg Seal, MD, Louisiana Clinical Research, LLC; Principal Investigator: Horacio Capote, MD, Dent Neurologic Institute; Principal Investigator: Michael Lesem, MD, Claghorn-Lesem Reserach Clinic, Ltd.; Principal Investigator: Miguel Martelli, MD, MG Martelli, MD, PC and Associates; Principal Investigator: Ananda Pandurangi, MD, Virginia Commonwealth University; Principal Investigator: Peter Thompson, MD, The University of Texas Health Science Center at San Antonio; Principal Investigator: Theodore Goodman, MD, Sutter Institute for Medical Research; Principal Investigator: Francisco Moreno, MD, University of Arizona; Principal Investigator: Martha Edelman, MD, Jamaica Hospital Medical Center; Principal Investigator: Peter Bulow, MD, Columbia University; Study Director: Mark Bunker, Cyberonics, Inc.; Principal Investigator: Mahendra Bhati, MD, University of Pennsylvania; Principal Investigator: Ronald Warnell, MD, Loma Linda University; Principal Investigator: Robert Cohen, MD, Cedars-Sinai Hospital; Principal Investigator: Janak Mehtani, MD, Fair Oaks Psychiatric Associates; Principal Investigator: Mounir Soliman, MD, University of California, San Diego; Principal Investigator: Francisco Fernandez, MD, University of South Florida; Principal Investigator: Arthur Holt, MD, Arthur Holt, Private Practice; Principal Investigator: Harold McGrath, MD, McGarth Clinic; Principal Investigator: Anthony D'Agostino, MD, Alexian Brothers Behavioral Health Hospital; Principal Investigator: Anne Gilbert, MD, 3c Methodist Hospital; Principal Investigator: Michael Burke, MD, Clinical Research Institute; Principal Investigator: Ed Coffey, MD, Henry Ford Health Services; Principal Investigator: Joseph Kwentus, MD, University of Mississippi Medical Center; Principal Investigator: David Ginsberg, MD, New York University of Medical Center; Principal Investigator: Melissa Martinez, MD, Baylor College of Medicine; Principal Investigator: Arnold Mech, MD, The Mech Center; Principal Investigator: Joseph Simpson, MD, Alamo Superior Research

Publications and helpful links

General Publications

• George MS, Rush AJ, Marangell LB, Sackeim HA, Brannan SK, Davis SM, Howland R, Kling MA, Moreno F, Rittberg B, Dunner D, Schwartz T, Carpenter L, Burke M, Ninan P, Goodnick P. A one-year comparison of vagus nerve stimulation with treatment as usual for treatment-resistant depression. Biol Psychiatry. 2005 Sep 1;58(5):364-73. doi: 10.1016/j.biopsych.2005.07.028.
• Rush AJ, Sackeim HA, Marangell LB, George MS, Brannan SK, Davis SM, Lavori P, Howland R, Kling MA, Rittberg B, Carpenter L, Ninan P, Moreno F, Schwartz T, Conway C, Burke M, Barry JJ. Effects of 12 months of vagus nerve stimulation in treatment-resistant depression: a naturalistic study. Biol Psychiatry. 2005 Sep 1;58(5):355-63. doi: 10.1016/j.biopsych.2005.05.024.
• Rush AJ, Marangell LB, Sackeim HA, George MS, Brannan SK, Davis SM, Howland R, Kling MA, Rittberg BR, Burke WJ, Rapaport MH, Zajecka J, Nierenberg AA, Husain MM, Ginsberg D, Cooke RG. Vagus nerve stimulation for treatment-resistant depression: a randomized, controlled acute phase trial. Biol Psychiatry. 2005 Sep 1;58(5):347-54. doi: 10.1016/j.biopsych.2005.05.025.
• Bajbouj M, Merkl A, Schlaepfer TE, Frick C, Zobel A, Maier W, O'Keane V, Corcoran C, Adolfsson R, Trimble M, Rau H, Hoff HJ, Padberg F, Muller-Siecheneder F, Audenaert K, van den Abbeele D, Matthews K, Christmas D, Eljamel S, Heuser I. Two-year outcome of vagus nerve stimulation in treatment-resistant depression. J Clin Psychopharmacol. 2010 Jun;30(3):273-81. doi: 10.1097/JCP.0b013e3181db8831.
• McAllister-Williams RH, Sousa S, Kumar A, Greco T, Bunker MT, Aaronson ST, Conway CR, Rush AJ. The effects of vagus nerve stimulation on the course and outcomes of patients with bipolar disorder in a treatment-resistant depressive episode: a 5-year prospective registry. Int J Bipolar Disord. 2020 May 2;8(1):13. doi: 10.1186/s40345-020-0178-4.
• Aaronson ST, Sears P, Ruvuna F, Bunker M, Conway CR, Dougherty DD, Reimherr FW, Schwartz TL, Zajecka JM. A 5-Year Observational Study of Patients With Treatment-Resistant Depression Treated With Vagus Nerve Stimulation or Treatment as Usual: Comparison of Response, Remission, and Suicidality. Am J Psychiatry. 2017 Jul 1;174(7):640-648. doi: 10.1176/appi.ajp.2017.16010034. Epub 2017 Mar 31. Erratum In: Am J Psychiatry. 2017 Sep 1;174(9):907.

Study record dates

Study Major Dates

• Study Start: January 1, 2006
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: May 1, 2006
• First Submitted That Met QC Criteria: May 1, 2006
• First Posted (Estimate): May 3, 2006

Study Record Updates

• Last Update Posted (Estimate): December 23, 2015
• Last Update Submitted That Met QC Criteria: December 22, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: Major Depressive Disorder; Treatment-resistant Depression
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant
• Other Study ID Numbers: TRD Registry