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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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) |
| 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 \ |
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Inclusion Criteria:
Exclusion Criteria:
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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.
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| Name | Affiliation | Role |
|---|---|---|
| Adam K. Ashton, MD | Suburban Psychiatric Associates | Principal Investigator |
| Herbert Ward, MD | University of Florida | 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Arizona | Tucson | Arizona | 85724 | United States | ||
| Cedars-Sinai Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16139581 | Background | 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. | |
| 16139580 |
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A total of 878 subjects were screened in the TRD Registry Study. Thirty-seven were not eligible and 46 were eligible but not treated for various reasons. This left a total of 795 patients in the Safety Population (SP).
The TRD Registry was to enroll over a maximum period of 6 years & patients were to be followed for at least 60 months. All sites were to first recruit patients who had agreed to have adjunctive VNS Therapy. Sites were also asked to enroll patients with TRD who would not be implanted with VNS Therapy and would act as a concurrent control group.
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| ID | Title | Description |
|---|---|---|
| FG000 | VNS Therapy | Disposition of study patients from baseline to the end of the study. The VNS Therapy arm, was comprised of D-23 Original patients (Patients that entered the TRD Registry without previous VNS Therapy treatment and selected the VNS Therapy study arm) and D-21 Rollover patients (Patients that entered the TRD Registry, having previously participated in the D-21 study-NCT00305565 and still being treated with VNS Therapy). |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| 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 |
| Florida Atlantic University |
| Principal Investigator |
| Robert Howland, MD | Western Psychiatric Institute & Clinic (WPIC) | Principal Investigator |
| Anthony Rothschild, MD | University of Massachusetts, Worcester | 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 |
| Mark George, MD | Medical University of South Carolina | 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 | Endeavor Health | Principal Investigator |
| Greg Seal, MD | Louisiana Clinical Research, LLC | Principal Investigator |
| Horacio Capote, MD | Dent Neurologic Institute | Principal Investigator |
| Charles Conway, MD | Washington University School of Medicine | 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 | Principal Investigator |
| Mark Bunker | Cyberonics, Inc. | Study Director |
| 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 | Principal Investigator |
| Beverly Hills |
| California |
| United States |
| Mark Zetin, MD - Private Practice | Garden Grove | California | 92840 | United States |
| Loma Linda University | Loma Linda | California | United States |
| Sutter Institute for Medical Research | Sacramento | California | 95816 | United States |
| Fair Oaks Psychiatric Associates | Sacramento | California | United States |
| University of Connecticut Health Center | Farmington | Connecticut | 06030-1410 | United States |
| Florida Atlantic University | Boca Raton | Florida | 33431 | United States |
| University of Florida | Gainesville | Florida | 32610-0256 | United States |
| MG Martelli, MD, PC and Associates | Brunswick | Georgia | 31520 | United States |
| Arthur Holt, Private Practice | Columbus | Georgia | United States |
| Pact Atlanta, LLC | Decatur | Georgia | 30030 | United States |
| Private Practice | Macon | Georgia | 31201 | United States |
| Northwest Behavioral Research Center | Marietta | Georgia | 30060 | United States |
| Valdosta Psychiatric Associates LLC | Valdosta | Georgia | 31602 | United States |
| Northshore University Health System | Evanston | Illinois | 60201 | United States |
| McGrath Clinic | Evergreen Park | Illinois | United States |
| Alexian Brothers Behavioral Health Hospital | Hoffman Estates | Illinois | United States |
| Psychiatric Medicine Associates, LLC | Skokie | Illinois | 60076 | United States |
| Dupage Mental Health Services | Wheaton | Illinois | 60187 | United States |
| 3c Methodist Hospital | Indianapolis | Indiana | United States |
| Clinical Research Institute | Wichita | Kansas | United States |
| Louisiana Clinical Research, LLC | Shreveport | Louisiana | 71115 | United States |
| Pharmasite Research Inc. | Baltimore | Maryland | 21208 | United States |
| Sheppard Pratt Health Systems, Inc. | Baltimore | Maryland | 21285 | United States |
| Clinical Insights | Glen Burnie | Maryland | 21061 | United States |
| Massachusetts General Hospital | Charlestown | Massachusetts | 02129 | United States |
| University of Massachusetts Medical School | Worcester | Massachusetts | 01605 | United States |
| Rochester Center for Behavioral Medicine | Rochester Hills | Michigan | 48307 | United States |
| Psychiatric Recovery | Saint Paul | Minnesota | 55114 | United States |
| Precise Research Centers | Flowood | Mississippi | United States |
| Washington University in St. Louis | St Louis | Missouri | 63110 | United States |
| Psych Care Consultants Research | St Louis | Missouri | 63128 | United States |
| Dent Neurologic Institute | Amherst | New York | 14226 | United States |
| Suburban Psychiatric Associates | Amherst | New York | 14228 | United States |
| Jamaica Hospital Medical Center | Jamaica | New York | 11418 | United States |
| Columbia University | New York | New York | 10032 | United States |
| SUNY UMU at Syracuse | Syracuse | New York | 13210 | United States |
| Wake Forest University - Health Sciences | Winston-Salem | North Carolina | 27157 | United States |
| University Hospitals Case Medical Center | Cleveland | Ohio | 44106 | United States |
| Century Health | Findlay | Ohio | 45840 | United States |
| Oregon Health & Science University | Portland | Oregon | 97239 | United States |
| University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
| Western Psychiatric Institute & Clinic (WPIC) | Pittsburgh | Pennsylvania | 15213 | United States |
| Medical University of South Carolina | Charleston | South Carolina | 29403 | United States |
| UT Southwestern Medical Center at Dallas | Dallas | Texas | 75390-8898 | United States |
| Claghorn-Lesem Reserach Clinic, Ltd. | Houston | Texas | 77008 | United States |
| Baylor College of Medicine | Houston | Texas | United States |
| The Mech Center | Plano | Texas | United States |
| University of Texas Health Science Center at San Antonio | San Antonio | Texas | 78229 | United States |
| Alamo Superior Research | San Antonio | Texas | United States |
| Psychiatric & Behavioral Solutions | Salt Lake City | Utah | 84105 | United States |
| Virginia Commonwealth University | Richmond | Virginia | 23298 | United States |
| Center for Anxiety and Depression | Mercer Island | Washington | 98040 | United States |
| Medical College of Wisconsin | Milwaukee | Wisconsin | 53226 | United States |
| 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. |
| 16139582 | Background | 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. |
| 20473062 | Background | 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. |
| 32358769 | Derived | 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. |
| 28359201 | Derived | 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. |
| FG001 | Treatment as Usual (TAU) | Disposition of study patients from baseline to the end of the study. The TAU arm were subjects that entered the TRD Registry without previous VNS Therapy treatment and selected the TAU study arm. |
| VNS Therapy D-23 Original |
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| VNS Therapy D-21 (NCT00305565) Rollovers |
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| COMPLETED |
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| NOT COMPLETED |
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A total of 878 subjects were screened. Thirty-seven were not eligible and 46 were eligible but not treated for various reasons. This left a total of 795 patients in the Safety Population (SP). The total number of patients in each group may be lower than SP if there was missing D-21 assessment data, as D-21 baseline data was not identical to D-23.
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| ID | Title | Description |
|---|---|---|
| BG000 | VNS Therapy D-23 Original | Subjects that entered the TRD Registry without previous VNS Therapy treatment and selected the VNS Therapy study arm. |
| BG001 | VNS Therapy D-21 Rollover | Subjects that entered the TRD Registry, having previously participated in the D-21 study and still being treated with VNS Therapy treatment were included within the VNS Therapy group. Based on the duration from initial implant to enrollment date, the D-21 rollover patients entered at the appropriate D-23 follow-up interval (i.e., patient enrolls at 24 months post implant for their first D-23 follow up visit. This 24 month visit corresponds to the 24 month follow up in the TRD Registry). Starting with the first TRD Registry visit, the D-21 long-term patients were to follow the same data collection schedule as other Original VNS and TAU Registry patients. |
| BG002 | Treatment as Usual (TAU) | Non-VNS Patients - Treatment-resistant depression patients not receiving VNS Therapy. Subjects that entered the TRD Registry without previous VNS Therapy treatment and selected the TAU study arm. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Ethnic Orgin of participants in the study | Number | Participants |
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| Lifetime Episodes of Depression Diagnosed (n=335, n=0, n=301) | Mean | Standard Deviation | Lifetime Episodes of Depression |
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| Number of Failed Treatments (n=335, n=159, n=301) | Mean | Standard Deviation | Number of Failed Treatments |
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| Suicide Attempts in Lifetime (n=335, n=159, n=301) | Mean | Standard Deviation | Number of Suicide Attempts in a Lifetime |
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| Diagnosis Disorder (Major Depressive Disorder (MDD) or Bipolar Disorder (BPD) | Number | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | 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. | Intent-To-Treat (ITT) Population: VNS Therapy Population (n=489 (D-23=330 + D-21=159)) + (n= 276) TAU population | Posted | Number | Percentage of Participants | 3-Month Through 60-Month (Post Baseline) |
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| Secondary | 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 \ | Intent-To-Treat (ITT) Population: VNS Therapy Population (n=489 (D-23=330 + D-21=159)) + (n= 276) TAU population | Posted | Median | 95% Confidence Interval | Months | 3-Month Through 60-Month (Post Baseline) | Censored Patients | Participants |
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| Secondary | 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. | Intent-To-Treat (ITT) Population: VNS Therapy Population (n=489 (D-23=330 + D-21=159)) + (n= 276) TAU population | Posted | Number | Percentage of Participants | 3-Month Through 60-Month (Post Baseline) |
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| Post-Hoc | Mortality and Suicidality in Safety Population (Total Number of Deaths) | The number of deaths on the study were collected from the baseline visit. | Safety Population (SP): VNS Therapy Population (n=494 (D-23=335 + D-21=159)) + (n= 301) TAU population | Posted | Number | Number of Deaths | 3-Month (baseline or implantation) Through 60-Month (Post Baseline) |
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| Post-Hoc | Mortality and Suicidality in Safety Population (Total Patient Years Exposed) | Treatment exposure time in years for all patients for all treatment groups were calculated in 1000 person year measure. | Safety Population (SP): VNS Therapy Population (n=494 (D-23=335 + D-21=159)) + (n= 301) TAU population | Posted | Number | Exposure Per 1000 Patient Years | 3-Month Through 60-Month (Post Baseline) |
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| Post-Hoc | Mortality and Suicidality in Safety Population (All-Cause Mortality/1000 Person Years) | All cause mortality is defined as the number of deaths per calculated 1000 person years. | Safety Population (SP): VNS Therapy Population (n=494 (D-23=335 + D-21=159)) + (n= 301) TAU population | Posted | Number | Deaths Per 1000 Person Years | 3-Month Through 60-Month (Post Baseline) |
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| Post-Hoc | Mortality and Suicidality in Safety Population (Number of Suicides) | The number suicides on the study were collected from the baseline visit. | Safety Population (SP): VNS Therapy Population (n=494 (D-23=335 + D-21=159)) + (n= 301) TAU population | Posted | Number | Number of Suicides | 3-Month Through 60-Month (Post Baseline) |
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| Post-Hoc | Mortality and Suicidality in Safety Population (Suicides/1000 Person Years) | The number of suicides per calculated 1000 person years. | Safety Population (SP): VNS Therapy Population (n=494 (D-23=335 + D-21=159)) + (n= 301) TAU population | Posted | Number | Number of Suicides Per 1000 Person Years | 3-Month Through 60-Month (Post Baseline) |
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| Secondary | 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. | D-23 Original + TAU [(n= 330) + (n= 276)] minus 2 missing assessment data. These risk factors assessed at baseline and pre-baseline were not collected with respect to treatment, therefore this information is not presented by treatment arm. | Posted | Number | Percentage of Patients | 1 Week Pre-Baseline |
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| Post-Hoc | Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Change From Baseline by Visit Month | The Q-LES-Q-SF is a self-report scale to assess the degree of enjoyment and satisfaction experienced by the patient during the past week. There are 2 forms of this instrument: the short form and the long form. The short form employs the 14 general activities included in the long form, as well as 2 global items. Five-point item scores (1 to 5) are aggregated, with higher scores indicative of greater enjoyment or satisfaction in each domain. The scoring of the Q-LESQ-SF involves summing only the first 14 items to yield a raw total score. The last 2 items are not included in the total score but stand alone. The raw total score ranges from 14 (worst score) to 70 (best score). Higher Q-LES-QSF score indicates more enjoyment and satisfaction (Endicott, Nee et al. 1993). | ITT Population minus D-21 Subjects: VNS Therapy Population (D-23=330) + (n= 276) TAU population. The total number of patients in each group is lower than ITT due to missing assessment data, for which a large portion is that of D-21 subjects. The Q-LES-Q-SF was not collected in the D-21 Study. | Posted | Mean | Standard Deviation | units on a scale | 3-Month Through 60-Month (Post Baseline) |
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| Secondary | 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. | D-23 Original + TAU [(n= 330) + (n= 276)] minus 159 missing assessment data. These risk factors assessed at baseline and pre-baseline were not collected with respect to treatment, therefore this information is not presented by treatment arm. | Posted | Number | Percentage of Patients | Baseline |
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| Secondary | 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. | D-23 Original + TAU [(n= 330) + (n= 276)] minus 159 missing assessment data. These risk factors assessed at baseline and pre-baseline were not collected with respect to treatment, therefore this information is not presented by treatment arm. | Posted | Number | Percentage of Patients | Baseline |
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| Secondary | 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. | D-23 Original + TAU [(n= 330) + (n= 276)]. These risk factors assessed at baseline and pre-baseline were not collected with respect to treatment, therefore this information is not presented by treatment arm. | Posted | Number | Percentage of Patients | Screening |
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N/A (Adverse event information was not collected as part of the TRD Registry Protocol)
Physicians were instructed to notify Cyberonics' Clinical Technical Support (CTS) department of all Medical Devices Reporting (MDR) events that occurred in TRD Registry participants receiving VNS Therapy.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Safety Events | N/A (not collected) | 0 | 0 | 0 | 0 |
Not provided
Not provided
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Mark Bunker, PharmD, Sr. Director, Global Medical Affairs | Cyberonics, Inc | 281-228-7223 | mark.bunker@cyberonics.com |
| ID | Term |
|---|---|
| D003865 | Depressive Disorder, Major |
| D061218 | Depressive Disorder, Treatment-Resistant |
| ID | Term |
|---|---|
| D003866 | Depressive Disorder |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
Not provided
Not provided
| Age-Initial Onset of Depression(n=334,n=159,n=301) |
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| Age-Initial Dx. of Depression(n=334,n=159,n=301) |
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| Male |
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| African-American |
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| Hispanic |
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| Asian |
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| Other |
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| MDD, Recurrent, Severe w/o Psychotic Features |
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| MDD, Single Episode, Moderate Severity |
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| MDD, Single Episode, Severe w/o Psychotic Features |
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| BPD I, MRE Depressed, Moderate Severity |
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| BPD I, MRE Depressed,Severe w/o Psychotic Features |
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| BPD II, MRE Depressed |
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| 9-Month (n=408, n=193) |
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| 12-Month (n=403, n=194) |
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| 18-Month (n=223, n=162) |
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| 24-Month (n=233, n=146) |
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| 30-Month (n=224, n=138) |
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| 36-Month (n=245, n=133) |
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| 42-Month (n=245, n=121) |
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| 48-Month (n=246, n=109) |
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| 54-Month (n=222, n=102) |
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| 60-Month (n=250, n=116) |
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| Null Hypothesis: Percentage of responders across groups is the same. Alternate Hypothesis: Percentage of responders across groups is different. | MMRM Least Squares Mean | 17.0 | 2-Sided | 95 | 15.2 | 19.0 | Mixed Model Repeated Measure analysis on MADRS responders (binary variable with 1=yes, 0=no) as the response variable in the model. The covariates are treatment, visit and propensity quintile. This analysis of covariance produced least square means. | No | Superiority or Other |
| Null Hypothesis: Percentage of responders across groups is the same. Alternate Hypothesis: Percentage of responders across groups is different. | ANCOVA | <.0001 | 2-Sided | No | Superiority or Other |
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