Treatment-Resistant Depression Registry

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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.

Conditions
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Major Depressive Disorder

Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1. 500 VNS Patients<br>VNS Patients - Treatment-resistant depression patients treated with VNS Therapy. | |
| 2. 300 Non-VNS Patients<br>Non-VNS Patients - Treatment-resistant depression patients not receiving VNS Therapy. | |

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Major Depressive Disorder, Treatment-resistant Depression