Major Depressive Disorder
Conditions
Keywords
Major Depressive Disorder, Treatment-resistant Depression
Brief summary
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
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.
Interventions
None listed
Sponsors
Cyberonics, Inc.
Study design
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Montgomery Asberg Depression Rating Scale (MADRS)% Responders (>/= 50% Improvement From Baseline) | 3-Month Through 60-Month (Post 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Montgomery Asberg Depression Rating Scale (MADRS)% Remitters (MADRS Total Score ≤9 at Visit Month Assessment Post-Baseline) | 3-Month Through 60-Month (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. |
| Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Baseline MADRS Item 10 Suicidal Ideation | 1 Week Pre-Baseline | 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. |
| Time Until Recurrence (TUR) for Patients That Achieved Remission, Based on Montgomery Asberg Depression Rating Scale (MADRS) | 3-Month Through 60-Month (Post Baseline) | 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. |
| Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Intent of Most Recent Suicidal Gesture | Baseline | 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. |
| Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Primary Diagnosis of MDE | Screening | 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. |
| Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Medical Threat to Life of Most Recent Suicidal Gesture | Baseline | 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. |
Countries
United States
Participant flow
Recruitment details
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.
Pre-assignment details
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).
Participants by arm
| Arm | Count |
|---|---|
| VNS Therapy D-23 Original Subjects that entered the TRD Registry without previous VNS Therapy treatment and selected the VNS Therapy study arm. | 335 |
| 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. | 159 |
| 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. | 301 |
| Total | 795 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 7 | 8 |
| Overall Study | Did not Meet (I/E) | 3 | 1 |
| Overall Study | Non-Compliance | 40 | 39 |
| Overall Study | Other (i.e. lost to f/u, site closure) | 86 | 71 |
| Overall Study | Physician Decision | 4 | 7 |
| Overall Study | Withdrawal by Subject | 55 | 37 |
Baseline characteristics
| Characteristic | VNS Therapy D-23 Original | VNS Therapy D-21 Rollover | Treatment as Usual (TAU) | Total |
|---|---|---|---|---|
| Age, Customized Age at Baseline (n=335, n=159, n=301) | 48.9 Years STANDARD_DEVIATION 10.41 | 48.9 Years STANDARD_DEVIATION 9.51 | 49.9 Years STANDARD_DEVIATION 11.07 | 49.3 Years STANDARD_DEVIATION 10.49 |
| Age, Customized Age-Initial Dx. of Depression(n=334,n=159,n=301) | 29.0 Years STANDARD_DEVIATION 10.95 | 28.6 Years STANDARD_DEVIATION 10.5 | 29.5 Years STANDARD_DEVIATION 11.89 | 29.1 Years STANDARD_DEVIATION 11.22 |
| Age, Customized Age-Initial Onset of Depression(n=334,n=159,n=301) | 20.8 Years STANDARD_DEVIATION 12.13 | 21.1 Years STANDARD_DEVIATION 11.11 | 21.1 Years STANDARD_DEVIATION 11.4 | 21.0 Years STANDARD_DEVIATION 11.64 |
| Diagnosis Disorder (Major Depressive Disorder (MDD) or Bipolar Disorder (BPD) BPD II, MRE Depressed | 32 Participants | 15 Participants | 38 Participants | 85 Participants |
| Diagnosis Disorder (Major Depressive Disorder (MDD) or Bipolar Disorder (BPD) BPD I, MRE Depressed, Moderate Severity | 19 Participants | 6 Participants | 21 Participants | 46 Participants |
| Diagnosis Disorder (Major Depressive Disorder (MDD) or Bipolar Disorder (BPD) BPD I, MRE Depressed,Severe w/o Psychotic Features | 46 Participants | 16 Participants | 12 Participants | 74 Participants |
| Diagnosis Disorder (Major Depressive Disorder (MDD) or Bipolar Disorder (BPD) MDD, Recurrent, Moderate Severity | 42 Participants | 21 Participants | 69 Participants | 132 Participants |
| Diagnosis Disorder (Major Depressive Disorder (MDD) or Bipolar Disorder (BPD) MDD, Recurrent, Severe w/o Psychotic Features | 135 Participants | 90 Participants | 95 Participants | 320 Participants |
| Diagnosis Disorder (Major Depressive Disorder (MDD) or Bipolar Disorder (BPD) MDD, Single Episode, Moderate Severity | 12 Participants | 4 Participants | 30 Participants | 46 Participants |
| Diagnosis Disorder (Major Depressive Disorder (MDD) or Bipolar Disorder (BPD) MDD, Single Episode, Severe w/o Psychotic Features | 49 Participants | 7 Participants | 36 Participants | 92 Participants |
| Lifetime Episodes of Depression Diagnosed (n=335, n=0, n=301) | 14.9 Lifetime Episodes of Depression STANDARD_DEVIATION 24.14 | NA Lifetime Episodes of Depression | 12.0 Lifetime Episodes of Depression STANDARD_DEVIATION 23.86 | 13.5 Lifetime Episodes of Depression STANDARD_DEVIATION 24.03 |
| Number of Failed Treatments (n=335, n=159, n=301) | 8.0 Number of Failed Treatments STANDARD_DEVIATION 3.05 | 8.6 Number of Failed Treatments STANDARD_DEVIATION 3.74 | 7.3 Number of Failed Treatments STANDARD_DEVIATION 2.92 | 7.9 Number of Failed Treatments STANDARD_DEVIATION 3.19 |
| Race/Ethnicity, Customized African-American | 4 Participants | 4 Participants | 6 Participants | 14 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Caucasian | 323 Participants | 155 Participants | 274 Participants | 752 Participants |
| Race/Ethnicity, Customized Hispanic | 3 Participants | 0 Participants | 19 Participants | 22 Participants |
| Race/Ethnicity, Customized Other | 3 Participants | 0 Participants | 1 Participants | 4 Participants |
| Sex: Female, Male Female | 231 Participants | 119 Participants | 211 Participants | 561 Participants |
| Sex: Female, Male Male | 104 Participants | 40 Participants | 90 Participants | 234 Participants |
| Suicide Attempts in Lifetime (n=335, n=159, n=301) | 2.1 Number of Suicide Attempts in a Lifetime STANDARD_DEVIATION 4.38 | 1.2 Number of Suicide Attempts in a Lifetime STANDARD_DEVIATION 2.95 | 1.2 Number of Suicide Attempts in a Lifetime STANDARD_DEVIATION 2.41 | 1.6 Number of Suicide Attempts in a Lifetime STANDARD_DEVIATION 3.49 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
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.
Time frame: 3-Month Through 60-Month (Post Baseline)
Population: Intent-To-Treat (ITT) Population: VNS Therapy Population (n=489 (D-23=330 + D-21=159)) + (n= 276) TAU population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VNS Therapy | Montgomery Asberg Depression Rating Scale (MADRS)% Responders (>/= 50% Improvement From Baseline) | 3-Month (n=454, n=249) | 24 Percentage of Participants |
| VNS Therapy | Montgomery Asberg Depression Rating Scale (MADRS)% Responders (>/= 50% Improvement From Baseline) | 6-Month (n=432, n=224) | 28 Percentage of Participants |
| VNS Therapy | Montgomery Asberg Depression Rating Scale (MADRS)% Responders (>/= 50% Improvement From Baseline) | 9-Month (n=408, n=193) | 33.8 Percentage of Participants |
| VNS Therapy | Montgomery Asberg Depression Rating Scale (MADRS)% Responders (>/= 50% Improvement From Baseline) | 12-Month (n=403, n=194) | 38.2 Percentage of Participants |
| VNS Therapy | Montgomery Asberg Depression Rating Scale (MADRS)% Responders (>/= 50% Improvement From Baseline) | 18-Month (n=223, n=162) | 34.1 Percentage of Participants |
| VNS Therapy | Montgomery Asberg Depression Rating Scale (MADRS)% Responders (>/= 50% Improvement From Baseline) | 24-Month (n=233, n=146) | 38.6 Percentage of Participants |
| VNS Therapy | Montgomery Asberg Depression Rating Scale (MADRS)% Responders (>/= 50% Improvement From Baseline) | 30-Month (n=224, n=138) | 34.8 Percentage of Participants |
| VNS Therapy | Montgomery Asberg Depression Rating Scale (MADRS)% Responders (>/= 50% Improvement From Baseline) | 36-Month (n=245, n=133) | 38.8 Percentage of Participants |
| VNS Therapy | Montgomery Asberg Depression Rating Scale (MADRS)% Responders (>/= 50% Improvement From Baseline) | 42-Month (n=245, n=121) | 41.2 Percentage of Participants |
| VNS Therapy | Montgomery Asberg Depression Rating Scale (MADRS)% Responders (>/= 50% Improvement From Baseline) | 48-Month (n=246, n=109) | 46.3 Percentage of Participants |
| VNS Therapy | Montgomery Asberg Depression Rating Scale (MADRS)% Responders (>/= 50% Improvement From Baseline) | 54-Month (n=222, n=102) | 48.2 Percentage of Participants |
| VNS Therapy | Montgomery Asberg Depression Rating Scale (MADRS)% Responders (>/= 50% Improvement From Baseline) | 60-Month (n=250, n=116) | 49.6 Percentage of Participants |
| Treatment As Usual (TAU) | Montgomery Asberg Depression Rating Scale (MADRS)% Responders (>/= 50% Improvement From Baseline) | 54-Month (n=222, n=102) | 27.5 Percentage of Participants |
| Treatment As Usual (TAU) | Montgomery Asberg Depression Rating Scale (MADRS)% Responders (>/= 50% Improvement From Baseline) | 3-Month (n=454, n=249) | 8.8 Percentage of Participants |
| Treatment As Usual (TAU) | Montgomery Asberg Depression Rating Scale (MADRS)% Responders (>/= 50% Improvement From Baseline) | 30-Month (n=224, n=138) | 22.5 Percentage of Participants |
| Treatment As Usual (TAU) | Montgomery Asberg Depression Rating Scale (MADRS)% Responders (>/= 50% Improvement From Baseline) | 6-Month (n=432, n=224) | 13.8 Percentage of Participants |
| Treatment As Usual (TAU) | Montgomery Asberg Depression Rating Scale (MADRS)% Responders (>/= 50% Improvement From Baseline) | 48-Month (n=246, n=109) | 22.0 Percentage of Participants |
| Treatment As Usual (TAU) | Montgomery Asberg Depression Rating Scale (MADRS)% Responders (>/= 50% Improvement From Baseline) | 9-Month (n=408, n=193) | 13.5 Percentage of Participants |
| Treatment As Usual (TAU) | Montgomery Asberg Depression Rating Scale (MADRS)% Responders (>/= 50% Improvement From Baseline) | 36-Month (n=245, n=133) | 17.3 Percentage of Participants |
| Treatment As Usual (TAU) | Montgomery Asberg Depression Rating Scale (MADRS)% Responders (>/= 50% Improvement From Baseline) | 12-Month (n=403, n=194) | 17.5 Percentage of Participants |
| Treatment As Usual (TAU) | Montgomery Asberg Depression Rating Scale (MADRS)% Responders (>/= 50% Improvement From Baseline) | 60-Month (n=250, n=116) | 25.9 Percentage of Participants |
| Treatment As Usual (TAU) | Montgomery Asberg Depression Rating Scale (MADRS)% Responders (>/= 50% Improvement From Baseline) | 18-Month (n=223, n=162) | 15.4 Percentage of Participants |
| Treatment As Usual (TAU) | Montgomery Asberg Depression Rating Scale (MADRS)% Responders (>/= 50% Improvement From Baseline) | 42-Month (n=245, n=121) | 19.0 Percentage of Participants |
| Treatment As Usual (TAU) | Montgomery Asberg Depression Rating Scale (MADRS)% Responders (>/= 50% Improvement From Baseline) | 24-Month (n=233, n=146) | 18.5 Percentage of Participants |
Comparison: Null Hypothesis: Percentage of responders across groups is the same. Alternate Hypothesis: Percentage of responders across groups is different.95% CI: [36.3, 39.9]
Comparison: Null Hypothesis: Percentage of responders across groups is the same. Alternate Hypothesis: Percentage of responders across groups is different.95% CI: [15.2, 19]
Comparison: Null Hypothesis: Percentage of responders across groups is the same. Alternate Hypothesis: Percentage of responders across groups is different.p-value: <0.0001ANCOVA
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.
Time frame: 3-Month Through 60-Month (Post Baseline)
Population: Intent-To-Treat (ITT) Population: VNS Therapy Population (n=489 (D-23=330 + D-21=159)) + (n= 276) TAU population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VNS Therapy | Montgomery Asberg Depression Rating Scale (MADRS)% Remitters (MADRS Total Score ≤9 at Visit Month Assessment Post-Baseline) | 3-Month (n=454, n=249) | 8.6 Percentage of Participants |
| VNS Therapy | Montgomery Asberg Depression Rating Scale (MADRS)% Remitters (MADRS Total Score ≤9 at Visit Month Assessment Post-Baseline) | 6-Month (n=432, n=224) | 15 Percentage of Participants |
| VNS Therapy | Montgomery Asberg Depression Rating Scale (MADRS)% Remitters (MADRS Total Score ≤9 at Visit Month Assessment Post-Baseline) | 9-Month (n=408, n=193) | 16.2 Percentage of Participants |
| VNS Therapy | Montgomery Asberg Depression Rating Scale (MADRS)% Remitters (MADRS Total Score ≤9 at Visit Month Assessment Post-Baseline) | 12-Month (n=403, n=194) | 19.4 Percentage of Participants |
| VNS Therapy | Montgomery Asberg Depression Rating Scale (MADRS)% Remitters (MADRS Total Score ≤9 at Visit Month Assessment Post-Baseline) | 18-Month (n=223, n=162) | 14.3 Percentage of Participants |
| VNS Therapy | Montgomery Asberg Depression Rating Scale (MADRS)% Remitters (MADRS Total Score ≤9 at Visit Month Assessment Post-Baseline) | 24-Month (n=233, n=146) | 21.9 Percentage of Participants |
| VNS Therapy | Montgomery Asberg Depression Rating Scale (MADRS)% Remitters (MADRS Total Score ≤9 at Visit Month Assessment Post-Baseline) | 30-Month (n=224, n=138) | 20.5 Percentage of Participants |
| VNS Therapy | Montgomery Asberg Depression Rating Scale (MADRS)% Remitters (MADRS Total Score ≤9 at Visit Month Assessment Post-Baseline) | 36-Month (n=245, n=133) | 19.2 Percentage of Participants |
| VNS Therapy | Montgomery Asberg Depression Rating Scale (MADRS)% Remitters (MADRS Total Score ≤9 at Visit Month Assessment Post-Baseline) | 42-Month (n=245, n=121) | 24.9 Percentage of Participants |
| VNS Therapy | Montgomery Asberg Depression Rating Scale (MADRS)% Remitters (MADRS Total Score ≤9 at Visit Month Assessment Post-Baseline) | 48-Month (n=246, n=109) | 25.6 Percentage of Participants |
| VNS Therapy | Montgomery Asberg Depression Rating Scale (MADRS)% Remitters (MADRS Total Score ≤9 at Visit Month Assessment Post-Baseline) | 54-Month (n=222, n=102) | 28.4 Percentage of Participants |
| VNS Therapy | Montgomery Asberg Depression Rating Scale (MADRS)% Remitters (MADRS Total Score ≤9 at Visit Month Assessment Post-Baseline) | 60-Month (n=250, n=116) | 27.6 Percentage of Participants |
| Treatment As Usual (TAU) | Montgomery Asberg Depression Rating Scale (MADRS)% Remitters (MADRS Total Score ≤9 at Visit Month Assessment Post-Baseline) | 54-Month (n=222, n=102) | 13.7 Percentage of Participants |
| Treatment As Usual (TAU) | Montgomery Asberg Depression Rating Scale (MADRS)% Remitters (MADRS Total Score ≤9 at Visit Month Assessment Post-Baseline) | 3-Month (n=454, n=249) | 2.8 Percentage of Participants |
| Treatment As Usual (TAU) | Montgomery Asberg Depression Rating Scale (MADRS)% Remitters (MADRS Total Score ≤9 at Visit Month Assessment Post-Baseline) | 30-Month (n=224, n=138) | 12.3 Percentage of Participants |
| Treatment As Usual (TAU) | Montgomery Asberg Depression Rating Scale (MADRS)% Remitters (MADRS Total Score ≤9 at Visit Month Assessment Post-Baseline) | 6-Month (n=432, n=224) | 6.3 Percentage of Participants |
| Treatment As Usual (TAU) | Montgomery Asberg Depression Rating Scale (MADRS)% Remitters (MADRS Total Score ≤9 at Visit Month Assessment Post-Baseline) | 48-Month (n=246, n=109) | 14.7 Percentage of Participants |
| Treatment As Usual (TAU) | Montgomery Asberg Depression Rating Scale (MADRS)% Remitters (MADRS Total Score ≤9 at Visit Month Assessment Post-Baseline) | 9-Month (n=408, n=193) | 5.7 Percentage of Participants |
| Treatment As Usual (TAU) | Montgomery Asberg Depression Rating Scale (MADRS)% Remitters (MADRS Total Score ≤9 at Visit Month Assessment Post-Baseline) | 36-Month (n=245, n=133) | 11.3 Percentage of Participants |
| Treatment As Usual (TAU) | Montgomery Asberg Depression Rating Scale (MADRS)% Remitters (MADRS Total Score ≤9 at Visit Month Assessment Post-Baseline) | 12-Month (n=403, n=194) | 8.2 Percentage of Participants |
| Treatment As Usual (TAU) | Montgomery Asberg Depression Rating Scale (MADRS)% Remitters (MADRS Total Score ≤9 at Visit Month Assessment Post-Baseline) | 60-Month (n=250, n=116) | 19 Percentage of Participants |
| Treatment As Usual (TAU) | Montgomery Asberg Depression Rating Scale (MADRS)% Remitters (MADRS Total Score ≤9 at Visit Month Assessment Post-Baseline) | 18-Month (n=223, n=162) | 7.4 Percentage of Participants |
| Treatment As Usual (TAU) | Montgomery Asberg Depression Rating Scale (MADRS)% Remitters (MADRS Total Score ≤9 at Visit Month Assessment Post-Baseline) | 42-Month (n=245, n=121) | 13.2 Percentage of Participants |
| Treatment As Usual (TAU) | Montgomery Asberg Depression Rating Scale (MADRS)% Remitters (MADRS Total Score ≤9 at Visit Month Assessment Post-Baseline) | 24-Month (n=233, n=146) | 11 Percentage of Participants |
Comparison: Null Hypothesis: Percentage of remitters across groups is the same. Alternate Hypothesis: Percentage of remitters across groups is different.95% CI: [18.4, 21.3]
Comparison: Null Hypothesis: Percentage of remitters across groups is the same. Alternate Hypothesis: Percentage of remitters across groups is different.95% CI: [6.9, 9.5]
Comparison: Null Hypothesis: Percentage of responders across groups is the same. Alternate Hypothesis: Percentage of responders across groups is different.p-value: <0.0001ANCOVA
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.
Time frame: 1 Week Pre-Baseline
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VNS Therapy | Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Baseline MADRS Item 10 Suicidal Ideation | 0 Enjoys Life | 6.03 Percentage of Patients |
| VNS Therapy | Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Baseline MADRS Item 10 Suicidal Ideation | 1 | 28.83 Percentage of Patients |
| VNS Therapy | Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Baseline MADRS Item 10 Suicidal Ideation | 2 Weary of Life | 25.56 Percentage of Patients |
| VNS Therapy | Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Baseline MADRS Item 10 Suicidal Ideation | 3 | 18.87 Percentage of Patients |
| VNS Therapy | Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Baseline MADRS Item 10 Suicidal Ideation | 4 Probably Better Off Dead | 14.81 Percentage of Patients |
| VNS Therapy | Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Baseline MADRS Item 10 Suicidal Ideation | 5 | 4.72 Percentage of Patients |
| VNS Therapy | Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Baseline MADRS Item 10 Suicidal Ideation | 6 Explicit Plans for Suicide | 1.18 Percentage of Patients |
Comparison: The statistical modeling of predictors of suicide attempts and suicidal ideations considered 15 variables, defined in the protocol a priori to determine which ones were predictive of suicide attempts and suicidal ideations. Four variables representing the baseline disease and patient factors were considered predictors of suicidality. This outcome measure presents the underlying data collected and the corresponding correlation coefficient for one of the 4 variables identified.p-value: <0.0001Pearson Correlation Coefficients
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.
Time frame: Baseline
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VNS Therapy | Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Intent of Most Recent Suicidal Gesture | Patient Never Made an Attempt | 46.86 Percentage of Patients |
| VNS Therapy | Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Intent of Most Recent Suicidal Gesture | No Information or Not Sure | 3.80 Percentage of Patients |
| VNS Therapy | Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Intent of Most Recent Suicidal Gesture | Obviously no Intent | 2.31 Percentage of Patients |
| VNS Therapy | Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Intent of Most Recent Suicidal Gesture | Not Sure or Only Minimal Intent | 5.12 Percentage of Patients |
| VNS Therapy | Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Intent of Most Recent Suicidal Gesture | Definite But Very Ambivalent | 11.06 Percentage of Patients |
| VNS Therapy | Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Intent of Most Recent Suicidal Gesture | Serious | 12.05 Percentage of Patients |
| VNS Therapy | Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Intent of Most Recent Suicidal Gesture | Very Serious | 9.57 Percentage of Patients |
| VNS Therapy | Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Intent of Most Recent Suicidal Gesture | Extreme | 9.24 Percentage of Patients |
Comparison: The statistical modeling of predictors of suicide attempts and suicidal ideations considered 15 variables, defined in the protocol a priori to determine which ones were predictive of suicide attempts and suicidal ideations. Four variables representing the baseline disease and patient factors were considered predictors of suicidality. This outcome measure presents the underlying data collected and the corresponding correlation coefficient for one of the 4 variables identified.p-value: <0.0001Pearson Correlation Coefficients
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.
Time frame: Baseline
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VNS Therapy | Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Medical Threat to Life of Most Recent Suicidal Gesture | Patient Never Made an Attempt | 46.70 Percentage of Patients |
| VNS Therapy | Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Medical Threat to Life of Most Recent Suicidal Gesture | No Information or Not Sure | 3.14 Percentage of Patients |
| VNS Therapy | Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Medical Threat to Life of Most Recent Suicidal Gesture | No Danger | 5.61 Percentage of Patients |
| VNS Therapy | Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Medical Threat to Life of Most Recent Suicidal Gesture | Minimal | 3.47 Percentage of Patients |
| VNS Therapy | Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Medical Threat to Life of Most Recent Suicidal Gesture | Mild | 8.91 Percentage of Patients |
| VNS Therapy | Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Medical Threat to Life of Most Recent Suicidal Gesture | Moderate | 18.15 Percentage of Patients |
| VNS Therapy | Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Medical Threat to Life of Most Recent Suicidal Gesture | Severe | 11.39 Percentage of Patients |
| VNS Therapy | Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Medical Threat to Life of Most Recent Suicidal Gesture | Extreme | 2.64 Percentage of Patients |
Comparison: The statistical modeling of predictors of suicide attempts and suicidal ideations considered 15 variables, defined in the protocol a priori to determine which ones were predictive of suicide attempts and suicidal ideations. Four variables representing the baseline disease and patient factors were considered predictors of suicidality. This outcome measure presents the underlying data collected and the corresponding correlation coefficient for one of the 4 variables identified.p-value: <0.0001Pearson Correlation Coefficients
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.
Time frame: Screening
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VNS Therapy | Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Primary Diagnosis of MDE | MDD, Recurrent, Moderate Severity | 16.99 Percentage of Patients |
| VNS Therapy | Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Primary Diagnosis of MDE | MDD, Recurrent, Severe w/o Psychotic Features | 40.39 Percentage of Patients |
| VNS Therapy | Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Primary Diagnosis of MDE | MDD, Single Episode, Moderate Severity | 5.88 Percentage of Patients |
| VNS Therapy | Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Primary Diagnosis of MDE | MDD, Single Episode, Severe w/o Psychotic Features | 11.24 Percentage of Patients |
| VNS Therapy | Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Primary Diagnosis of MDE | BPD I, MRE Depressed, Moderate Severity | 5.75 Percentage of Patients |
| VNS Therapy | Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Primary Diagnosis of MDE | BPD I, MRE Depressed,Severe w/o Psychotic Features | 9.41 Percentage of Patients |
| VNS Therapy | Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Primary Diagnosis of MDE | BPD II, MRE Depressed | 10.33 Percentage of Patients |
Comparison: The statistical modeling of predictors of suicide attempts and suicidal ideations considered 15 variables, defined in the protocol a priori to determine which ones were predictive of suicide attempts and suicidal ideations. Four variables representing the baseline disease and patient factors were considered predictors of suicidality. This outcome measure presents the underlying data collected and the corresponding correlation coefficient for one of the 4 variables identified.p-value: 0.0012Pearson Correlation Coefficients
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 \</=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.
Time frame: 3-Month Through 60-Month (Post Baseline)
Population: Intent-To-Treat (ITT) Population: VNS Therapy Population (n=489 (D-23=330 + D-21=159)) + (n= 276) TAU population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| VNS Therapy | Time Until Recurrence (TUR) for Patients That Achieved Remission, Based on Montgomery Asberg Depression Rating Scale (MADRS) | 1st Quartile (25%);Time (Mo.) Until Recurrence | 14 Months |
| VNS Therapy | Time Until Recurrence (TUR) for Patients That Achieved Remission, Based on Montgomery Asberg Depression Rating Scale (MADRS) | Kaplan-Meier Median;Time (Mo.) Until Recurrence | 40 Months |
| Treatment As Usual (TAU) | Time Until Recurrence (TUR) for Patients That Achieved Remission, Based on Montgomery Asberg Depression Rating Scale (MADRS) | 1st Quartile (25%);Time (Mo.) Until Recurrence | 9 Months |
| Treatment As Usual (TAU) | Time Until Recurrence (TUR) for Patients That Achieved Remission, Based on Montgomery Asberg Depression Rating Scale (MADRS) | Kaplan-Meier Median;Time (Mo.) Until Recurrence | 19 Months |
p-value: 0.1015Log Rank
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.
Time frame: 3-Month Through 60-Month (Post Baseline)
Population: Safety Population (SP): VNS Therapy Population (n=494 (D-23=335 + D-21=159)) + (n= 301) TAU population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VNS Therapy | Mortality and Suicidality in Safety Population (All-Cause Mortality/1000 Person Years) | 3.53 Deaths Per 1000 Person Years |
| Treatment As Usual (TAU) | Mortality and Suicidality in Safety Population (All-Cause Mortality/1000 Person Years) | 8.63 Deaths Per 1000 Person Years |
Post Hoc
Mortality and Suicidality in Safety Population (Number of Suicides)
The number suicides on the study were collected from the baseline visit.
Time frame: 3-Month Through 60-Month (Post Baseline)
Population: Safety Population (SP): VNS Therapy Population (n=494 (D-23=335 + D-21=159)) + (n= 301) TAU population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VNS Therapy | Mortality and Suicidality in Safety Population (Number of Suicides) | 2 Number of Suicides |
| Treatment As Usual (TAU) | Mortality and Suicidality in Safety Population (Number of Suicides) | 2 Number of Suicides |
Post Hoc
Mortality and Suicidality in Safety Population (Suicides/1000 Person Years)
The number of suicides per calculated 1000 person years.
Time frame: 3-Month Through 60-Month (Post Baseline)
Population: Safety Population (SP): VNS Therapy Population (n=494 (D-23=335 + D-21=159)) + (n= 301) TAU population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VNS Therapy | Mortality and Suicidality in Safety Population (Suicides/1000 Person Years) | 1.01 Number of Suicides Per 1000 Person Years |
| Treatment As Usual (TAU) | Mortality and Suicidality in Safety Population (Suicides/1000 Person Years) | 2.20 Number of Suicides Per 1000 Person Years |
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.
Time frame: 3-Month (baseline or implantation) Through 60-Month (Post Baseline)
Population: Safety Population (SP): VNS Therapy Population (n=494 (D-23=335 + D-21=159)) + (n= 301) TAU population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VNS Therapy | Mortality and Suicidality in Safety Population (Total Number of Deaths) | 7 Number of Deaths |
| Treatment As Usual (TAU) | Mortality and Suicidality in Safety Population (Total Number of Deaths) | 8 Number of Deaths |
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.
Time frame: 3-Month Through 60-Month (Post Baseline)
Population: Safety Population (SP): VNS Therapy Population (n=494 (D-23=335 + D-21=159)) + (n= 301) TAU population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VNS Therapy | Mortality and Suicidality in Safety Population (Total Patient Years Exposed) | 1985.083 Exposure Per 1000 Patient Years |
| Treatment As Usual (TAU) | Mortality and Suicidality in Safety Population (Total Patient Years Exposed) | 926.493 Exposure Per 1000 Patient Years |
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).
Time frame: 3-Month Through 60-Month (Post Baseline)
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VNS Therapy | Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Change From Baseline by Visit Month | 3 Months (n=322, n=261) | 7.92 units on a scale | Standard Deviation 16.2 |
| VNS Therapy | Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Change From Baseline by Visit Month | 6 Months (n=298, n=239) | 9.11 units on a scale | Standard Deviation 15.66 |
| VNS Therapy | Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Change From Baseline by Visit Month | 9 Months (n=270, n=216) | 10.50 units on a scale | Standard Deviation 16.74 |
| VNS Therapy | Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Change From Baseline by Visit Month | 12 Months (n=266, n=211) | 11.04 units on a scale | Standard Deviation 18.36 |
| VNS Therapy | Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Change From Baseline by Visit Month | 18 Months (n=264, n=179) | 11.40 units on a scale | Standard Deviation 18.29 |
| VNS Therapy | Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Change From Baseline by Visit Month | 24 Months (n=240, n=159) | 13.15 units on a scale | Standard Deviation 18.13 |
| VNS Therapy | Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Change From Baseline by Visit Month | 30 Months (n=223, n=147) | 13.06 units on a scale | Standard Deviation 18.63 |
| VNS Therapy | Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Change From Baseline by Visit Month | 36 Months (n=219, n=149) | 15.59 units on a scale | Standard Deviation 18.43 |
| VNS Therapy | Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Change From Baseline by Visit Month | 42 Months (n=196, n=141) | 14.67 units on a scale | Standard Deviation 17.46 |
| VNS Therapy | Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Change From Baseline by Visit Month | 48 Months (n=179, n=127) | 14.70 units on a scale | Standard Deviation 19.02 |
| VNS Therapy | Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Change From Baseline by Visit Month | 54 Months (n=156, n=128) | 16.44 units on a scale | Standard Deviation 18.63 |
| VNS Therapy | Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Change From Baseline by Visit Month | 60 Months (n=173, n=136) | 17.20 units on a scale | Standard Deviation 17.59 |
| Treatment As Usual (TAU) | Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Change From Baseline by Visit Month | 54 Months (n=156, n=128) | 10.49 units on a scale | Standard Deviation 16.74 |
| Treatment As Usual (TAU) | Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Change From Baseline by Visit Month | 3 Months (n=322, n=261) | 1.38 units on a scale | Standard Deviation 16.61 |
| Treatment As Usual (TAU) | Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Change From Baseline by Visit Month | 30 Months (n=223, n=147) | 8.13 units on a scale | Standard Deviation 16.73 |
| Treatment As Usual (TAU) | Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Change From Baseline by Visit Month | 6 Months (n=298, n=239) | 4.36 units on a scale | Standard Deviation 17.46 |
| Treatment As Usual (TAU) | Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Change From Baseline by Visit Month | 48 Months (n=179, n=127) | 9.88 units on a scale | Standard Deviation 17.28 |
| Treatment As Usual (TAU) | Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Change From Baseline by Visit Month | 9 Months (n=270, n=216) | 3.97 units on a scale | Standard Deviation 17.07 |
| Treatment As Usual (TAU) | Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Change From Baseline by Visit Month | 36 Months (n=219, n=149) | 8.34 units on a scale | Standard Deviation 16.11 |
| Treatment As Usual (TAU) | Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Change From Baseline by Visit Month | 12 Months (n=266, n=211) | 5.49 units on a scale | Standard Deviation 17.56 |
| Treatment As Usual (TAU) | Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Change From Baseline by Visit Month | 60 Months (n=173, n=136) | 10.11 units on a scale | Standard Deviation 17.93 |
| Treatment As Usual (TAU) | Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Change From Baseline by Visit Month | 18 Months (n=264, n=179) | 3.88 units on a scale | Standard Deviation 16.03 |
| Treatment As Usual (TAU) | Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Change From Baseline by Visit Month | 42 Months (n=196, n=141) | 8.55 units on a scale | Standard Deviation 17.95 |
| Treatment As Usual (TAU) | Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Change From Baseline by Visit Month | 24 Months (n=240, n=159) | 7.50 units on a scale | Standard Deviation 16.73 |
Comparison: 3 Month Time pointp-value: <0.0001F-Test
Comparison: 6 Month Time pointp-value: 0.0068F-Test
Comparison: 9 Month Time pointp-value: 0.0008F-Test
Comparison: 12 Month Time pointp-value: 0.0003F-Test
Comparison: 18 Month Time pointp-value: <0.0001F-Test
Comparison: 24 Month Time pointp-value: 0.0059F-Test
Comparison: 30 Month Time pointp-value: 0.0028F-Test
Comparison: 36 Month Time pointp-value: 0.0002F-Test
Comparison: 42 Month Time pointp-value: 0.0051F-Test
Comparison: 48 Month Time pointp-value: 0.0363F-Test
Comparison: 54 Month Time pointp-value: 0.0048F-Test
Comparison: 60 Month Time pointp-value: 0.0009F-Test
Comparison: Null Hypothesis: Difference between change from baseline value of two treatment groups equals zero.~Alternate Hypothesis: Difference between change from baseline value of two treatment groups is not equal to zero.95% CI: [10.8979, 13.3039]
Comparison: Null Hypothesis: Difference between change from baseline value of two treatment groups equals zero.~Alternate Hypothesis: Difference between change from baseline value of two treatment groups is not equal to zero.95% CI: [6.1327, 9.0602]
Comparison: Null Hypothesis: Difference between change from baseline value of two treatment groups equals zero.~Alternate Hypothesis: Difference between change from baseline value of two treatment groups is not equal to zero.p-value: <0.0001ANCOVA