Depression
Conditions
Keywords
Depression, Chronic Depression, Bipolar Disorder
Brief summary
This is a postmarket medical device study. The objective of this study is to compare the safety and effectiveness of Vagus Nerve Stimulation (VNS) Therapy administered at different amounts of electrical charge for the treatment of patients with treatment-resistant depression (TRD).
Detailed description
This is a postmarket medical device study. This study will examine treatment outcomes for patients with TRD who are randomized to VNS Therapy administered at different amounts of electrical charge. The Sponsor, Cyberonics, provides funding for this study. Patients are followed for 54 weeks, 50 of those weeks are following implantation of the VNS Therapy system. No study sites will be permitted to enroll study subjects until Institutional Review Board (IRB) approval has been received. Sites are permitted to be approved by a local or a central IRB.
Interventions
DEVICEVNS Therapy
Received output current of 0.25 milliamps (mA)
Sponsors
Cyberonics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient has a diagnosis of chronic or recurrent depression and is currently experiencing a major depressive episode. * Patient has not had an adequate response to four or more adequate antidepressant treatments from at least two different antidepressant treatment categories. * Patient has (in the investigator's judgment) sufficient impairment from his/her depression and/or depression treatment that the potential benefits/risks of VNS Therapy are warranted. * Patient must currently be receiving at least one antidepressant treatment; the patient must be receiving all current antidepressant treatments in a stable regimen. * If the patient has a current diagnosis of bipolar disorder, the patient must be receiving a mood stabilizer. * Patient must be 18 years of age or older and of legal age of consent. * Patient must be able to complete the evaluations specified in the study procedures flow chart. * Patient must provide written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization.
Exclusion criteria
* Patient has had a bilateral or left cervical vagotomy. * Patient currently uses, or is expected to use during the study, short-wave diathermy, microwave diathermy, or therapeutic ultrasound diathermy. * A VNS Therapy System implant would pose an unacceptable surgical or medical risk for the patient. * Patient is expected to require full body magnetic resonance imaging during the clinical study. * Patient is acutely suicidal. * Patient has a history of schizophrenia, schizoaffective disorder, or other psychotic disorder or a current major depressive episode that includes psychotic features (commonly referred to as psychotic depression). * Patient has a history of rapid cycling bipolar disorder or a current diagnosis of bipolar disorder mixed phase. * Patient has a history of borderline personality disorder. * Patient has a history of drug or alcohol dependence within the 12 months prior to the baseline visit or currently takes a narcotic drug five or more days per week. * Patient is currently enrolled in another investigational study. * Patient has had a prior VNS Therapy System implant. Note: Some IRBs may require additional conditions for enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Mean Change From Baseline to Week 22 of the Acute Phase (ITT Population). | From Baseline to Study Week 22 | The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Percent Remitters From Baseline to Week 22 of the Acute Phase (ITT Population). | From baseline to Study Week 22 | The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-C percent of remitters at week 22. Remission was defined as a score of less than or equal to 14 on the IDS-C. |
| Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Percent Responders From Baseline to Week 50 of the Long-term Phase (ITT Population). | From baseline to Study Week 50 | The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-C percent of responders at week 50. Response was defined as greater than or equal to 50% improvement from baseline. |
| Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Percent Sustained Responders at Study Week 50 (ITT Population). | From baseline to Study Week 50 | The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. Sustained Response is defined as the percentage of Acute Phase responders (week 22) who were also responders at the end of the Long-term (week 50) phase. An analysis of sustained response was performed using the IDS-C to evaluate the long-term durability of the improvements in depression scores observed with adjunctive VNS Therapy. |
| Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Percent Remitters From Baseline to Week 50 of the Long-term Phase (ITT Population). | From baseline to Study Week 50 | The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-C percent of remitters at week 50. Remission was defined as a score of less than or equal to 14 on the IDS-C. |
| Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Percent Responders From Baseline to Week 22 of the Acute Phase (ITT Population). | From baseline to Study Week 22 | The 16-item Inventory of Depressive Symptomatology (QIDS) (Rush et al. 2003) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 27. Higher values are considered to be worse outcomes. The QIDS-C percent of responders at week 22. Response was defined as greater than or equal to 50% improvement from baseline. |
| Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Percent Remitters From Baseline to Week 22 of the Acute Phase (ITT Population). | From baseline to Study Week 22 | The 16-item Inventory of Depressive Symptomatology (QIDS) (Rush et al. 2003) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 27. Higher values are considered to be worse outcomes. The QIDS-C percent of remitters at week 22. Remission was defined as a score of less than or equal to 5 on the QIDS-C. |
| Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Percent Responders From Baseline to Week 50 of the Long-term Phase (ITT Population). | From baseline to Study Week 50 | The 16-item Inventory of Depressive Symptomatology (QIDS) (Rush et al. 2003) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 27. Higher values are considered to be worse outcomes. The QIDS-C percent of responders at week 50. Response was defined as greater than or equal to 50% improvement from baseline. |
| Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Percent Remitters From Baseline to Week 50 of the Long-term Phase (ITT Population). | From baseline to Study Week 50 | The 16-item Inventory of Depressive Symptomatology (QIDS) (Rush et al. 2003) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 27. Higher values are considered to be worse outcomes. The QIDS-C percent of remitters at week 50. Remission was defined as a score of less than or equal to 5 on the QIDS-C. |
| Montgomery-Asberg Depression Rating Scale (MADRS) Percent Responders From Baseline to Week 22 of the Acute Phase (ITT Population). | From baseline to Study Week 22 | The 10-item Montgomery-Asberg Scale (Montgomery and Asberg 1979) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 60. Higher values are considered to be worse outcomes. The MADRS percent of responders at week 22. Response was defined as greater than or equal to 50% improvement from baseline. |
| Montgomery-Asberg Depression Rating Scale (MADRS) Percent Remitters From Baseline to Week 22 of the Acute Phase (ITT Population). | From baseline to Study Week 22 | The 10-item Montgomery-Asberg Scale (Montgomery and Asberg 1979) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 60. Higher values are considered to be worse outcomes. The MADRS percent of remitters at week 22. Remission was defined as a score of less than or equal to 9 on the MADRS. |
| Montgomery-Asberg Depression Rating Scale (MADRS) Percent Responders From Baseline to Week 50 of the Long-term Phase (ITT Population). | From baseline to Study Week 50 | The 10-item Montgomery-Asberg Scale (Montgomery and Asberg 1979) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 60. Higher values are considered to be worse outcomes. The MADRS percent of responders at week 50. Response was defined as greater than or equal to 50% improvement from baseline. |
| Montgomery-Asberg Depression Rating Scale (MADRS) Percent Sustained Responders at Study Week 50 (ITT Population). | From Baseline to Study Week 50 | The 10-item Montgomery-Asberg Scale (Montgomery and Asberg 1979) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 60. Higher values are considered to be worse outcomes. Sustained Response is defined as the percentage of Acute Phase responders (week 22) who were also responders at the end of the Long-term (week 50) phase. An analysis of sustained response was performed using the MADRS to evaluate the long-term durability of the improvements in depression scores observed with adjunctive VNS Therapy. |
| Montgomery-Asberg Depression Rating Scale (MADRS) Percent Remitters From Baseline to Week 50 of the Long-term Phase (ITT Population). | From baseline to Study Week 50 | The 10-item Montgomery-Asberg Scale (Montgomery and Asberg 1979) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 60. Higher values are considered to be worse outcomes. The MADRS percent of remitters at week 50. Remission was defined as a score of less than or equal to 9 on the MADRS. |
| Clinical Global Impressions Improvement Scale (CGI-I) Percent Response at Week 22 of the Acute Phase (ITT Population) | At Study Week 22 | Originally, the Clinical Global Impressions-Improvement (CGI-I) (Guy W 1976)was designed as a 7-item scale used to assess how much the patient's illness had improved or worsened relative to a baseline state at the beginning of the intervention.(1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse.) In this study, the CGI-I was categorized into just two groups. A value of 1 (considered a response) was assigned for very much improved (at least 85% improvement) & much improved (at least 60% improvement). A value of 0 (considered non-response) was assigned for: minimally improved (at least 20-25% improvement), no change (between ±15% change), minimally worse (at least 20-55% worse), much worse (at least 60% worse), and very much worse (at least 80% worse). No score was assigned if the investigator did not provide a categorical rating at a particular follow-up visit. |
| Clinical Global Impressions Improvement Scale (CGI-I) Percent Response at Week 50 of the Long-term Phase (ITT Population). | At Study Week 50 | Originally, the Clinical Global Impressions-Improvement (CGI-I) (Guy W 1976)was designed as a 7-item scale used to assess how much the patient's illness had improved or worsened relative to a baseline state at the beginning of the intervention.(1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse.) In this study, the CGI-I was categorized into just two groups. A value of 1 (considered a response) was assigned for very much improved (at least 85% improvement) & much improved (at least 60% improvement). A value of 0 (considered non-response) was assigned for: minimally improved (at least 20-25% improvement), no change (between ±15% change), minimally worse (at least 20-55% worse), much worse (at least 60% worse), and very much worse (at least 80% worse). No score was assigned if the investigator did not provide a categorical rating at a particular follow-up visit. |
| Inventory of Depressive Symptomatology Self-Report (IDS-SR) Percent Responders From Baseline to Week 22 of the Acute Phase (ITT Population). | From baseline to Study Week 22 | The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-SR percent of responders at week 22. Response was defined as greater than or equal to 50% improvement from baseline. |
| Inventory of Depressive Symptomatology Self-Report (IDS-SR) Percent Remitters From Baseline to Week 22 of the Acute Phase (ITT Population). | From baseline to Study Week 22 | The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-SR percent of remitters at week 22. Remission was defined as a score of less than or equal to 14 on the IDS-C. |
| Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Percent Responders From Baseline to Week 22 of the Acute Phase (ITT Population). | From baseline to Study Week 22 | The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-C percent of responders at week 22. Response was defined as greater than or equal to 50% improvement from baseline. |
| Inventory of Depressive Symptomatology Self-Report (IDS-SR) Percent Responders From Baseline to Week 50 of the Long-term Phase (ITT Population). | From baseline to Study Week 50 | The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-SR percent of responders at week 50. Response was defined as greater than or equal to 50% improvement from baseline. |
| Inventory of Depressive Symptomatology Self-Report (IDS-SR) Percent Remitters From Baseline to Week 50 of the Long-term Phase (ITT Population). | From baseline to Study Week 50 | The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-SR percent of remitters at week 50. Remission was defined as a score of less than or equal to 14 on the IDS-C. |
| Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Mean Change From Baseline to Week 50 of the Long-term Phase (ITT Population). | From baseline to Study Week 50 | The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-C mean change at week 50 |
| Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Mean Percent Change From Baseline to Week 50 of the Long-term Phase (ITT Population). | From baseline to Study Week 50 | The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-C mean percent change at week 50 |
| Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Mean Change From Baseline to Week 22 of the Acute Phase (ITT Population). | From baseline to Study Week 22 | The 16-item Inventory of Depressive Symptomatology (QIDS) (Rush et al. 2003) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 27. Higher values are considered to be worse outcomes. The QIDS-C mean change at week 22 |
| Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Mean Percent Change From Baseline to Week 22 of the Acute Phase (ITT Population). | From baseline to Study Week 22 | The 16-item Inventory of Depressive Symptomatology (QIDS) (Rush et al. 2003) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 27. Higher values are considered to be worse outcomes. The QIDS-C mean percent change at week 22 |
| Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Mean Change From Baseline to Week 50 of the Long-term Phase (ITT Population). | From baseline to Study Week 50 | The 16-item Inventory of Depressive Symptomatology (QIDS) (Rush et al. 2003) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 27. Higher values are considered to be worse outcomes. The QIDS-C mean change at week 50 |
| Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Mean Percent Change From Baseline to Week 50 of the Long-term Phase (ITT Population). | From baseline to Study Week 50 | The 16-item Inventory of Depressive Symptomatology (QIDS) (Rush et al. 2003) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 27. Higher values are considered to be worse outcomes. The QIDS-C mean percent change at week 50 |
| Montgomery-Asberg Depression Rating Scale (MADRS) Mean Change From Baseline to Week 22 of the Acute Phase (ITT Population). | From baseline to Study Week 22 | The 10-item Montgomery-Asberg Scale (Montgomery and Asberg 1979) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 60. Higher values are considered to be worse outcomes. The MADRS mean change at week 22 |
| Montgomery-Asberg Depression Rating Scale (MADRS) Mean Percent Change From Baseline to Week 22 of the Acute Phase (ITT Population). | From baseline to Study Week 22 | The 10-item Montgomery-Asberg Scale (Montgomery and Asberg 1979) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 60. Higher values are considered to be worse outcomes. The MADRS mean percent change at week 22 |
| Montgomery-Asberg Depression Rating Scale (MADRS) Mean Change From Baseline to Week 50 of the Long-term Phase (ITT Population). | From baseline to Study Week 50 | The 10-item Montgomery-Asberg Scale (Montgomery and Asberg 1979) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 60. Higher values are considered to be worse outcomes. The MADRS mean change at week 50 |
| Montgomery-Asberg Depression Rating Scale (MADRS) Mean Percent Change From Baseline to Week 50 of the Long-term Phase (ITT Population). | From baseline to Study Week 50 | The 10-item Montgomery-Asberg Scale (Montgomery and Asberg 1979) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 60. Higher values are considered to be worse outcomes. The MADRS mean percent change at week 50 |
| Inventory of Depressive Symptomatology Self-Report (IDS-SR) Mean Change From Baseline to Week 22 of the Acute Phase (ITT Population). | From baseline to Study Week 22 | The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-SR mean change at week 22 |
| Inventory of Depressive Symptomatology Self-Report (IDS-SR) Mean Percent Change From Baseline to Week 22 of the Acute Phase (ITT Population). | From baseline to Study Week 22 | The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-SR mean percent change at week 22 |
| Inventory of Depressive Symptomatology Self-Report (IDS-SR) Mean Change From Baseline to Week 50 of the Long-term Phase (ITT Population). | From baseline to Study Week 50 | The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-SR mean change at week 50 |
| Inventory of Depressive Symptomatology Self-Report (IDS-SR) Mean Percent Change From Baseline to Week 50 of the Long-term Phase (ITT Population). | From baseline to Study Week 50 | The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-SR mean percent change at week 50 |
| Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Mean Percent Change From Baseline to Week 22 of the Acute Phase (ITT Population). | From baseline to Study Week 22 | The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-C mean percent change at week 22 |
Countries
United States
Participant flow
Pre-assignment details
A total of 331 subjects at 29 sites were actually enrolled and implanted with the Vagus Nerve Stimulation (VNS) Therapy System, and were included in the safety dataset. Twenty-one subjects were excluded from the intent-to-treat (ITT) dataset, leaving 310 in the ITT population.
Participants by arm
| Arm | Count |
|---|---|
| Low Dose Received output current 0.25 mA | 102 |
| Medium Dose Received output current 0.5-1.0 mA | 101 |
| High Dose Received output current 1.0-1.5 mA | 107 |
| Total | 310 |
Baseline characteristics
| Characteristic | Total | High Dose | Medium Dose | Low Dose |
|---|---|---|---|---|
| Age, Continuous | 47.9 years STANDARD_DEVIATION 10.8 | 47.4 years STANDARD_DEVIATION 10.8 | 47.2 years STANDARD_DEVIATION 11 | 49.1 years STANDARD_DEVIATION 10.5 |
| Duration of Illness | 27.7 Years STANDARD_DEVIATION 11.8 | 27.0 Years STANDARD_DEVIATION 12.1 | 26.3 Years STANDARD_DEVIATION 10.9 | 29.8 Years STANDARD_DEVIATION 12.1 |
| Length of Current Major Depressive Episode | 108.1 Months STANDARD_DEVIATION 126.5 | 111.3 Months STANDARD_DEVIATION 146.3 | 106.1 Months STANDARD_DEVIATION 107.3 | 106.7 Months STANDARD_DEVIATION 122.8 |
| Lifetime Episodes of Depression 0-2 Episodes | 61 participants | 28 participants | 17 participants | 16 participants |
| Lifetime Episodes of Depression >10 Episodes | 135 participants | 39 participants | 46 participants | 50 participants |
| Lifetime Episodes of Depression 3-5 Episodes | 66 participants | 22 participants | 21 participants | 23 participants |
| Lifetime Episodes of Depression 6-10 Episodes | 47 participants | 18 participants | 16 participants | 13 participants |
| Race/Ethnicity, Customized African-American | 8 participants | 3 participants | 3 participants | 2 participants |
| Race/Ethnicity, Customized Asian | 4 participants | 0 participants | 1 participants | 3 participants |
| Race/Ethnicity, Customized Caucasian | 297 participants | 104 participants | 96 participants | 97 participants |
| Race/Ethnicity, Customized Hispanic | 1 participants | 0 participants | 1 participants | 0 participants |
| Region of Enrollment United States | 310 participants | 107 participants | 101 participants | 102 participants |
| Sex: Female, Male Female | 210 Participants | 73 Participants | 69 Participants | 68 Participants |
| Sex: Female, Male Male | 100 Participants | 34 Participants | 32 Participants | 34 Participants |
| Unipolar or Bipolar Depression Bipolar Depression | 66 participants | 26 participants | 20 participants | 20 participants |
| Unipolar or Bipolar Depression Unipolar Depression (Recurrent) | 213 participants | 66 participants | 71 participants | 76 participants |
| Unipolar or Bipolar Depression Unipolar Depression (Single Episode) | 31 participants | 15 participants | 10 participants | 6 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 103 / 111 | 104 / 107 | 111 / 113 |
| serious Total, serious adverse events | 31 / 111 | 19 / 107 | 16 / 113 |
Outcome results
Primary
Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Mean Change From Baseline to Week 22 of the Acute Phase (ITT Population).
The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes.
Time frame: From Baseline to Study Week 22
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Low Dose | Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Mean Change From Baseline to Week 22 of the Acute Phase (ITT Population). | -9.96 units on a scale | Standard Error 0.99 |
| Medium Dose | Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Mean Change From Baseline to Week 22 of the Acute Phase (ITT Population). | -10.29 units on a scale | Standard Error 1 |
| High Dose | Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Mean Change From Baseline to Week 22 of the Acute Phase (ITT Population). | -10.30 units on a scale | Standard Error 0.97 |
Comparison: The primary analysis consisted of contrasts comparing High Dose vs. Low Dose and Medium Dose vs. Low Dose averaged over the 4 Acute Phase visits using the Hochberg approach to adjust for multiplicity. If both comparisons involving the Low Dose were significant, then a test of High Dose vs. Medium Dose was evaluated at the P≤0.05 level. The pivotal analysis was performed on the ITT population using the last-observation-carried-forward (LOCF) approach to impute missing data.p-value: 0.80395% CI: [-2.34, 3.02]Mixed Models Analysis
Comparison: The primary analysis consisted of contrasts comparing High Dose vs. Low Dose and Medium Dose vs. Low Dose averaged over the 4 Acute Phase visits using the Hochberg approach to adjust for multiplicity. If both comparisons involving the Low Dose were significant, then a test of High Dose vs. Medium Dose was evaluated at the P≤0.05 level. The pivotal analysis was performed on the ITT population using the last-observation-carried-forward (LOCF) approach to impute missing data.p-value: 0.81395% CI: [-2.39, 3.05]Mixed Models Analysis
Secondary
Clinical Global Impressions Improvement Scale (CGI-I) Percent Response at Week 22 of the Acute Phase (ITT Population)
Originally, the Clinical Global Impressions-Improvement (CGI-I) (Guy W 1976)was designed as a 7-item scale used to assess how much the patient's illness had improved or worsened relative to a baseline state at the beginning of the intervention.(1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse.) In this study, the CGI-I was categorized into just two groups. A value of 1 (considered a response) was assigned for very much improved (at least 85% improvement) & much improved (at least 60% improvement). A value of 0 (considered non-response) was assigned for: minimally improved (at least 20-25% improvement), no change (between ±15% change), minimally worse (at least 20-55% worse), much worse (at least 60% worse), and very much worse (at least 80% worse). No score was assigned if the investigator did not provide a categorical rating at a particular follow-up visit.
Time frame: At Study Week 22
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Dose | Clinical Global Impressions Improvement Scale (CGI-I) Percent Response at Week 22 of the Acute Phase (ITT Population) | 20.6 percentage of participants |
| Medium Dose | Clinical Global Impressions Improvement Scale (CGI-I) Percent Response at Week 22 of the Acute Phase (ITT Population) | 28.1 percentage of participants |
| High Dose | Clinical Global Impressions Improvement Scale (CGI-I) Percent Response at Week 22 of the Acute Phase (ITT Population) | 31.4 percentage of participants |
Secondary
Clinical Global Impressions Improvement Scale (CGI-I) Percent Response at Week 50 of the Long-term Phase (ITT Population).
Originally, the Clinical Global Impressions-Improvement (CGI-I) (Guy W 1976)was designed as a 7-item scale used to assess how much the patient's illness had improved or worsened relative to a baseline state at the beginning of the intervention.(1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse.) In this study, the CGI-I was categorized into just two groups. A value of 1 (considered a response) was assigned for very much improved (at least 85% improvement) & much improved (at least 60% improvement). A value of 0 (considered non-response) was assigned for: minimally improved (at least 20-25% improvement), no change (between ±15% change), minimally worse (at least 20-55% worse), much worse (at least 60% worse), and very much worse (at least 80% worse). No score was assigned if the investigator did not provide a categorical rating at a particular follow-up visit.
Time frame: At Study Week 50
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Dose | Clinical Global Impressions Improvement Scale (CGI-I) Percent Response at Week 50 of the Long-term Phase (ITT Population). | 41.6 percentage of participants |
| Medium Dose | Clinical Global Impressions Improvement Scale (CGI-I) Percent Response at Week 50 of the Long-term Phase (ITT Population). | 53.3 percentage of participants |
| High Dose | Clinical Global Impressions Improvement Scale (CGI-I) Percent Response at Week 50 of the Long-term Phase (ITT Population). | 48.0 percentage of participants |
Secondary
Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Mean Change From Baseline to Week 50 of the Long-term Phase (ITT Population).
The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-C mean change at week 50
Time frame: From baseline to Study Week 50
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose | Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Mean Change From Baseline to Week 50 of the Long-term Phase (ITT Population). | -16.9 units on a scale | Standard Deviation 13.9 |
| Medium Dose | Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Mean Change From Baseline to Week 50 of the Long-term Phase (ITT Population). | -17.0 units on a scale | Standard Deviation 14.6 |
| High Dose | Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Mean Change From Baseline to Week 50 of the Long-term Phase (ITT Population). | -15.3 units on a scale | Standard Deviation 12.9 |
Secondary
Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Mean Percent Change From Baseline to Week 22 of the Acute Phase (ITT Population).
The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-C mean percent change at week 22
Time frame: From baseline to Study Week 22
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose | Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Mean Percent Change From Baseline to Week 22 of the Acute Phase (ITT Population). | -22.3 mean percent change | Standard Deviation 25.3 |
| Medium Dose | Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Mean Percent Change From Baseline to Week 22 of the Acute Phase (ITT Population). | -24.9 mean percent change | Standard Deviation 28.9 |
| High Dose | Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Mean Percent Change From Baseline to Week 22 of the Acute Phase (ITT Population). | -25.4 mean percent change | Standard Deviation 31.4 |
Secondary
Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Mean Percent Change From Baseline to Week 50 of the Long-term Phase (ITT Population).
The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-C mean percent change at week 50
Time frame: From baseline to Study Week 50
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose | Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Mean Percent Change From Baseline to Week 50 of the Long-term Phase (ITT Population). | -36.6 mean percent change | Standard Deviation 28.8 |
| Medium Dose | Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Mean Percent Change From Baseline to Week 50 of the Long-term Phase (ITT Population). | -36.5 mean percent change | Standard Deviation 32.5 |
| High Dose | Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Mean Percent Change From Baseline to Week 50 of the Long-term Phase (ITT Population). | -34.6 mean percent change | Standard Deviation 30.7 |
Secondary
Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Percent Remitters From Baseline to Week 22 of the Acute Phase (ITT Population).
The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-C percent of remitters at week 22. Remission was defined as a score of less than or equal to 14 on the IDS-C.
Time frame: From baseline to Study Week 22
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Dose | Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Percent Remitters From Baseline to Week 22 of the Acute Phase (ITT Population). | 6.2 percentage of participants |
| Medium Dose | Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Percent Remitters From Baseline to Week 22 of the Acute Phase (ITT Population). | 9.3 percentage of participants |
| High Dose | Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Percent Remitters From Baseline to Week 22 of the Acute Phase (ITT Population). | 11.4 percentage of participants |
Secondary
Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Percent Remitters From Baseline to Week 50 of the Long-term Phase (ITT Population).
The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-C percent of remitters at week 50. Remission was defined as a score of less than or equal to 14 on the IDS-C.
Time frame: From baseline to Study Week 50
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Dose | Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Percent Remitters From Baseline to Week 50 of the Long-term Phase (ITT Population). | 14.6 percentage of participants |
| Medium Dose | Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Percent Remitters From Baseline to Week 50 of the Long-term Phase (ITT Population). | 15.6 percentage of participants |
| High Dose | Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Percent Remitters From Baseline to Week 50 of the Long-term Phase (ITT Population). | 17.6 percentage of participants |
Secondary
Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Percent Responders From Baseline to Week 22 of the Acute Phase (ITT Population).
The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-C percent of responders at week 22. Response was defined as greater than or equal to 50% improvement from baseline.
Time frame: From baseline to Study Week 22
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Dose | Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Percent Responders From Baseline to Week 22 of the Acute Phase (ITT Population). | 16.5 percentage of participants |
| Medium Dose | Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Percent Responders From Baseline to Week 22 of the Acute Phase (ITT Population). | 17.5 percentage of participants |
| High Dose | Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Percent Responders From Baseline to Week 22 of the Acute Phase (ITT Population). | 21.0 percentage of participants |
Secondary
Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Percent Responders From Baseline to Week 50 of the Long-term Phase (ITT Population).
The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-C percent of responders at week 50. Response was defined as greater than or equal to 50% improvement from baseline.
Time frame: From baseline to Study Week 50
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Dose | Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Percent Responders From Baseline to Week 50 of the Long-term Phase (ITT Population). | 27.0 percentage of participants |
| Medium Dose | Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Percent Responders From Baseline to Week 50 of the Long-term Phase (ITT Population). | 38.9 percentage of participants |
| High Dose | Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Percent Responders From Baseline to Week 50 of the Long-term Phase (ITT Population). | 27.5 percentage of participants |
Secondary
Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Percent Sustained Responders at Study Week 50 (ITT Population).
The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. Sustained Response is defined as the percentage of Acute Phase responders (week 22) who were also responders at the end of the Long-term (week 50) phase. An analysis of sustained response was performed using the IDS-C to evaluate the long-term durability of the improvements in depression scores observed with adjunctive VNS Therapy.
Time frame: From baseline to Study Week 50
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Dose | Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Percent Sustained Responders at Study Week 50 (ITT Population). | 43.8 percentage of participants |
| Medium Dose | Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Percent Sustained Responders at Study Week 50 (ITT Population). | 88.2 percentage of participants |
| High Dose | Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Percent Sustained Responders at Study Week 50 (ITT Population). | 81.8 percentage of participants |
Secondary
Inventory of Depressive Symptomatology Self-Report (IDS-SR) Mean Change From Baseline to Week 22 of the Acute Phase (ITT Population).
The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-SR mean change at week 22
Time frame: From baseline to Study Week 22
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose | Inventory of Depressive Symptomatology Self-Report (IDS-SR) Mean Change From Baseline to Week 22 of the Acute Phase (ITT Population). | -9.0 units on a scale | Standard Deviation 11.4 |
| Medium Dose | Inventory of Depressive Symptomatology Self-Report (IDS-SR) Mean Change From Baseline to Week 22 of the Acute Phase (ITT Population). | -11.1 units on a scale | Standard Deviation 13.9 |
| High Dose | Inventory of Depressive Symptomatology Self-Report (IDS-SR) Mean Change From Baseline to Week 22 of the Acute Phase (ITT Population). | -10.2 units on a scale | Standard Deviation 13.7 |
Secondary
Inventory of Depressive Symptomatology Self-Report (IDS-SR) Mean Change From Baseline to Week 50 of the Long-term Phase (ITT Population).
The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-SR mean change at week 50
Time frame: From baseline to Study Week 50
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose | Inventory of Depressive Symptomatology Self-Report (IDS-SR) Mean Change From Baseline to Week 50 of the Long-term Phase (ITT Population). | -15.9 units on a scale | Standard Deviation 15 |
| Medium Dose | Inventory of Depressive Symptomatology Self-Report (IDS-SR) Mean Change From Baseline to Week 50 of the Long-term Phase (ITT Population). | -16.7 units on a scale | Standard Deviation 15 |
| High Dose | Inventory of Depressive Symptomatology Self-Report (IDS-SR) Mean Change From Baseline to Week 50 of the Long-term Phase (ITT Population). | -14.5 units on a scale | Standard Deviation 13.5 |
Secondary
Inventory of Depressive Symptomatology Self-Report (IDS-SR) Mean Percent Change From Baseline to Week 22 of the Acute Phase (ITT Population).
The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-SR mean percent change at week 22
Time frame: From baseline to Study Week 22
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose | Inventory of Depressive Symptomatology Self-Report (IDS-SR) Mean Percent Change From Baseline to Week 22 of the Acute Phase (ITT Population). | -19.6 mean percent change | Standard Deviation 24.7 |
| Medium Dose | Inventory of Depressive Symptomatology Self-Report (IDS-SR) Mean Percent Change From Baseline to Week 22 of the Acute Phase (ITT Population). | -22.6 mean percent change | Standard Deviation 29.4 |
| High Dose | Inventory of Depressive Symptomatology Self-Report (IDS-SR) Mean Percent Change From Baseline to Week 22 of the Acute Phase (ITT Population). | -22.7 mean percent change | Standard Deviation 31.1 |
Secondary
Inventory of Depressive Symptomatology Self-Report (IDS-SR) Mean Percent Change From Baseline to Week 50 of the Long-term Phase (ITT Population).
The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-SR mean percent change at week 50
Time frame: From baseline to Study Week 50
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose | Inventory of Depressive Symptomatology Self-Report (IDS-SR) Mean Percent Change From Baseline to Week 50 of the Long-term Phase (ITT Population). | -33.5 mean percent change | Standard Deviation 29.6 |
| Medium Dose | Inventory of Depressive Symptomatology Self-Report (IDS-SR) Mean Percent Change From Baseline to Week 50 of the Long-term Phase (ITT Population). | -35.5 mean percent change | Standard Deviation 32.2 |
| High Dose | Inventory of Depressive Symptomatology Self-Report (IDS-SR) Mean Percent Change From Baseline to Week 50 of the Long-term Phase (ITT Population). | -32.4 mean percent change | Standard Deviation 31.3 |
Secondary
Inventory of Depressive Symptomatology Self-Report (IDS-SR) Percent Remitters From Baseline to Week 22 of the Acute Phase (ITT Population).
The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-SR percent of remitters at week 22. Remission was defined as a score of less than or equal to 14 on the IDS-C.
Time frame: From baseline to Study Week 22
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Dose | Inventory of Depressive Symptomatology Self-Report (IDS-SR) Percent Remitters From Baseline to Week 22 of the Acute Phase (ITT Population). | 5.3 percentage of participants |
| Medium Dose | Inventory of Depressive Symptomatology Self-Report (IDS-SR) Percent Remitters From Baseline to Week 22 of the Acute Phase (ITT Population). | 9.4 percentage of participants |
| High Dose | Inventory of Depressive Symptomatology Self-Report (IDS-SR) Percent Remitters From Baseline to Week 22 of the Acute Phase (ITT Population). | 11.4 percentage of participants |
Secondary
Inventory of Depressive Symptomatology Self-Report (IDS-SR) Percent Remitters From Baseline to Week 50 of the Long-term Phase (ITT Population).
The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-SR percent of remitters at week 50. Remission was defined as a score of less than or equal to 14 on the IDS-C.
Time frame: From baseline to Study Week 50
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Dose | Inventory of Depressive Symptomatology Self-Report (IDS-SR) Percent Remitters From Baseline to Week 50 of the Long-term Phase (ITT Population). | 17.0 percentage of participants |
| Medium Dose | Inventory of Depressive Symptomatology Self-Report (IDS-SR) Percent Remitters From Baseline to Week 50 of the Long-term Phase (ITT Population). | 17.0 percentage of participants |
| High Dose | Inventory of Depressive Symptomatology Self-Report (IDS-SR) Percent Remitters From Baseline to Week 50 of the Long-term Phase (ITT Population). | 14.9 percentage of participants |
Secondary
Inventory of Depressive Symptomatology Self-Report (IDS-SR) Percent Responders From Baseline to Week 22 of the Acute Phase (ITT Population).
The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-SR percent of responders at week 22. Response was defined as greater than or equal to 50% improvement from baseline.
Time frame: From baseline to Study Week 22
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Dose | Inventory of Depressive Symptomatology Self-Report (IDS-SR) Percent Responders From Baseline to Week 22 of the Acute Phase (ITT Population). | 9.5 percentage of participants |
| Medium Dose | Inventory of Depressive Symptomatology Self-Report (IDS-SR) Percent Responders From Baseline to Week 22 of the Acute Phase (ITT Population). | 15.6 percentage of participants |
| High Dose | Inventory of Depressive Symptomatology Self-Report (IDS-SR) Percent Responders From Baseline to Week 22 of the Acute Phase (ITT Population). | 19.0 percentage of participants |
Secondary
Inventory of Depressive Symptomatology Self-Report (IDS-SR) Percent Responders From Baseline to Week 50 of the Long-term Phase (ITT Population).
The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-SR percent of responders at week 50. Response was defined as greater than or equal to 50% improvement from baseline.
Time frame: From baseline to Study Week 50
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Dose | Inventory of Depressive Symptomatology Self-Report (IDS-SR) Percent Responders From Baseline to Week 50 of the Long-term Phase (ITT Population). | 28.4 percentage of participants |
| Medium Dose | Inventory of Depressive Symptomatology Self-Report (IDS-SR) Percent Responders From Baseline to Week 50 of the Long-term Phase (ITT Population). | 36.4 percentage of participants |
| High Dose | Inventory of Depressive Symptomatology Self-Report (IDS-SR) Percent Responders From Baseline to Week 50 of the Long-term Phase (ITT Population). | 26.7 percentage of participants |
Secondary
Montgomery-Asberg Depression Rating Scale (MADRS) Mean Change From Baseline to Week 22 of the Acute Phase (ITT Population).
The 10-item Montgomery-Asberg Scale (Montgomery and Asberg 1979) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 60. Higher values are considered to be worse outcomes. The MADRS mean change at week 22
Time frame: From baseline to Study Week 22
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose | Montgomery-Asberg Depression Rating Scale (MADRS) Mean Change From Baseline to Week 22 of the Acute Phase (ITT Population). | -8.4 units on a scale | Standard Deviation 8.8 |
| Medium Dose | Montgomery-Asberg Depression Rating Scale (MADRS) Mean Change From Baseline to Week 22 of the Acute Phase (ITT Population). | -9.1 units on a scale | Standard Deviation 10.7 |
| High Dose | Montgomery-Asberg Depression Rating Scale (MADRS) Mean Change From Baseline to Week 22 of the Acute Phase (ITT Population). | -9.6 units on a scale | Standard Deviation 11 |
Secondary
Montgomery-Asberg Depression Rating Scale (MADRS) Mean Change From Baseline to Week 50 of the Long-term Phase (ITT Population).
The 10-item Montgomery-Asberg Scale (Montgomery and Asberg 1979) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 60. Higher values are considered to be worse outcomes. The MADRS mean change at week 50
Time frame: From baseline to Study Week 50
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose | Montgomery-Asberg Depression Rating Scale (MADRS) Mean Change From Baseline to Week 50 of the Long-term Phase (ITT Population). | -13.5 units on a scale | Standard Deviation 11.6 |
| Medium Dose | Montgomery-Asberg Depression Rating Scale (MADRS) Mean Change From Baseline to Week 50 of the Long-term Phase (ITT Population). | -14.3 units on a scale | Standard Deviation 11.6 |
| High Dose | Montgomery-Asberg Depression Rating Scale (MADRS) Mean Change From Baseline to Week 50 of the Long-term Phase (ITT Population). | -13.7 units on a scale | Standard Deviation 10.8 |
Secondary
Montgomery-Asberg Depression Rating Scale (MADRS) Mean Percent Change From Baseline to Week 22 of the Acute Phase (ITT Population).
The 10-item Montgomery-Asberg Scale (Montgomery and Asberg 1979) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 60. Higher values are considered to be worse outcomes. The MADRS mean percent change at week 22
Time frame: From baseline to Study Week 22
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose | Montgomery-Asberg Depression Rating Scale (MADRS) Mean Percent Change From Baseline to Week 22 of the Acute Phase (ITT Population). | -25.0 mean percent change | Standard Deviation 26.1 |
| Medium Dose | Montgomery-Asberg Depression Rating Scale (MADRS) Mean Percent Change From Baseline to Week 22 of the Acute Phase (ITT Population). | -26.7 mean percent change | Standard Deviation 31.3 |
| High Dose | Montgomery-Asberg Depression Rating Scale (MADRS) Mean Percent Change From Baseline to Week 22 of the Acute Phase (ITT Population). | 28.2 mean percent change | Standard Deviation 33.5 |
Secondary
Montgomery-Asberg Depression Rating Scale (MADRS) Mean Percent Change From Baseline to Week 50 of the Long-term Phase (ITT Population).
The 10-item Montgomery-Asberg Scale (Montgomery and Asberg 1979) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 60. Higher values are considered to be worse outcomes. The MADRS mean percent change at week 50
Time frame: From baseline to Study Week 50
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose | Montgomery-Asberg Depression Rating Scale (MADRS) Mean Percent Change From Baseline to Week 50 of the Long-term Phase (ITT Population). | -39.3 mean percent change | Standard Deviation 33.8 |
| Medium Dose | Montgomery-Asberg Depression Rating Scale (MADRS) Mean Percent Change From Baseline to Week 50 of the Long-term Phase (ITT Population). | -42.0 mean percent change | Standard Deviation 34.2 |
| High Dose | Montgomery-Asberg Depression Rating Scale (MADRS) Mean Percent Change From Baseline to Week 50 of the Long-term Phase (ITT Population). | -40.8 mean percent change | Standard Deviation 33.4 |
Secondary
Montgomery-Asberg Depression Rating Scale (MADRS) Percent Remitters From Baseline to Week 22 of the Acute Phase (ITT Population).
The 10-item Montgomery-Asberg Scale (Montgomery and Asberg 1979) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 60. Higher values are considered to be worse outcomes. The MADRS percent of remitters at week 22. Remission was defined as a score of less than or equal to 9 on the MADRS.
Time frame: From baseline to Study Week 22
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Dose | Montgomery-Asberg Depression Rating Scale (MADRS) Percent Remitters From Baseline to Week 22 of the Acute Phase (ITT Population). | 5.2 percentage of participants |
| Medium Dose | Montgomery-Asberg Depression Rating Scale (MADRS) Percent Remitters From Baseline to Week 22 of the Acute Phase (ITT Population). | 11.3 percentage of participants |
| High Dose | Montgomery-Asberg Depression Rating Scale (MADRS) Percent Remitters From Baseline to Week 22 of the Acute Phase (ITT Population). | 11.4 percentage of participants |
Secondary
Montgomery-Asberg Depression Rating Scale (MADRS) Percent Remitters From Baseline to Week 50 of the Long-term Phase (ITT Population).
The 10-item Montgomery-Asberg Scale (Montgomery and Asberg 1979) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 60. Higher values are considered to be worse outcomes. The MADRS percent of remitters at week 50. Remission was defined as a score of less than or equal to 9 on the MADRS.
Time frame: From baseline to Study Week 50
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Dose | Montgomery-Asberg Depression Rating Scale (MADRS) Percent Remitters From Baseline to Week 50 of the Long-term Phase (ITT Population). | 22.5 percentage of participants |
| Medium Dose | Montgomery-Asberg Depression Rating Scale (MADRS) Percent Remitters From Baseline to Week 50 of the Long-term Phase (ITT Population). | 21.1 percentage of participants |
| High Dose | Montgomery-Asberg Depression Rating Scale (MADRS) Percent Remitters From Baseline to Week 50 of the Long-term Phase (ITT Population). | 22.5 percentage of participants |
Secondary
Montgomery-Asberg Depression Rating Scale (MADRS) Percent Responders From Baseline to Week 22 of the Acute Phase (ITT Population).
The 10-item Montgomery-Asberg Scale (Montgomery and Asberg 1979) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 60. Higher values are considered to be worse outcomes. The MADRS percent of responders at week 22. Response was defined as greater than or equal to 50% improvement from baseline.
Time frame: From baseline to Study Week 22
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Dose | Montgomery-Asberg Depression Rating Scale (MADRS) Percent Responders From Baseline to Week 22 of the Acute Phase (ITT Population). | 16.5 percentage of participants |
| Medium Dose | Montgomery-Asberg Depression Rating Scale (MADRS) Percent Responders From Baseline to Week 22 of the Acute Phase (ITT Population). | 25.8 percentage of participants |
| High Dose | Montgomery-Asberg Depression Rating Scale (MADRS) Percent Responders From Baseline to Week 22 of the Acute Phase (ITT Population). | 28.6 percentage of participants |
Secondary
Montgomery-Asberg Depression Rating Scale (MADRS) Percent Responders From Baseline to Week 50 of the Long-term Phase (ITT Population).
The 10-item Montgomery-Asberg Scale (Montgomery and Asberg 1979) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 60. Higher values are considered to be worse outcomes. The MADRS percent of responders at week 50. Response was defined as greater than or equal to 50% improvement from baseline.
Time frame: From baseline to Study Week 50
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Dose | Montgomery-Asberg Depression Rating Scale (MADRS) Percent Responders From Baseline to Week 50 of the Long-term Phase (ITT Population). | 36.0 percentage of participants |
| Medium Dose | Montgomery-Asberg Depression Rating Scale (MADRS) Percent Responders From Baseline to Week 50 of the Long-term Phase (ITT Population). | 47.8 percentage of participants |
| High Dose | Montgomery-Asberg Depression Rating Scale (MADRS) Percent Responders From Baseline to Week 50 of the Long-term Phase (ITT Population). | 37.3 percentage of participants |
Secondary
Montgomery-Asberg Depression Rating Scale (MADRS) Percent Sustained Responders at Study Week 50 (ITT Population).
The 10-item Montgomery-Asberg Scale (Montgomery and Asberg 1979) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 60. Higher values are considered to be worse outcomes. Sustained Response is defined as the percentage of Acute Phase responders (week 22) who were also responders at the end of the Long-term (week 50) phase. An analysis of sustained response was performed using the MADRS to evaluate the long-term durability of the improvements in depression scores observed with adjunctive VNS Therapy.
Time frame: From Baseline to Study Week 50
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Dose | Montgomery-Asberg Depression Rating Scale (MADRS) Percent Sustained Responders at Study Week 50 (ITT Population). | 68.8 percentage of participants |
| Medium Dose | Montgomery-Asberg Depression Rating Scale (MADRS) Percent Sustained Responders at Study Week 50 (ITT Population). | 92.0 percentage of participants |
| High Dose | Montgomery-Asberg Depression Rating Scale (MADRS) Percent Sustained Responders at Study Week 50 (ITT Population). | 76.7 percentage of participants |
Secondary
Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Mean Change From Baseline to Week 22 of the Acute Phase (ITT Population).
The 16-item Inventory of Depressive Symptomatology (QIDS) (Rush et al. 2003) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 27. Higher values are considered to be worse outcomes. The QIDS-C mean change at week 22
Time frame: From baseline to Study Week 22
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose | Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Mean Change From Baseline to Week 22 of the Acute Phase (ITT Population). | -4.4 units on a scale | Standard Deviation 5 |
| Medium Dose | Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Mean Change From Baseline to Week 22 of the Acute Phase (ITT Population). | -5.0 units on a scale | Standard Deviation 5.4 |
| High Dose | Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Mean Change From Baseline to Week 22 of the Acute Phase (ITT Population). | -4.7 units on a scale | Standard Deviation 5.3 |
Secondary
Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Mean Change From Baseline to Week 50 of the Long-term Phase (ITT Population).
The 16-item Inventory of Depressive Symptomatology (QIDS) (Rush et al. 2003) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 27. Higher values are considered to be worse outcomes. The QIDS-C mean change at week 50
Time frame: From baseline to Study Week 50
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose | Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Mean Change From Baseline to Week 50 of the Long-term Phase (ITT Population). | -7.1 units on a scale | Standard Deviation 5.7 |
| Medium Dose | Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Mean Change From Baseline to Week 50 of the Long-term Phase (ITT Population). | -7.2 units on a scale | Standard Deviation 6.2 |
| High Dose | Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Mean Change From Baseline to Week 50 of the Long-term Phase (ITT Population). | -6.7 units on a scale | Standard Deviation 5.1 |
Secondary
Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Mean Percent Change From Baseline to Week 22 of the Acute Phase (ITT Population).
The 16-item Inventory of Depressive Symptomatology (QIDS) (Rush et al. 2003) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 27. Higher values are considered to be worse outcomes. The QIDS-C mean percent change at week 22
Time frame: From baseline to Study Week 22
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose | Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Mean Percent Change From Baseline to Week 22 of the Acute Phase (ITT Population). | -23.7 mean percent change | Standard Deviation 27.4 |
| Medium Dose | Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Mean Percent Change From Baseline to Week 22 of the Acute Phase (ITT Population). | -26.5 mean percent change | Standard Deviation 29.8 |
| High Dose | Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Mean Percent Change From Baseline to Week 22 of the Acute Phase (ITT Population). | -26.3 mean percent change | Standard Deviation 31.6 |
Secondary
Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Mean Percent Change From Baseline to Week 50 of the Long-term Phase (ITT Population).
The 16-item Inventory of Depressive Symptomatology (QIDS) (Rush et al. 2003) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 27. Higher values are considered to be worse outcomes. The QIDS-C mean percent change at week 50
Time frame: From baseline to Study Week 50
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose | Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Mean Percent Change From Baseline to Week 50 of the Long-term Phase (ITT Population). | -37.9 mean percent change | Standard Deviation 30.2 |
| Medium Dose | Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Mean Percent Change From Baseline to Week 50 of the Long-term Phase (ITT Population). | 38.5 mean percent change | Standard Deviation 32.8 |
| High Dose | Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Mean Percent Change From Baseline to Week 50 of the Long-term Phase (ITT Population). | 38.2 mean percent change | Standard Deviation 30.6 |
Secondary
Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Percent Remitters From Baseline to Week 22 of the Acute Phase (ITT Population).
The 16-item Inventory of Depressive Symptomatology (QIDS) (Rush et al. 2003) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 27. Higher values are considered to be worse outcomes. The QIDS-C percent of remitters at week 22. Remission was defined as a score of less than or equal to 5 on the QIDS-C.
Time frame: From baseline to Study Week 22
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Dose | Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Percent Remitters From Baseline to Week 22 of the Acute Phase (ITT Population). | 6.2 percentage of participants |
| Medium Dose | Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Percent Remitters From Baseline to Week 22 of the Acute Phase (ITT Population). | 9.3 percentage of participants |
| High Dose | Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Percent Remitters From Baseline to Week 22 of the Acute Phase (ITT Population). | 9.5 percentage of participants |
Secondary
Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Percent Remitters From Baseline to Week 50 of the Long-term Phase (ITT Population).
The 16-item Inventory of Depressive Symptomatology (QIDS) (Rush et al. 2003) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 27. Higher values are considered to be worse outcomes. The QIDS-C percent of remitters at week 50. Remission was defined as a score of less than or equal to 5 on the QIDS-C.
Time frame: From baseline to Study Week 50
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Dose | Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Percent Remitters From Baseline to Week 50 of the Long-term Phase (ITT Population). | 15.7 percentage of participants |
| Medium Dose | Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Percent Remitters From Baseline to Week 50 of the Long-term Phase (ITT Population). | 16.7 percentage of participants |
| High Dose | Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Percent Remitters From Baseline to Week 50 of the Long-term Phase (ITT Population). | 16.7 percentage of participants |
Secondary
Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Percent Responders From Baseline to Week 22 of the Acute Phase (ITT Population).
The 16-item Inventory of Depressive Symptomatology (QIDS) (Rush et al. 2003) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 27. Higher values are considered to be worse outcomes. The QIDS-C percent of responders at week 22. Response was defined as greater than or equal to 50% improvement from baseline.
Time frame: From baseline to Study Week 22
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Dose | Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Percent Responders From Baseline to Week 22 of the Acute Phase (ITT Population). | 20.6 percentage of participants |
| Medium Dose | Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Percent Responders From Baseline to Week 22 of the Acute Phase (ITT Population). | 21.6 percentage of participants |
| High Dose | Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Percent Responders From Baseline to Week 22 of the Acute Phase (ITT Population). | 23.8 percentage of participants |
Secondary
Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Percent Responders From Baseline to Week 50 of the Long-term Phase (ITT Population).
The 16-item Inventory of Depressive Symptomatology (QIDS) (Rush et al. 2003) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 27. Higher values are considered to be worse outcomes. The QIDS-C percent of responders at week 50. Response was defined as greater than or equal to 50% improvement from baseline.
Time frame: From baseline to Study Week 50
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Dose | Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Percent Responders From Baseline to Week 50 of the Long-term Phase (ITT Population). | 36.0 percentage of participants |
| Medium Dose | Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Percent Responders From Baseline to Week 50 of the Long-term Phase (ITT Population). | 44.4 percentage of participants |
| High Dose | Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Percent Responders From Baseline to Week 50 of the Long-term Phase (ITT Population). | 34.3 percentage of participants |
Post Hoc
Regression Analysis of Change in IDS-C Score vs. Total Charge Delivered Per Day
Mixed models multivariate regression model was fitted for the outcome change from baseline IDS-C score as a function of log dose, where dose is measured by millicoulombs (mC), adjusting for other important covariates (e.g., visit number, total number of major depressive episodes, prior electroconvulsive therapy (ECT) history, total number of adequate drug trials and prior medication regimen). The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes.
Time frame: 50 Weeks
Population: 50 Week Completers
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Low Dose | Regression Analysis of Change in IDS-C Score vs. Total Charge Delivered Per Day | -4.91 Units on a scale per log(mC/Day) | Standard Error 1.34 |
Post Hoc
Regression Analysis of Change in MADRS Score vs. Total Charge Delivered Per Day
Mixed models multivariate regression model was fitted for the outcome change from baseline MADRS score as a function of log dose, where dose is measured by millicoulombs (mC), adjusting for other important covariates (e.g., visit number, total number of major depressive episodes, prior ECT history, total number of adequate drug trials and prior medication regimen). The 10-item Montgomery-Asberg Scale (Montgomery and Asberg 1979) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 60. Higher values are considered to be worse outcomes.
Time frame: 50 Weeks
Population: 50 Week Completers
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Low Dose | Regression Analysis of Change in MADRS Score vs. Total Charge Delivered Per Day | -2.17 Units on a scale per log(mC/Day) | Standard Error 0.93 |