Trial Outcomes & Findings for Study Comparing Outcomes for Patients With Treatment Resistant Depression Who Receive VNS Therapy at Different Doses (NCT NCT00305565)

NCT ID: NCT00305565

Last Updated: 2014-01-07

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

331 participants

Primary outcome timeframe

From Baseline to Study Week 22

Results posted on

2014-01-07

Participant Flow

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.

Participant milestones

Participant milestones
Measure
Low Dose
Received output current 0.25 milliamps (mA)
Medium Dose
Received output current 0.5-1.0 mA
High Dose
Received output current 1.0-1.5 mA
Overall Study (Safety Population)
STARTED
111
107
113
Overall Study (Safety Population)
COMPLETED
97
95
106
Overall Study (Safety Population)
NOT COMPLETED
14
12
7
Overall Study (ITT Population)
STARTED
102
101
107
Overall Study (ITT Population)
COMPLETED
89
90
102
Overall Study (ITT Population)
NOT COMPLETED
13
11
5

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study Comparing Outcomes for Patients With Treatment Resistant Depression Who Receive VNS Therapy at Different Doses

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Low Dose
n=102 Participants
Received output current 0.25 mA
Medium Dose
n=101 Participants
Received output current 0.5-1.0 mA
High Dose
n=107 Participants
Received output current 1.0-1.5 mA
Total
n=310 Participants
Total of all reporting groups
Age, Continuous
49.1 years
STANDARD_DEVIATION 10.5 • n=99 Participants
47.2 years
STANDARD_DEVIATION 11.0 • n=107 Participants
47.4 years
STANDARD_DEVIATION 10.8 • n=206 Participants
47.9 years
STANDARD_DEVIATION 10.8 • n=7 Participants
Sex: Female, Male
Female
68 Participants
n=99 Participants
69 Participants
n=107 Participants
73 Participants
n=206 Participants
210 Participants
n=7 Participants
Sex: Female, Male
Male
34 Participants
n=99 Participants
32 Participants
n=107 Participants
34 Participants
n=206 Participants
100 Participants
n=7 Participants
Race/Ethnicity, Customized
Caucasian
97 participants
n=99 Participants
96 participants
n=107 Participants
104 participants
n=206 Participants
297 participants
n=7 Participants
Race/Ethnicity, Customized
Asian
3 participants
n=99 Participants
1 participants
n=107 Participants
0 participants
n=206 Participants
4 participants
n=7 Participants
Race/Ethnicity, Customized
African-American
2 participants
n=99 Participants
3 participants
n=107 Participants
3 participants
n=206 Participants
8 participants
n=7 Participants
Race/Ethnicity, Customized
Hispanic
0 participants
n=99 Participants
1 participants
n=107 Participants
0 participants
n=206 Participants
1 participants
n=7 Participants
Region of Enrollment
United States
102 participants
n=99 Participants
101 participants
n=107 Participants
107 participants
n=206 Participants
310 participants
n=7 Participants
Unipolar or Bipolar Depression
Unipolar Depression (Single Episode)
6 participants
n=99 Participants
10 participants
n=107 Participants
15 participants
n=206 Participants
31 participants
n=7 Participants
Unipolar or Bipolar Depression
Unipolar Depression (Recurrent)
76 participants
n=99 Participants
71 participants
n=107 Participants
66 participants
n=206 Participants
213 participants
n=7 Participants
Unipolar or Bipolar Depression
Bipolar Depression
20 participants
n=99 Participants
20 participants
n=107 Participants
26 participants
n=206 Participants
66 participants
n=7 Participants
Lifetime Episodes of Depression
0-2 Episodes
16 participants
n=99 Participants
17 participants
n=107 Participants
28 participants
n=206 Participants
61 participants
n=7 Participants
Lifetime Episodes of Depression
3-5 Episodes
23 participants
n=99 Participants
21 participants
n=107 Participants
22 participants
n=206 Participants
66 participants
n=7 Participants
Lifetime Episodes of Depression
6-10 Episodes
13 participants
n=99 Participants
16 participants
n=107 Participants
18 participants
n=206 Participants
47 participants
n=7 Participants
Lifetime Episodes of Depression
>10 Episodes
50 participants
n=99 Participants
46 participants
n=107 Participants
39 participants
n=206 Participants
135 participants
n=7 Participants
Duration of Illness
29.8 Years
STANDARD_DEVIATION 12.1 • n=99 Participants
26.3 Years
STANDARD_DEVIATION 10.9 • n=107 Participants
27.0 Years
STANDARD_DEVIATION 12.1 • n=206 Participants
27.7 Years
STANDARD_DEVIATION 11.8 • n=7 Participants
Length of Current Major Depressive Episode
106.7 Months
STANDARD_DEVIATION 122.8 • n=99 Participants
106.1 Months
STANDARD_DEVIATION 107.3 • n=107 Participants
111.3 Months
STANDARD_DEVIATION 146.3 • n=206 Participants
108.1 Months
STANDARD_DEVIATION 126.5 • n=7 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Low Dose
n=396 repeated measures IDS-C observations
Received output current 0.25 mA
Medium Dose
n=390 repeated measures IDS-C observations
Received output current 0.5-1.0 mA
High Dose
n=417 repeated measures IDS-C observations
Received output current 1.0-1.5 mA
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
-10.29 units on a scale
Standard Error 1.00
-10.30 units on a scale
Standard Error 0.97

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Low Dose
n=97 Participants
Received output current 0.25 mA
Medium Dose
n=97 Participants
Received output current 0.5-1.0 mA
High Dose
n=105 Participants
Received output current 1.0-1.5 mA
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
17.5 percentage of participants
21.0 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Low Dose
n=97 Participants
Received output current 0.25 mA
Medium Dose
n=97 Participants
Received output current 0.5-1.0 mA
High Dose
n=105 Participants
Received output current 1.0-1.5 mA
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
9.3 percentage of participants
11.4 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Low Dose
n=89 Participants
Received output current 0.25 mA
Medium Dose
n=90 Participants
Received output current 0.5-1.0 mA
High Dose
n=102 Participants
Received output current 1.0-1.5 mA
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
38.9 percentage of participants
27.5 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Low Dose
n=16 Participants
Received output current 0.25 mA
Medium Dose
n=17 Participants
Received output current 0.5-1.0 mA
High Dose
n=22 Participants
Received output current 1.0-1.5 mA
Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Percent Sustained Responders at Study Week 50 (ITT Population).
43.8 percentage of participants
88.2 percentage of participants
81.8 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Low Dose
n=89 Participants
Received output current 0.25 mA
Medium Dose
n=90 Participants
Received output current 0.5-1.0 mA
High Dose
n=102 Participants
Received output current 1.0-1.5 mA
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
15.6 percentage of participants
17.6 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Low Dose
n=97 Participants
Received output current 0.25 mA
Medium Dose
n=97 Participants
Received output current 0.5-1.0 mA
High Dose
n=105 Participants
Received output current 1.0-1.5 mA
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
21.6 percentage of participants
23.8 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Low Dose
n=97 Participants
Received output current 0.25 mA
Medium Dose
n=97 Participants
Received output current 0.5-1.0 mA
High Dose
n=105 Participants
Received output current 1.0-1.5 mA
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
9.3 percentage of participants
9.5 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Low Dose
n=89 Participants
Received output current 0.25 mA
Medium Dose
n=90 Participants
Received output current 0.5-1.0 mA
High Dose
n=102 Participants
Received output current 1.0-1.5 mA
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
44.4 percentage of participants
34.3 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Low Dose
n=89 Participants
Received output current 0.25 mA
Medium Dose
n=90 Participants
Received output current 0.5-1.0 mA
High Dose
n=102 Participants
Received output current 1.0-1.5 mA
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
16.7 percentage of participants
16.7 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Low Dose
n=97 Participants
Received output current 0.25 mA
Medium Dose
n=97 Participants
Received output current 0.5-1.0 mA
High Dose
n=105 Participants
Received output current 1.0-1.5 mA
Montgomery-Asberg Depression Rating Scale (MADRS) Percent Responders From Baseline to Week 22 of the Acute Phase (ITT Population).
16.5 percentage of participants
25.8 percentage of participants
28.6 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Low Dose
n=97 Participants
Received output current 0.25 mA
Medium Dose
n=97 Participants
Received output current 0.5-1.0 mA
High Dose
n=105 Participants
Received output current 1.0-1.5 mA
Montgomery-Asberg Depression Rating Scale (MADRS) Percent Remitters From Baseline to Week 22 of the Acute Phase (ITT Population).
5.2 percentage of participants
11.3 percentage of participants
11.4 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Low Dose
n=89 Participants
Received output current 0.25 mA
Medium Dose
n=90 Participants
Received output current 0.5-1.0 mA
High Dose
n=102 Participants
Received output current 1.0-1.5 mA
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
47.8 percentage of participants
37.3 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Low Dose
n=16 Participants
Received output current 0.25 mA
Medium Dose
n=25 Participants
Received output current 0.5-1.0 mA
High Dose
n=30 Participants
Received output current 1.0-1.5 mA
Montgomery-Asberg Depression Rating Scale (MADRS) Percent Sustained Responders at Study Week 50 (ITT Population).
68.8 percentage of participants
92.0 percentage of participants
76.7 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Low Dose
n=89 Participants
Received output current 0.25 mA
Medium Dose
n=90 Participants
Received output current 0.5-1.0 mA
High Dose
n=102 Participants
Received output current 1.0-1.5 mA
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
21.1 percentage of participants
22.5 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Low Dose
n=97 Participants
Received output current 0.25 mA
Medium Dose
n=96 Participants
Received output current 0.5-1.0 mA
High Dose
n=105 Participants
Received output current 1.0-1.5 mA
Clinical Global Impressions Improvement Scale (CGI-I) Percent Response at Week 22 of the Acute Phase (ITT Population)
20.6 percentage of participants
28.1 percentage of participants
31.4 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Low Dose
n=89 Participants
Received output current 0.25 mA
Medium Dose
n=90 Participants
Received output current 0.5-1.0 mA
High Dose
n=102 Participants
Received output current 1.0-1.5 mA
Clinical Global Impressions Improvement Scale (CGI-I) Percent Response at Week 50 of the Long-term Phase (ITT Population).
41.6 percentage of participants
53.3 percentage of participants
48.0 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Low Dose
n=95 Participants
Received output current 0.25 mA
Medium Dose
n=96 Participants
Received output current 0.5-1.0 mA
High Dose
n=105 Participants
Received output current 1.0-1.5 mA
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
15.6 percentage of participants
19.0 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Low Dose
n=95 Participants
Received output current 0.25 mA
Medium Dose
n=96 Participants
Received output current 0.5-1.0 mA
High Dose
n=105 Participants
Received output current 1.0-1.5 mA
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
9.4 percentage of participants
11.4 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Low Dose
n=88 Participants
Received output current 0.25 mA
Medium Dose
n=88 Participants
Received output current 0.5-1.0 mA
High Dose
n=101 Participants
Received output current 1.0-1.5 mA
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
36.4 percentage of participants
26.7 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Low Dose
n=88 Participants
Received output current 0.25 mA
Medium Dose
n=88 Participants
Received output current 0.5-1.0 mA
High Dose
n=101 Participants
Received output current 1.0-1.5 mA
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
17.0 percentage of participants
14.9 percentage of participants

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure
Low Dose
n=97 Participants
Received output current 0.25 mA
Medium Dose
n=97 Participants
Received output current 0.5-1.0 mA
High Dose
n=105 Participants
Received output current 1.0-1.5 mA
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
-24.9 mean percent change
Standard Deviation 28.9
-25.4 mean percent change
Standard Deviation 31.4

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure
Low Dose
n=89 Participants
Received output current 0.25 mA
Medium Dose
n=90 Participants
Received output current 0.5-1.0 mA
High Dose
n=102 Participants
Received output current 1.0-1.5 mA
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
-17.0 units on a scale
Standard Deviation 14.6
-15.3 units on a scale
Standard Deviation 12.9

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure
Low Dose
n=89 Participants
Received output current 0.25 mA
Medium Dose
n=90 Participants
Received output current 0.5-1.0 mA
High Dose
n=102 Participants
Received output current 1.0-1.5 mA
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
-36.5 mean percent change
Standard Deviation 32.5
-34.6 mean percent change
Standard Deviation 30.7

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure
Low Dose
n=97 Participants
Received output current 0.25 mA
Medium Dose
n=97 Participants
Received output current 0.5-1.0 mA
High Dose
n=105 Participants
Received output current 1.0-1.5 mA
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 5.0
-5.0 units on a scale
Standard Deviation 5.4
-4.7 units on a scale
Standard Deviation 5.3

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure
Low Dose
n=97 Participants
Received output current 0.25 mA
Medium Dose
n=97 Participants
Received output current 0.5-1.0 mA
High Dose
n=105 Participants
Received output current 1.0-1.5 mA
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
-26.5 mean percent change
Standard Deviation 29.8
-26.3 mean percent change
Standard Deviation 31.6

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure
Low Dose
n=89 Participants
Received output current 0.25 mA
Medium Dose
n=90 Participants
Received output current 0.5-1.0 mA
High Dose
n=102 Participants
Received output current 1.0-1.5 mA
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
-7.2 units on a scale
Standard Deviation 6.2
-6.7 units on a scale
Standard Deviation 5.1

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure
Low Dose
n=89 Participants
Received output current 0.25 mA
Medium Dose
n=90 Participants
Received output current 0.5-1.0 mA
High Dose
n=102 Participants
Received output current 1.0-1.5 mA
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
38.5 mean percent change
Standard Deviation 32.8
38.2 mean percent change
Standard Deviation 30.6

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure
Low Dose
n=97 Participants
Received output current 0.25 mA
Medium Dose
n=97 Participants
Received output current 0.5-1.0 mA
High Dose
n=105 Participants
Received output current 1.0-1.5 mA
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
-9.1 units on a scale
Standard Deviation 10.7
-9.6 units on a scale
Standard Deviation 11.0

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure
Low Dose
n=97 Participants
Received output current 0.25 mA
Medium Dose
n=97 Participants
Received output current 0.5-1.0 mA
High Dose
n=105 Participants
Received output current 1.0-1.5 mA
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
-26.7 mean percent change
Standard Deviation 31.3
28.2 mean percent change
Standard Deviation 33.5

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure
Low Dose
n=89 Participants
Received output current 0.25 mA
Medium Dose
n=90 Participants
Received output current 0.5-1.0 mA
High Dose
n=102 Participants
Received output current 1.0-1.5 mA
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
-14.3 units on a scale
Standard Deviation 11.6
-13.7 units on a scale
Standard Deviation 10.8

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure
Low Dose
n=89 Participants
Received output current 0.25 mA
Medium Dose
n=90 Participants
Received output current 0.5-1.0 mA
High Dose
n=102 Participants
Received output current 1.0-1.5 mA
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
-42.0 mean percent change
Standard Deviation 34.2
-40.8 mean percent change
Standard Deviation 33.4

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure
Low Dose
n=95 Participants
Received output current 0.25 mA
Medium Dose
n=96 Participants
Received output current 0.5-1.0 mA
High Dose
n=105 Participants
Received output current 1.0-1.5 mA
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
-11.1 units on a scale
Standard Deviation 13.9
-10.2 units on a scale
Standard Deviation 13.7

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure
Low Dose
n=95 Participants
Received output current 0.25 mA
Medium Dose
n=96 Participants
Received output current 0.5-1.0 mA
High Dose
n=105 Participants
Received output current 1.0-1.5 mA
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
-22.6 mean percent change
Standard Deviation 29.4
-22.7 mean percent change
Standard Deviation 31.1

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure
Low Dose
n=88 Participants
Received output current 0.25 mA
Medium Dose
n=88 Participants
Received output current 0.5-1.0 mA
High Dose
n=101 Participants
Received output current 1.0-1.5 mA
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 15.0
-16.7 units on a scale
Standard Deviation 15.0
-14.5 units on a scale
Standard Deviation 13.5

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure
Low Dose
n=88 Participants
Received output current 0.25 mA
Medium Dose
n=88 Participants
Received output current 0.5-1.0 mA
High Dose
n=101 Participants
Received output current 1.0-1.5 mA
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
-35.5 mean percent change
Standard Deviation 32.2
-32.4 mean percent change
Standard Deviation 31.3

POST_HOC outcome

Timeframe: 50 Weeks

Population: 50 Week Completers

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.

Outcome measures

Outcome measures
Measure
Low Dose
n=314 Participants
Received output current 0.25 mA
Medium Dose
Received output current 0.5-1.0 mA
High Dose
Received output current 1.0-1.5 mA
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 outcome

Timeframe: 50 Weeks

Population: 50 Week Completers

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.

Outcome measures

Outcome measures
Measure
Low Dose
n=314 Participants
Received output current 0.25 mA
Medium Dose
Received output current 0.5-1.0 mA
High Dose
Received output current 1.0-1.5 mA
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

Adverse Events

Low Dose

Serious events: 31 serious events
Other events: 103 other events
Deaths: 0 deaths

Medium Dose

Serious events: 19 serious events
Other events: 104 other events
Deaths: 0 deaths

High Dose

Serious events: 16 serious events
Other events: 111 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Low Dose
n=111 participants at risk
Received output current 0.25 mA
Medium Dose
n=107 participants at risk
Received output current 0.5-1.0 mA
High Dose
n=113 participants at risk
Received output current 1.0-1.5 mA
General disorders
Body as a Whole
17.1%
19/111 • 54 Weeks
8.4%
9/107 • 54 Weeks
11.5%
13/113 • 54 Weeks
Cardiac disorders
Cardiovascular System
0.90%
1/111 • 54 Weeks
0.93%
1/107 • 54 Weeks
0.88%
1/113 • 54 Weeks
Gastrointestinal disorders
Digestive System
2.7%
3/111 • 54 Weeks
0.93%
1/107 • 54 Weeks
0.88%
1/113 • 54 Weeks
Endocrine disorders
Endocrine System
0.00%
0/111 • 54 Weeks
0.93%
1/107 • 54 Weeks
0.00%
0/113 • 54 Weeks
Nervous system disorders
Nervous System
8.1%
9/111 • 54 Weeks
9.3%
10/107 • 54 Weeks
3.5%
4/113 • 54 Weeks
Respiratory, thoracic and mediastinal disorders
Respiratory System
1.8%
2/111 • 54 Weeks
0.93%
1/107 • 54 Weeks
0.88%
1/113 • 54 Weeks
Skin and subcutaneous tissue disorders
Skin and Appendages System
0.00%
0/111 • 54 Weeks
0.93%
1/107 • 54 Weeks
0.00%
0/113 • 54 Weeks
Renal and urinary disorders
Urogenital System
1.8%
2/111 • 54 Weeks
0.93%
1/107 • 54 Weeks
0.00%
0/113 • 54 Weeks

Other adverse events

Other adverse events
Measure
Low Dose
n=111 participants at risk
Received output current 0.25 mA
Medium Dose
n=107 participants at risk
Received output current 0.5-1.0 mA
High Dose
n=113 participants at risk
Received output current 1.0-1.5 mA
General disorders
Body as a Whole
72.1%
80/111 • 54 Weeks
72.9%
78/107 • 54 Weeks
81.4%
92/113 • 54 Weeks
Cardiac disorders
Cardiovascular System
10.8%
12/111 • 54 Weeks
12.1%
13/107 • 54 Weeks
13.3%
15/113 • 54 Weeks
Gastrointestinal disorders
Digestive System
33.3%
37/111 • 54 Weeks
42.1%
45/107 • 54 Weeks
41.6%
47/113 • 54 Weeks
Endocrine disorders
Endocrine System
3.6%
4/111 • 54 Weeks
0.00%
0/107 • 54 Weeks
0.88%
1/113 • 54 Weeks
Blood and lymphatic system disorders
Hemic System
3.6%
4/111 • 54 Weeks
1.9%
2/107 • 54 Weeks
1.8%
2/113 • 54 Weeks
Metabolism and nutrition disorders
Metabolic System
6.3%
7/111 • 54 Weeks
8.4%
9/107 • 54 Weeks
12.4%
14/113 • 54 Weeks
Musculoskeletal and connective tissue disorders
Musculoskeletal System
5.4%
6/111 • 54 Weeks
11.2%
12/107 • 54 Weeks
9.7%
11/113 • 54 Weeks
Nervous system disorders
Nervous System
65.8%
73/111 • 54 Weeks
57.9%
62/107 • 54 Weeks
75.2%
85/113 • 54 Weeks
Respiratory, thoracic and mediastinal disorders
Respiratory System
78.4%
87/111 • 54 Weeks
90.7%
97/107 • 54 Weeks
87.6%
99/113 • 54 Weeks
Skin and subcutaneous tissue disorders
Skin and Appendages System
8.1%
9/111 • 54 Weeks
6.5%
7/107 • 54 Weeks
5.3%
6/113 • 54 Weeks
Ear and labyrinth disorders
Special Senses System
9.9%
11/111 • 54 Weeks
5.6%
6/107 • 54 Weeks
13.3%
15/113 • 54 Weeks
Renal and urinary disorders
Urogenital System
7.2%
8/111 • 54 Weeks
12.1%
13/107 • 54 Weeks
7.1%
8/113 • 54 Weeks

Additional Information

Mark Bunker Sr. Director, Global Medical Affairs

Cyberonics Inc.

Phone: 281-228-7223

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place

Restriction type: LTE60