Trial Outcomes & Findings for Ketamine for Depression and Suicide Risk (NCT NCT02094898)

NCT ID: NCT02094898

Last Updated: 2017-08-11

Results Overview

The Montgomery Asberg Depression Scale (MADRS) is a 10-item observer rating scale assessing symptoms of depression. The score ranges from 0 (no depression) to 60 (very depressed). For this study a score of less than or equal to 9 was considered clinical remission of depression.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 12 participants
• Primary outcome timeframe: baseline, last acute phase observation (approximately 2 weeks)
• Results posted on: 2017-08-11

Participant Flow

Subjects were enrolled at Mayo Clinic in Rochester, Minnesota between 12/30/14 and 5/18/16.

Participant milestones

Measure	Ketamine Infusion This trial was conducted in 2 phases. During the acute-phase, i.v. ketamine was administered thrice-weekly for up to 2 weeks.Those who achieved depressive symptom remission received continuation-phase treatment that consisted of once-weekly i.v. ketamine infusions for 4 additional weeks. Remission could occur after any of the 6 acute-phase infusions, at which point the next infusion was the first (of four) continuation-phase infusions. Individuals who remitted during acute-phase and completed continuation-phase treatment had 4 additional weekly post-continuation follow-up visits. Ketamine: 0.3 mg/kg/hr of ketamine infused for 100 minutes
Overall Study STARTED	12
Overall Study COMPLETED	7
Overall Study NOT COMPLETED	5

Reasons for withdrawal

Measure	Ketamine Infusion This trial was conducted in 2 phases. During the acute-phase, i.v. ketamine was administered thrice-weekly for up to 2 weeks.Those who achieved depressive symptom remission received continuation-phase treatment that consisted of once-weekly i.v. ketamine infusions for 4 additional weeks. Remission could occur after any of the 6 acute-phase infusions, at which point the next infusion was the first (of four) continuation-phase infusions. Individuals who remitted during acute-phase and completed continuation-phase treatment had 4 additional weekly post-continuation follow-up visits. Ketamine: 0.3 mg/kg/hr of ketamine infused for 100 minutes
Overall Study Clinical Worsening	2
Overall Study Adverse Event	2
Overall Study Lack of Efficacy	1

Baseline Characteristics

Ketamine for Depression and Suicide Risk

Baseline characteristics by cohort

Measure	Ketamine Infusion n=12 Participants This trial was conducted in 2 phases. During the acute-phase, i.v. ketamine was administered thrice-weekly for up to 2 weeks.Those who achieved depressive symptom remission received continuation-phase treatment that consisted of once-weekly i.v. ketamine infusions for 4 additional weeks. Remission could occur after any of the 6 acute-phase infusions, at which point the next infusion was the first (of four) continuation-phase infusions. Individuals who remitted during acute-phase and completed continuation-phase treatment had 4 additional weekly post-continuation follow-up visits. Ketamine: 0.3 mg/kg/hr of ketamine infused for 100 minutes
Age, Continuous	45.8 years STANDARD_DEVIATION 8 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants
Region of Enrollment United States	12 participants n=5 Participants

PRIMARY outcome

Timeframe: baseline, last acute phase observation (approximately 2 weeks)

Population: Statistical analyses included all subjects who received at least one acute-phase ketamine infusion.

The Montgomery Asberg Depression Scale (MADRS) is a 10-item observer rating scale assessing symptoms of depression. The score ranges from 0 (no depression) to 60 (very depressed). For this study a score of less than or equal to 9 was considered clinical remission of depression.

Outcome measures

Measure	Entire Cohort n=12 Participants All enrolled subjects receiving at least one acute-phase ketamine infusion.	Remission n=5 Participants Remission was defined as a MADRS total score of less than or equal to 9 measured 24 hours after any acute phase infusion.	Non-Remission n=7 Participants Subjects who did not have a MADRS total score less than or equal to 9 measured 24 h after any acute phase infusion
MADRS Total Score at Baseline and Last Acute Phase Observation Baseline	29.4 units on a scale Standard Deviation 7.5	29.4 units on a scale Standard Deviation 8.2	29.4 units on a scale Standard Deviation 7.7
MADRS Total Score at Baseline and Last Acute Phase Observation Last acute phase observation	15.9 units on a scale Standard Deviation 10.6	5.4 units on a scale Standard Deviation 3.4	23.4 units on a scale Standard Deviation 6.3

SECONDARY outcome

Timeframe: baseline, last acute phase observation (approximately 2 weeks)

Population: Statistical analyses included all subjects who received at least one acute-phase ketamine infusion.

The Montgomery Asberg Depression Scale (MADRS) is a 10-item observer rating scale assessing symptoms of depression. The score ranges from 0 (no depression) to 60 (very depressed). For this study a score of less than or equal to 9 was considered clinical remission of depression.

Outcome measures

Measure	Entire Cohort n=12 Participants All enrolled subjects receiving at least one acute-phase ketamine infusion.	Remission n=5 Participants Remission was defined as a MADRS total score of less than or equal to 9 measured 24 hours after any acute phase infusion.	Non-Remission n=7 Participants Subjects who did not have a MADRS total score less than or equal to 9 measured 24 h after any acute phase infusion
MADRS Total Score, Percent Change From Baseline at Last Acute Phase Observation	-41.5 percentage change in score Standard Deviation 40.3	-79.1 percentage change in score Standard Deviation 13.0	-14.5 percentage change in score Standard Deviation 11.0

SECONDARY outcome

Timeframe: baseline, last acute phase observation (approximately 2 weeks)

Population: Statistical analyses included all subjects who received at least one acute-phase ketamine infusion.

The MADRS test includes 10 items and uses a 0 to 6 severity scale for each item, with higher scores indicating increasing depressive symptoms. MADRS Factor 1 (Sadness) consisted of MADRS items 1 (Apparent Sadness) and 2 (Reported Sadness). The MADRS Factor 1 Score is derived by adding all the scores from the 2 items, meaning the lowest possible score is 0 and the highest possible is 12.

Outcome measures

Measure	Entire Cohort n=12 Participants All enrolled subjects receiving at least one acute-phase ketamine infusion.	Remission n=5 Participants Remission was defined as a MADRS total score of less than or equal to 9 measured 24 hours after any acute phase infusion.	Non-Remission n=7 Participants Subjects who did not have a MADRS total score less than or equal to 9 measured 24 h after any acute phase infusion
MADRS Factor 1 Score at Baseline and Last Acute Phase Observation Last acute phase observation	3.5 units on a scale Standard Deviation 2.3	1.2 units on a scale Standard Deviation 0.5	5.1 units on a scale Standard Deviation 0.5
MADRS Factor 1 Score at Baseline and Last Acute Phase Observation Baseline	7.4 units on a scale Standard Deviation 2.0	7.4 units on a scale Standard Deviation 2.6	7.4 units on a scale Standard Deviation 1.7

SECONDARY outcome

Timeframe: baseline, last acute phase observation

Population: Statistical analyses included all subjects who received at least one acute-phase ketamine infusion.

The MADRS test includes 10 items and uses a 0 to 6 severity scale for each item, with higher scores indicating increasing depressive symptoms. MADRS Factor 1 (Sadness) consisted of MADRS items 1 (Apparent Sadness) and 2 (Reported Sadness). The MADRS Factor 1 Score is derived by adding all the scores from the 2 items, meaning the lowest possible score is 0 and the highest possible is 12.

Outcome measures

Measure	Entire Cohort n=12 Participants All enrolled subjects receiving at least one acute-phase ketamine infusion.	Remission n=5 Participants Remission was defined as a MADRS total score of less than or equal to 9 measured 24 hours after any acute phase infusion.	Non-Remission n=7 Participants Subjects who did not have a MADRS total score less than or equal to 9 measured 24 h after any acute phase infusion
MADRS Factor 1 Score, Percent Change From Baseline at Last Acute Phase Observation	-50.3 percentage change in score Standard Deviation 35.7	-83.6 percentage change in score Standard Deviation 15.7	-26.5 percentage change in score Standard Deviation 24.2

SECONDARY outcome

Timeframe: baseline, last acute phase observation (approximately 2 weeks)

Population: Statistical analyses included all subjects who received at least one acute-phase ketamine infusion.

The MADRS test includes 10 items and uses a 0 to 6 severity scale for each item, with higher scores indicating increasing depressive symptoms. MADRS Factor 2 (Negative Thoughts) consisted of MADRS items 9 (Pessimistic Thoughts) and 10 (Suicidal Thoughts). The MADRS Factor 2 Score is derived by adding all the scores from the 2 items, meaning the lowest possible score is 0 and the highest possible is 12.

Outcome measures

Measure	Entire Cohort n=12 Participants All enrolled subjects receiving at least one acute-phase ketamine infusion.	Remission n=5 Participants Remission was defined as a MADRS total score of less than or equal to 9 measured 24 hours after any acute phase infusion.	Non-Remission n=7 Participants Subjects who did not have a MADRS total score less than or equal to 9 measured 24 h after any acute phase infusion
MADRS Factor 2 Score at Baseline and Last Acute Phase Observation Baseline	6.0 units on a scale Standard Deviation 1.5	6.2 units on a scale Standard Deviation 1.6	5.9 units on a scale Standard Deviation 1.6
MADRS Factor 2 Score at Baseline and Last Acute Phase Observation Last acute phase observation	3.4 units on a scale Standard Deviation 1.7	1.8 units on a scale Standard Deviation 1.5	4.6 units on a scale Standard Deviation 0.5

SECONDARY outcome

Timeframe: baseline, last acute phase observation (approximately 2 weeks)

Population: Statistical analyses included all subjects who received at least one acute-phase ketamine infusion.

The MADRS test includes 10 items and uses a 0 to 6 severity scale for each item, with higher scores indicating increasing depressive symptoms. MADRS Factor 2 (negative thoughts) consisted of MADRS items 9 (Pessimistic Thoughts) and 10 (Suicidal Thoughts). The MADRS Factor 2 Score is derived by adding all the scores from the 2 items, meaning the lowest possible score is 0 and the highest possible is 12.

Outcome measures

Measure	Entire Cohort n=12 Participants All enrolled subjects receiving at least one acute-phase ketamine infusion.	Remission n=5 Participants Remission was defined as a MADRS total score of less than or equal to 9 measured 24 hours after any acute phase infusion.	Non-Remission n=7 Participants Subjects who did not have a MADRS total score less than or equal to 9 measured 24 h after any acute phase infusion
MADRS Factor 2 Score, Percentage Change From Baseline at Last Acute Phase Observation	-37.0 percentage change in score Standard Deviation 36.5	-65.4 percentage change in score Standard Deviation 31.4	-16.7 percentage change in score Standard Deviation 25.2

SECONDARY outcome

Timeframe: baseline, last acute phase observation (approximately 2 weeks)

Population: Statistical analyses included all subjects who received at least one acute-phase ketamine infusion.

The MADRS test includes 10 items and uses a 0 to 6 severity scale for each item, with higher scores indicating increasing depressive symptoms. MADRS Factor 3 (Detachment) consisted of MADRS items 6 - 8 (Concentration Difficulties, Lassitude, and Inability to Feel). The MADRS Factor 3 Score is derived by adding all the scores from the 3 items, meaning the lowest possible score is 0 and the highest possible is 18.

Outcome measures

Measure	Entire Cohort n=12 Participants All enrolled subjects receiving at least one acute-phase ketamine infusion.	Remission n=5 Participants Remission was defined as a MADRS total score of less than or equal to 9 measured 24 hours after any acute phase infusion.	Non-Remission n=7 Participants Subjects who did not have a MADRS total score less than or equal to 9 measured 24 h after any acute phase infusion
MADRS Factor 3 Score at Baseline and Last Acute Phase Observation Baseline	9.5 units on a scale Standard Deviation 3.1	9.8 units on a scale Standard Deviation 2.7	9.3 units on a scale Standard Deviation 3.5
MADRS Factor 3 Score at Baseline and Last Acute Phase Observation Last acute phase observation	4.9 units on a scale Standard Deviation 3.5	1.4 units on a scale Standard Deviation 1.3	7.4 units on a scale Standard Deviation 1.8

SECONDARY outcome

Timeframe: baseline, last acute phase observation (approximately 2 weeks)

Population: Statistical analyses included all subjects who received at least one acute-phase ketamine infusion.

The MADRS test includes 10 items and uses a 0 to 6 severity scale for each item, with higher scores indicating increasing depressive symptoms. MADRS Factor 3 (detachment) consisted of MADRS items 6 - 8 (Concentration Difficulties, Lassitude, and Inability to Feel). The MADRS Factor 3 Score is derived by adding all the scores from the 3 items, meaning the lowest possible score is 0 and the highest possible is 18.

Outcome measures

Measure	Entire Cohort n=12 Participants All enrolled subjects receiving at least one acute-phase ketamine infusion.	Remission n=5 Participants Remission was defined as a MADRS total score of less than or equal to 9 measured 24 hours after any acute phase infusion.	Non-Remission n=7 Participants Subjects who did not have a MADRS total score less than or equal to 9 measured 24 h after any acute phase infusion
MADRS Factor 3 Score, Percentage Change From Baseline at Last Acute Phase Observation	-40.2 percentage change in score Standard Deviation 48.5	-84.3 percentage change in score Standard Deviation 14.8	-8.9 percentage change in score Standard Deviation 37.3

SECONDARY outcome

Timeframe: baseline, last acute phase observation (approximately 2 weeks)

Population: Statistical analyses included all subjects who received at least one acute-phase ketamine infusion

The MADRS test includes 10 items and uses a 0 to 6 severity scale for each item, with higher scores indicating increasing depressive symptoms. MADRS Factor 4 (Neurovegetative Symptoms) consisted of MADRS items 3-5 (Inner Tension, Reduced Sleep, and Reduced Appetite). The MADRS Factor 4 Score is derived by adding all the scores from the 3 items, meaning the lowest possible score is 0 and the highest possible is 18.

Outcome measures

Measure	Entire Cohort n=12 Participants All enrolled subjects receiving at least one acute-phase ketamine infusion.	Remission n=5 Participants Remission was defined as a MADRS total score of less than or equal to 9 measured 24 hours after any acute phase infusion.	Non-Remission n=7 Participants Subjects who did not have a MADRS total score less than or equal to 9 measured 24 h after any acute phase infusion
MADRS Factor 4 Score at Baseline and Last Acute Phase Observation Baseline	6.5 units on a scale Standard Deviation 3.0	6.0 units on a scale Standard Deviation 3.8	6.9 units on a scale Standard Deviation 2.6
MADRS Factor 4 Score at Baseline and Last Acute Phase Observation Last acute phase observation	3.8 units on a scale Standard Deviation 3.6	1.0 units on a scale Standard Deviation 1.2	5.9 units on a scale Standard Deviation 3.4

SECONDARY outcome

Timeframe: baseline, last acute phase observation (approximately 2 weeks)

Population: Statistical analyses included all subjects who received at least one acute-phase ketamine infusion.

The MADRS test includes 10 items and uses a 0 to 6 severity scale for each item, with higher scores indicating increasing depressive symptoms. MADRS Factor 4 (neurovegetative symptoms) consisted of MADRS items 3-5 (Inner Tension, Reduced Sleep, and Reduced Appetite). The MADRS Factor 4 Score is derived by adding all the scores from the 3 items, meaning the lowest possible score is 0 and the highest possible is 18.

Outcome measures

Measure	Entire Cohort n=12 Participants All enrolled subjects receiving at least one acute-phase ketamine infusion.	Remission n=5 Participants Remission was defined as a MADRS total score of less than or equal to 9 measured 24 hours after any acute phase infusion.	Non-Remission n=7 Participants Subjects who did not have a MADRS total score less than or equal to 9 measured 24 h after any acute phase infusion
MADRS Factor 4 Score, Percentage Change From Baseline at Last Acute Phase Observation	-36.0 percentage change in score Standard Deviation 58.0	-84.3 percentage change in score Standard Deviation 20.4	-8.4 percentage change in score Standard Deviation 54.4

SECONDARY outcome

Timeframe: baseline, last acute phase observation (approximately 2 weeks)

Population: Statistical analyses included all subjects who received at least one acute-phase ketamine infusion.

The MADRS test includes 10 items and uses a 0 to 6 severity scale for each item, with higher scores indicating increasing depressive symptoms. Item 10 scores can range from 0 to 6 (with 0 indicating enjoying life, and 6 indicating explicit plans for suicide.)

Outcome measures

Measure	Entire Cohort n=12 Participants All enrolled subjects receiving at least one acute-phase ketamine infusion.	Remission n=5 Participants Remission was defined as a MADRS total score of less than or equal to 9 measured 24 hours after any acute phase infusion.	Non-Remission n=7 Participants Subjects who did not have a MADRS total score less than or equal to 9 measured 24 h after any acute phase infusion
MADRS Suicide Thoughts (Item 10) Score at Last Acute Phase Observation Baseline	2.9 units on a scale Standard Deviation 1.1	3.2 units on a scale Standard Deviation 1.1	2.7 units on a scale Standard Deviation 1.1
MADRS Suicide Thoughts (Item 10) Score at Last Acute Phase Observation Last acute phase observation	1.7 units on a scale Standard Deviation 0.8	1.2 units on a scale Standard Deviation 0.8	2.2 units on a scale Standard Deviation 0.4

SECONDARY outcome

Timeframe: baseline, last acute phase observation (approximately 2 weeks)

Population: Statistical analyses included all subjects who received at least one acute-phase ketamine infusion.

The MADRS test includes 10 items and uses a 0 to 6 severity scale for each item, with higher scores indicating increasing depressive symptoms. Item 10 scores can range from 0 to 6 (with 0 indicating enjoying life, and 6 indicating explicit plans for suicide.)

Outcome measures

Measure	Entire Cohort n=12 Participants All enrolled subjects receiving at least one acute-phase ketamine infusion.	Remission n=5 Participants Remission was defined as a MADRS total score of less than or equal to 9 measured 24 hours after any acute phase infusion.	Non-Remission n=7 Participants Subjects who did not have a MADRS total score less than or equal to 9 measured 24 h after any acute phase infusion
MADRS Suicide (Item 10) Score, Percentage Change From Baseline at Last Acute Phase Observation	-26.7 percentage change in score Standard Deviation 45.4	-50.0 percentage change in score Standard Deviation 46.8	-7.2 percentage change in score Standard Deviation 37.1

SECONDARY outcome

Timeframe: baseline, last acute phase observation (approximately 2 weeks)

Population: Statistical analyses included all subjects who received at least one acute-phase ketamine infusion.

The Clinical Global Impression Severity Subscale is an observer rated scale that measures illness severity. It has a range of responses from 1 (normal) through to 7 (among the most extremely ill patients).

Outcome measures

Measure	Entire Cohort n=12 Participants All enrolled subjects receiving at least one acute-phase ketamine infusion.	Remission n=5 Participants Remission was defined as a MADRS total score of less than or equal to 9 measured 24 hours after any acute phase infusion.	Non-Remission n=7 Participants Subjects who did not have a MADRS total score less than or equal to 9 measured 24 h after any acute phase infusion
Clinical Global Impression-severity Subscale (CGI-S) at Baseline and Last Acute Phase Observation Baseline	5.6 units on a scale Standard Deviation 0.5	5.4 units on a scale Standard Deviation 0.5	5.7 units on a scale Standard Deviation 0.5
Clinical Global Impression-severity Subscale (CGI-S) at Baseline and Last Acute Phase Observation Last acute phase observation	3.9 units on a scale Standard Deviation 1.7	2.6 units on a scale Standard Deviation 0.9	4.9 units on a scale Standard Deviation 1.6

SECONDARY outcome

Timeframe: baseline, last acute phase observation (approximately 2 weeks)

Population: Statistical analyses included all subjects who received at least one acute-phase ketamine infusion.

The Clinical Global Impression Severity Subscale is an observer rated scale that measures illness severity. It has a range of responses from 1 (normal) through to 7 (among the most extremely ill patients).

Outcome measures

Measure	Entire Cohort n=12 Participants All enrolled subjects receiving at least one acute-phase ketamine infusion.	Remission n=5 Participants Remission was defined as a MADRS total score of less than or equal to 9 measured 24 hours after any acute phase infusion.	Non-Remission n=7 Participants Subjects who did not have a MADRS total score less than or equal to 9 measured 24 h after any acute phase infusion
CGI-S Score, Percentage Change From Baseline at Last Acute Phase Observation	-29.4 percentage change in score Standard Deviation 30.8	-50.7 percentage change in score Standard Deviation 20.3	-14.3 percentage change in score Standard Deviation 28.7

Adverse Events

Ketamine Infusion

Serious events: 2 serious events

Other events: 12 other events

Deaths: 1 deaths

Serious adverse events

Measure	Ketamine Infusion n=12 participants at risk This trial was conducted in 2 phases. During the acute-phase, i.v. ketamine was administered thrice-weekly for up to 2 weeks.Those who achieved depressive symptom remission received continuation-phase treatment that consisted of once-weekly i.v. ketamine infusions for 4 additional weeks. Remission could occur after any of the 6 acute-phase infusions, at which point the next infusion was the first (of four) continuation-phase infusions. Individuals who remitted during acute-phase and completed continuation-phase treatment had 4 additional weekly post-continuation follow-up visits. Ketamine: 0.3 mg/kg/hr of ketamine infused for 100 minutes
Psychiatric disorders Clinical worsening - behavioral outburst and suicide threats	8.3% 1/12 • Number of events 1 • 10 weeks
Psychiatric disorders Suicide	8.3% 1/12 • Number of events 1 • 10 weeks

Other adverse events

Measure	Ketamine Infusion n=12 participants at risk This trial was conducted in 2 phases. During the acute-phase, i.v. ketamine was administered thrice-weekly for up to 2 weeks.Those who achieved depressive symptom remission received continuation-phase treatment that consisted of once-weekly i.v. ketamine infusions for 4 additional weeks. Remission could occur after any of the 6 acute-phase infusions, at which point the next infusion was the first (of four) continuation-phase infusions. Individuals who remitted during acute-phase and completed continuation-phase treatment had 4 additional weekly post-continuation follow-up visits. Ketamine: 0.3 mg/kg/hr of ketamine infused for 100 minutes
Psychiatric disorders Dissociation	75.0% 9/12 • Number of events 9 • 10 weeks
General disorders Dizziness	58.3% 7/12 • Number of events 7 • 10 weeks
General disorders Numbness or tingling in extremities	58.3% 7/12 • Number of events 7 • 10 weeks
General disorders Sleepiness or sedation	50.0% 6/12 • Number of events 6 • 10 weeks
Psychiatric disorders tearfulness/emotionality	33.3% 4/12 • Number of events 4 • 10 weeks
Nervous system disorders Facial numbness	25.0% 3/12 • Number of events 3 • 10 weeks
Blood and lymphatic system disorders Transient increases in systolic blood pressure	100.0% 12/12 • Number of events 12 • 10 weeks
Blood and lymphatic system disorders Transient increases in diastolic blood pressue	100.0% 12/12 • Number of events 12 • 10 weeks

Additional Information

William V. Bobo, M.D.

Mayo Clinic

Phone: 507-538-9041

Email: Bobo.William@mayo.edu

Results disclosure agreements

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