Trial Outcomes & Findings for Intravenous Ketamine Plus Neurocognitive Training for Depression (NCT NCT03237286)

NCT ID: NCT03237286

Last Updated: 2024-03-19

Results Overview

Clinician-rated depression (range: 0-60; higher scores = worse outcome)

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 154 participants
• Primary outcome timeframe: Trajectories from 24 hours through Day 30 post-infusion, Day 30 reported
• Results posted on: 2024-03-19

Participant Flow

Participant milestones

Measure	Ketamine + Cognitive Training Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression. Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.	Ketamine + Sham Training Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression.	Saline + Cognitive Training Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.
Overall Study STARTED	53	50	51
Overall Study COMPLETED	52	50	48
Overall Study NOT COMPLETED	1	0	3

Reasons for withdrawal

Measure	Ketamine + Cognitive Training Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression. Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.	Ketamine + Sham Training Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression.	Saline + Cognitive Training Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.
Overall Study Withdrawal by Subject	1	0	2
Overall Study Study withdrew participant due to repeated non-compliance	0	0	1

Baseline Characteristics

Intravenous Ketamine Plus Neurocognitive Training for Depression

Baseline characteristics by cohort

Measure	Ketamine + Cognitive Training n=53 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression. Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.	Ketamine + Sham Training n=50 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression.	Saline + Cognitive Training n=51 Participants Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.	Total n=154 Participants Total of all reporting groups
Age, Continuous	34.70 years STANDARD_DEVIATION 10.10 • n=5 Participants	34.60 years STANDARD_DEVIATION 11.60 • n=7 Participants	33.50 years STANDARD_DEVIATION 9.90 • n=5 Participants	34.26 years STANDARD_DEVIATION 10.50 • n=4 Participants
Sex: Female, Male Female	32 Participants n=5 Participants	32 Participants n=7 Participants	33 Participants n=5 Participants	97 Participants n=4 Participants
Sex: Female, Male Male	21 Participants n=5 Participants	18 Participants n=7 Participants	18 Participants n=5 Participants	57 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	11 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	45 Participants n=5 Participants	45 Participants n=7 Participants	47 Participants n=5 Participants	137 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	6 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	9 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants
Race (NIH/OMB) White	44 Participants n=5 Participants	40 Participants n=7 Participants	41 Participants n=5 Participants	125 Participants n=4 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	5 Participants n=7 Participants	4 Participants n=5 Participants	11 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Montgomery Asberg Depression Rating Scale	32.28 units on a scale STANDARD_DEVIATION 5.70 • n=5 Participants	33.48 units on a scale STANDARD_DEVIATION 4.90 • n=7 Participants	32.61 units on a scale STANDARD_DEVIATION 5.10 • n=5 Participants	32.78 units on a scale STANDARD_DEVIATION 5.30 • n=4 Participants
Number of failed antidepressant trials	2.66 trials STANDARD_DEVIATION 1.59 • n=5 Participants	2.60 trials STANDARD_DEVIATION 1.67 • n=7 Participants	2.67 trials STANDARD_DEVIATION 2.46 • n=5 Participants	2.64 trials STANDARD_DEVIATION 1.93 • n=4 Participants

PRIMARY outcome

Timeframe: Trajectories from 24 hours through Day 30 post-infusion, Day 30 reported

Population: All participants who were assigned to the arm and were willing and able to complete this specific measure.

Clinician-rated depression (range: 0-60; higher scores = worse outcome)

Outcome measures

Measure	Ketamine + Cognitive Training n=53 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression. Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.	Ketamine + Sham Training n=50 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression.	Saline + Cognitive Training n=51 Participants Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.
Montgomery Asberg Depression Scale	19.72 score on a scale Standard Deviation 10.20	22.87 score on a scale Standard Deviation 11.63	23.51 score on a scale Standard Deviation 9.66

PRIMARY outcome

Timeframe: Trajectories from 24 hours through Day 30 post-infusion, 24 hours reported

Population: All participants who were assigned to the arm and were willing and able to complete this specific measure.

fMRI measure (beta weights where larger beta weight = stronger connectivity)

Outcome measures

Measure	Ketamine + Cognitive Training n=53 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression. Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.	Ketamine + Sham Training n=49 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression.	Saline + Cognitive Training n=47 Participants Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.
Executive-salience Network Functional Connectivity	0.55 beta weights Standard Deviation 0.11	0.59 beta weights Standard Deviation 0.11	0.57 beta weights Standard Deviation 0.10

PRIMARY outcome

Timeframe: Trajectories from 24 hours through Day 30 post-infusion, Day 5 reported

Population: All participants who were assigned to the arm and were willing and able to complete this specific measure.

Implicit Association Test composite difference score (performance-based measure; range = -inf-inf; high score=worse outcome; negatively signed value indicates associating oneself more strongly with positive than negative attributes)

Outcome measures

Measure	Ketamine + Cognitive Training n=51 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression. Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.	Ketamine + Sham Training n=43 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression.	Saline + Cognitive Training n=44 Participants Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.
Implicit Self-representations	-.16 factor score Standard Deviation 1.00	0.15 factor score Standard Deviation 1.03	0.03 factor score Standard Deviation 0.97

PRIMARY outcome

Timeframe: Trajectories from 24 hours through Day 30 post-infusion, Day 30 reported

Population: All participants who were assigned to the arm and were willing and able to complete this specific measure.

Neurocognitive testing via NIH Toolbox DCCS fully-corrected T-scores (range = 0-100; high score=better outcome)

Outcome measures

Measure	Ketamine + Cognitive Training n=37 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression. Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.	Ketamine + Sham Training n=35 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression.	Saline + Cognitive Training n=36 Participants Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.
Cognitive Flexibility	54.51 score on a scale Standard Deviation 13.33	49.34 score on a scale Standard Deviation 12.48	53.25 score on a scale Standard Deviation 12.98

PRIMARY outcome

Timeframe: Trajectories from Day 30 through 12 months post-infusion (naturalistic follow-up), Month 12 reported

Population: All participants who were assigned to the arm and were willing and able to complete this specific measure.

Self-reported depression (range: 0-27; higher scores = worse outcome)

Outcome measures

Measure	Ketamine + Cognitive Training n=26 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression. Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.	Ketamine + Sham Training n=29 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression.	Saline + Cognitive Training n=26 Participants Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.
Quick Inventory of Depressive Symptoms	10.77 score on a scale Standard Deviation 6.84	12.03 score on a scale Standard Deviation 5.94	10.42 score on a scale Standard Deviation 4.38

SECONDARY outcome

Timeframe: Trajectories from 24 hours through Day 30 post-infusion, 24 hours reported

Population: All participants who were assigned to the arm and were willing and able to complete this specific measure.

fMRI measure (beta weights where larger beta weight = stronger connectivity)

Outcome measures

Measure	Ketamine + Cognitive Training n=53 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression. Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.	Ketamine + Sham Training n=49 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression.	Saline + Cognitive Training n=47 Participants Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.
Executive-salience Network Functional Connectivity During Resting State	0.53 beta weights Standard Deviation 0.10	0.50 beta weights Standard Deviation 0.09	0.51 beta weights Standard Deviation 0.12

SECONDARY outcome

Timeframe: Trajectories from 24 hours through Day 30 post-infusion, Day 30 reported

Population: All participants who were assigned to the arm and were willing and able to complete this specific measure.

'D-Prime' discrimination Z-score measured via accuracy of responses during the Affective Go/No-Go task (range: -inf-inf; high score=better performance; Z-score of 0=the sample mean)

Outcome measures

Measure	Ketamine + Cognitive Training n=45 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression. Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.	Ketamine + Sham Training n=43 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression.	Saline + Cognitive Training n=43 Participants Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.
Affective Flexibility	-.18 Z-score Standard Deviation 1.71	-.07 Z-score Standard Deviation 1.52	0.26 Z-score Standard Deviation 1.62

SECONDARY outcome

Timeframe: Trajectories from 24 hours through Month 12 post-infusion, Month 12 reported

Population: All participants who were assigned to the arm and were willing and able to complete this specific measure.

Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported depression T-score range: 0-100 (higher score = worse outcome)

Outcome measures

Measure	Ketamine + Cognitive Training n=35 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression. Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.	Ketamine + Sham Training n=38 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression.	Saline + Cognitive Training n=35 Participants Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.
PROMIS Measures-depression	58.97 score on a scale Standard Deviation 12.15	61.01 score on a scale Standard Deviation 9.54	57.13 score on a scale Standard Deviation 9.57

SECONDARY outcome

Timeframe: Trajectories from 24 hours through Month 12 post-infusion, Month 12 reported

Population: All participants who were assigned to the arm and were willing and able to complete this specific measure.

Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported anxiety T-score range: 0-100 (higher score = worse outcome)

Outcome measures

Measure	Ketamine + Cognitive Training n=35 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression. Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.	Ketamine + Sham Training n=38 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression.	Saline + Cognitive Training n=35 Participants Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.
PROMIS Measures-anxiety	58.07 score on a scale Standard Deviation 9.42	62.49 score on a scale Standard Deviation 9.26	57.88 score on a scale Standard Deviation 8.87

SECONDARY outcome

Timeframe: Trajectories from 24 hours through Month 12 post-infusion, Month 12 reported

Population: All participants who were assigned to the arm and were willing and able to complete this specific measure.

Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported anger T-score range: 0-100 (higher score = worse outcome)

Outcome measures

Measure	Ketamine + Cognitive Training n=35 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression. Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.	Ketamine + Sham Training n=38 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression.	Saline + Cognitive Training n=35 Participants Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.
PROMIS Measures-anger	50.27 score on a scale Standard Deviation 13.03	54.21 score on a scale Standard Deviation 10.44	49.59 score on a scale Standard Deviation 10.23

SECONDARY outcome

Timeframe: Trajectories from 24 hours through Month 12 post-infusion, Month 12 reported

Population: All participants who were assigned to the arm and were willing and able to complete this specific measure.

Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported positive affect/well-being T-score range: 0-100 (higher score = better outcome)

Outcome measures

Measure	Ketamine + Cognitive Training n=35 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression. Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.	Ketamine + Sham Training n=38 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression.	Saline + Cognitive Training n=35 Participants Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.
PROMIS Measures-positive Affect	44.12 score on a scale Standard Deviation 7.72	44.02 score on a scale Standard Deviation 7.76	45.98 score on a scale Standard Deviation 7.60

SECONDARY outcome

Timeframe: Trajectories from 24 hours through Month 12 post-infusion, Month 12 reported

Population: All participants who were assigned to the arm and were willing and able to complete this specific measure.

Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported sleep disturbance T-score range: 0-100 (higher score = worse outcome)

Outcome measures

Measure	Ketamine + Cognitive Training n=35 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression. Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.	Ketamine + Sham Training n=38 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression.	Saline + Cognitive Training n=35 Participants Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.
PROMIS Measures-sleep Disturbance	53.06 score on a scale Standard Deviation 9.91	53.78 score on a scale Standard Deviation 8.63	51.41 score on a scale Standard Deviation 10.29

SECONDARY outcome

Timeframe: Trajectories from 24 hours through Month 12 post-infusion, Month 12 reported

Population: All participants who were assigned to the arm and were willing and able to complete this specific measure.

Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported cognitive function T-score range: 0-100 (higher score = better outcome)

Outcome measures

Measure	Ketamine + Cognitive Training n=36 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression. Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.	Ketamine + Sham Training n=38 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression.	Saline + Cognitive Training n=35 Participants Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.
PROMIS Measures-cognitive Function	43.61 score on a scale Standard Deviation 9.54	39.19 score on a scale Standard Deviation 8.07	44.87 score on a scale Standard Deviation 8.81

SECONDARY outcome

Timeframe: Trajectories from 24 hours through Month 12 post-infusion, Month 12 reported

Population: All participants who were assigned to the arm and were willing and able to complete this specific measure.

Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported substance use Raw score range: 0-35 (higher score = worse outcome)

Outcome measures

Measure	Ketamine + Cognitive Training n=34 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression. Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.	Ketamine + Sham Training n=38 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression.	Saline + Cognitive Training n=35 Participants Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.
PROMIS Measures-substance Use	3.00 score on a scale Standard Deviation 5.22	2.32 score on a scale Standard Deviation 5.09	3.03 score on a scale Standard Deviation 5.94

SECONDARY outcome

Timeframe: Trajectories from 24 hours through Month 12 post-infusion, Month 12 reported

Population: All participants who were assigned to the arm and were willing and able to complete this specific measure.

Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported alcohol use T-score range: 0-100 (higher score = worse outcome)

Outcome measures

Measure	Ketamine + Cognitive Training n=35 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression. Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.	Ketamine + Sham Training n=38 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression.	Saline + Cognitive Training n=35 Participants Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.
PROMIS Measures-alcohol	46.29 score on a scale Standard Deviation 8.56	47.82 score on a scale Standard Deviation 5.35	47.25 score on a scale Standard Deviation 7.04

SECONDARY outcome

Timeframe: Trajectories from 24 hours through Month 12 post-infusion, Month 12 reported

Population: All participants who were assigned to the arm and were willing and able to complete this specific measure.

Negative perceptions of self, future, & world (range=36-252; higher score = better outcome)

Outcome measures

Measure	Ketamine + Cognitive Training n=36 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression. Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.	Ketamine + Sham Training n=38 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression.	Saline + Cognitive Training n=35 Participants Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.
Cognitive Triad Inventory	133.89 score on a scale Standard Deviation 35.15	126.00 score on a scale Standard Deviation 39.02	138.97 score on a scale Standard Deviation 28.50

SECONDARY outcome

Timeframe: Trajectories from 24 hours through Month 12 post-infusion, Month 12 reported

Population: All participants who were assigned to the arm and were willing and able to complete this specific measure.

Suicidality and patient safety (most severe ideation score, range=0-5; higher score = worse outcome)

Outcome measures

Measure	Ketamine + Cognitive Training n=27 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression. Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.	Ketamine + Sham Training n=30 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression.	Saline + Cognitive Training n=29 Participants Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.
Columbia-Suicide Severity Rating Scale	0.70 score on a scale Standard Deviation 1.14	1.30 score on a scale Standard Deviation 1.24	1.10 score on a scale Standard Deviation 1.29

SECONDARY outcome

Timeframe: Trajectories from 24 hours through Month 12 post-infusion, Month 12 reported

Population: All participants who were assigned to the arm and were willing and able to complete this specific measure.

Global functioning (range=0-48; higher score = worse outcome)

Outcome measures

Measure	Ketamine + Cognitive Training n=33 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression. Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.	Ketamine + Sham Training n=36 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression.	Saline + Cognitive Training n=33 Participants Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.
WHO Disability Assessment Scale (SR)	10.58 score on a scale Standard Deviation 9.28	15.75 score on a scale Standard Deviation 10.87	12.64 score on a scale Standard Deviation 10.72

SECONDARY outcome

Timeframe: Trajectories from 24 hours through Month 12 post-infusion, Month 12 reported

Population: All participants who were assigned to the arm and were willing and able to complete this specific measure.

Self-reported cognitive flexibility (range=12-72; higher score = better outcome)

Outcome measures

Measure	Ketamine + Cognitive Training n=36 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression. Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.	Ketamine + Sham Training n=38 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression.	Saline + Cognitive Training n=35 Participants Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.
Cognitive Flexibility Scale	52.64 score on a scale Standard Deviation 8.82	50.82 score on a scale Standard Deviation 10.81	51.20 score on a scale Standard Deviation 10.46

SECONDARY outcome

Timeframe: 40min post-infusion

Population: All participants who were assigned to the arm and were willing and able to complete this specific measure.

ketamine metabolite (2R,6R)-HNK concentration levels (range=0-inf; higher score = greater concentration in blood)

Outcome measures

Measure	Ketamine + Cognitive Training n=50 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression. Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.	Ketamine + Sham Training n=50 Participants Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression.	Saline + Cognitive Training Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.
Neuroplasticity-related Markers in Blood	26.94 ng/mL Standard Deviation 11.59	27.35 ng/mL Standard Deviation 11.76	—

Adverse Events

Ketamine

Serious events: 0 serious events

Other events: 102 other events

Deaths: 0 deaths

Saline

Serious events: 0 serious events

Other events: 38 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Ketamine n=103 participants at risk Includes all participants receiving the study drug (0.5 mg/kg IV ketamine over 40min), irrespective of Cognitive Training condition (active and sham collapsed)	Saline n=51 participants at risk Includes all participants receiving a placebo infusion of saline (over 40min). All participants in this arm later went on to receive the active Cognitive Training condition.
Psychiatric disorders anxiety	9.7% 10/103 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.	3.9% 2/51 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.
General disorders decreased energy	15.5% 16/103 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.	5.9% 3/51 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.
Nervous system disorders difficulty focusing vision	1.9% 2/103 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.	0.00% 0/51 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.
Psychiatric disorders difficulty sleeping: too little	0.97% 1/103 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.	2.0% 1/51 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.
Psychiatric disorders difficulty sleeping: too much	4.9% 5/103 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.	7.8% 4/51 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.
Renal and urinary disorders difficulty urinating	0.97% 1/103 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.	0.00% 0/51 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.
Psychiatric disorders dissociative effects	97.1% 100/103 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.	21.6% 11/51 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.
Nervous system disorders dizziness	68.0% 70/103 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.	19.6% 10/51 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.
Gastrointestinal disorders dry mouth	38.8% 40/103 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.	9.8% 5/51 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.
Cardiac disorders elevated blood pressure	6.8% 7/103 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.	3.9% 2/51 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.
Cardiac disorders elevated heart rate	2.9% 3/103 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.	0.00% 0/51 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.
Gastrointestinal disorders emesis	3.9% 4/103 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.	0.00% 0/51 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.
Psychiatric disorders emotional indifference	7.8% 8/103 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.	2.0% 1/51 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.
General disorders feeling "discombobulated"	0.97% 1/103 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.	0.00% 0/51 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.
Psychiatric disorders feeling "high" (per verbal report)	0.97% 1/103 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.	0.00% 0/51 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.
Nervous system disorders headache	16.5% 17/103 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.	7.8% 4/51 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.
Gastrointestinal disorders increased appetite	11.7% 12/103 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.	2.0% 1/51 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.
Metabolism and nutrition disorders increased weight	0.97% 1/103 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.	0.00% 0/51 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.
Reproductive system and breast disorders loss of sexual desire	1.9% 2/103 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.	0.00% 0/51 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.
Cardiac disorders lowered pulse	0.97% 1/103 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.	0.00% 0/51 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.
Gastrointestinal disorders nausea	30.1% 31/103 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.	13.7% 7/51 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.
Cardiac disorders palpitations	10.7% 11/103 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.	0.00% 0/51 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.
General disorders restlessness	17.5% 18/103 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.	3.9% 2/51 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.
Psychiatric disorders suicidal ideation	0.97% 1/103 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.	0.00% 0/51 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.
General disorders sweating	17.5% 18/103 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.	5.9% 3/51 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.
Nervous system disorders tinnitus	0.97% 1/103 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.	0.00% 0/51 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.
Nervous system disorders tremors	5.8% 6/103 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.	2.0% 1/51 • 4 hours Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.

Additional Information

Dr. Rebecca Price

University of Pittsburgh

Phone: 412-383-2150

Email: pricerb@upmc.edu

Results disclosure agreements

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