NCT01627782

A Study of Ketamine in Patients With Treatment-resistant Depression

Completed Phase 2 Results posted Last updated 29 April 2025

What this trial tests

Phase 2 trial testing Placebo in Major Depressive Disorder in 68 participants. Completed in 12 September 2013.

Timeline

6 August 2012

Primary endpoint
12 September 2013

12 September 2013

Quick facts

Lead sponsor	Janssen Research & Development, LLC
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	68
Start date	6 August 2012
Primary completion	12 September 2013
Estimated completion	12 September 2013
Sites	13 locations across United States

Drugs / interventions tested

• Placebo
• Ketamine (ketamine) — full drug profile →

Conditions studied

• Major Depressive Disorder — all drugs for Major Depressive Disorder →

Sponsor

Janssen Research & Development, LLC — full company profile →

Who can join

Adults 18 to 64, any sex, with Major Depressive Disorder. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline to Day 15 Primary · Baseline (Day 1) and Day 15

The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total score of 60. Higher scores represent a more severe condition.

Baseline (n=16,18,16,17)

Group	Value	95% CI
Placebo: 2 Times Per Week	35.6	± 3.79
Ketamine: 2 Times Per Week	33.3	± 4.91
Placebo: 3 Times Per Week	36.8	± 5.83
Ketamine: 3 Times Per Week	35.4	± 5.28

Change at Day 15 (n=13,16,16,13)

Group	Value	95% CI
Placebo: 2 Times Per Week	-5.7	± 10.23
Ketamine: 2 Times Per Week	-18.4	± 12.01
Placebo: 3 Times Per Week	-3.1	± 5.67
Ketamine: 3 Times Per Week	-17.7	± 7.27

Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline to Day 29 Secondary · Baseline (Day 1) and Day 29

The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total score of 60. Higher scores represent a more severe condition.

Baseline (n=16,18,16,17)

Group	Value	95% CI
Placebo: 2 Times Per Week	35.6	± 3.79
Ketamine: 2 Times Per Week	33.3	± 4.91
Placebo: 3 Times Per Week	36.8	± 5.83
Ketamine: 3 Times Per Week	35.4	± 5.28

Change at Day 29 (n=2,13,1,13)

Group	Value	95% CI
Placebo: 2 Times Per Week	-23.5	± 10.61
Ketamine: 2 Times Per Week	-27.1	± 6.60
Placebo: 3 Times Per Week	-1	± NA
Ketamine: 3 Times Per Week	-22.9	± 10.61

Number of Responders Based on Montgomery-Asberg Depression Rating Scale (MADRS) Total Score Secondary · Day 15 and Day 29

Participants with a reduction in the MADRS total score of greater than or equal to (\>=) 50 percent from baseline were defined as responders. The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total score of 60. Higher scores represent a more severe condition.

Day 15 (n=13,16,16,13)

Group	Value	95% CI
Placebo: 2 Times Per Week	2	± 3.79
Ketamine: 2 Times Per Week	11	± 4.91
Placebo: 3 Times Per Week	1	± 5.83
Ketamine: 3 Times Per Week	7	± 5.28

Day 29 (n=2,13,1,13)

Group	Value	95% CI
Placebo: 2 Times Per Week	1	± 10.61
Ketamine: 2 Times Per Week	13	± 6.60
Placebo: 3 Times Per Week	0	± NA
Ketamine: 3 Times Per Week	9	± 10.61

Number of Remitters Based on Montgomery-Asberg Depression Rating Scale (MADRS) Total Score Secondary · Day 15 and Day 29

Participants who had a MADRS total score of less than or equal to (\<=) 10 were considered remitters. The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total score of 60. Higher scores represent a more severe condition.

Day 15 (n=13,16,16,13)

Group	Value	95% CI
Placebo: 2 Times Per Week	1	± 3.79
Ketamine: 2 Times Per Week	6	± 4.91
Placebo: 3 Times Per Week	0	± 5.83
Ketamine: 3 Times Per Week	3	± 5.28

Day 29 (n=2,13,1,13)

Group	Value	95% CI
Placebo: 2 Times Per Week	1	± 10.61
Ketamine: 2 Times Per Week	12	± 6.60
Placebo: 3 Times Per Week	0	± NA
Ketamine: 3 Times Per Week	5	± 10.61

Number of Sustained Responders Based on Montgomery-Asberg Depression Rating Scale (MADRS) Total Score Secondary · Day 15

Sustained response on Day 15 was defined as achieving an onset of antidepressant response within the first week that is maintained to the end of study Day 15. The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total score of 60. Higher scores represent a more severe condition.

Group	Value	95% CI
Placebo: 2 Times Per Week	1	± 3.79
Ketamine: 2 Times Per Week	7	± 4.91
Placebo: 3 Times Per Week	0	± 5.83
Ketamine: 3 Times Per Week	4	± 5.28

Change in Clinical Global Impression-Severity (CGI-S) Score From Baseline to Endpoint (Day 29) Secondary · Baseline (Day 1) and Endpoint (Day 29)

The CGI-S was used to rate the severity of the participants illness at the time of assessment, relative to the clinician's past experience with participants who had the same diagnosis and improvement with treatment. Considering total clinical experience, a participant was assessed on severity of mental illness at the time of rating according to: 0= not assessed; 1=normal (not at all ill); 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill participants.

Baseline (n=15,18,16,17)

Group	Value	95% CI
Placebo: 2 Times Per Week	5.0	4 – 6
Ketamine: 2 Times Per Week	5.0	4 – 6
Placebo: 3 Times Per Week	5.0	4 – 6
Ketamine: 3 Times Per Week	5.0	4 – 6

Change at Endpoint (n=15,18,16,17)

Group	Value	95% CI
Placebo: 2 Times Per Week	0.0	-4 – 0
Ketamine: 2 Times Per Week	-2.0	-4 – 1
Placebo: 3 Times Per Week	0.0	-1 – 1
Ketamine: 3 Times Per Week	-2.0	-4 – 0

Clinical Global Impression of Improvement (CGI-I) Score at Endpoint of Double Blind Phase Secondary · Endpoint (Day 29)

The CGI-I is a 7-point scale that was used to assess how much the participants illness was improved or worsened relative to a baseline state at the beginning of the intervention and rated as: 0= not assessed; 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse.

Group	Value	95% CI
Placebo: 2 Times Per Week	4.0	1 – 5
Ketamine: 2 Times Per Week	2.0	1 – 5
Placebo: 3 Times Per Week	4.0	2 – 5
Ketamine: 3 Times Per Week	2.0	1 – 5

Change in Patient Global Impression-Severity (PGI-S) Score From Baseline to Endpoint (Day 29) Secondary · Baseline (Day 1) and Endpoint (Day 29)

The PGI-S is an 11-point (0 to 10) scale that required the participant to rate the severity of their illness at the time of assessment, relative to the participants past experience. Considering their total experience, the participant was to assess the severity of their depression illness at the time of rating as none, mild, moderate or severe. The scale is rated as, 0=very well and 10=very poor.

Baseline (n=15,18,16,17)

Group	Value	95% CI
Placebo: 2 Times Per Week	8.0	4 – 9
Ketamine: 2 Times Per Week	7.5	5 – 9
Placebo: 3 Times Per Week	8.0	5 – 10
Ketamine: 3 Times Per Week	7.0	5 – 9

Change at Endpoint (n=15,18,16,17)

Group	Value	95% CI
Placebo: 2 Times Per Week	0.0	-3 – 2
Ketamine: 2 Times Per Week	-4.0	-8 – 0
Placebo: 3 Times Per Week	-1.0	-3 – 1
Ketamine: 3 Times Per Week	-3.0	-8 – 1

Patient Global Impression-Change (PGI-C) Score at Endpoint of Double Blind Phase Secondary · Endpoint (Day 29)

The PGI-C is a 7-point scale that required the subject to assess how much their illness had improved or worsened relative to a baseline state at the beginning of the intervention. The response options were: very much improved; much improved; improved (just enough to make a difference); no change; worse (just enough to make a difference); much worse; or very much worse. The scale is rated as, 1=very much improved and 7=very much worse.

Group	Value	95% CI
Placebo: 2 Times Per Week	4.0	2 – 6
Ketamine: 2 Times Per Week	2.0	1 – 4
Placebo: 3 Times Per Week	4.0	3 – 6
Ketamine: 3 Times Per Week	3.0	1 – 4

Maximum Observed Plasma Concentration (Cmax) of Ketamine Secondary · Pre-infusion, 20, 40 (End of the Infusion), 45, 50, 60, 90, 120, 180, 240 and 360 minutes post-infusion on Day 1 and Day 15

The Cmax is the maximum observed plasma concentration of drug.

Day 1 (n=16,16)

Group	Value	95% CI
Ketamine: 2 Times Per Week	207	5 – 9
Ketamine: 3 Times Per Week	168	5 – 9

Day 15 (n=14,15)

Group	Value	95% CI
Ketamine: 2 Times Per Week	219	-8 – 0
Ketamine: 3 Times Per Week	189	-8 – 1

Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ketamine Secondary · Pre-infusion, 20, 40 (End of the Infusion), 45, 50, 60, 90, 120, 180, 240 and 360 minutes post-infusion on Day 1 and Day 15

The Tmax is defined as actual sampling time to reach maximum observed drug concentration.

Day 1 (n=16,16)

Group	Value	95% CI
Ketamine: 2 Times Per Week	0.67	0.63 – 0.83
Ketamine: 3 Times Per Week	0.66	0.33 – 0.75

Day 15 (n=14,15)

Group	Value	95% CI
Ketamine: 2 Times Per Week	0.67	0.63 – 1.00
Ketamine: 3 Times Per Week	0.67	0.5 – 0.83

Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC[0-last]) Secondary · Pre-infusion, 20, 40 (End of the Infusion), 45, 50, 60, 90, 120, 180, 240 and 360 minutes post-infusion on Day 1 and Day 15

The AUC(0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.

Day 1 (n=16,15)

Group	Value	95% CI
Ketamine: 2 Times Per Week	312	0.63 – 0.83
Ketamine: 3 Times Per Week	295	0.33 – 0.75

Day 15 (n=14,14)

Group	Value	95% CI
Ketamine: 2 Times Per Week	342	0.63 – 1.00
Ketamine: 3 Times Per Week	293	0.5 – 0.83

Adverse events — posted to ClinicalTrials.gov

Time frame: Screening up to Follow up (3 Weeks After Last Dose of Study Drug Administration). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo: 2 Times Per Week

Serious: 0/16 (0%)

Deaths: —

Ketamine: 2 Times Per Week

Serious: 2/18 (11%)

Deaths: —

Placebo: 3 Times Per Week

Serious: 0/16 (0%)

Deaths: —

Ketamine: 3 Times Per Week

Serious: 0/17 (0%)

Deaths: —

Serious adverse events (2 terms)

Reaction	System	Placebo: 2 Times Per Week	Ketamine: 2 Times Per Week	Placebo: 3 Times Per Week	Ketamine: 3 Times Per Week
Anxiety	Psychiatric disorders	—	—	—	—
Suicide Attempt	Psychiatric disorders	—	—	—	—

Other adverse events (76 terms — click to expand)

Reaction	System	Placebo: 2 Times Per Week	Ketamine: 2 Times Per Week	Placebo: 3 Times Per Week	Ketamine: 3 Times Per Week
Headache	Nervous system disorders	—	—	—	—
Dissociation	Psychiatric disorders	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—
Anxiety	Psychiatric disorders	—	—	—	—
Hypoaesthesia	Nervous system disorders	—	—	—	—
Vision Blurred	Eye disorders	—	—	—	—
Fatigue	General disorders	—	—	—	—
Blood Pressure Increased	Investigations	—	—	—	—
Paraesthesia	Nervous system disorders	—	—	—	—
Hypertension	Vascular disorders	—	—	—	—
Cardiac Flutter	Cardiac disorders	—	—	—	—
Palpitations	Cardiac disorders	—	—	—	—
Ventricular Extrasystoles	Cardiac disorders	—	—	—	—
Hyperacusis	Ear and labyrinth disorders	—	—	—	—
Altered Visual Depth Perception	Eye disorders	—	—	—	—
Diplopia	Eye disorders	—	—	—	—
Abdominal Discomfort	Gastrointestinal disorders	—	—	—	—
Abdominal Pain Upper	Gastrointestinal disorders	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—
Dyspepsia	Gastrointestinal disorders	—	—	—	—
Hypoaesthesia Oral	Gastrointestinal disorders	—	—	—	—
Paraesthesia Oral	Gastrointestinal disorders	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—
Feeling Abnormal	General disorders	—	—	—	—
Feeling Cold	General disorders	—	—	—	—
Inflammation	General disorders	—	—	—	—
Infusion Site Pain	General disorders	—	—	—	—
Injection Site Extravasation	General disorders	—	—	—	—
Irritability	General disorders	—	—	—	—
Groin Abscess	Infections and infestations	—	—	—	—
Pharyngitis	Infections and infestations	—	—	—	—
Urinary Tract Infection	Infections and infestations	—	—	—	—
Animal Bite	Injury, poisoning and procedural complications	—	—	—	—
Ligament Sprain	Injury, poisoning and procedural complications	—	—	—	—
Wound	Injury, poisoning and procedural complications	—	—	—	—
Blood Potassium Decreased	Investigations	—	—	—	—
Drug Screen Positive	Investigations	—	—	—	—
Electrocardiogram St-T Change	Investigations	—	—	—	—

Most-reported serious reactions: Anxiety, Suicide Attempt.

Data from ClinicalTrials.gov NCT01627782 adverse events section.

Sponsor's own description

The purpose of this study is to explore the optimal dose frequency of ketamine in patients with treatment-resistant depression (TRD).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Ketamine and rapid-acting antidepressants: a window into a new neurobiology for mood disorder therapeutics.
   Abdallah CG, Sanacora G, Duman RS, Krystal JH. · · 2015 · cited 312× · PMID 25341010 · DOI 10.1146/annurev-med-053013-062946
2. Ketamine for treatment-resistant depression: recent developments and clinical applications.
   Schwartz J, Murrough JW, Iosifescu DV. · · 2016 · cited 85× · PMID 27053196 · DOI 10.1136/eb-2016-102355
3. Metabolomic signatures of drug response phenotypes for ketamine and esketamine in subjects with refractory major depressive disorder: new mechanistic insights for rapid acting antidepressants.
   Rotroff DM, Corum DG, Motsinger-Reif A, Fiehn O, et al · · 2016 · cited 80× · PMID 27648916 · DOI 10.1038/tp.2016.145
4. Novel drug developmental strategies for treatment-resistant depression.
   Borbély É, Simon M, Fuchs E, Wiborg O, et al · · 2022 · cited 70× · PMID 34822719 · DOI 10.1111/bph.15753
5. The promise of ketamine for treatment-resistant depression: current evidence and future directions.
   DeWilde KE, Levitch CF, Murrough JW, Mathew SJ, et al · · 2015 · cited 59× · PMID 25649308 · DOI 10.1111/nyas.12646
6. Genome-wide association study meta-analysis of suicide death and suicidal behavior.
   Li QS, Shabalin AA, DiBlasi E, Gopal S, et al · · 2023 · cited 53× · PMID 36253440 · DOI 10.1038/s41380-022-01828-9
7. Ketamine and other glutamate receptor modulators for depression in adults with unipolar major depressive disorder.
   Dean RL, Hurducas C, Hawton K, Spyridi S, et al · · 2021 · cited 52× · PMID 34510411 · DOI 10.1002/14651858.cd011612.pub3
8. Investigational drugs in recent clinical trials for treatment-resistant depression.
   Garay RP, Zarate CA, Charpeaud T, Citrome L, et al · · 2017 · cited 50× · PMID 28092469 · DOI 10.1080/14737175.2017.1283217