Rapid Antidepressant Effects of Ketamine in Major Depression

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ClinicalTrials.gov Identifier: NCT00088699

Recruitment Status : Completed

First Posted : August 2, 2004

Results First Posted : October 12, 2018

Last Update Posted : October 12, 2018

Sponsor:

Information provided by (Responsible Party):

National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Other
Conditions	Depression Mood Disorders Major Depresssion
Interventions	Drug: Ketamine Drug: Placebo
Enrollment	67

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	MDD: Ketamine, Then Placebo	MDD: Placebo, Then Ketamine	Healthy Volunteers: Ketamine, Then Placebo	Healthy Volunteers:Placebo, Then Ketamine
Arm/Group Description	Ketamine and placebo infusions were...	Placebo and Ketamine infusions were...	Placebo and Ketamine infusions were...	Placebo and Ketamine infusions were...
Arm/Group Description	Ketamine and placebo infusions were administered two weeks apart, with Ketamine's dose being 0.5 mg/kg.	Placebo and Ketamine infusions were administered two weeks apart, with Ketamine's dose being 0.5 mg/kg	Placebo and Ketamine infusions were administered two weeks apart, with Ketamine's dose being 0.5 mg/kg	Placebo and Ketamine infusions were administered two weeks apart, with Ketamine's dose being 0.5 mg/kg
Period Title: Infusion 1
Started	23	19	13	12
Completed	22	19	12	10
Not Completed	1	0	1	2
Period Title: Infusion 2
Started	19	18	11	11
Completed	19	18	11	10
Not Completed	0	0	0	1

Baseline Characteristics

Arm/Group Title		Healthy Volunteer	Major Depressive Disorder (MDD)	Total
Arm/Group Description		Healthy volunteer patients	Patients diagnosed with Major Depre...	Total of all reporting groups
Arm/Group Description		Healthy volunteer patients	Patients diagnosed with Major Depressive Disorder (MDD)	Total of all reporting groups
Overall Number of Baseline Participants		25	42	67
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Categorical Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	25 participants	42 participants	67 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	25 100.0%	41 97.6%	66 98.5%
	>=65 years	0 0.0%	1 2.4%	1 1.5%
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	25 participants	42 participants	67 participants
	Female	16 64.0%	25 59.5%	41 61.2%
	Male	9 36.0%	17 40.5%	26 38.8%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	25 participants	42 participants	67 participants
	Hispanic or Latino	4 16.0%	3 7.1%	7 10.4%
	Not Hispanic or Latino	21 84.0%	39 92.9%	60 89.6%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	25 participants	42 participants	67 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	1 4.0%	1 2.4%	2 3.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	6 24.0%	3 7.1%	9 13.4%
	White	16 64.0%	36 85.7%	52 77.6%
	More than one race	1 4.0%	2 4.8%	3 4.5%
	Unknown or Not Reported	1 4.0%	0 0.0%	1 1.5%

Outcome Measures

1.Primary Outcome


Title	MADRS Score - Baseline
Description	Antidepressant effects were assessed using the Montgomery-Åsberg ...
Description	Antidepressant effects were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). It is a ten-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

The analyses included subjects who were given Ketamine or Placebo.


Arm/Group Title	Ketamine - Healthy Volunteers	Placebo - Healthy Volunteers	Ketamine - MDD Patients	Placebo - MDD Patients
Arm/Group Description:	Ketamine and placebo infusions were...	Ketamine and placebo infusions were...	Ketamine and placebo infusions were...	Ketamine and placebo infusions were...
Arm/Group Description:	Ketamine and placebo infusions were administered two weeks apart, with Ketamine's dose being 0.5 mg/kg to healthy volunteer patients	Ketamine and placebo infusions were administered two weeks apart, with Ketamine's dose being 0.5 mg/kg to healthy volunteer patients	Ketamine and placebo infusions were administered two weeks apart, with Ketamine's dose being 0.5 mg/kg to patients with Major Depressive Disorders (MDD)	Ketamine and placebo infusions were administered two weeks apart, with Ketamine's dose being 0.5 mg/kg to patients with Major Depressive Disorders (MDD)
Overall Number of Participants Analyzed	24	23	41	38
Mean (Standard Deviation) Unit of Measure: units on a scale
	1.17 (1.37)	1.48 (1.78)	33.83 (4.23)	31.82 (5.84)

2.Primary Outcome


Title	MADRS Score - Day 1 Following Intervention
Description	Antidepressant effects were assessed using the Montgomery-Åsberg ...
Description	Antidepressant effects were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). It is a ten-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60.
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

The analyses included subjects who were given Ketamine or Placebo.


Arm/Group Title	Ketamine - Healthy Volunteers	Placebo - Healthy Volunteers	Ketamine - MDD Patients	Placebo - MDD Patients
Arm/Group Description:	Ketamine and placebo infusions were...	Ketamine and placebo infusions were...	Ketamine and placebo infusions were...	Ketamine and placebo infusions were...
Arm/Group Description:	Ketamine and placebo infusions were administered two weeks apart, with Ketamine's dose being 0.5 mg/kg to healthy volunteer patients	Ketamine and placebo infusions were administered two weeks apart, with Ketamine's dose being 0.5 mg/kg to healthy volunteer patients	Ketamine and placebo infusions were administered two weeks apart, with Ketamine's dose being 0.5 mg/kg to patients with Major Depressive Disorders (MDD)	Ketamine and placebo infusions were administered two weeks apart, with Ketamine's dose being 0.5 mg/kg to patients with Major Depressive Disorders (MDD)
Overall Number of Participants Analyzed	22	21	40	38
Mean (Standard Deviation) Unit of Measure: units on a scale
	2.45 (3.79)	0.67 (1.15)	23.73 (10.32)	30.68 (5.50)

Adverse Events

Time Frame	28 days
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Healthy Volunteer: Ketamine	MDD: Ketamine	Healthy Volunteer: Placebo	MDD: Placebo
Arm/Group Description	Ketamine and placebo infusions were...	Ketamine and placebo infusions were...	Placebo and Ketamine infusions were...	Placebo and Ketamine infusions were...
Arm/Group Description	Ketamine and placebo infusions were administered two weeks apart, with Ketamine's dose being 0.5 mg/kg.	Ketamine and placebo infusions were administered two weeks apart, with Ketamine's dose being 0.5 mg/kg.	Placebo and Ketamine infusions were administered two weeks apart, with Ketamine's dose being 0.5 mg/kg	Placebo and Ketamine infusions were administered two weeks apart, with Ketamine's dose being 0.5 mg/kg
All-Cause Mortality
	Healthy Volunteer: Ketamine	MDD: Ketamine	Healthy Volunteer: Placebo	MDD: Placebo
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/24 (0.00%)	0/41 (0.00%)	0/23 (0.00%)	0/38 (0.00%)
Serious Adverse Events Serious Adverse Events
	Healthy Volunteer: Ketamine	MDD: Ketamine	Healthy Volunteer: Placebo	MDD: Placebo
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/24 (0.00%)	0/41 (0.00%)	0/23 (0.00%)	0/38 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Healthy Volunteer: Ketamine	MDD: Ketamine	Healthy Volunteer: Placebo	MDD: Placebo
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	24/24 (100.00%)	36/41 (87.80%)	8/23 (34.78%)	16/38 (42.11%)
Cardiac disorders
Dizziness ^†	19/24 (79.17%)	27/41 (65.85%)	1/23 (4.35%)	0/38 (0.00%)
Dyspnoea ^†	0/24 (0.00%)	2/41 (4.88%)	0/23 (0.00%)	0/38 (0.00%)
Ear and labyrinth disorders
Auditory disorder ^†	6/24 (25.00%)	7/41 (17.07%)	0/23 (0.00%)	0/38 (0.00%)
Ear pain ^†	0/24 (0.00%)	1/41 (2.44%)	0/23 (0.00%)	0/38 (0.00%)
Motion sickness ^†	0/24 (0.00%)	1/41 (2.44%)	0/23 (0.00%)	0/38 (0.00%)
Tinnitus ^†	0/24 (0.00%)	1/41 (2.44%)	0/23 (0.00%)	0/38 (0.00%)
Vertigo ^†	1/24 (4.17%)	0/41 (0.00%)	0/23 (0.00%)	0/38 (0.00%)
Eye disorders
Diplopia ^†	1/24 (4.17%)	4/41 (9.76%)	0/23 (0.00%)	0/38 (0.00%)
Vision blurred ^†	5/24 (20.83%)	11/41 (26.83%)	0/23 (0.00%)	0/38 (0.00%)
Visual impairment ^†	14/24 (58.33%)	20/41 (48.78%)	0/23 (0.00%)	0/38 (0.00%)
Gastrointestinal disorders
Abdominal discomfort ^†	2/24 (8.33%)	2/41 (4.88%)	0/23 (0.00%)	0/38 (0.00%)
Constipation ^†	0/24 (0.00%)	0/41 (0.00%)	0/23 (0.00%)	1/38 (2.63%)
Diarrhoea ^†	1/24 (4.17%)	0/41 (0.00%)	0/23 (0.00%)	0/38 (0.00%)
Dry mouth ^†	6/24 (25.00%)	5/41 (12.20%)	0/23 (0.00%)	0/38 (0.00%)
Dysgeusia ^†	1/24 (4.17%)	2/41 (4.88%)	0/23 (0.00%)	0/38 (0.00%)
Flatulence ^†	0/24 (0.00%)	1/41 (2.44%)	0/23 (0.00%)	0/38 (0.00%)
Mouth ulceration ^†	0/24 (0.00%)	0/41 (0.00%)	0/23 (0.00%)	1/38 (2.63%)
Nausea ^†	5/24 (20.83%)	4/41 (9.76%)	0/23 (0.00%)	0/38 (0.00%)
Oropharyngeal pain ^†	0/24 (0.00%)	0/41 (0.00%)	0/23 (0.00%)	1/38 (2.63%)
Vomiting ^†	3/24 (12.50%)	1/41 (2.44%)	0/23 (0.00%)	0/38 (0.00%)
General disorders
Decreased appetite ^†	4/24 (16.67%)	5/41 (12.20%)	0/23 (0.00%)	1/38 (2.63%)
Energy increased ^†	2/24 (8.33%)	3/41 (7.32%)	0/23 (0.00%)	0/38 (0.00%)
Fatigue ^†	7/24 (29.17%)	2/41 (4.88%)	1/23 (4.35%)	0/38 (0.00%)
Feeling abnormal ^†	20/24 (83.33%)	32/41 (78.05%)	1/23 (4.35%)	0/38 (0.00%)
Flushing ^†	2/24 (8.33%)	7/41 (17.07%)	0/23 (0.00%)	0/38 (0.00%)
Hyperhidrosis ^†	1/24 (4.17%)	3/41 (7.32%)	0/23 (0.00%)	0/38 (0.00%)
Increased appetite ^†	0/24 (0.00%)	2/41 (4.88%)	0/23 (0.00%)	1/38 (2.63%)
Irritability ^†	0/24 (0.00%)	2/41 (4.88%)	0/23 (0.00%)	1/38 (2.63%)
Oedema ^†	0/24 (0.00%)	0/41 (0.00%)	1/23 (4.35%)	0/38 (0.00%)
Thirst ^†	1/24 (4.17%)	0/41 (0.00%)	0/23 (0.00%)	0/38 (0.00%)
Investigations
Body temperature decreased ^†	2/24 (8.33%)	6/41 (14.63%)	0/23 (0.00%)	1/38 (2.63%)
Body temperature increased ^†	4/24 (16.67%)	7/41 (17.07%)	0/23 (0.00%)	0/38 (0.00%)
Musculoskeletal and connective tissue disorders
Muscle spasms ^†	0/24 (0.00%)	3/41 (7.32%)	2/23 (8.70%)	1/38 (2.63%)
Nervous system disorders
Abnormal dreams ^†	1/24 (4.17%)	2/41 (4.88%)	0/23 (0.00%)	0/38 (0.00%)
Amnesia ^†	3/24 (12.50%)	5/41 (12.20%)	0/23 (0.00%)	1/38 (2.63%)
Balance disorder ^†	0/24 (0.00%)	1/41 (2.44%)	0/23 (0.00%)	0/38 (0.00%)
Confusional state ^†	6/24 (25.00%)	17/41 (41.46%)	0/23 (0.00%)	0/38 (0.00%)
Disturbance in attention ^†	15/24 (62.50%)	3/41 (7.32%)	1/23 (4.35%)	0/38 (0.00%)
Dysarthria ^†	3/24 (12.50%)	4/41 (9.76%)	0/23 (0.00%)	0/38 (0.00%)
Headache ^†	2/24 (8.33%)	4/41 (9.76%)	1/23 (4.35%)	1/38 (2.63%)
Hypoaesthesia ^†	14/24 (58.33%)	24/41 (58.54%)	1/23 (4.35%)	0/38 (0.00%)
Hypokinesia ^†	6/24 (25.00%)	2/41 (4.88%)	0/23 (0.00%)	1/38 (2.63%)
Insomnia ^†	5/24 (20.83%)	7/41 (17.07%)	2/23 (8.70%)	5/38 (13.16%)
Paraesthesia ^†	6/24 (25.00%)	9/41 (21.95%)	1/23 (4.35%)	0/38 (0.00%)
Parosmia ^†	0/24 (0.00%)	2/41 (4.88%)	0/23 (0.00%)	0/38 (0.00%)
Psychomotor hyperactivity ^†	1/24 (4.17%)	0/41 (0.00%)	0/23 (0.00%)	0/38 (0.00%)
Sedation ^†	8/24 (33.33%)	7/41 (17.07%)	0/23 (0.00%)	3/38 (7.89%)
Slow speech ^†	6/24 (25.00%)	17/41 (41.46%)	0/23 (0.00%)	0/38 (0.00%)
Speech disorder ^†	11/24 (45.83%)	20/41 (48.78%)	0/23 (0.00%)	0/38 (0.00%)
Terminal insomnia ^†	0/24 (0.00%)	1/41 (2.44%)	0/23 (0.00%)	2/38 (5.26%)
Tremor ^†	0/24 (0.00%)	1/41 (2.44%)	0/23 (0.00%)	0/38 (0.00%)
Vibratory sense increased ^†	1/24 (4.17%)	5/41 (12.20%)	0/23 (0.00%)	0/38 (0.00%)
Psychiatric disorders
Anxiety ^†	2/24 (8.33%)	0/41 (0.00%)	0/23 (0.00%)	0/38 (0.00%)
Depression ^†	0/24 (0.00%)	1/41 (2.44%)	0/23 (0.00%)	0/38 (0.00%)
Dissociation ^†	12/24 (50.00%)	19/41 (46.34%)	0/23 (0.00%)	0/38 (0.00%)
Euphoric mood ^†	4/24 (16.67%)	7/41 (17.07%)	0/23 (0.00%)	0/38 (0.00%)
Fear ^†	1/24 (4.17%)	5/41 (12.20%)	0/23 (0.00%)	0/38 (0.00%)
Hallucination ^†	0/24 (0.00%)	2/41 (4.88%)	0/23 (0.00%)	0/38 (0.00%)
Libido decreased ^†	1/24 (4.17%)	0/41 (0.00%)	0/23 (0.00%)	0/38 (0.00%)
Premenstrual syndrome ^†	0/24 (0.00%)	1/41 (2.44%)	0/23 (0.00%)	1/38 (2.63%)
Suicidal ideation ^†	0/24 (0.00%)	2/41 (4.88%)	0/23 (0.00%)	0/38 (0.00%)
Renal and urinary disorders
Dysuria ^†	0/24 (0.00%)	2/41 (4.88%)	0/23 (0.00%)	0/38 (0.00%)
Respiratory, thoracic and mediastinal disorders
Cough ^†	0/24 (0.00%)	0/41 (0.00%)	0/23 (0.00%)	1/38 (2.63%)
Nasal congestion ^†	0/24 (0.00%)	1/41 (2.44%)	0/23 (0.00%)	1/38 (2.63%)
Skin and subcutaneous tissue disorders
Alopecia ^†	0/24 (0.00%)	0/41 (0.00%)	1/23 (4.35%)	0/38 (0.00%)
Skin irritation ^†	0/24 (0.00%)	0/41 (0.00%)	0/23 (0.00%)	1/38 (2.63%)
Vascular disorders
Hypertension ^†	3/24 (12.50%)	6/41 (14.63%)	0/23 (0.00%)	0/38 (0.00%)
Hypotension ^†	0/24 (0.00%)	1/41 (2.44%)	0/23 (0.00%)	0/38 (0.00%)
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Zarate, Carlos
Organization:	National Institute of Mental Health
Phone:	+1 301 451 0861
EMail:	zaratec@mail.nih.gov

Publications of Results:

Nugent AC, Ballard ED, Gould TD, Park LT, Moaddel R, Brutsche NE, Zarate CA Jr. Ketamine has distinct electrophysiological and behavioral effects in depressed and healthy subjects. Mol Psychiatry. 2019 Jul;24(7):1040-1052. doi: 10.1038/s41380-018-0028-2. Epub 2018 Feb 27.

Evans JW, Lally N, An L, Li N, Nugent AC, Banerjee D, Snider SL, Shen J, Roiser JP, Zarate CA Jr. 7T (1)H-MRS in major depressive disorder: a Ketamine Treatment Study. Neuropsychopharmacology. 2018 Aug;43(9):1908-1914. doi: 10.1038/s41386-018-0057-1. Epub 2018 Apr 5.

Gilbert JR, Yarrington JS, Wills KE, Nugent AC, Zarate CA Jr. Glutamatergic Signaling Drives Ketamine-Mediated Response in Depression: Evidence from Dynamic Causal Modeling. Int J Neuropsychopharmacol. 2018 Apr 13. doi: 10.1093/ijnp/pyy041. [Epub ahead of print]

Evans JW, Szczepanik J, Brutsché N, Park LT, Nugent AC, Zarate CA Jr. Default Mode Connectivity in Major Depressive Disorder Measured Up to 10 Days After Ketamine Administration. Biol Psychiatry. 2018 Oct 15;84(8):582-590. doi: 10.1016/j.biopsych.2018.01.027. Epub 2018 Feb 15.

Nugent AC, Zarate CA Jr. Using Neuroimaging to Decipher the Mechanism of Action of Ketamine: A Pathway to Novel Therapeutics? Biol Psychiatry Cogn Neurosci Neuroimaging. 2017 Oct;2(7):549-551. doi: 10.1016/j.bpsc.2017.08.006. Epub 2017 Oct 5.

Kadriu B, Gold PW, Luckenbaugh DA, Lener MS, Ballard ED, Niciu MJ, Henter ID, Park LT, De Sousa RT, Yuan P, Machado-Vieira R, Zarate CA. Acute ketamine administration corrects abnormal inflammatory bone markers in major depressive disorder. Mol Psychiatry. 2018 Jul;23(7):1626-1631. doi: 10.1038/mp.2017.109. Epub 2017 May 30.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Reed JL, Nugent AC, Furey ML, Szczepanik JE, Evans JW, Zarate CA Jr. Effects of Ketamine on Brain Activity During Emotional Processing: Differential Findings in Depressed Versus Healthy Control Participants. Biol Psychiatry Cogn Neurosci Neuroimaging. 2019 Jul;4(7):610-618. doi: 10.1016/j.bpsc.2019.01.005. Epub 2019 Jan 25.

Nugent AC, Wills KE, Gilbert JR, Zarate CA Jr. Synaptic potentiation and rapid antidepressant response to ketamine in treatment-resistant major depression: A replication study. Psychiatry Res Neuroimaging. 2019 Jan 30;283:64-66. doi: 10.1016/j.pscychresns.2018.09.001. Epub 2018 Sep 12.

Ballard ED, Yarrington JS, Farmer CA, Richards E, Machado-Vieira R, Kadriu B, Niciu MJ, Yuan P, Park L, Zarate CA Jr. Characterizing the course of suicidal ideation response to ketamine. J Affect Disord. 2018 Dec 1;241:86-93. doi: 10.1016/j.jad.2018.07.077. Epub 2018 Jul 30.

Reed JL, Nugent AC, Furey ML, Szczepanik JE, Evans JW, Zarate CA Jr. Ketamine normalizes brain activity during emotionally valenced attentional processing in depression. Neuroimage Clin. 2018 Jul 5;20:92-101. doi: 10.1016/j.nicl.2018.07.006. eCollection 2018.

Ballard ED, Yarrington JS, Farmer CA, Lener MS, Kadriu B, Lally N, Williams D, Machado-Vieira R, Niciu MJ, Park L, Zarate CA Jr. Parsing the heterogeneity of depression: An exploratory factor analysis across commonly used depression rating scales. J Affect Disord. 2018 Apr 15;231:51-57. doi: 10.1016/j.jad.2018.01.027. Epub 2018 Feb 5.

Duncan WC Jr, Slonena E, Hejazi NS, Brutsche N, Yu KC, Park L, Ballard ED, Zarate CA Jr. Motor-Activity Markers of Circadian Timekeeping Are Related to Ketamine's Rapid Antidepressant Properties. Biol Psychiatry. 2017 Sep 1;82(5):361-369. doi: 10.1016/j.biopsych.2017.03.011. Epub 2017 Mar 28. Erratum in: Biol Psychiatry. 2017 Sep 1;82(5):380.

Vande Voort JL, Ballard ED, Luckenbaugh DA, Bernert RA, Richards EM, Niciu MJ, Park LT, Machado-Vieira R, Duncan WC Jr, Zarate CA Jr. Antisuicidal Response Following Ketamine Infusion Is Associated With Decreased Nighttime Wakefulness in Major Depressive Disorder and Bipolar Disorder. J Clin Psychiatry. 2017 Sep/Oct;78(8):1068-1074. doi: 10.4088/JCP.15m10440.

Lepow L, Luckenbaugh DA, Park L, Henter ID, Zarate CA Jr. Case series: Antidepressant effects of low-affinity and low-trapping NMDA receptor antagonists did not predict response to ketamine in seven subjects. J Psychiatr Res. 2017 Mar;86:55-57. doi: 10.1016/j.jpsychires.2016.10.023. Epub 2016 Nov 22.

Pennybaker SJ, Niciu MJ, Luckenbaugh DA, Zarate CA. Symptomatology and predictors of antidepressant efficacy in extended responders to a single ketamine infusion. J Affect Disord. 2017 Jan 15;208:560-566. doi: 10.1016/j.jad.2016.10.026. Epub 2016 Oct 26. Review.

Bernert RA, Luckenbaugh DA, Duncan WC, Iwata NG, Ballard ED, Zarate CA. Sleep architecture parameters as a putative biomarker of suicidal ideation in treatment-resistant depression. J Affect Disord. 2017 Jan 15;208:309-315. doi: 10.1016/j.jad.2016.08.050. Epub 2016 Oct 14.

Park M, Newman LE, Gold PW, Luckenbaugh DA, Yuan P, Machado-Vieira R, Zarate CA Jr. Change in cytokine levels is not associated with rapid antidepressant response to ketamine in treatment-resistant depression. J Psychiatr Res. 2017 Jan;84:113-118. doi: 10.1016/j.jpsychires.2016.09.025. Epub 2016 Sep 30.

Berg HE, Ballard ED, Luckenbaugh DA, Nugent AC, Ionescu DF, Zarate CA Jr. Recognition of emotional facial expressions in anxious and nonanxious depression. Compr Psychiatry. 2016 Oct;70:1-8. doi: 10.1016/j.comppsych.2016.06.007. Epub 2016 Jun 14.

Ballard ED, Vande Voort JL, Luckenbaugh DA, Machado-Vieira R, Tohen M, Zarate CA. Acute risk factors for suicide attempts and death: prospective findings from the STEP-BD study. Bipolar Disord. 2016 Jun;18(4):363-72. doi: 10.1111/bdi.12397. Epub 2016 May 27.

Ballard ED, Luckenbaugh DA, Richards EM, Walls TL, Brutsché NE, Ameli R, Niciu MJ, Vande Voort JL, Zarate CA Jr. Assessing measures of suicidal ideation in clinical trials with a rapid-acting antidepressant. J Psychiatr Res. 2015 Sep;68:68-73. doi: 10.1016/j.jpsychires.2015.06.003. Epub 2015 Jun 16.

Luckenbaugh DA, Ameli R, Brutsche NE, Zarate CA Jr. Rating depression over brief time intervals with the Hamilton Depression Rating Scale: standard vs. abbreviated scales. J Psychiatr Res. 2015 Feb;61:40-5. doi: 10.1016/j.jpsychires.2014.12.015. Epub 2014 Dec 27.

Ortiz R, Niciu MJ, Lukkahati N, Saligan LN, Nugent AC, Luckenbaugh DA, Machado-Vieira R, Zarate CA Jr. Shank3 as a potential biomarker of antidepressant response to ketamine and its neural correlates in bipolar depression. J Affect Disord. 2015 Feb 1;172:307-11. doi: 10.1016/j.jad.2014.09.015. Epub 2014 Oct 16.

Ionescu DF, Luckenbaugh DA, Niciu MJ, Richards EM, Zarate CA Jr. A single infusion of ketamine improves depression scores in patients with anxious bipolar depression. Bipolar Disord. 2015 Jun;17(4):438-43. doi: 10.1111/bdi.12277. Epub 2014 Nov 14.

Ionescu DF, Luckenbaugh DA, Niciu MJ, Richards EM, Slonena EE, Vande Voort JL, Brutsche NE, Zarate CA Jr. Effect of baseline anxious depression on initial and sustained antidepressant response to ketamine. J Clin Psychiatry. 2014 Sep;75(9):e932-8. doi: 10.4088/JCP.14m09049.

Ballard ED, Ionescu DF, Vande Voort JL, Niciu MJ, Richards EM, Luckenbaugh DA, Brutsché NE, Ameli R, Furey ML, Zarate CA Jr. Improvement in suicidal ideation after ketamine infusion: relationship to reductions in depression and anxiety. J Psychiatr Res. 2014 Nov;58:161-6. doi: 10.1016/j.jpsychires.2014.07.027. Epub 2014 Aug 12.

Cornwell BR, Salvadore G, Furey M, Marquardt CA, Brutsche NE, Grillon C, Zarate CA Jr. Synaptic potentiation is critical for rapid antidepressant response to ketamine in treatment-resistant major depression. Biol Psychiatry. 2012 Oct 1;72(7):555-61. doi: 10.1016/j.biopsych.2012.03.029. Epub 2012 Apr 21.

Zarate CA Jr, Brutsche NE, Ibrahim L, Franco-Chaves J, Diazgranados N, Cravchik A, Selter J, Marquardt CA, Liberty V, Luckenbaugh DA. Replication of ketamine's antidepressant efficacy in bipolar depression: a randomized controlled add-on trial. Biol Psychiatry. 2012 Jun 1;71(11):939-46. doi: 10.1016/j.biopsych.2011.12.010. Epub 2012 Jan 31.

Diazgranados N, Ibrahim L, Brutsche NE, Newberg A, Kronstein P, Khalife S, Kammerer WA, Quezado Z, Luckenbaugh DA, Salvadore G, Machado-Vieira R, Manji HK, Zarate CA Jr. A randomized add-on trial of an N-methyl-D-aspartate antagonist in treatment-resistant bipolar depression. Arch Gen Psychiatry. 2010 Aug;67(8):793-802. doi: 10.1001/archgenpsychiatry.2010.90.

DiazGranados N, Ibrahim LA, Brutsche NE, Ameli R, Henter ID, Luckenbaugh DA, Machado-Vieira R, Zarate CA Jr. Rapid resolution of suicidal ideation after a single infusion of an N-methyl-D-aspartate antagonist in patients with treatment-resistant major depressive disorder. J Clin Psychiatry. 2010 Dec;71(12):1605-11. doi: 10.4088/JCP.09m05327blu. Epub 2010 Jul 13.

Machado-Vieira R, Yuan P, Brutsche N, DiazGranados N, Luckenbaugh D, Manji HK, Zarate CA Jr. Brain-derived neurotrophic factor and initial antidepressant response to an N-methyl-D-aspartate antagonist. J Clin Psychiatry. 2009 Dec;70(12):1662-6. doi: 10.4088/JCP.08m04659. Epub 2009 Sep 8.

Phelps LE, Brutsche N, Moral JR, Luckenbaugh DA, Manji HK, Zarate CA Jr. Family history of alcohol dependence and initial antidepressant response to an N-methyl-D-aspartate antagonist. Biol Psychiatry. 2009 Jan 15;65(2):181-4. doi: 10.1016/j.biopsych.2008.09.029. Epub 2008 Nov 8.

Zarate CA Jr, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, Charney DS, Manji HK. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006 Aug;63(8):856-64.

Layout table for additonal information

Responsible Party:	National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )
ClinicalTrials.gov Identifier:	NCT00088699 History of Changes
Other Study ID Numbers:	040222 04-M-0222
First Submitted:	July 30, 2004
First Posted:	August 2, 2004
Results First Submitted:	July 30, 2018
Results First Posted:	October 12, 2018
Last Update Posted:	October 12, 2018

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