Ketamine Infusion for Treatment-resistant Major Depressive Disorder

• ClinicalTrials.gov Identifier: NCT01582945
• Recruitment Status: Completed
• First Posted: April 23, 2012
• Results First Posted: April 20, 2017
• Last Update Posted: April 20, 2017
• Sponsor: Massachusetts General Hospital
• Information provided by (Responsible Party): Cristina Cusin, MD, Massachusetts General Hospital

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Major Depressive Disorder
• Intervention: Drug: Ketamine
• Enrollment: 14

Participant Flow

Recruitment Details	Patients were referred to the study by their primary psychiatrists and no compensation was provided for participation.
Pre-assignment Details	Subjects underwent a psychiatric screening evaluation, physical exam, EKG, laboratory testing, and a urine screening for substances of abuse to determine study eligibility.

Arm/Group Title	Treatment-resistant Depression Patients
Arm/Group Description	Outpatient sample of patients (18-65 years old) with treatment-resistant major depressive disorder (TRD).
Period Title: Overall Study
Started	14
Completed	12
Not Completed	2
Reason Not Completed
Intolerable side-effects	1
Scheduling conflicts	1

Baseline Characteristics

Arm/Group Title		Treatment-resistant Depression Patients
Arm/Group Description		Outpatient sample of patients (18-65 years old) with treatment-resistant major depressive disorder (TRD).
Overall Number of Baseline Participants		14
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	14 participants
	<=18 years	0 0.0%
	Between 18 and 65 years	14 100.0%
	>=65 years	0 0.0%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	14 participants
		50.0 (7.8)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	14 participants
	Female	11 78.6%
	Male	3 21.4%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	14 participants
		14
Hamilton Rating Scale for Depression [1]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	14 participants
		28.6 (4.8)
		[1] Measure Description: Scores may range from 0-81 with higher scores indicate greater depression severity. In order to be included in the study, participants must have had a Hamilton Depression Rating Scale-28 items (HAM-D28) score ⩾20 at screening.

Outcome Measures

1. Primary Outcome

Title	Response to Ketamine as Measured by Hamilton Depression Rating Scale -28 Items (HAMD28)
Description	Patients will be assessed with HAMD-28 weekly for the first 8 weeks, then every two weeks for another 8 weeks. Participants were considered as responders if there was a ⩾50% improvement on the HAM-D28.
Time Frame	Weekly for total duration of 4 months

Outcome Measure Data

Analysis Population Description

The subjects received a total of 6 infusions, twice a week for three weeks.

Arm/Group Title	Ketamine IV
Arm/Group Description:	Patients will receive open label augmentation with IV Ketamine at 0.5mg/kg over the course of 45 minutes, twice a week for 3 weeks. Participants received this dosage for the first three of six IV ketamine infusions. If participants do not experience an improvement of greater or equal to 30% in HAM-D scores after the first three infusions, the dose will be increased to 0.75mg/kg for the subsequent three infusions. Ketamine: Ketamine IV 0.5mg/kg infusion twice a week for 3 weeks as augmentation of ongoing antidepressant regimen
Overall Number of Participants Analyzed	12
Measure Type: Number; Unit of Measure: participants who met response criteria
	5

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Ketamine IV
Arm/Group Description	Patients will receive open label augmentation with IV Ketamine at 0.5mg/kg, twice a week for 3 weeks Ketamine: Ketamine IV 0.5mg/kg infusion twice a week for 3 weeks as augmentation of ongoing antidepressant regimen
All-Cause Mortality
	Ketamine IV
	Affected / at Risk (%)
Total	0/14 (0.00%)
Serious Adverse Events
	Ketamine IV
	Affected / at Risk (%)
Total	0/14 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Ketamine IV
	Affected / at Risk (%)
Total	0/14 (0.00%)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Dr. Cristina Cusin
• Organization: Massachusetts General Hospital
• Phone: 6177266421
• EMail: ccusin@mgh.harvard.edu

Publications of Results:

Ionescu DF, Swee MB, Pavone KJ, Taylor N, Akeju O, Baer L, Nyer M, Cassano P, Mischoulon D, Alpert JE, Brown EN, Nock MK, Fava M, Cusin C. Rapid and Sustained Reductions in Current Suicidal Ideation Following Repeated Doses of Intravenous Ketamine: Secondary Analysis of an Open-Label Study. J Clin Psychiatry. 2016 Jun;77(6):e719-25. doi: 10.4088/JCP.15m10056.

Cusin C, Ionescu DF, Pavone KJ, Akeju O, Cassano P, Taylor N, Eikermann M, Durham K, Swee MB, Chang T, Dording C, Soskin D, Kelley J, Mischoulon D, Brown EN, Fava M. Ketamine augmentation for outpatients with treatment-resistant depression: Preliminary evidence for two-step intravenous dose escalation. Aust N Z J Psychiatry. 2017 Jan;51(1):55-64. doi: 10.1177/0004867416631828.

• Responsible Party: Cristina Cusin, MD, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT01582945
• Other Study ID Numbers: 2010-P-002800
• First Submitted: April 17, 2012
• First Posted: April 23, 2012
• Results First Submitted: March 2, 2017
• Results First Posted: April 20, 2017
• Last Update Posted: April 20, 2017