Ketamine Infusion for Treatment-resistant Major Depressive Disorder

N-methyl-D-aspartate Antagonist (Ketamine) Infusion for Treatment-resistant Major Depressive Disorder With Suicidal Ideation

Ketamine infusion has been shown to have rapid antidepressant properties, however the possible use of ketamine in treatment-resistant depression as augmentation has not been investigated. The overall aim of this study is to assess the feasibility, safety and tolerability, efficacy and duration of the effect of intravenous N-methyl-D-aspartate antagonist ketamine as augmentation of antidepressants for chronic suicidal ideation in subjects with severe treatment-resistant depression (TRD).

This is an open-label study (pilot).

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Ketamine

Detailed Description

Patients will undergo two weeks of prospective observation, they will then receive ketamine IV 0.5mg/kg over 45 minutes as augmentation of their ongoing antidepressant regimen; after three infusions this dose will be increased increase to 0.75 mg/kg in non-responders. The schedule of administration will be twice a week for 3 weeks. After this phase, the patient will be followed with assessments every two weeks for three months.

Total duration of the study is 5 months.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Depression Clinical and Research Program - MGH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Outpatients with severe treatment-resistant MDD
• Currently depressed
• Currently under regular psychiatric care
• On an aggressive antidepressant regimen, stable for 4 weeks

Exclusion Criteria:

• No history of other major psychiatric illnesses, including bipolar disorder
• No history of psychosis
• No history of drug abuse
• No major medical illness or unstable medical conditions

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketamine IV; Patients will receive open label augmentation with IV Ketamine at 0.5mg/kg, twice a week for 3 weeks	Drug: Ketamine; Ketamine IV 0.5mg/kg infusion twice a week for 3 weeks as augmentation of ongoing antidepressant regimen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response to Ketamine as Measured by Hamilton Depression Rating Scale -28 Items (HAMD28)	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.	Weekly for total duration of 4 months

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Cristina Cusin, MD, MGH Department of Psychiatry

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: April 17, 2012
• First Submitted That Met QC Criteria: April 19, 2012
• First Posted (Estimate): April 23, 2012

Study Record Updates

• Last Update Posted (Actual): April 20, 2017
• Last Update Submitted That Met QC Criteria: April 18, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: major depressive disorder; suicidal ideation; Treatment resistant
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Pathologic Processes; Mood Disorders; Self-Injurious Behavior; Suicide; Depression; Depressive Disorder; Disease; Suicidal Ideation; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: 2010-P-002800