Administration of Subanesthetic Dose of Ketamine and Electroconvulsive Treatment for Treatment Resistant Depression

Not Applicable

Completed

Conditions: Treatment Resistant Depression
Severe Depression
Major Depressive Disorder

Brief Summary: In this proof of concept study, the investigators plan to administer iv ketamine interleaved with ECT days.

Patients with treatment resistant depression who are deemed to be eligible for ECT treatment will randomly be assigned to either ketamine or active placebo.

Detailed Description: The study will compare the effects of standard ketamine dosing with an active placebo arm.

Hypothesis 1:

The investigators hypothesize that interleaved Electroconvulsive Treatment and active ketamine treatment will lead to a meaningful clinical improvement compared to Electroconvulsive Treatment and placebo treatment arm.

Hypothesis 2:

The investigators hypothesize that interleaved Electroconvulsive Treatment and active ketamine treatment will attenuate cognitive side effects.

Methods and Design:

Patients with treatment resistant depression who are deemed to be eligible for Electroconvulsive Treatment will randomly be assigned to either ketamine or active placebo

Electroconvulsive Treatments:

All patients (independent of their depression scores) will receive the same Electroconvulsive Treatment parameters: Bi-frontal brief pulse (0.5 miliseconds) Electroconvulsive Treatment administered by using Thymatron Electroconvulsive Treatment machine.

Study blinding:

Neither the patients, nor the treating psychiatrist or the nurse will be aware of the patient's assigned arm. The success of blinding will be tested after each ketamine treatment with a questionnaire given to the subject, raters, and treating physician.

Recruitment & Eligibility

Inclusion Criteria

Males/females at least 18 years of age but no older than 65 years of age
Meet Diagnostic and Statistical Manual of Mental Disorders-4th Edition (DSM-IV) criteria for Major Depression or Bipolar Disorder, depressed phase, as determined by a clinician's diagnostic evaluation and confirmed by interview using the Mini International Neuropsychiatric Interview (MINI PLUS 5.0.0)
A current depressive episode that has lasted a minimum of 4 weeks.
Have > 3 trials of antidepressants/augmentation strategies.
Have a support system capable of transporting the patient post-treatment.

Exclusion Criteria

Meeting Diagnostic and Statistical Manual of Mental Disorders criteria for schizophrenia, schizophreniform disorder, schizoaffective disorder, mental retardation, pervasive developmental disorder.
Meeting Diagnostic and Statistical Manual of Mental Disorders criteria for other substance/alcohol dependence within the past 6 months or abuse in the past 3 months.
Patients who meet exclusion criteria for ketamine and/or midazolam infusion.

Arm && Interventions

Group	Intervention	Description
Midazolam	Midazolam	Subjects who are randomized to be on this group will receive midazolam infusions interleaved with Electroconvulsive Treatments.
Ketamine Infusions	Ketamine	Subjects who are randomized to be on this group will receive a standard dose of ketamine interleaved with Electroconvulsive Treatments.

Primary Outcome Measures

Name	Time	Method
Montgomery Asberg Depression Rating Scale (MADRS) at Last Infusion	visit 17	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
Hamilton Depression Rating Scale (HAMD-17) at Last Infusion	visit 17	Change in HAMD-17 at Infusion 6. Scores range from 0 to 50, with higher scores representing more depression.

Secondary Outcome Measures

Name	Time	Method
Controlled Oral Word Association Test (COWAT) at Last Infusion	visit 17	This is a verbal fluency measure. Outcome is the count of words that meet criteria within 1 minute, so the minimum is 0 and no fixed maximum exists. Higher scores reflect a better outcome.
Hopkins Verbal Learning Test - Revised (HVLT-R) at Last Infusion	visit 17	The number of words remembered are recorded. Scores range from 0 to 12 with higher scores reflecting better acquisition.
Montreal Cognitive Assessment (MOCA) at Last Infusion	visit 17	MoCA scores range between 0 and 30. Higher scores reflect higher cognition.
Responder Rate on HAMD-17 by Last Infusion	visit 17	Count of the patients who showed response (\>50% decrease).