Ketamine Anesthesia for Improvement of Depression in ECT
Condition: Major Depressive Disorder
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Study type: Interventional

Summary: 
      The purpose of this prospective randomized clinical trial is to determine if patients
      receiving ketamine as a part of general anesthesia during electroconvulsive therapy (ECT)
      rather than standard of care will have improvement in symptoms of depression after a course
      of ECT treatments. The investigators hypothesize that utilization of ketamine for induction
      of general anesthesia during ECT treatments will improve symptoms of depression better than
      standard care.

      This study is ONLY open to patients eligible to receive healthcare services through the
      Department of Veterans Affairs at the VA Puget Sound, which means service in the active
      military, naval or air service or separation under any condition other than dishonorable.
      Qualifications for VA health care benefits can be found at va.gov.
    

Detailed description: 
      The purpose of this prospective randomized clinical trial is to determine if patients
      receiving ketamine as a part of general anesthesia during electroconvulsive therapy (ECT)
      rather than standard of care will have improvement in symptoms of depression after a course
      of ECT treatments. The investigators hypothesize that utilization of ketamine for induction
      of general anesthesia during ECT treatments will improve symptoms of depression better than
      standard care.

      For induction of general anesthesia for ECT, patients will receive either 1mg/kg of
      methohexital (standard arm) or 1.0 mg/kg IV ketamine (experimental arm) intravenously (IV)
      for the duration of their ECT index course over 2-3 weeks. The primary outcome in this trial
      is change in symptoms of depression assessed by standard questionnaires: Patient Health
      Questionnaire 9 (PHQ9) and Hamilton Depression Rating Scale (HAM-D) score changes from
      baseline and final ECT administration. Secondary outcomes are changes in cognitive status as
      assessed by the Montreal Cognitive Assessment (MoCA) scale, quality of seizures and after
      seizure, changes in serum metabolites (including kynurenine, D/L-serine and other glutamate
      intermediates) after treatment and need for further ECT courses (relapse) within 1 year after
      initial course.

      Approximately 50 veterans with the diagnosis of major depressive disorder older than 18 years
      of age undergoing ECT will be randomized and blinded to the intervention. Operative ECT
      clinicians will not be blinded; clinicians evaluating patients will be blinded. Exclusion
      criteria for this study include uncontrolled hypertension, blood pressure > 180/90 mmHg at
      the pre-anesthesia clinic visit, renal failure, neurologic disorders (e.g. epilepsy, space
      occupying lesions, traumatic brain injuries in the past 6 months), myocardial infarction in
      the past 6 months, known allergies or adverse reactions to ketamine, American Society of
      Anesthesiology Physical Class greater than 3, concomitant psychosis, schizophrenia or current
      abuse of alcohol or illicit substances and pregnancy.

      The long term objective of this trial is to systematically characterize ketamine's effect on
      depression outcomes utilizing validated scoring tools, its safety profile throughout an ECT
      index course, ketamine's effect on seizure quality and changes in novel translational
      endpoints to better understand mechanisms of action of ketamine and its potential role in
      treatment of psychiatric disorders.
    

Intervention name(s): Ketamine; Methohexital
Intervention type(s): Drug; Drug
Intervention description(s): Ketamine anesthesia for ECT index course with measurement cerebral metabolic regional oximetry, EEG seizure quality, cognitive scoring and serum metabolites.; Methohexital anesthesia for ECT index course with measurement cerebral metabolic regional oximetry, EEG seizure quality, cognitive scoring and serum metabolites.
Other intervention name(s): Ketalar; Brevital
Intervention MeSH terms: Ketamine; Methohexital
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment
Keywords: major depressive disorder; electroconvulsive therapy; metabolomics; treatment resistant depression; anesthesiology; ketamine; prospective randomized clinical trial