Ketamine as an Augmentation Strategy for Electroconvulsive Therapy (ECT) in Depression
Condition: Unipolar Depression; Bipolar Depression
MeSH terms: Depression; Depressive Disorder; Bipolar Disorder
Study type: Interventional
Phase: Phase 4

Summary: 
      The study aims to compare outcomes of Electroconvulsive Therapy (ECT) using ketamine versus
      methohexital anesthesia in depressed patients. The investigators hypothesize that patients
      who receive ketamine anesthesia during ECT will achieve remission status faster than those
      receiving methohexital anesthesia. Also, at the end of the ECT course subjects will display
      fewer cognitive side effects compared to those treated with methohexital anesthesia.
    

Detailed description: 
      Despite major advances in the treatment of mood disorders, depression remains a serious
      public health problem. Delayed onset of response and lack of efficacy in a significant
      portion of patients are the limitations of pharmacotherapy. Electroconvulsive therapy (ECT)
      has been shown to provide fast amelioration of depressive symptoms and its efficacy is
      reported to be 65 to 85%. However, one of the main limiting factors for its use is the
      cognitive impairment, which is directly related to the number of ECT sessions.

      There is increased evidence for the mediation of glutamate in the pathophysiology of
      depression, as suggested by the potential antidepressant effect of drugs that modulate
      glutamate transmission. Open studies and recent case reports demonstrate a rapid
      antidepressant effect of intravenous ketamine - a non-competitive antagonist at the glutamate
      N-methyl-D-aspartate (NMDA) receptor. Ketamine is a general anesthetic used commonly for
      procedural sedation. Ketamine has no anticonvulsant properties. It is used as an alternative
      to methohexital - a barbiturate with anticonvulsant properties - in patients with high
      seizure threshold. A recent open non-randomized trial by Okamoto shows a faster response when
      ECT is given with ketamine anesthesia. In a recent review Gregory-Roberts et al suggest that
      available evidence in animals and humans supports the prediction that ketamine could
      effectively prevent ECT -induced persistent retrograde amnesia and improve or hasten
      therapeutic response.

      We propose a double-blind randomized controlled pilot study to measure both therapeutic
      efficacy and cognitive side effects of ECT using ketamine compared to methohexital - the gold
      standard anesthetic in ECT - in depressed patients.

      Thirty patients who are scheduled to receive an acute course of ECT for major depressive
      episode. Inpatients and outpatients will be screened by the ECT psychiatrists who participate
      in this study. Patients who are able and willing to provide written informed consent will be
      randomly assigned on a 1:1 ratio to receive either a course of bifrontal ECT using ketamine
      1-2 mg/kg or methohexital anesthesia0.5-1.0 mg/kg. Subjects will receive a standard acute
      course of ECT (3X/week. Raters and subjects will be masked to group assignment.

      Parallel with these procedures we will also collect magnetic resonance imaging (MRI) data on
      these subjects. The timeline of neuroimaging and it relation to ECT is a baseline MRI prior
      to first ECT, and then a follow up MRI after the first ECT (< 36hrs after), and a final MRI
      after 9 ECTs or if patient remits. All subjects will receive structural (i.e. diffusion
      tensor imaging and spectroscopy) and functional MRI exams.

      In addition to the imaging procedures detailed above, we also plan to acquire imaging data on
      healthy individuals with similar timeline. Healthy volunteers will be scanned three times;
      the first and second scans will be 24-48 hours apart, while the second and third scans will
      be two weeks apart. The imaging sessions will follow the same protocol as in the patients.
      The collection of control data is necessary in order to demonstrate that imaging findings are
      not due to acclimatization to scanner environment or other confounding sources. Compensation
      for participating in the MRI component is $75 per MRI.
    

Intervention name(s): Ketamine; Methohexital
Intervention type(s): Drug; Drug
Intervention description(s): Ketamine 1-2 mgr/ kg IV; Methohexital 0.5-1mg/kg IV
Other intervention name(s): Ketalar; Brevatol
Intervention MeSH terms: Ketamine; Methohexital
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Electroconvulsive Therapy; Ketamine; anesthesia; depression; unipolar; bipolar