Focal Electroconvulsive Therapy for Depression
Condition: Major Depressive Disorder
MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Major
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      This pilot, open label investigation evaluates the safety and efficacy of a new form of
      electroconvulsive therapy (ECT). Both the efficacy and adverse cognitive effects of ECT are
      highly contingent on the intracerebral current paths and current density of the ECT stimulus.
      However, the impedance of the skull and individual differences in skull anatomy severely
      limit the spatial targeting of stimulation, and create marked individual differences in
      intracerebral current density. To address these problems, the investigators are exploring
      various means of overcoming this limitation.

      An approach is to modify the electrical stimulus to induce focal seizures. The most common
      methods of ECT administration in the US use a bidirectional, constant current, brief pulse,
      with large (approximately 3 sq. in. surface area) and identically sized and shaped
      electrodes. In contrast, in this protocol the investigators have coupled unidirectional
      current flow with an electrode geometry involving a small and large electrode that differ by
      more than 3:1 in surface area.

      Unidirectional currents were widely used in ECT during the, 1940's and continue to be used in
      European and American devices today. Transcranial electrical stimulation can be made focal by
      stimulating with an anode-cathode arrangement, with the electrodes differing in surface area.
      The investigators have shown in nonhuman primates the capacity to produce focal frontal
      seizure induction under conditions when a unidirectional current flows from a small anterior
      anode (placed on the forehead over the nasion) to a large posterior cathode just anterior to
      the motor strip. Furthermore, the investigators expect that some, if not all, of these
      seizures do not result in motor convulsions.

      Thirty outpatients referred for ECT will participate. Relative to concurrent reference data
      from our ongoing ECT protocols, the investigators hypothesize that acute and subacute adverse
      cognitive effects of FEAST will be substantially less than those in patients receiving
      state-of-the art ECT, but with a traditional bidirectional, nonfocal stimulus. The
      investigators also hypothesize that the majority of patients will remit with FEAST. Thus, by
      improving the efficiency of the ECT stimulus with the switch to unidirectional current and
      the use of a new electrode geometry, the investigators expect to be able to induce focal
      seizures. The investigators hypothesize that this pilot study will provide evidence that this
      treatment is superior to traditional ECT in having lower dosing requirements and a superior
      side effect profile.
    

Detailed description: 
      This study will provide preliminary evaluation of the following:

        1. Determination of whether focal seizures can be induced with the FEAST methodology
           (unidirectional stimulation, small anterior and large posterior electrode).

             1. Focality will be assessed by the occurrence of non-motor seizures.

             2. Electroencephalographic evidence of pronounced asymmetry in frontal leads.

        2. Determination of whether the FEAST methodology results in reduced seizure threshold.

           a. Seizure threshold will be quantified at the start of the treatment course using the
           standard method of limits titration procedure and compared to threshold determinations
           in matched patients who were treated with conventional ECT methods.

        3. Characterization of dynamic impedance using the FEAST methodology.

           a. Dynamic impedance during the passage of the electrical stimulus will be quantified
           during each administration and compared to the values obtained in matched patients who
           were treated with conventional ECT methods.

        4. Characterization of the efficacy of the FEAST methods and the safety of the treatment.

             1. The primary efficacy measure will be the 24-item Hamilton Rating Scale for
                Depression. The changes in these scores from before to immediately following the
                treatment course will be compared in patients treated with the FEAST methodology
                and matched patients who were treated with conventional ECT methods.

             2. Acute, subacute, and long-term cognitive side effects following FEAST will be
                assessed with comprehensive neuropsychological batteries. The primary acute
                measures will include the time to return of orientation following seizure induction
                and retrograde amnesia for words and shapes. The primary subacute measures will
                include assessments of anterograde amnesia (forgetting over a delay) for a verbal
                list and for reproduction of a complex figure, as well as retrograde amnesia for
                autobiographical information. The primary long-term measure will be retrograde
                amnesia for autobiographical information, assessed 6-months following the FEAST
                course. The neuropsychological measures will be compared in the patients treated
                with the FEAST methodology and matched patients who were treated with conventional
                ECT methods, as well as in healthy participants who receive were administered the
                neuropsychological battery at the same intervals as the FEAST patients, but without
                Intervention.

             3. Safety will also be determined by examining the number and frequency of serious
                adverse advents and adverse events, as well as scores on the Columbia University
                ECT Side Effect Scale.
    

Intervention name(s): focal ECT
Intervention type(s): Device
Intervention description(s): FEAST, ECT, unidirectional stimulation
Other intervention name(s): FEAST, ultra-brief unidirectional right ECT
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: ECT; FEAST; brain stimulation; depression