ECT Pulse Amplitude and Medial Temporal Lobe Engagement
Condition: Major Depressive Disorder
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Study type: Interventional
Phase: Phase 4

Summary: 
      Electroconvulsive therapy (ECT) remains the gold-standard treatment for patients with
      depressive episodes. During a typical four-week ECT series, most depressive episodes will
      respond to treatment and people will improve their level of functioning (return to work or
      family). Independent of the antidepressant effect of ECT, many patients experience transient
      memory impairment. This investigation will examine the impact of one ECT parameter (pulse
      amplitude or current) on brain changes (structure of connections within the brain) and
      clinical outcomes. The goal of this investigation is to determine the optimal parameter for
      an individual patient that will maintain the clinical response (reduce depression severity)
      and minimize side effects (eliminate memory issues related to treatment).
    

Detailed description: 
      Electroconvulsive therapy (ECT) remains the gold-standard treatment for patients with
      depressive episodes. During a typical four-week ECT series, most depressive episodes remit,
      and formerly suicidal or psychotically depressed patients will resume their premorbid levels
      of functioning. Independent of the antidepressant effect of ECT, many patients experience
      debilitating but transient cognitive effects such as attention and memory deficits. These
      unwanted side effects are particularly troubling for older patients who are more likely to
      have existing cognitive deficits. Both the stimulus delivery (electrode placement, pulse
      amplitude, and pulse width) and seizure induction appear to work in synergy, but the
      underlying mechanism of action for successful response has yet to be fully elucidated.
      Moreover, further work is needed to understand the relationship between clinical improvement
      and cognitive impairment. This investigation will examine the clinical and neurocognitive
      impact of targeted medial temporal lobe engagement as a function of pulse amplitude, one of
      several variable factors influencing the ECT charge. The ECT charge is measured in
      millicoulombs (mC) and derived from multiplying pulse train duration, pulse-pair frequency,
      pulse width, and pulse amplitude. Pulse amplitude determines the induced electric field
      strength in the brain and is presently fixed at 900 milliamperes (mA) with no clinical or
      scientific justification. The central hypothesis of this investigation is that the optimal
      pulse amplitude for an individual patient will enhance neuroplasticity (clinical response)
      while minimizing the disruption of dominant hemisphere hippocampal cognitive circuitry
      (resulting in cognitive stability). The preliminary data informs the dosage range between 600
      and 800 mA. Pulse amplitudes outside of this range compromise efficacy (500 mA) or may
      increase risk of cognitive impairment (900 mA). The first aim of this investigation will
      identify the electric field strength and neuroplasticity associated with clinical response.
      Critically, this aim will establish the neuroplasticity threshold, which is defined as the
      electric field strength necessary to induce neuroplasticity. The second aim will detect the
      neural correlates of ECT-mediated cognitive changes, which may be related to disrupted
      dominant hemisphere long-term potentiation. The third aim will use data-driven dual
      regression to predict the optimal pulse amplitude for an individual patient. This
      contribution will be significant because the electric field, when manipulated by pulse
      amplitude, can subsequently maximize hippocampal neuroplasticity (efficacy) and minimize
      disrupted connectivity (cognitive stability) thus improving clinical outcomes.
    

Intervention name(s): MECTA Spectrum 5000Q Amplitude
Intervention type(s): Device
Intervention description(s): Current
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Subjects randomized to right unilateral ECT with 600, 700, or 800 mA pulse amplitude.
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment
Keywords: electroconvulsive therapy; MRI; major depressive disorder