This open label investigation further evaluates the safety, efficacy and potential mechanisms of action of a new form of electroconvulsive therapy (ECT). The investigators have recently completed preliminary open-label studies with FEAST, first at Columbia University, and then at the Medical University of South Carolina in Charleston (Nahas et al., 2013b). The investigators have published the outcomes of the first 17 patients studied. One patient withdrew from the study after a single titration session. After the course of FEAST (median 10 sessions), there was a 46.1 + 35.5% improvement in Hamilton Rating Scale for Depression (HRSD24) scores compared to baseline (33.1 + 6.8, 16.8 + 10.9; P < 0.0001). Eight of 16 patients met response criteria (≥50% decrease in HRSD24) and 5/16 met remission criteria (HRSD24≤10). Patients achieved full re-orientation (4 of 5 items correct) in 5.5 + 6.4 min (median time = 3.6 min), timed from when their eyes first opened after treatment. The investigators have now studied 18 more patients (see results below), and we are completing the study in the original IDE with another two more patients still to enroll. This work allowed us to refine the treatment. For example, the investigators selectively modified the electrode geometry to decrease interelectrode resistance. Additionally the investigators modified the titration schedule, now only administering a standard 800 ma ultrabrief pulse, and thus no longer titrating in the current domain. In this next proposed trial we will continue to gather efficacy and safety data, and compare these to a parallel non-randomized group receiving ECT standard of care. ECT is typically delivered in a dynamically adaptive manner, with each person having a different number of treatments, averaging between 8-12 treatment over 4-5 weeks. We thus have to use imprecise time points such as 'at the end of the acute treatment course' rather than specified dates or visits.

Brief Title

Focal Electrically-Administered Seizure Therapy (FEAST) Studies at Two Enrolling Sites to Further Test and Refine the Treatment

Official Title

Focal Electrically-Administered Seizure Therapy (FEAST): Studies at Two Enrolling Sites to Further Test and Refine the Treatment

Brief Summary

This open label investigation further evaluates the safety, efficacy and potential mechanisms <br /> of action of a new form of electroconvulsive therapy (ECT). The investigators have recently <br /> completed preliminary open-label studies with FEAST, first at Columbia University, and then <br /> at the Medical University of South Carolina in Charleston (Nahas et al., 2013b). The <br /> investigators have published the outcomes of the first 17 patients studied. One patient <br /> withdrew from the study after a single titration session. After the course of FEAST (median <br /> 10 sessions), there was a 46.1 + 35.5% improvement in Hamilton Rating Scale for Depression <br /> (HRSD24) scores compared to baseline (33.1 + 6.8, 16.8 + 10.9; P < 0.0001). Eight of 16 <br /> patients met response criteria (≥50% decrease in HRSD24) and 5/16 met remission criteria <br /> (HRSD24≤10). Patients achieved full re-orientation (4 of 5 items correct) in 5.5 + 6.4 min <br /> (median time = 3.6 min), timed from when their eyes first opened after treatment. The <br /> investigators have now studied 18 more patients (see results below), and we are completing <br /> the study in the original IDE with another two more patients still to enroll. <br /> <br /> This work allowed us to refine the treatment. For example, the investigators selectively <br /> modified the electrode geometry to decrease interelectrode resistance. Additionally the <br /> investigators modified the titration schedule, now only administering a standard 800 ma <br /> ultrabrief pulse, and thus no longer titrating in the current domain. <br /> <br /> In this next proposed trial we will continue to gather efficacy and safety data, and compare <br /> these to a parallel non-randomized group receiving ECT standard of care. <br /> <br /> ECT is typically delivered in a dynamically adaptive manner, with each person having a <br /> different number of treatments, averaging between 8-12 treatment over 4-5 weeks. We thus have <br /> to use imprecise time points such as 'at the end of the acute treatment course' rather than <br /> specified dates or visits.

Detailed Description

This study will provide preliminary evaluation of the following:

1. Further characterization of the efficacy of FEAST 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 (typically after 4 weeks) will be compared in patients treated
with the FEAST methodology and matched to nonrandomized patients at our facilities
who were treated with conventional ECT methods (ultrabrief right unilateral [RUL]
ECT).

2. Acute and subacute cognitive side effects following FEAST will be assessed with a
brief neuropsychological battery. The primary acute measures will be the time to
return of orientation following seizure induction. The primary subacute measures
will be assessment of retrograde amnesia for autobiographical information. The
neuropsychological measures will be compared in the patients treated with the FEAST
methodology (under this IDE) and matched (but nonrandomized) patients who are
treated with conventional ECT methods (also covered under this IDE).

3. Safety will also be determined by examining the number and frequency of serious
adverse advents and adverse events.

2. Characterization of the focal nature of the seizure onset with FEAST and RUL ECT. We
will use two main methods to address the issue of focality.

1. Resting state fMRI before and after a course of FEAST (or conventional RUL ECT). We
will address whether FEAST causes changes in hyper connected prefrontal cortical
subcortical networks, and whether such an effect is more restricted to prefrontal
cortex with FEAST relative to conventional RUL ECT.

2. Peri-ictal EEG acquired immediately before, during and immediately after the FEAST
seizure. We will acquire this in all patients at all treatment sessions. Again, for
comparison, we will use identical EEG acquisition methods in patients treated with
conventional RUL ECT.

Outcome Measures

Outcome measures are the tests that investigators perform to prove whether or not a treatment being tested in a clinical trial is having any effect.