Overview

Background

People with TRD are often helped by electroconvulsive therapy (ECT). But ECT can affect memory and thinking. Researchers want to study a treatment called TEST that uses less electricity.

Objective

To study the safety and feasibility of TEST and assess its antidepressant effects.

Eligibility

Adults aged 25-64 with major depression that has not been relieved by current treatments.

Design

Participants will be admitted to the NIH Clinical Center for 5 18 weeks over 2 3 treatment phases. Their medications may be adjusted.

Participants will be interviewed about their depression, side effects, and other treatments they are receiving. They will complete questionnaires. They will give blood and urine samples. Their brain waves and heart rhythm will be recorded. They will take tests of memory, attention, mental functioning, and thinking.

Participants will have magnetic resonance imaging (MRI) scans of the head and brain. They will lie on a table that slides in and out of the scanner. Pictures of brain chemicals will also be taken. They may complete tasks during the MRI.

Participants will receive TEST and/or sham treatments. They may receive optional ECT. An intravenous catheter will be placed in an arm vein to receive general anesthesia. Two electrodes will be placed on the front of their head. An electric current will be passed from the ECT machine through the electrodes. For sham treatments, they will not receive the electric current. Their breathing, heart rate, brain function, blood pressure, and body movements will be measured.

Participants will have 7 follow-up visits over 6 months. Visits can be done via telehealth.

Participation will last for up to 42 weeks.

Eligibility

• INCLUSION CRITERIA:

        In order to be eligible to participate in this study, an individual must meet all of the
        following criteria:
          1. Provision of a signed and dated informed consent form.
          2. Stated willingness to comply with all study procedures and availability for the
             duration of the study.
          3. Male or female, ages 25 through 64 years.
          4. Meeting structured clinical interview for the DSM 5 (SCID) criteria for major
             depressive disorder, bipolar I disorder, or bipolar II disorder.
          5. Currently have TRD as defined by a major depressive episode with lack of remission of
             depressive symptoms following two trials of different medication or one medication
             trial and one rTMS trial approved for unipolar or bipolar depression at adequate
             dosage and duration treatment consistent with an Antidepressant Treatment History Form
             (ATHF) confidence level >=3.
          6. Score >= 25 on the Montgomery-Asberg Depression Rating Scale (MADRS) and a score >=2
             on item 1 at screening.
          7. Score <=12 on the Young Mania Rating Scale (YMRS) and a score <= 1 on item 1 at
             screening.
          8. Willingness to: (a) provide written permission, as requested, to allow any and all
             forms of communication between the Investigator/Research Staff and any healthcare
             provider who currently provides and/or has provided service to the patient/subject
             within two years of study enrollment; and (b) provide the name and verifiable contact
             information of a person whom they trust to be an emergency contact whom research staff
             is at liberty to contact for the duration of study participation and who could serve
             as a legally authorized representative (LAR) if needed.
          9. Agreement to remain on the same daily dose of all psychiatric medication(s) without
             taking any new psychiatric medication(s) for a minimum of 6 weeks (42 days) prior to
             the baseline assessment and through the completion of Study Phase III (Study Phase IV
             is the 6-month Follow-up Phase) unless advised otherwise by the Investigator
         10. Agreement that dosage reduction of any medication taken for a psychiatric condition
             must be completed at least 4 weeks (28 days) prior to the baseline assessment and must
             remain unchanged thereafter through the completion of Study Phase III (Study Phase IV
             is the 6- month Follow-up Phase), unless advised otherwise by the Investigator
         11. Agreement to remain on the same daily dose of psychiatric medication from the start of
             the baseline assessment / Phase I through the completion of the final treatment Study
             Phase III (Study Phase IV is the 6-month Follow-up Phase), unless advised otherwise by
             the Investigator.
         12. For females of reproductive potential: use of contraception, which in the opinion of
             the Investigator is highly effective, for at least 1 month prior to screening and
             agreement to use such a method during study participation, except during the 6-month
             follow up.
         13. Ability of the participant to understand and be willing to sign a written informed
             consent document as determined by the Investigator.
        ECLUSION CRITERIA:
        An individual who meets any of the following criteria will be excluded from participation
        in this study:
          1. Pregnancy or nursing or women planning to become pregnant during study period, except
             for the 6-month follow up phase.
          2. A history of addiction to, dependence on, abuse of, or misuse of alcohol or any
             controlled, illicit, or illegal substance (excluding nicotine) within the past one
             year
          3. Expression of recent or current active suicidal ideas and an explicit plan or intent,
             in the opinion of the Investigator or answering YES to questions 4 or 5 on the
             Columbia-Suicide Severity Rating Scale (C-SSRS) or scoring >4 on Montgomery-Asberg
             Depression Rating Scale (MADRS) item 10.
          4. Presence of any disease, medical condition or physical condition that, in the opinion
             of the Investigator, may compromise, interfere with, limit, effect or reduce the:
               1. subject s ability to participate in any of the items listed in the Schedule of
                  Activities
               2. integrity of the data or
               3. subject s ability to complete the full duration of the study.
          5. Mood disorder is, in the opinion of the Investigator, significantly influenced or
             caused by an underlying medical or neurological condition, for example, multiple
             sclerosis or fibromyalgia
          6. History of serious, potentially life-threatening reaction to methohexital or
             succinylcholine.
          7. Clinically significant psychiatric comorbidity as determined by clinical interview and
             in the opinion of the Investigator
          8. Past or present medical or neurological condition, disease, disorder or injury that,
             in the opinion of the Investigator, may significantly increase the potential risks of
             study participation, reduce or compromise a subject s ability to fully comply with all
             study requirements for the duration of the study or may compromise the integrity of
             the data. Past or present medical or neurological condition, disease, disorder or
             injury that, in the opinion of the Investigator, may significantly increase the
             potential risks of study participation, reduce or compromise a subject s ability to
             fully comply with all study requirements for the duration of the study or may
             compromise the integrity of the data.
          9. History of seizure except those therapeutically induced by ECT, except for childhood
             febrile seizures.
         10. History of any of the following:
               1. intracranial surgery
               2. cranial metal implants
               3. presence of devices that may be affected by MRI (pacemaker, medication pump,
                  cochlear implant, implanted brain stimulator, vagus nerve stimulator
               4. history of head trauma associated with a brain imaging study that shows probable
                  or definite evidence of a post-traumatic abnormality as determined by a
                  neuroradiologist and which the Investigator deems clinically significant at
                  screening.
         11. Any of the following treatment histories:
             Failure to respond to adequate ECT treatment consistent with an ATHF confidence level
             >=3 in current or any previous episode
             Lifetime history of treatment with deep brain stimulation
             Use of any investigational drug or device within 4 weeks of the screening
         12. Inability to pass the Evaluation to Sign A Consent Form test for adequate
             comprehension of the study for any reason including limitations related to use of the
             English language.
         13. Positive HIV test.
         14. Being an NIMH employee or an immediate family member of an NIMH employee.
         15. Presence of any condition that, in the judgment of the investigator, may hinder
             completion of the procedures required by the study protocol.