Comparing the Effects of Four Types of Electroconvulsive Therapy on Mood and Thinking in People With Depression

Study Overview
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Brief Summary
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This study will compare four types of electroconvulsive therapy to determine if they differ in their effects on mood, thinking, brain activity, and biochemistry in people with major depressive disorder.

Detailed Description
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Major depressive disorder (MDD) is a serious condition that can interfere with a person's ability to work, study, sleep, eat, and enjoy activities that were once pleasurable. Depression may occur only once in a lifetime, but usually occurs several times. There are several types of medications and therapies that have been successful in improving symptoms of depression. Electroconvulsive therapy (ECT) has been particularly successful in treating individuals whose depression is severe or life threatening or who cannot take antidepressant medication. In ECT, electrodes are placed at precise locations on the head to deliver electrical impulses. The stimulation causes a brief seizure within the brain. The person receiving ECT does not consciously experience the electrical stimulus and does not feel pain. This study will compare four types of ECT to determine if they differ in their effects on mood, thinking, brain activity, and biochemistry in people with MDD. Participants in this double-blind study will be randomly assigned to receive one of four types of ECT. Treatments will occur three times a week for 2 to 6 weeks, depending on each participant's individual needs. All participants will stop taking any psychiatric medications at least 5 days before receiving ECT. Before beginning each ECT session, participants will be interviewed by study staff about their current psychiatric condition, any psychological problems they have had, any history of psychological problems in their families, their medical history, and their attitudes about receiving ECT. A family member may also be asked to participate in some interviews. In addition, before each treatment, monitoring sensors will be placed on each participant's head and other areas of the body and a blood pressure cuff will be placed on an arm. These devices will be used to monitor each participant's brain waves, heart, and blood pressure before, during, and after treatment. Because ECT entails the use of general anesthesia, participants will not eat for at least 8 hours before each treatment. An intravenous catheter will be placed in participants' arms to administer the anesthesia and a muscle relaxant. Just before receiving ECT, participants will be asked to remember a set of information. Upon waking after treatment, participants will be asked to recall or recognize this material and complete a set of brief neuropsychological tasks. Electroencephalogram (EEG) tests (to measure electrical activity of the brain), transcranial magnetic stimulation (TMS) (to measure muscle activity), blood collection, and magnetic resonance imaging (MRI) tests (to image the inside of the body) will be performed at selected sessions and follow-up visits to assess outcomes. Follow-up interviews will be held via telephone every 2 weeks for 2 months post-treatment, and then monthly for the remainder of the year. Follow-up neuropsychological tests will also be administered at Months 2, 4, and 6 post-treatment.

Official Title
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Affective and Cognitive Consequences of ECT

Conditions
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Depression

Intervention / Treatment
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* Device: Electroconvulsive Therapy (ECT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of major depressive disorder Pretreatment score of at least 18 on the Hamilton Rating Scale for Depression Able to tolerate psychotropic washout and no psychotropic medication, other than lorazepam (up to 3 mg/d PRN), during the study Recommended to receive ECT Exclusion Criteria: History of schizophrenia, schizoaffective disorder, other functional psychosis, or rapid cycling bipolar disorder Secondary diagnosis of a delirium, dementia, or amnestic disorder, or epilepsy Pregnant History of neurological illness other than conditions associated with psychotropic exposure (e.g., tardive dyskinesia) History of alcohol or substance abuse within the year prior to study entry History of ECT within the 6 months prior to study entry

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ultrabrief, Right Unilateral ECT<br>Right unilateral ECT administered with an ultrabrief pulse width (0.3 ms), at a dose 6 times the initial seizure threshold | Device: Electroconvulsive Therapy (ECT)<br>* Electroconvulsive therapy involves applying a small electrical charge to the scalp while the patient is anesthetized and provoking a short-lasting generalized seizure<br>* Other names: shock therapy;|
| Experimental: Ultrabrief, Bilateral ECT (2.5 X ST)<br>Bilateral (frontotemporal) ECT with an ultrabrief pulse width with dosage 2.5 times the initial seizure threshold | Device: Electroconvulsive Therapy (ECT)<br>* Electroconvulsive therapy involves applying a small electrical charge to the scalp while the patient is anesthetized and provoking a short-lasting generalized seizure<br>* Other names: shock therapy;|
| Active Comparator: Brief Pulse, Right Unilateral ECT<br>Right unilateral ECT, with a standard brief pulse (1.5 ms), with dosage 6 times the initial seizure threshold | Device: Electroconvulsive Therapy (ECT)<br>* Electroconvulsive therapy involves applying a small electrical charge to the scalp while the patient is anesthetized and provoking a short-lasting generalized seizure<br>* Other names: shock therapy;|
| Active Comparator: Brief Pulse, Bilateral ECT<br>Bilateral (frontotemporal) ECT with a standard brief pulse (1.5 ms), with dosage 2.5 times the initial seizure threshold | Device: Electroconvulsive Therapy (ECT)<br>* Electroconvulsive therapy involves applying a small electrical charge to the scalp while the patient is anesthetized and provoking a short-lasting generalized seizure<br>* Other names: shock therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Short-term antidepressant efficacy | Primary outcome reflected change in HRSD depression symptom scores. | Measured immediately post-treatment and 2, 4, and 6 months post-treatment | 
| Specific acute, short-term, and long-term objective and subjective cognitive outcome measures (e.g., autobiographical amnesia, global self-rating of amnesia) | Specific neuropsychological measures were preselected as primary in safety analyses | Measured immediately post-treatment and 2, 4, and 6 months post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antidepressant efficacy | Treatment groups were also compared in rates of response and remission, as well as post-treatment relapse. | Measured immediately post-treatment and 2, 4, and 6 months post-treatment | 
| Assessments of functional outcomes | Repeated measurement using the SF-36 | Measured immediately post-treatment and 2, 4, and 6 months post-treatment | 
| Memory, non-memory, and executive functions (acute, short-term, and long-term measures) | Remaining measures in the neuropsychological battery other than those pre-selected as primary outcome measures | Measured immediately post-treatment and 2, 4, and 6 months post-treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Major Depressive Disorder, Electroconvulsive Therapy