Electro-Magnetic Convulsive Therapies for Depression: a Non-inferiority Study

Study Overview
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Brief Summary
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This study aims to compare the efficacy and safety profile of Magnetic Seizure Therapy and Electroconvulsive therapy.

Detailed Description
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Magnetic seizure therapy (MST) is a novel, experimental therapeutic intervention, which combines therapeutic aspects of electroconvulsive therapy (ECT) and transcranial magnetic stimulation, in order to achieve the efficacy of the former with the safety of the latter. While ECT remains the most efficacious treatment available for severe and treatment-resistant depression, it is hampered by its side effect profile, specially cognitive deficits, which albeit transitory might be particularly distressing for patient, not to mention the stigma that still clings to this method. MST employs high frequency magnetic pulses applied to the head to the patient in order to induce generalized epileptic activity, thus emulating the core feature of ECT. Though distributed over a large area, such pulses do not penetrate deeper areas of the brain, therefore sparing deeper areas such as the hippocampi, which are crucial for memory encoding. The goal of this study is to compare the antidepressant action of MST to ECT, using a non-inferiority approach. It also aims to compare the cognitive side effects profile of both interventions, as well as investigate possible neuroimaging changes and response predictors before and after treatments.

Official Title
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Electroconvulsive Therapy Versus Magnetic Seizure Therapy: Clinical and Cognitive Outcomes

Conditions
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Major Depressive Disorder, Bipolar Depression

Intervention / Treatment
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* Device: Magnetic Seizure Therapy
* Device: Electroconvulsive Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Major Depressive Disorder or Bipolar Depression in accordance to the Diagnostic and Statistical Manual (DSM) criteria Score equal to or great than 17 points on the Hamilton Depression Rating Scale Treatment-resistant depression, defined as insufficient relief of symptoms after two different first line treatments using therapeutic doses and for four to six weeks Adequate health and clinical conditions, as assessed by an anaesthesiologist and a psychiatrist Exclusion Criteria: Pregnancy Other psychiatric conditions such as Schizophrenia, Schizoaffective Disorder, Substance Abuse, Borderline Personality Disorder, PTSD, or Intellectual Deficiency Depressive symptoms due to a clinical condition Any clinical or neurological conditions without proper management ECT or any other neuromodulation treatment on the last six months Inability to consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Parallel Assignment
Interventional Model Description: Subjects will be randomly and blindly allocated to either of two interventions, namely, MST or ECT. Clinical and cognitive parameters will be assessedat baseline, weeks 6, 12 and 18.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MST<br>Subjects will receive 12-18 sessions of frontal Magnetic Seizure Therapy under general anaesthesia, twice a week. Clinical and cognitive measures will be assessed before, during and after the treatment | Device: Magnetic Seizure Therapy<br>* Subjects will receive a train of magnetic pulses (between 600 and 1400 pulses) at 100Hz under general anaesthesia using a Magventure device with a Twin Coil<br>* Other names: MST;|
| Active Comparator: ECT<br>Subjects will receive 12-18 sessions of bilateral Electroconvulsive Therapy under general anaesthesia, twice a week. Clinical and cognitive measures will be assessed before, during and after the treatment | Device: Electroconvulsive Therapy<br>* Subjects will receive a brief-pulse electrical stimulus (between 25 and 1008mC) under general anaesthesia using a ECT device<br>* Other names: ECT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Depressive symptoms | Score on the 17 items Hamilton Depression Rating Scale (HDRS-17). It measures the severity of clinical symptoms, ranging from 0 to 52, with higher scores indicating greater severity. | Change from baseline to endpoint (week 18). However, the endpoint can be at week 12 if the patient is remitted at this time period. | 
| Biographical memory | Score on the Autobiographical Memory Inventory (AMI). Interviewer-rated measure with 10 items that indexes autobiographical memory recall and specificity. | Change from baseline to endpoint (week 18). However, the endpoint can be at week 12 if the patient is remitted at this time period. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Depressive Symptoms | Score on the Montgomery-Asberg Depression Rating Scale (MADRS). It measures the severity of clinical symptoms, ranging from 0 to 60, with higher scores indicating greater severity. | Change from baseline to endpoint (week 18). However, the endpoint can be at week 12 if the patient is remitted at this time period. | 
| Depressive Symptoms | Score on the Beck Depression Inventory (BDI). It measures the severity of clinical symptoms, ranging from 0 to 63, with higher scores indicating greater severity. | Change from baseline to endpoint (week 18). However, the endpoint can be at week 12 if the patient is remitted at this time period. | 
| Suicidal Thoughts | Score on the Beck Scale for Suicidal Ideation (BSS). The BSS contains 19 items that measure the severity of actual suicidal wishes and plans. Scores range from 0 to 38, a higher score indicating a higher level of suicide ideation. | Change from baseline to endpoint (week 18). However, the endpoint can be at week 12 if the patient is remitted at this time period. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Depression, Magnetic Seizure Therapy, Electroconvulsive Therapy, Major Depressive Disorder, Bipolar Depression, Cognition