Confirmatory Efficacy and Safety Trial of Magnetic Seizure Therapy for Depression

The study will involve a randomized, double blind, non-inferiority clinical trial with two
treatment arms conducted in two international academic medical centers (the Centre for
Addiction and Mental Health in Toronto, Canada and UT Southwestern in Dallas, Texas). The
investigators are pursuing a non-inferiority clinical trial in an effort to compare MST - a
new treatment for TRD - to RUL-UB-ECT. Treatment will be administered two to three days per
week. Depression symptoms will be assessed with the 24-item Hamilton Depression Rating Scale
(HRSD-24) and suicidality will be assessed with the Scale for Suicidal Ideation (SSI).
Remission will be defined as HRSD-24 < or = 10 and a > 60% decrease in scores from baseline
on two consecutive ratings. Once a participant reaches remission, a second rating to confirm
remission will be conducted immediately before their next scheduled treatment. If remission
is confirmed, they will then be considered a completer of the acute treatment course.
Remission of suicidal ideation is defined as a score of 0 on the SSI. Therefore, there will
be no specific minimum number of treatments that patients must receive to be classified as
remitters. However, patients who do not meet remission criteria after 21 treatment sessions
will be considered non-remitters and will cease treatment sessions. This maximum treatment
number was chosen allowing for the possibility that MST may require more treatment sessions
to achieve remission, similar to RUL-UB ECT. The blind will not be broken to participants
until the completion of the entire study.

Inclusion Criteria

Patients will be included if they:

1. are inpatients or outpatients;

2. are voluntary and competent to consent to treatment and research procedures according
to ECT/MST attending psychiatrist;

3. have a MINI International Neuropsychiatric Interview diagnosis, Version 6 (MINI-6.0)
diagnosis of non-psychotic MDD

4. are 18 years of age or older

5. have a baseline HRSD-24 score > or = 21;

6. are considered to be appropriate to receive convulsive therapy as assessed by an ECT
attending psychiatrist and a consultant anaesthesiologist

7. are agreeable to keeping their current antidepressant treatment constant during the
intervention;

8. are likely able to adhere to the intervention schedule;

9. meet the MST safety criteria [75];

10. If a woman of child-bearing potential: is willing to provide a negative pregnancy test
and agrees not to become pregnant during trial participation.

Exclusion Criteria

Patients will be excluded if they:

1. have a history of MINI diagnosis of substance dependence or abuse within the past
three months;

2. have a concomitant major unstable medical illness;

3. are pregnant or intend to get pregnant during the study;

4. have a MINI diagnosis of any primary psychotic disorder

5. have a MINI diagnosis of obsessive compulsive disorder, or post-traumatic stress
disorder deemed to be primary and causing more functional impairment than the
depressive disorder

6. have probable dementia based on study investigator assessment;

7. have any significant neurological disorder or condition likely to be associated with
increased intracranial pressure or a space occupying brain lesion, e.g., cerebral
aneurysm;

8. present with a medical condition, a medication, or a laboratory abnormality that could
cause a major depressive episode or significant cognitive impairment in the opinion of
the investigator (e.g., hypothyroidism with low TSH, rheumatoid arthritis requiring
high dose prednisone, or Cushing's disease);

9. have an intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear
implants, or electrodes) or any other metal object within or near the head, excluding
the mouth, that cannot be safely removed;

10. require a benzodiazepine with a dose > lorazepam 2 mg/day or equivalent or any
anticonvulsant due to the potential of these medications to limit the efficacy of both
MST and ECT;

11. are unable to communicate in English fluently enough to complete the
neuropsychological tests;

12. have a non-correctable clinically significant sensory impairment (i.e., cannot hear or
see well enough to complete the neuropsychological tests).