Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Pilot Study of the Use of Magnetic Seizure Therapy for Treatment Resistant Depression
Brief Summary: Electro convulsive therapy (ECT) remains the only established therapy for the large percentage of patients with depression who fail to respond to standard treatments. It is commonly used but has substantial problems including the occurrence of cognitive side effects that are often highly distressing for patients. The development of a new treatment with similar efficacy but which minimises these side effects would have great clinical value. One highly promising possibility is magnetic seizure therapy (MST). MST involves replacing the electrical stimulation used in ECT with a magnetic stimulus. This appears to be able to produce similar clinical effects but without the disabling cognitive side effects related to ECT. However, substantive trials using the newest MST equipment are required. Due to the rarity of the equipment available so far, these are only being undertaken in a handful of places internationally and no research with MST has occurred in Australia. The investigators are fortunate to have been able to obtain one of the very limited number of MST devices available internationally and are proposing a pilot study of this technique. Conduct of a successful pilot study would be strong justification for an application for a large head-to-head MST - ECT comparison trial. Should MST be shown to have similar efficacy to ECT but with reduced side-effects, it is envisioned that it could rapidly replace ECT in clinical practice throughout Australia and indeed internationally with substantial ongoing benefits to patients. These would include enhanced use of it as an outpatient therapy as well as the reduction in side-effects.

The study will be an open label trial of MST in 15 patients with treatment resistant depression who have been referred for ECT. All patients will undergo a dose titration procedure to establish seizure threshold, six MST treatment sessions will then be provided at 120% of threshold. If the patients have not achieved a 50% reduction in their depressive symptoms (as measured by the Montgomery Asberg Depression Rating Scale rating scale) patients will receive another 12 sessions. MST will be administered three times a week. Patients will undergo a series of assessments to determine both the efficacy of MST and the cognitive outcomes. The primary outcome measure will be the MADRS measure of depression severity. The investigators will additionally measure patient rated depression severity and cognitive functioning The overall aim of the current project is to, via an open label pilot trial, investigate the clinical response to magnetic seizure therapy in patients with treatment resistant depression who have been referred for electroconvulsive therapy.


Options:
A: Inclusion Criteria:

1. Have a DSM-IV diagnosis of a major depressive episode
2. Are referred for or an outpatient course of ECT at the Alfred Hospital
3. Age 18-75
4. Have a Montgomery-Asberg Depression Rating Scale (MADRS) score of \> 25 (moderate - severe depression)
5. Demonstration of capacity to give informed consent: this will be assessed by the study psychiatrist as well as the patient's primary treating psychiatrist.

Exclusion Criteria:

1. Have an unstable medical condition, or neurological disorder or are currently pregnant or lactating.
2. Patients not considered sufficiently well to undergo general anaesthesia for any reason
3. Patients with cardiac pacemakers, cochlear implants or other implanted electronic devices. Patients with non-electric metallic implants will also be excluded.
4. Significant concurrent axis 1 or 11 psychiatric comorbidity.
B: Inclusion Criteria:

* ages 18 to 85
* DSM-IV diagnosis of major depressive episode with or without psychotic features in the context of MDD or bipolar disorder; OCD or Schizophrenia
* 24-item HRSD score of ≥ 21 (for depression subjects)
* 18-item BPRS score of ≥ 37 (for schizophrenia subjects)
* Y-BOCS score of ≥ 16 (for OCD subjects)
* demonstrate capacity to give informed consent
* are a Canadian resident

Exclusion Criteria:

* have an unstable medical and/or neurological condition
* are currently pregnant or lactating
* are not considered sufficiently well to undergo general anesthesia for any reason
* have a cardiac pacemaker, cochlear implant, implanted electronic device or non-electric metallic implant
* are taking a benzodiazepine at a dose greater than lorazepam 2mg or equivalent
* are taking any non-benzodiazepine anticonvulsant
* have active substance misuse or dependence within the past 3 months
* have a current diagnosis of delirium, dementia or another cognitive disorder secondary to a general medical condition
* have a co-morbid borderline personality disorder and/or antisocial personality disorder
* have had a history of any suicide attempts in the past 6 months
C: Inclusion Criteria:

* Age 18-90
* Clinical diagnosis of major depressive episode, in the context of unipolar or bipolar disorder
* Use of effective method of birth control for women of child-bearing capacity
* Willing and capable to provide informed consent
* Convulsive therapy clinically indicated
* Hamilton Rating Scale for Depression (HRSD24) ≥ 20

Exclusion Criteria:

* Current unstable or serious medical condition, or any comorbid medical condition that substantially increases the risks of ECT (such as acute myocardial infarction, space occupying brain lesion or other cause of increased intracranial pressure, unstable aneurysm or vascular malformation, poorly controlled diabetes mellitus, carcinoma, renal failure, hepatic failure)
* Pregnancy
* History of neurological disorder, epilepsy, stroke, brain surgery, metal in the head, history of known structural brain lesion
* Presence of devices that may be affected by MST (pacemaker, medication pump, cochlear implant, implanted brain stimulator)
* Breast-feeding
* History of head trauma with loss of consciousness for greater than 5 minutes
* History of schizophrenia, schizoaffective disorder, or rapid cycling bipolar disorder
* Vagus nerve stimulator implanted
* History of substance abuse or dependence in past 3 months
* Failure to respond to an adequate course of ECT in the current depressive episode
* History of ECT in the past 6 months and/or failure to respond to an adequate trial of ECT lifetime
* Presence of intracardiac lines
D: 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).

Answer: A