Magnetic Seizure Therapy in Bipolar Depression (MST-BpD) and Treatment Resistant Depression (MST-TRD)

Inclusion Criteria:

• The condition under study: Patients who are diagnosed by Bipolar I or II, currentepisode depressed according to the ICD-10 diagnostic criteria (F31.3, F31.4, F31.5,F31.81) or treatment resistant depression defined below who require a rapid responsedue to the severity of their psychiatric or medical condition. ICD-10 DiagnosticCriteria for Bipolar Depression is as follows: A disorder characterized by two ormore episodes in which the patient's mood and activity levels are significantlydisturbed, this disturbance consisting on some occasions of an elevation of mood andincreased energy and activity (hypomania or mania) and on others of a lowering ofmood and decreased energy and activity (depression). Repeated episodes of hypomaniaor mania only are classified as bipolar. The patient is currently depressed, as in adepressive episode and has had at least one authenticated hypomanic, manic, or mixedaffective episode in the past. Subjects with treatment resistant depression and havesevere depression will be enrolled to the study. Severe depression will be definedas Hamilton Depression Severity Rating Scale score above 19 and also treatmentresistance is described as a lack of clinically meaningful improvement in depressivesymptoms after treatment with at least two different oral antidepressant medicationsas monotherapy, taken at adequate doses for adequate duration (at least 6 weeks) fortheir current episode of depression. The previous oral antidepressants could be fromthe same or different drug classes, which could include SSRIs, SNRIs, tricyclicantidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), or any other oralantidepressants (FDA, 2019). Since its development in 1960 by Dr. Max Hamilton ofthe University of Leeds, England, Hamilton Depression Severity Rating Scale has beenwidely used in clinical practice and become a standard in pharmaceutical trials

• Both males and females any race and ethnic group.

• Age range between 22-85 years old.

• Ability to provide informed consent or assent.

• Ability to adhere to the study procedures.

• For females of reproductive potential: use of highly effective contraception for atleast 1 month prior to screening and agreement to use such a method during studyparticipation and for an additional one week after the end of ECT/TMSadministration. Of note, ECT is indicated in depression during pregnancy and hasbeen safely used for decades but MST's effects on fetus are still unknown

• For males of reproductive potential: use of condoms or other methods to ensureeffective contraception with partner.

• Has sufficient English in completing self-rated scales.

• Good general health evidenced by obtained medical clearance before the proceduresfrom another provider.

• On a stable drug regimen of psychotropic medication for at least 6 weeks at the timeof entry into the study. Medication changes can be made during patient's studyparticipation but would be limited to the clinical judgment of the PI.

Exclusion Criteria:

• Condition or diagnosis that precludes participation, including: Patients who have animplanted device that is activated or controlled in any way by physiological signals (examples: pacemakers, implantable cardioverter defibrillators [ICD's], vagus nervestimulators [VNS] and wearable cardioverter-defibrillators [WCD's],ocular implants,deep brain stimulators, implanted medication pumps, intracardiac lines, even whenremoved; Patients who have conductive, ferromagnetic or other magnetic sensitivemetals implanted in their head or within 30 cm of the treatment coil such as stentsand bullet fragments). NOTE: Standard amalgam dental fillings are not affected bythe magnetic field and are acceptable in patients]; Patients suffering fromvascular, traumatic, infectious, or metabolic lesions of the brain, even without ahistory of seizure, or without anticonvulsant medication; Patient suffering fromsleep deprivation or alcoholism; Current or unstably remitted substance use disorderexcept nicotine or caffeine use disorder. Stable remission is defined as remissionfor at least 6 months; Pregnant or nursing patients; Patients with a history ofepilepsy or unexplained seizures; Subjects with a history of space-occupyingintracranial pathology; diseases which render a patient likely to suffer hemorrhage,including subdural hematoma, and aortic aneurysm; degenerative diseases of thecentral nervous system such as dementia or medical illness affecting brain function;Any anesthesia contraindications including significant cardiac or other medical riskfactors; Body Mass Index over 60, as our ECT suite stretchers are not equipped tohandle overweight patients; History of severe personality disorder, where, based onthe judgment of the investigators, the personality disorder will interfere with thepatient's ability to complete the follow-up protocol, e.g. borderline personalitydisorder; Imminent risk of suicide (based on the judgment of the investigators; e.g.patient has a plan for suicide, patient is not likely to seek medical attention incase of suicide, patient exhibits the presence of current suicidal ideation; Notable to comply with the operational and administrative requirements of participationin the study (based on the judgment of the investigators); Terminal illnessassociated with expected survival of <12 months; Bipolar Depression with psychoticfeatures (ICD-10 code:F31.5)

• Known allergic reactions to components of anaesthetic or induction agents includingsuccinylcholine, metohexitol, ketamine, propofol, ketorolac.

• Participation in another drug, device, or biologics trial within the preceding 30days

• Disallowed concomitant medications: antiepileptics and benzodiazepines as they areagainst seizure therapies, short or mid acting benzodiazepines such as alprazolam,temazepam, midazolam, lorazepam will be allowed but they should be skipped at least 10 hours before the procedures. Medications that are supposed to have weakantiepileptic features such as lamotrigine, topiramate, gabapentin will be reviewedby the PI and either tapered down or discontinued based upon clinical judgment.Lithium will be tapered off before the procedure because of the increased risk ofpostictal disorientation and delirium.