Accelerated LFR for Bipolar Patients During the COVID-19 Pandemic

Study Overview
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Brief Summary
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The current study aims to assess the feasibility, acceptance and clinical outcomes of a practical high-dose LFR protocol, including tapering treatments and symptom-based relapse prevention treatments, in patients with bipolar depression previously responsive to ECT and patients needing urgent treatment due to symptom severity during the COVID-19 pandemic.

Detailed Description
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Treatment resistant bipolar depression is a leading cause of disability and socioeconomic burden of disease, and current treatment options all suffer from critical deficiencies of efficacy, capacity, or tolerability, especially given the current COVID-19 pandemic. rTMS and aLFR in particular has the potential to overcome many of these deficiencies, and is safe and well-tolerated. Taken together with the reported findings of other groups, aLFR may be feasible, tolerable, and capable of achieving comparable and potentially better remission rates than longer 20 to 30-day courses and it may also be beneficial to taper treatments and use symptom-based relapse prevention treatments in an aLFR protocol. Importantly, our pilot data in two patients previously responsive to ECT and data from the Cole et al. study suggest that accelerated rTMS may be a potential substitute for ECT as it may be possible to achieve remission in patients with severe depressive symptoms who would otherwise receive ECT. Furthermore, there is a burden of being able to provide care to as many people as possible based on severity of illness during the pandemic.

Official Title
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A Novel and Practical Accelerated Low-frequency Right-sided Stimulation Protocol as a Substitute for Patients With Bipolar Depression Needing Electroconvulsive Therapy During the COVID-19 Pandemic

Conditions
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Bipolar Depression

Intervention / Treatment
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* Device: MagPro X100 Stimulator, B70 Fluid-Cooled Coil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Currently are experiencing a bipolar depressive episode (bipolar disorder type 1 or 2) based on the MINI with or without psychotic symptoms Have previous response to ECT or high symptom severity warranting acute ECT in the opinion of one of the brain stimulation psychiatrists Are over the age of 18 Pass the TMS adult safety screening (TASS) questionnaire Are voluntary and competent to consent to treatment Exclusion Criteria: have a Mini-International Neuropsychiatric Interview (MINI) confirmed diagnosis of substance dependence or abuse within the last 1 month Currently experiencing a mixed or manic episode (YMRS >12) have a concomitant major unstable medical illness, cardiac pacemaker or implanted medication pump have a lifetime Mini-International Neuropsychiatric Interview (MINI) diagnosis of schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder have any significant neurological disorder or insult including, but not limited to: any condition likely to be associated with increased intracranial pressure, space occupying brain lesion, any history of seizure except those therapeutically induced by ECT or a febrile seizure of infancy or single seizure related to a known drug related event, cerebral aneurysm, significant head trauma with loss of consciousness for greater than 5 minutes 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 currently take more than lorazepam 2 mg daily (or equivalent) or any dose of an anticonvulsant due to the potential to limit rTMS efficacy Lack of response to accelerated course of rTMS in the past

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Accelerated LFR<br>In the acute treatment phase, treatment will occur 8 times daily (50 min pause between treatments) on weekdays, until symptom remission is achieved (HRSD-24 score < to 10) or a maximum of 10 working days of daily treatment. In the tapering phase, treatments will be reduced to 2 treatment days per week for 2 weeks and then 1 treatment day per week for 2 weeks (4 weeks total). Patients that have responded to treatment will then enter the symptom-based relapse prevention phase including virtual check-in with study staff and a treatment schedule based on symptom level according to a modified relapse prevention algorithm that has been developed to prevent relapse after a successful course of ECT (known as the STABLE algorithm). The relapse prevention phase will last a maximum of 6 months. | Device: MagPro X100 Stimulator, B70 Fluid-Cooled Coil<br>* Treatment will occur 8 times per treatment day (50 min pause between treatments). Each treatment session will consist of a single LFR treatment, with 360 pulses of LFR delivered in one continuous train of 6 minutes at 1Hz at 120% of the patient's resting motor threshold.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion achieving remission on Hamilton Rating Scale for Depresion 24-it (HRSD-24) | Less than or equal to 10 This scale is used to quantify the severity of symptoms of depression Scale range: 0-76 (total score) Lower scores indicate lower severity of depressive symptoms (i.e., better outcome) Higher scores indicate higher severity of depressive symptoms (i.e., worse outcome) | Up to 10 days (From screening/baseline to end of the acute treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hamilton Rating Scale for Depresion 24-it (HRSD-24) | changes in scores This scale is used to quantify the severity of symptoms of depression Scale range: 0-76 (total score) Lower scores indicate lower severity of depressive symptoms (i.e., better outcome) Higher scores indicate higher severity of depressive symptoms (i.e., worse outcome) | Up to 10 days (From screening/baseline to end of the acute treatment) | 
| Response on Hamilton Rating Scale for Depresion 24-it (HRSD-24) | 50% Reduction in score This scale is used to quantify the severity of symptoms of depression Scale range: 0-76 (total score) Lower scores indicate lower severity of depressive symptoms (i.e., better outcome) Higher scores indicate higher severity of depressive symptoms (i.e., worse outcome) | Up to 10 days (From screening/baseline to end of the acute treatment) | 
| Change in Young Mania Rating Scale (YMRS) | changes in scores This scale is used to quantify the severity of symptoms of mania Scale range: 0-60 (total score) Lower scores indicate lower severity of manic symptoms (i.e., better outcome) Higher scores indicate higher severity of manic symptoms (i.e., worse outcome) | Up to 10 days (From screening/baseline to end of the acute treatment) | 
| Remission on Patient Health Questionnaire (PHQ-9) | Less than or equal to 4 This scale is used to quantify the severity of symptoms of depression Scale range: 0-27 (total score) Lower scores indicate lower severity of depressive symptoms (i.e., better outcome) Higher scores indicate higher severity of depressive symptoms (i.e., worse outcome) | Up to 10 days (From screening/baseline to end of the acute treatment) | 
| Response on Patient Health Questionnaire (PHQ-9) | 50% Reduction in score This scale is used to quantify the severity of symptoms of depression Scale range: 0-27 (total score) Lower scores indicate lower severity of depressive symptoms (i.e., better outcome) Higher scores indicate higher severity of depressive symptoms (i.e., worse outcome) | Up to 10 days (From screening/baseline to end of the acute treatment) | 
| Change in Patient Health Questionnaire (PHQ-9) | changes in scores This scale is used to quantify the severity of symptoms of depression Scale range: 0-27 (total score) Lower scores indicate lower severity of depressive symptoms (i.e., better outcome) Higher scores indicate higher severity of depressive symptoms (i.e., worse outcome) | Up to 10 days (From screening/baseline to end of the acute treatment) | 
| Remission on General Anxiety Disorder 7 item (GAD-7) | Less than or equal to 4 This scale is used to quantify the severity of symptoms of anxiety Scale range: 0-21 (total score) Lower scores indicate lower severity of anxiety symptoms (i.e., better outcome) Higher scores indicate higher severity of anxiety symptoms (i.e., worse outcome) | Up to 10 days (From screening/baseline to end of the acute treatment) | 
| Response on General Anxiety Disorder 7 item (GAD-7) | 50% Reduction in score This scale is used to quantify the severity of symptoms of anxiety Scale range: 0-21 (total score) Lower scores indicate lower severity of anxiety symptoms (i.e., better outcome) Higher scores indicate higher severity of anxiety symptoms (i.e., worse outcome) | Up to 10 days (From screening/baseline to end of the acute treatment) | 
| Change in General Anxiety Disorder 7 item (GAD-7) | changes in scores This scale is used to quantify the severity of symptoms of anxiety Scale range: 0-21 (total score) Lower scores indicate lower severity of anxiety symptoms (i.e., better outcome) Higher scores indicate higher severity of anxiety symptoms (i.e., worse outcome) | Up to 10 days (From screening/baseline to end of the acute treatment) | 
| Remission on Beck Depression Inventory (BDI-II) | Less than or equal to 12 This scale is used to quantify the severity of symptoms of depression Scale range: 0-63 (total score) Lower scores indicate lower severity of depressive symptoms (i.e., better outcome) Higher scores indicate higher severity of depressive symptoms (i.e., worse outcome) | Up to 10 days (From screening/baseline to end of the acute treatment) | 
| Response on Beck Depression Inventory (BDI-II) | 50% Reduction in Score This scale is used to quantify the severity of symptoms of depression Scale range: 0-63 (total score) Lower scores indicate lower severity of depressive symptoms (i.e., better outcome) Higher scores indicate higher severity of depressive symptoms (i.e., worse outcome) | Up to 10 days (From screening/baseline to end of the acute treatment) | 
| Change on Beck Depression Inventory (BDI-II) | changes in scores This scale is used to quantify the severity of symptoms of depression Scale range: 0-63 (total score) Lower scores indicate lower severity of depressive symptoms (i.e., better outcome) Higher scores indicate higher severity of depressive symptoms (i.e., worse outcome) | Up to 10 days (From screening/baseline to end of the acute treatment) | 
| Remission on Beck Scale for Suicidal Ideation (SSI) | Score of 0 This scale is used to assess the presence or absence of suicidal ideation and the degree of severity of suicidal ideas Scale range: 0 - 38 (total score) Lower scores indicate lower severity of suicidal ideation (i.e., better outcome) Higher scores indicate higher severity of suicidal ideation (i.e., worse outcome) | Up to 10 days (From screening/baseline to end of the acute treatment) | 
| Change on Beck Scale for Suicidal Ideation (SSI) | changes in scores This scale is used to assess the presence or absence of suicidal ideation and the degree of severity of suicidal ideas Scale range: 0 - 38 (total score) Lower scores indicate lower severity of suicidal ideation (i.e., better outcome) Higher scores indicate higher severity of suicidal ideation (i.e., worse outcome) | Up to 10 days (From screening/baseline to end of the acute treatment) | 
| Change in WHO Disability Assessment Schedule (WHODAS) Range 0-38 | changes in scores | Up to 10 days (From screening/baseline to end of the acute treatment) | 
| Proportion of Patients Maintaining Response During Relapse Prevention | Includes number of treatment days needed and number going on to receive ECT | 24 weeks (Tapering and Relapse prevention phase) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bipolar depression, transcranial magnetic stimulation, treatment resistance, low-frequency right-side stimulation