Accelerated LFR for Bipolar Patients During the COVID-19 Pandemic

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

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.

Study Overview

• Status: Completed
• Conditions: Bipolar Depression
• Intervention / Treatment: Device: MagPro X100 Stimulator, B70 Fluid-Cooled Coil

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M6H3J7
      • CAMH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Accelerated LFR; 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; 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.

What is the study measuring?

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
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)
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)

Collaborators and Investigators

• Sponsor: Centre for Addiction and Mental Health
• Investigators: Principal Investigator: Daniel Blumberger, MD, CAMH

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2020
• Primary Completion (Actual): January 9, 2022
• Study Completion (Actual): November 9, 2022

Study Registration Dates

• First Submitted: June 10, 2020
• First Submitted That Met QC Criteria: June 10, 2020
• First Posted (Actual): June 11, 2020

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 16, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: transcranial magnetic stimulation; bipolar depression; treatment resistance; low-frequency right-side stimulation
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Mood Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Bipolar and Related Disorders; Depression; Depressive Disorder; COVID-19; Bipolar Disorder
• Other Study ID Numbers: 071-2020

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No