Accelerated iTBS for Depressed Patients During the COVID-19 Pandemic

A Novel and Practical Accelerated Intermittent Theta Burst Protocol as a Substitute for Depressed Patients 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 aiTBS protocol, including tapering treatments and symptom-based relapse prevention treatments, in patients with unipolar depression previously responsive to ECT and patients needing urgent treatment due to symptom severity during the COVID-19 pandemic.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Device: MagPro X100 Stimulator, B70 Fluid-Cooled Coil

• Study Type: Interventional
• Enrollment (Actual): 176
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M6J1H4
      • CAMH

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Have unipolar depressive episode 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 a consultant brain stimulation psychiatrist
• 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
• Have a concomitant major unstable medical illness, cardiac pacemaker or implanted medication pump
• Have a lifetime Mini-International Neuropsychiatric Interview (MINI) diagnosis of bipolar I or II disorder, 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, or 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 iTBS or 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 iTBS; 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 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 iTBS treatment, delivering 600 pulses of iTBS (bursts of 3 pulses at 50 Hz, bursts repeated at 5 Hz, with a duty cycle of 2 seconds on, 8 seconds off, over 60 cycles / ~3 minutes) at a target of 110% of the subject's resting MT.

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	Up to 10 days (From screening/baseline to end of the acute treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HRSD-24	changes in scores	Up to 10 days (From screening/baseline to end of the acute treatment)
Response on HRSD-24	50% Reduction in score	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	Up to 10 days (From screening/baseline to end of the acute treatment)
Response on PHQ-9	50% Reduction in score	Up to 10 days (From screening/baseline to end of the acute treatment)
Change in PHQ-9	changes in scores	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	Up to 10 days (From screening/baseline to end of the acute treatment)
Response on GAD-7	50% Reduction in score	Up to 10 days (From screening/baseline to end of the acute treatment)
Change in GAD-7	changes in scores	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	Up to 10 days (From screening/baseline to end of the acute treatment)
Response on BDI-II	50% Reduction in Score	Up to 10 days (From screening/baseline to end of the acute treatment)
Change on BDI-II	changes in scores	Up to 10 days (From screening/baseline to end of the acute treatment)
Remission on Beck Scale for Suicidal Ideation (SSI)	Score of 0	Up to 10 days (From screening/baseline to end of the acute treatment)
Change on SSI	changes in scores	Up to 10 days (From screening/baseline to end of the acute treatment)
Change in WHO Disability Assessment Schedule (WHODAS)	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)

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): May 12, 2020
• Primary Completion (Actual): May 18, 2022
• Study Completion (Actual): November 1, 2022

Study Registration Dates

• First Submitted: May 8, 2020
• First Submitted That Met QC Criteria: May 9, 2020
• First Posted (Actual): May 12, 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: depression; transcranial magnetic stimulation; treatment resistance; theta burst stimulation
• Additional Relevant MeSH Terms: 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; Depressive Disorder; COVID-19; Depressive Disorder, Major
• Other Study ID Numbers: 059/2020

Drug and device information, study documents

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