Accelerated intermittent theta burst as a substitute for patients needing electroconvulsive therapy during the COVID-19 pandemic: study protocol for an open-label clinical trial

  1. Daniel M. Blumberger
  2. Zafiris J. Daskalakis
  3. Fidel Vila-Rodriguez
  4. David Boivin-Lafleur
  5. Michelle S. Goodman
  6. Tyler Kaster
  7. Yuliya Knyahnytska
  8. Gerasimos Konstantinou
  9. Alisson P. Trevizol
  10. Daphne Voineskos
  11. Cory R. Weissman
  12. Jonathan Downar

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Abstract

Background

Treatment resistant depression (TRD) is one of the leading causes of disability in Canada and is associated with significant societal costs. Repetitive transcranial magnetic stimulation (rTMS) is an approved, safe, and well-tolerated intervention for TRD. In the setting of the COVID-19 pandemic, reducing the number of visits to the clinic is a potential approach to significantly minimize exposure and transmission risks to patients. This can be accomplished by administering multiple treatment sessions in a single day, using an rTMS protocol known as accelerated intermittent theta burst stimulation (aiTBS). The objective of this novel study is 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 electroconvulsive therapy (ECT) or patients warranting ECT due to symptom severity.

Methods

All patients with unipolar depression referred to the brain stimulation service at the Centre for Addiction and Mental Health (CAMH) who warrant ECT will be offered screening to assess for eligibility to enroll in this trial. This open label, single group trial consists of 3 phases. In the acute treatment phase, treatment will occur 8 times daily for 5 days a week, until symptom remission is achieved or a maximum of 10 days of treatment. In the tapering phase, treatments will be reduced to 2 treatment days per week for 2 weeks, followed by 1 treatment day per week for 2 weeks. Patients will then enter the symptom-based relapse prevention phase including virtual check-ins and a treatment schedule based on symptom level. Remission, response and change in scores on several clinical measures from baseline to the end of the acute, tapering and relapse prevention phases represent the clinical outcomes of interest.

Discussion

Findings from this novel clinical trial may provide support for the use of aiTBS, including tapering treatments and symptom-based relapse prevention treatments, as a safe and effective alternative intervention for patients needing ECT during the COVID-19 pandemic.

Trial registration

Clinicaltrials.gov: NCT04384965

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2020.12.15.20248260: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementConsent: Prior to the screening visit, participants will be provided a link to a read-only copy of the consent form.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Following the consent discussion, research personnel will obtain the participant’s informed e-consent to participate in the trial, using REDCap.
    REDCap
    suggested: (REDCap, RRID:SCR_003445)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Ultimately, this has led to a number of important modifications in how research is being conducted as well as several potential limitations. While a definitive assessment of aiTBS would require a randomized sham-controlled study, the ethical considerations of sham-controlled trials during this pandemic are more complicated than usual. Therefore, we have selected a single group, open-label trial study design. Furthermore, unlike previous aiTBS protocols (23, 24) which include fMRI imaging to localize the treatment site, we will be using the modified BeamF3 scalp heuristic, given that neuroimaging is not feasible during a pandemic. We have also added a number of safety precautions, including virtual screening sessions and weekly assessments, daily symptom screening on site, and enhanced use of personal protective equipment and room cleaning. However, we will likely have to maintain a flexible study protocol to reflect the evolving infection prevention and control recommendations. Additionally, it is to be expected that COVID-19 may impact study recruitment and potentially increase the number of dropouts or missed treatments if patients screen or test positive. While the pandemic has complicated the way in which research is conducted, it is important to continue to adapt to keep rTMS services viable and perform it in the safest manner possible, both for patients and staff.

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04384965RecruitingAccelerated iTBS for Depressed Patients During the COVID-19 …

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2020.12.15.20248260v1 on medRxiv