Intermittent Theta-burst Stimulation for Major Depression: an Intensity-response Study

Summary

The United States Food and Drug Administration (FDA) approved intermittent theta-burst stimulation (iTBS) in 2018 as a form of repetitive transcranial magnetic stimulation (rTMS). Hospitals worldwide use it to treat major depressive disorder (MDD). It is safe, effective, even for depressed patients unable to respond to standard pharmacological treatment and is more efficient than standard rTMS. In accordance with the approved treatment protocol, patients experience considerable sensory discomfort at a stimulation intensity of 120% of their resting motor threshold (rMT). Antidepressant effects of iTBS are believed to be mediated by modulating prefrontal excitability. There is still a lack of evidence to support the choice of 120% rMT as the optimal stimulation intensity, and the presumed superiority of higher stimulation intensities over lower intensities has yet to be proven. This knowledge gap has clinical implications since more tolerated treatments may lead to greater adherence, resulting in improved outcomes.

The current study proposes a randomized, triple-arm, controlled trial to compare the efficacy of iTBS at 75% (iTBS75) and 120% (iTBS120) rMT with sham iTBS (SiTBS). Based on the following considerations, SiTBS was selected to be compared with iTBS75 and iTBS120: SiTBS will reveal placebo antidepressant effects and serve as a control. iTBS75 is selected because iTBS at 80% aMT exhibits significant excitatory effects on the motor cortex and corresponds to approximately 70% rMT. There is however, a distance of about 12.7mm between the coil and the motor cortex, whereas 14.4mm separates the coil from the dorsolateral prefrontal cortex (DLPFC). Accordingly, a resting motor threshold of 70% at the motor cortex corresponds to a distance-adjusted rMT of 75% at the DLPFC. Lastly, iTBS120 is chosen as the standard stimulation intensity in current iTBS depression trials.

It is our intention to investigate the potential antidepressant effects of iTBS treatment at a much lower stimulation intensity than the one currently employed by most centers in the United States and approved in these centers. Thus, our study can contribute to establishing a treatment regimen with increased adherence and lower withdrawal rates.

Conditions

• Depression, Unipolar

Interventions

DEVICE

intermittent theta-burst stimulation (iTBS)

iTBS treatment will be performed as comprising 3-pulse 50-Hz bursts, applied every 200 ms (at 5 Hz). iTBS consists of 2-second trains with an inter-train-interval of 8 seconds. Repeat trains (30 pulses; 10 bursts) 20 times to reach a total number of 600 pulses (3x10x20) which equals the standard number of pulses in a daily iTBS treatment session, as approved by the FDA. The stimulation site over the left DLPFC will be determined using the international 10-20 system for EEG electrodes corresponding to the F3 location. 20 daily treatment sessions will be performed from Mondays to Fridays for four weeks for all included patients. Treatments will be performed at the brain stimulation laboratory at the Hong Kong Polytechnic University. Stimulation will be delivered using a MagPro X100 model (details about MagPro X100: magventure.com/en\_eur/products/magpro-x100/ ) and a Cool-B65 A/P Butterfly Coil is used in this study.

Sponsors & Collaborators

• Health and Medical Research Fund

  collaborator OTHER_GOV

• The Hong Kong Polytechnic University

  lead OTHER

Principal Investigators

• Georg Kranz, PhD · The Hong Kong Polytechnic University

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-01-08

Primary Completion

2026-04-26

Completion

2026-10-26

Countries

• Hong Kong

Study Locations