One-Day cTBS Over the Precuneus

Summary

The goal of this clinical trial is to learn whether two forms of one-day accelerated transcranial magnetic stimulation (TMS) can reduce depressive symptoms in adults with treatment-resistant depression. Treatment-resistant depression is depression that has not improved enough after at least two adequate antidepressant medication treatments. TMS is a non-invasive treatment that uses magnetic pulses to stimulate specific areas of the brain.

The main questions this study aims to answer are:

* Does continuous theta-burst stimulation (cTBS) targeting the precuneus reduce depressive symptoms 4 weeks after treatment compared with sham stimulation?
* Does intermittent theta-burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex reduce depressive symptoms 4 weeks after treatment compared with sham stimulation?

Researchers will compare precuneus cTBS, left dorsolateral prefrontal cortex iTBS, and sham stimulation to determine whether either active treatment reduces depressive symptoms more than sham stimulation. Participants will be randomly assigned to one of the three groups and will not be told which treatment they initially receive.

Participants will:

* Complete screening procedures and baseline assessments of depression, rumination, and cognitive function
* Receive 20 sessions of active or sham TMS during one in-person study day
* Complete follow-up assessments 1, 2, 3, and 4 weeks after the intervention
* Report any side effects or medical problems experienced during the study

Participants initially assigned to sham stimulation may choose to receive active TMS after completing the 4-week follow-up period. Those who choose this option will receive either precuneus cTBS or left dorsolateral prefrontal cortex iTBS and will complete additional follow-up assessments.

Conditions

• Depressive Disorder, Treatment-Resistant
• Treatment Resistant Depression (TRD)
• Treatment Resistant Major Depression Disorder

Interventions

DEVICE

Precuneus-targeted continuous theta-burst stimulation

Active continuous theta-burst stimulation is delivered to the Pz location of the international 10-20 EEG system to target the precuneus. Stimulation is administered with a double-cone coil at 80% of the participant's resting motor threshold. Each session consists of 600 pulses delivered over approximately 40 seconds. Participants receive 20 sessions during a single day, for a total of 12,000 pulses, with session onsets separated by approximately 30 minutes. If 80% of resting motor threshold is not tolerated, the intensity may be reduced to the highest tolerable level.

DEVICE

Left dorsolateral prefrontal cortex intermittent theta-burst stimulation

Active intermittent theta-burst stimulation is delivered to the left dorsolateral prefrontal cortex. The stimulation target is identified using the Beam F3 method. Stimulation is administered with a figure-of-eight coil at 80% of the participant's resting motor threshold. Each session consists of 600 pulses delivered over approximately 3 minutes. Participants receive 20 sessions during a single day, for a total of 12,000 pulses, with session onsets separated by approximately 30 minutes. If 80% of resting motor threshold is not tolerated, the intensity may be reduced to the highest tolerable level.

DEVICE

Sham transcranial magnetic stimulation

Sham transcranial magnetic stimulation is administered at the left dorsolateral prefrontal cortex location identified using the Beam F3 method. A figure-of-eight coil is inverted so that the active surface faces away from the scalp. The stimulator is operated at 80% of the participant's resting motor threshold using the same intermittent theta-burst timing and approximate session duration as the active left dorsolateral prefrontal cortex intervention. Participants receive 20 sham sessions during a single day, with session onsets separated by approximately 30 minutes.

Sponsors & Collaborators

• Mclean Hospital

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-08-24

Primary Completion

2027-06-30

Completion

2027-06-30

FDA Device

Yes

Countries

• United States

Study Locations