Imaging- vs. Scalp-Targeted Accelerated TMS for Depression: The Number Needed to Scan Trial

NCT07043738 | Not Yet Recruiting FDA Device

• 1 other identifier: 2025P001570
• Study Type: interventional
• Target: 160
• Locations: 0 countries
• Sites: N/A

Brief Summary

Transcranial magnetic stimulation(TMS) is a non-invasive form of brain stimulation that is cleared by the United States Food and Drug Administration (FDA) for depression. Conventional TMS involves daily weekday treatments for 6-8 weeks. These treatments are targeted using each person's scalp measurements. With conventional TMS, approximately 50-55% of people show a 50% or more improvement in depressive symptoms (in other words, they "respond" to treatment). Studies are trying to make TMS work better and faster. A new form of TMS called accelerated TMS (aTMS) involves mutliple treatments a day. One specific aTMS protocol involves 10 treatments per day for 5 days. These treatments are targeted using each person's brain scan (magentic resonance imaging, MRI). With this specific aTMS protocol, approximately 70-90% of people show a 50% or more imporvement in depressive symptoms. While these results are exciting, scientists are not sure why this specific aTMS protocol works better than conventional TMS. It could be the dose and schedule of treatment, or it could be the MRI-based targeting. Answering this question is important because MRI-based targeting is expensive and difficult to do in many settings. This study aims to determine if MRI-based targeting is better than scalp-based targeting for aTMS for depression. In this study, everyone who enrolls and meets criteria will be randomly assigned to MRI- versus scalp-based aTMS targeting.

Conditions

Major Depressive Disorder (MDD)

Keywords

Accelerated Transcranial Magnetic Stimulation; Depression; Major Depressive Disorder; Treatment resistant depression; TMS; Transcranial Magnetic Stimulation; Neuromodulation

Outcome Measures

Primary Outcomes (1)

• Montgomery-Åsberg Depression Rating Scale (MADRS)

  Depression severity rating scale (0-60, higher numbers indicate higher depressive symptom severity). The MADRS is a clinician rated scale consisting of 10 items, with each item scored on a 7 point scale. For the primary outcome, investigators will assess MADRS as a continuous variable (i.e., MADRS change from baseline to one month after treatment) using a mixed-effects model for repeated measures (MMRM). The model will include group assignment, baseline MADRS score, assessment time point, and time point by treatment interaction as explanatory variables. Hypothesis: There will be a significant group x time interaction on MADRS score from baseline, immediately post-treatment (Day 5), one-week post-treatment, and one-month post-treatment.

  Baseline to one month post treatment

Secondary Outcomes (2)

• Montgomery-Åsberg Depression Rating Scale (MADRS)

  Baseline to one month post treatment

• Relationship between treatment target location and response in scalp-targeted aTMS for MDD

  Before treatment to 1 month post treatment

Other Outcomes (24)

• Beck Depression Inventory (BDI)

  Before treatment, daily throughout treatment, 1 week post treatment, and 1-12 months post treatment

• Beck Anxiety Inventory (BAI)

  Before treatment, daily throughout treatment, 1 week post treatment, and 1-12 months post treatment

• Clinically Useful Depression Outcome Scale - Daily Adaptation (CUDOS-D)

  Before treatment, daily throughout treatment, 1 week post treatment, and 1 month post treatment

Study Arms (2)

Connectivity-based targeting

OTHER

Participants in this group will receive aiTBS with neuronavigation to a treatment target identified with individualized resting state functional connectivity. Participants who receive connectivity-based targeting and who do not meet response criteria (\<50% MADRS improvement) at the post-treatment month 1 visit will be offered the opportunity to opt in and receive another course of aTMS at their scalp-based target.

Procedure: Transcranial Magnetic Stimulation

Scalp-based targeting

OTHER

Participants in this group will receive aiTBS with neuronavigation to a treatment target identified with scalp based measurements (i.e., Beam F3). Participants who receive scalp-based targeting and who do not meet response criteria (\<50% MADRS improvement) at the post-treatment month 1 visit will be offered the opportunity to opt in and receive another course of aTMS at their connectivity-based target.

Procedure: Transcranial Magnetic Stimulation

Interventions

Transcranial Magnetic Stimulation PROCEDURE

Transcranial magnetic stimulation (TMS) is a focal, non-invasive form of brain stimulation that has FDA clearance for depression. In this study, a form of TMS called accelerated intermittent theta burst stimulation (aiTBS) will be administered under the supervision of a physician with TMS expertise.

Also known as: TMS, Accelerated intermittent theta burst stimulation, aiTBS

Connectivity-based targeting; Scalp-based targeting

Eligibility Criteria

• Age: 22 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 22-80
• English proficiency sufficient for informed consent, questionnaires/tasks, and treatment
• Primary diagnosis of major depressive disorder per DSM-V criteria (Quick Structured Clinical Interview for DSM-5)
• \>20 on Beck Depression Inventory (BDI)
• \>20 on the Montgomery-Åsberg Depression Rating Scale (MADRS)
• Moderate to severe level of treatment resistance (Maudsley Staging Method)
• Stable antidepressant medication regimen, or remain medication free, for 4 weeks prior to treatment and to remain on this regimen throughout the study until the 1-month post-treatment visit.
• Primary clinician (e.g. psychiatrist, therapist, psychologist, APRN, PA, etc.) responsible for psychiatric care before, during, and after the trial
• Agreement to lifestyle considerations
• Abstain from becoming pregnant from screening to one-month after treatment (the MRI visit)
• Continue usual intake patterns of caffeine- or xanthine-containing products (e.g. coffee, tea, soft drinks, chocolate) throughout treatment
• Abstain from alcohol, tobacco, and recreational drugs for at least 24 hours before the start of each MRI and TMS session

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): collaborator
• Brigham and Women's Hospital: lead
• National Institutes of Health (NIH): collaborator

MeSH Terms

Conditions

Depressive Disorder, Major; Depression; Depressive Disorder, Treatment-Resistant

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Central Study Contacts

Interventional Psychiatry Research Group

CONTACT

6175253536; bwhtmstrials@bwh.harvard.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All study participants will get two treatment sites marked: 1) Their individualized target based on resting state functional connectivity data, and 2) Beam F3 target based on head measurements. One group will be treated at target #1, and the other group will be treated at target #2. The research assistant (RA) marking treatment sites is the only individual unblinded in this study. The unblinded RA will have no other interactions with participants after the treatment preparation visit. RAs delivering treatment with stimulate participants at a coordinate, given to them by the unblinded RA.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Psychiatry

Model Details: Parallel-group double-blind randomized controlled trial

Study Record Dates

• First Submitted: June 26, 2025
• First Posted: June 29, 2025
• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): May 1, 2031
• Last Updated: February 25, 2026

Record last verified: 2025-07