An interventional study of Transcranial Magnetic Stimulation in Major Depressive Disorder (MDD), sponsored by Brigham and Women's Hospital. Not yet recruiting. Open to participants aged 22 Years to 80 Years. Per ClinicalTrials.gov, last updated 2026-09-18.
Sponsored by Brigham and Women's Hospital · Not applicable, Interventional, and Treatment
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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.
Major depressive disorder (MDD) remains a leading cause of global disease burden and disability. In addition to increasing the risk of death by suicide, MDD also shows a graded positive association with all-cause mortality. Antidepressants are the most frequently prescribed medication class in psychiatry and, once started, are often continued for many year. However, antidepressants have a small-to-moderate effect size that might be inflated by publication bias. Most people with MDD do not achieve remission with their first antidepressant, and the probability of getting well and staying well diminishes with each sequential trial. By the fourth trial, remission rates approach single digits. Depression that does not improve with one or more antidepressant classes is often considered "difficult-to-treat" or "treatment-resistant" depression (TRD). Taken together, these data highlight the need for better and faster treatments for TRD.
TMS for TRD is safe, well-tolerated, and often covered by insurance. Unlike esketamine and ECT, TMS does not require supervised transportation after treatment. However, TMS is: 1) time intensive, requiring daily weekday treatments for 6-8 weeks; 2) imprecisely targeted based on scalp measurements, which means that each person is stimulated at a slightly different site; and 3) ineffective approximately half the time, with response and remission rates around 50% and 33%, respectively. A new form of accelerated TMS (aTMS) by Cole et. al was designed to address these limitations. In the open-label trial (n=21), the Cole et a. protocol significantly reduced Montgomery-Åsberg Depression Rating Scale (MADRS) in a single day and resulted in a 79.5% reduction one month after treatment. Remission rates were 86% and 57% one week and one month after open-label aTMS, respectively. From this perspective, this specific aTMS protocol works better and faster than conventional TMS and even rivals ECT. The only double-blind randomized controlled trial of this Cole et al. protocol was discontinued after an interim analysis (n=29) revealed a large effect size (Cohen's d>0.8) for active vs. sham (52.5% vs. 11.1% MADRS reduction, respectively). In this trial, remission rates were 57% and 46% one week and month after active aTMS, respectively. There are also emerging data on retreatment and durability. In a recent open-label extension study (n=27), 91% of people who achieved remission with an index course of this specific aTMS protocol (n=22) also achieved remission with aTMS retreatment 6 months later.
In July 2023, investigators launched the "AINT Trial" (NCT05680727). Our goal was to calculate an effect size to power a confirmatory trial. Investigators matched Cole et al. on schedule, dose, intensity, and precision. Investigators also matched Cole et al. inclusion/exclusion criteria (based on published trials and feedback from Stanford colleagues) and its primary outcome measure (i.e., MADRS reduction (% change) one month after aTMS). The goal was to isolate the variable of targeting. Based on our results (in preparation), a sample size of 40 per group will provide \~95% power to detect a between-group difference. Therefore, this study will be a fully powered, double-blind, confirmatory efficacy trial (n=80) for imaging- vs. scalp-targeted aTMS for TRD.
3,047 studies on the registry are indexed under Depressive Disorder, Major; 593 are open to participants now.
This study's planned enrollment of 160 is above the median of 79 across 2,533 interventional studies indexed under Depressive Disorder, Major.
Browse Depressive Disorder, Major studies →Brigham and Women's Hospital is the lead sponsor of 1,268 studies on the registry; 229 are open to participants now.
Of its 116 completed or terminated interventional studies of FDA-regulated products, 65 (56%) have results posted.
Counted across the registry records on this site, refreshed daily.
Inclusion Criteria:
Primary diagnosis of major depressive disorder per criteria (Quick Structured Clinical Interview for DSM-5)
Agreement to lifestyle considerations
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
DSM diagnostic criteria
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants in this group will receive aiTBS with neuronavigation to a treatment target identified with individualized resting state functional connectivity.
Procedure: Transcranial Magnetic Stimulation
Participants in this group will receive aiTBS with neuronavigation to a treatment target identified with scalp based measurements (i.e., Beam F3).
Procedure: Transcranial Magnetic Stimulation
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
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.
Time frame: Baseline to one month post treatment
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 secondary outcomes, investigators will assess MADRS as a categorical variable (i.e., MADRS response defined as ≥ 50% improvement one month after treatment) using a generalized estimating equations approach (GEE). Hypothesis: One month after treatment, there will be a significantly larger response rate (≥ 50% MADRS improvement) in the imaging- vs. scalp-targeted group using a z-test for proportions. This response rate will be used to calculate an absolute risk reduction and a "number needed to scan" (NNS) with confidence intervals.
Time frame: Baseline to one month post treatment
Relationship between treatment target location and response in scalp-targeted aTMS for MDD
The correlation between clinical improvement (i.e., BDI-II) and the distance between the actual (stimulated) scalp-based target and the (predicted but not stimulated) imaging-based target. The BDI-II is a depression severity rating scales (0-63, higher numbers indicate higher severity). Mediation analyses that includes the mediator variable (i.e., distance) in the multivariable model for the outcome (i.e., MADRS improvement). Investigators will implement a form (i.e., counterfactual-based) causal mediation analysis that estimates the controlled direct and indirect effects and the bias-corrected bootstrap confidence intervals while controlling for confounders such as age, sex, and other related variables (e.g., baseline antidepressant use, etc.). Hypothesis: In the scalp-targeted aTMS group, clinical improvement will negatively correlate with the distance between the actual (stimulated) scalp-based target and the (predicted but not stimulated) imaging-based target.
Time frame: Before treatment to 1 month post treatment
Beck Depression Inventory (BDI)
Depression severity rating scales (0-63, higher numbers indicate higher severity)
Time frame: Before treatment, daily throughout treatment, 1 week post treatment, and 1-12 months post treatment
Beck Anxiety Inventory (BAI)
Anxiety severity rating scale (0-63, higher numbers indicate higher severity)
Time frame: Before treatment, daily throughout treatment, 1 week post treatment, and 1-12 months post treatment
No study locations are listed for this record.
Plan to share: Undecided
No publications or documents are linked to this record.
Start is estimated for Oct 2026; primary completion for Oct 2031, 60 months later.
Of 649 non-industry interventional studies with no phase under Depressive Disorder, Major, half reached primary completion within 35 months of starting (the median), counting those still running; a quarter within 19 and three quarters within 55. This study's planned 60 months is above that.
Counting every sponsor, half of 689 studies reached it within 33 months; a quarter within 17 and three quarters within 55.
How these figures are worked out, and which studies are left out of them.
This study is not yet recruiting, as verified in Aug 2026. You cannot join it, but the record below documents what was studied.
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