DepressionPhase 2NCT04604210
Symptom-specific TMS Targets for Depression and Anxiety
A Phase 2 study testing Transcranial magnetic stimulation in people with Depression and Anxiety, run by Brigham and Women's Hospital at 1 site in United States.
Trial summary
This pilot study aims to compare two different treatment targets for transcranial magnetic stimulation, an FDA-approved treatment for major depressive disorder (MDD), in terms of their relative efficacy for depression versus anxiety. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Depression, Anxiety, Major Depressive Disorder
- What is being tested?
- Transcranial magnetic stimulation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Feb 2021to 28 Dec 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults age 18 to 65
- Meeting FDA guidelines for clinical TMS (DSM-5 diagnosis of major depressive disorder with at least one failed antidepressant trial)1
- Beck Depression Inventory (BDI) score of 20 or higher
- Beck Anxiety Inventory (BAI) score of 16 or higher
Who cannot join
- History of:
- Moderate or severe substance use disorder in the past six months as defined by DSM-5 criteria, with the exception of cannabis and nicotine use disorders.
- Dementia, as defined by treating neurologist
- Moderate or severe autism spectrum disorder
- Bipolar disorder
- Schizophrenia spectrum disorders
Show all 21Show fewer
- Current evidence of:
- Substance-induced mood disorder
- Active psychotic symptoms
- Active suicidal ideation
- Contraindications to rTMS treatment:
- Seizure disorder
- Significantly elevated seizure risk, as determined by clinician assessment
- Presence of metallic objects within the head
- Presence of an implanted neurostimulation device within the head
- Contraindications to MRI
- Severe claustrophobia
- Severe pain/illness exacerbated by lying prone in the scanner
- Presence of non-MRI compatible metal foreign bodies or implants
- Weight in excess of 350 lbs
- Shoulder width in excess of maximum tolerable width for scanner
Trial locations and contacts
1 site in 1 country.
United States1 site
Brigham & Women's Hospital
Boston, Massachusetts, 02115
About this study
Official title: A Pilot Randomized Trial of Distinct Symptom-specific Targets for Transcranial Magnetic Stimulation in Patients With Depression and Anxiety
This pilot study aims to compare two different treatment targets for transcranial magnetic stimulation, an FDA-approved treatment for major depressive disorder (MDD), in terms of their relative efficacy for depression versus anxiety.
Read the detailed description
Transcranial magnetic stimulation (TMS) is a safe, noninvasive FDA-cleared technique that is commonly used as a treatment for MDD. It has been shown to focally activate specific brain regions that are believed to be underactive in these patients. This study aims to compare two different TMS targets in the prefrontal cortex. TMS will be administered within FDA-approved guidelines under the supervision of a physician with experience in administering the treatment and monitoring for complications.
This will be a prospective double-blind randomized controlled trial to assess the comparative efficacy of two different TMS targets within the prefrontal cortex (PFC). The "dysphoric" target in the dorsolateral PFC is believed to be more effective for depression, while the "anxiosomatic" target in the dorsomedial PFC is believed to be more effective for anxiety.
Patients with comorbid depression and anxiety will receive 6 weeks of TMS following standard clinical parameters (30 treatments over 6 weeks, 10 Hz frequency, 3000 pulses) with MRI-guided neuronavigation. Participants will be randomized to either the dysphoric or anxiosomatic target. Both targets are believed to be effective treatments for this patient population. Participants and raters will remain blinded to the group assignment. All participants will receive resting-state functional MRI scans before and after the course of treatment in order to study physiological changes.
The dysphoric target is expected to induce greater relative improvement in depression, while the anxiosomatic target is expected to induce greater relative improvement in anxiety.
- Conditions
- Depression, Anxiety, Major Depressive Disorder
- Being tested
- Transcranial magnetic stimulation
- Keywords
- TMS, Transcranial, Neuromodulation, Brain stimulation, Depression, Anxiety
- Medical subject headings
- Depression, Anxiety Disorders, Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial magnetic stimulationProcedure or surgery
Also called TMS
Transcranial magnetic stimulation (TMS) is a noninvasive FDA-approved technique that is commonly used as a treatment for depression. It has been shown to focally activate specific brain regions that are believed to be underactive in patients suffering from depression. In this study, TMS will be administered within FDA-approved guidelines under the supervision of a physician with experience in administering the treatment and monitoring for complications.
| Study group | Role | What they receive |
|---|---|---|
| Dysphoric target | Experimental | The "dysphoric" target is a region in the dorsolateral prefrontal cortex. TMS targeted to this region has been shown to be more effective for depression than anxiety. Receives: Procedure: Transcranial magnetic stimulation |
| Anxiosomatic target | Experimental | The "anxiosomatic" target is a region in the dorsomedial prefrontal cortex. TMS targeted to this region has been shown to be more effective for anxiety than depression. Receives: Procedure: Transcranial magnetic stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Beck Anxiety Inventory (BAI)
The primary outcome will be the rank-transformed ratio of BDI change to BAI change
Measured: Baseline (before treatment), 3 weeks (after 15 treatments), and 6 weeks (after 30 treatments)
Beck Depression Inventory (BDI)
The primary outcome will be the rank-transformed ratio of BDI change to BAI change
Measured: Baseline (before treatment), 3 weeks (after 15 treatments), and 6 weeks (after 30 treatments)
Secondary outcomes (6)
Resting-state functional MRI (rsfMRI) scan
Functional MRI scan will be conducted before and after treatment in order to assess for treatment-induced changes in brain connectivity
Measured: Baseline (before treatment) and 6 weeks (after 30 treatments)
Temperament and Character Inventory, Revised 140-item (TCI-R 140)
Psychobiologically-based personality inventory which measures seven personality dimensions (harm avoidance, novelty seeking, reward dependence, persistence, self-directedness, cooperativeness, and persistence). For each dimension, this yields a scaled T-score (mean score of 50 with standard deviation of 10). This is an overall estimate of personality traits, and there are no "better" or "worse" traits.
Measured: Baseline (before treatment) and 6 weeks (after 30 treatments)
NIH Toolbox cognitive battery
An interactive computerized battery of cognitive tasks which is used to compute an overall index of crystallized and fluid cognition. For each cognitive subscale, this yields a scaled T-score (mean score of 100 with standard deviation of 10).
Measured: Baseline (before treatment) and 6 weeks (after 30 treatments)
Multidimensional task-based emotional assessment
An interactive computerized battery of emotional tasks, including Aversion-Reward Conflict, Emotion Conflict Resolution, Multiple Source Interference, Fear Conditioning/Extinction, Gambling, and Associative Learning Tasks. Each task will yield results for accuracy and reaction time.
Measured: Baseline (before treatment) and 6 weeks (after 30 treatments)
Pain at the stimulation site
Participants will be asked to rate treatment-induced pain/discomfort on a scale of 1 to 10
Measured: Baseline (before treatment) and 6 weeks (after 30 treatments)
Multidimensional battery of emotional questionnaires
A computerized battery of questionnaires including the Anxiety Sensitivity Index, Adult Temperament Questionnaire, Emotion Reactivity Scale, Barratt Impulsivity Scale, Adult ADHD Self-Rating Scale, Brief Inventory of Executive Functioning. Each scale yields a raw score.
Measured: Baseline (before treatment) and 6 weeks (after 30 treatments)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2020
- Study start3 Feb 2021
- Primary completion28 Dec 2023
- Study completion28 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for DepressionStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Parallel-group double-blind randomized, controlled trial
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Shan Siddiqi, MD, Brigham and Women's Hospital
- Investigators
- Shan H Siddiqi, MD, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04604210
- Sponsor's protocol ID
- 2020P002296
- Status last verified
- Jul 2024
- First submitted
- 16 Oct 2020
- Last updated
- 1 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Undecided: De-identified survey response data and/or neuroimaging data may be shared with collaborators for further analysis.
Publications
Taylor JJ, Li J, Lin C, Jones E, Frandsen S, Becker CR, Drew W, Haj-Darwish D, Jabbour S, Leach J, Palm S, Sanderson L, Santos E, Sterina L, Chiulli N, Miller J, Barantono S, Gonsalvez I, Lyndon S, Snider SB, Fox MD, Siddiqi SH. Circuit-targeted modulation of anxiety symptoms in individuals with major depression: A randomized head-to-head TMS trial. Mol Psychiatry. 2026 Aug;31(8):4525-4534. doi: 10.1038/s41380-026-03535-1. Epub 2026 Mar 30.
PubMed 41912790
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Randomized Trial of Distinct Symptom-specific Targets for Transcranial Magnetic Stimulation in Patients With Depression and Anxiety
- ClinicalTrials.gov ID
- NCT04604210
- Acronym / sponsor ID
- 2020P002296
- Conditions
- Depression, Anxiety, Major Depressive Disorder
- Keywords
- TMS, Transcranial, Neuromodulation, Brain stimulation, Depression, Anxiety
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Study start
- 3 Feb 2021 (actual)
- Primary completion
- 28 Dec 2023 (actual)
- Study completion
- 28 Dec 2023 (actual)
- First posted
- 27 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This pilot study aims to compare two different treatment targets for transcranial magnetic stimulation, an FDA-approved treatment for major depressive disorder (MDD), in terms of their relative efficacy for depression versus anxiety.
Detailed description
Transcranial magnetic stimulation (TMS) is a safe, noninvasive FDA-cleared technique that is commonly used as a treatment for MDD. It has been shown to focally activate specific brain regions that are believed to be underactive in these patients. This study aims to compare two different TMS targets in the prefrontal cortex. TMS will be administered within FDA-approved guidelines under the supervision of a physician with experience in administering the treatment and monitoring for complications.
This will be a prospective double-blind randomized controlled trial to assess the comparative efficacy of two different TMS targets within the prefrontal cortex (PFC). The "dysphoric" target in the dorsolateral PFC is believed to be more effective for depression, while the "anxiosomatic" target in the dorsomedial PFC is believed to be more effective for anxiety.
Patients with comorbid depression and anxiety will receive 6 weeks of TMS following standard clinical parameters (30 treatments over 6 weeks, 10 Hz frequency, 3000 pulses) with MRI-guided neuronavigation. Participants will be randomized to either the dysphoric or anxiosomatic target. Both targets are believed to be effective treatments for this patient population. Participants and raters will remain blinded to the group assignment. All participants will receive resting-state functional MRI scans before and after the course of treatment in order to study physiological changes.
The dysphoric target is expected to induce greater relative improvement in depression, while the anxiosomatic target is expected to induce greater relative improvement in anxiety.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Parallel-group double-blind randomized, controlled trial
| Arm | Type | Receives |
|---|---|---|
| Dysphoric target | Experimental | Procedure: Transcranial magnetic stimulationThe "dysphoric" target is a region in the dorsolateral prefrontal cortex. TMS targeted to this region has been shown to be more effective for depression than anxiety. |
| Anxiosomatic target | Experimental | Procedure: Transcranial magnetic stimulationThe "anxiosomatic" target is a region in the dorsomedial prefrontal cortex. TMS targeted to this region has been shown to be more effective for anxiety than depression. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Adults age 18 to 65
- Meeting FDA guidelines for clinical TMS (DSM-5 diagnosis of major depressive disorder with at least one failed antidepressant trial)1
- Beck Depression Inventory (BDI) score of 20 or higher
- Beck Anxiety Inventory (BAI) score of 16 or higher
Key exclusion criteria (21 listed)
- History of:
- Current evidence of:
- Contraindications to rTMS treatment:
- Contraindications to MRI
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcranial magnetic stimulationAlso: TMSTranscranial magnetic stimulation (TMS) is a noninvasive FDA-approved technique that is commonly used as a treatment for depression. It has been shown to focally activate specific brain regions that are believed to be underactive in patients suffering from depression. In this study, TMS will be administered within FDA-approved guidelines under the supervision of a physician with experience in administering the treatment and monitoring for complications. | Procedure or surgery | Anxiosomatic target, Dysphoric target |
Primary outcome
Beck Anxiety Inventory (BAI)
Time frame: Baseline (before treatment), 3 weeks (after 15 treatments), and 6 weeks (after 30 treatments)
The primary outcome will be the rank-transformed ratio of BDI change to BAI change
Beck Depression Inventory (BDI)
Time frame: Baseline (before treatment), 3 weeks (after 15 treatments), and 6 weeks (after 30 treatments)
The primary outcome will be the rank-transformed ratio of BDI change to BAI change
6 secondary outcomes
Resting-state functional MRI (rsfMRI) scan
Time frame: Baseline (before treatment) and 6 weeks (after 30 treatments)
Temperament and Character Inventory, Revised 140-item (TCI-R 140)
Time frame: Baseline (before treatment) and 6 weeks (after 30 treatments)
NIH Toolbox cognitive battery
Time frame: Baseline (before treatment) and 6 weeks (after 30 treatments)
Multidimensional task-based emotional assessment
Time frame: Baseline (before treatment) and 6 weeks (after 30 treatments)
Pain at the stimulation site
Time frame: Baseline (before treatment) and 6 weeks (after 30 treatments)
Multidimensional battery of emotional questionnaires
Time frame: Baseline (before treatment) and 6 weeks (after 30 treatments)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2024.
- Derived from this study: PubMed 41912790Taylor JJ, Li J, Lin C, Jones E, Frandsen S, Becker CR, Drew W, Haj-Darwish D, Jabbour S, Leach J, Palm S, Sanderson L, Santos E, Sterina L, Chiulli N, Miller J, Barantono S, Gonsalvez I, Lyndon S, Snider SB, Fox MD, Siddiqi SH. Circuit-targeted modulation of anxiety symptoms in individuals with major depression: A randomized head-to-head TMS trial. Mol Psychiatry. 2026 Aug;31(8):4525-4534. doi: 10.1038/s41380-026-03535-1. Epub 2026 Mar 30.
- Individual participant dataSharing planned: Undecided. De-identified survey response data and/or neuroimaging data may be shared with collaborators for further analysis.
Related trials for Depression
Recruiting
Regulated Stimulation for Optimized Network Activity and Therapeutic Equilibrium
Major Depressive Disorder
Recruiting
Metacognitive Bibliotherapy for Anxiety, Depression, and Metacognitions in University Students
Anxiety, Depression
Enrolling by invitation
Vagus Nerve Stimulation (VNS) Electroencephalogram (EEG) Protocol Supplement
Treatment Resistant Depression
Active, not recruiting
NYUCI-ES: Psychosocial Intervention to Improve Health Outcomes for Chinese and Korean ADRD Caregivers
Dementia Caregivers, Diabetes
Enrolling by invitation
Intervention to Reduce HIV Related Stigma Among Pregnant and Postpartum Women
HIV, HIV - Human Immunodeficiency Virus
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shan H Siddiqi, MD principal investigator
Brigham and Women's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Transcranial magnetic stimulation in people with Depression and Anxiety, run by Brigham and Women's Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Beck Anxiety Inventory (BAI) (time frame: Baseline (before treatment), 3 weeks (after 15 treatments), and 6 weeks (after 30 treatments)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04604210, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2024.