Symptom-specific TMS Targets for Depression and Anxiety

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.

Study Overview

• Status: Completed
• Conditions: Depression; Anxiety; Major Depressive Disorder
• Intervention / Treatment: Procedure: Transcranial magnetic stimulation

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 Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham & Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dysphoric target; 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.	Procedure: Transcranial magnetic stimulation; 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.; Other Names: TMS
Experimental: Anxiosomatic target; 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.	Procedure: Transcranial magnetic stimulation; 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.; Other Names: TMS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Beck Depression Inventory (BDI)	The primary outcome will be the rank-transformed ratio of BDI change to BAI change	Baseline (before treatment), 3 weeks (after 15 treatments), and 6 weeks (after 30 treatments)
Beck Anxiety Inventory (BAI)	The primary outcome will be the rank-transformed ratio of BDI change to BAI change	Baseline (before treatment), 3 weeks (after 15 treatments), and 6 weeks (after 30 treatments)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	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).	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.	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	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.	Baseline (before treatment) and 6 weeks (after 30 treatments)

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Investigators: Principal Investigator: Shan H Siddiqi, MD, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2021
• Primary Completion (Actual): December 28, 2023
• Study Completion (Actual): December 28, 2023

Study Registration Dates

• First Submitted: October 16, 2020
• First Submitted That Met QC Criteria: October 21, 2020
• First Posted (Actual): October 27, 2020

Study Record Updates

• Last Update Posted (Actual): August 1, 2024
• Last Update Submitted That Met QC Criteria: July 30, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Depression; Neuromodulation; Anxiety; TMS; Brain stimulation; Transcranial
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Anxiety Disorders; Depressive Disorder, Major
• Other Study ID Numbers: 2020P002296

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: De-identified survey response data and/or neuroimaging data may be shared with collaborators for further analysis.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes