No Placebo Group
Every participant receives an active treatment — no one gets a placebo.
Ready to participate?
Review the details below, then apply to join this clinical trial.
At a Glance
Age
18 – 70
Sex
Any
Study type
Interventional
Purpose
Treatment
Participants needed
20 (estimated)
Sponsor
Indiana University · Other
Who this trial is looking for
This trial is looking for adults with major depression that has not improved with medication. Participants will receive TMS treatment and undergo brain scans while completing related tasks.
Are You a Good Fit for This Trial?
Rules you outPost-traumatic stress disorderObsessive-compulsive disorderSubstance use disorderEpilepsyNeurological disorders
You may be able to join if
I have been diagnosed with major depression without psychotic features.
My first depressive episode started before I turned 50.
I currently have moderate to severe depression.
I have not responded to at least one antidepressant medication.
I am off all psychiatric medications or on a stable dose for 6 weeks.
I am able to consent to participate.
I can safely receive an MRI.
You may not be able to join if
I am currently suicidal.
My current episode of depression has lasted more than 5 years.
I have significant psychiatric issues other than depression.
I have cognitive impairment.
I have a significant substance use disorder.
I started new psychotherapy within 6 weeks of screening.
I have previously received TMS treatment.
I have had a history of seizures or a condition that lowers seizure threshold.
Summarized in plain language from this trial's official eligibility criteria.
The full criteria are further down this page — only the research team can
confirm whether you qualify.
Think this trial could be right for you?
Answer three quick questions written from this study's own rules to see if you may qualify. No account needed to find out.
The goal of this clinical trial is to learn if Transcranial Magnetic Stimulation (TMS) to part of the brain called the ventromedial prefrontal cortex (VMPFC) can treat a symptom called rumination in adults with major depression that has not responded to at least one medication trial. The main question it aims to answer are:
Does TMS to the VMPFC change brain activity on functional magnetic resona…
The goal of this clinical trial is to learn if Transcranial Magnetic Stimulation (TMS) to part of the brain called the ventromedial prefrontal cortex (VMPFC) can treat a symptom called rumination in adults with major depression that has not responded to at least one medication trial. The main question it aims to answer are:
Does TMS to the VMPFC change brain activity on functional magnetic resonance imaging (fMRI) during a negative self-referential processing task in adults with depression? Does TMS to the VMPFC affect rumination in adults with depression? Researchers will compare brain scans and rumination scores before, during, and immediately after TMS.
Participants will:
Undergo three functional MRI scans Undergo a course of 20 TMS treatments Respond to clinical questionnaires and complete a computer behavioral task
Trial Locations
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Eligibility Criteria
Inclusion Criteria:
* Diagnosis of unipolar major depressive disorder without psychotic features by the Mini-International Neuropsychiatric Interview (MINI) and confirmed by study psychiatrist
* First depressive episode prior to age 50
* Current moderate to severe depression, Hamilton Depression Ra…
Inclusion Criteria:
* Diagnosis of unipolar major depressive disorder without psychotic features by the Mini-International Neuropsychiatric Interview (MINI) and confirmed by study psychiatrist
* First depressive episode prior to age 50
* Current moderate to severe depression, Hamilton Depression Rating Scale (HDRS) ≥17)
* Failure to respond to ≥1 antidepressant medication at adequate dose and duration in the current depressive episode; (note: this criterion is designed to be consistent with the original 2008 FDA-labeled indication for TMS in Major Depressive Disorder, that specifies failure to respond to "one prior medication at or above the minimal effective dose and duration in the current episode" (https://www.accessdata.fda.gov/cdrh\_docs/pdf8/K083538.pdf). ))
* Off psychotropic medications OR on a stable dose of medication(s) for 6 weeks, and willing to remain on stable medication dosage throughout the study
* Capacity to consent
* Ability to safely receive MRI
Exclusion Criteria:
* Actively/imminently suicidal, Quick Inventory of Depressive Symptomatology (QIDS) item 12 score \>2)
* Current depressive episode duration \> 5 years
* Presence of clinically significant psychiatric diagnoses other than unipolar, non-psychotic major depression, such as post-traumatic stress disorder (PTSD) or obsessive-compulsive disorder (OCD)
* Evidence of cognitive impairment, Montreal Cognitive Assessment (MOCA) \< 23)
* Significant substance use disorder within past 6 months
* New-onset psychotherapy and/or somatic therapy (e.g., light therapy) within 6 weeks of screening
* Prior exposure to any form of TMS
* Have participated in any clinical trial with an investigational drug or device within the past 6 weeks prior to screening
* Failure to respond to Electroconvulsive therapy (ECT)
* Any history of neurosurgery to treat a neurologic or psychiatric disorder (e.g. Vagus nerve stimulation, cortical stimulation, deep brain stimulation, or ablative surgery)
* Unstable medical illness
* Evidence or history of significant neurological disorder, including moderate-severe head trauma, stroke, Parkinson's disease or other movement disorder (except benign essential tremor)
* Epilepsy
* History of seizures (except juvenile febrile seizures or provoked seizures at the PI's discretion) or any condition/concurrent medication that could notably lower seizure threshold
* Pregnancy or planned pregnancy during the study
* Presence of cardiac pacemaker, cochlear implant, or other implanted electronic device
* Any vision problem that will prevent them from seeing the adjectives presented inside the MRI scanner without glasses
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