One-Day cTBS Over the Precuneus

Summary

The goal of this clinical trial is to learn whether two forms of one-day accelerated transcranial magnetic stimulation (TMS) can reduce depressive symptoms in adults with treatment-resistant depression. Treatment-resistant depression is depression that has not improved enough after at least two adequate antidepressant medication treatments. TMS is a non-invasive treatment that uses magnetic pulses to stimulate specific areas of the brain. The main questions this study aims to answer are: * Does continuous theta-burst stimulation (cTBS) targeting the precuneus reduce depressive symptoms 4 weeks after treatment compared with sham stimulation? * Does intermittent theta-burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex reduce depressive symptoms 4 weeks after treatment compared with sham stimulation? Researchers will compare precuneus cTBS, left dorsolateral prefrontal cortex iTBS, and sham stimulation to determine whether either active treatment reduces depressive symptoms more than sham stimulation. Participants will be randomly assigned to one of the three groups and will not be told which treatment they initially receive. Participants will: * Complete screening procedures and baseline assessments of depression, rumination, and cognitive function * Receive 20 sessions of active or sham TMS during one in-person study day * Complete follow-up assessments 1, 2, 3, and 4 weeks after the intervention * Report any side effects or medical problems experienced during the study Participants initially assigned to sham stimulation may choose to receive active TMS after completing the 4-week follow-up period. Those who choose this option will receive either precuneus cTBS or left dorsolateral prefrontal cortex iTBS and will complete additional follow-up assessments.

Eligibility

Inclusion Criteria:

* Age 18 years or older.
* Able to speak, read, and understand English sufficiently to complete the study assessments and provide informed consent independently.
* Diagnosis of major depressive disorder according to DSM-5-TR criteria, confirmed by a qualified physician.
* Treatment-resistant depression, defined as an inadequate response to at least two adequate trials of antidepressant pharmacotherapy.
* Patient Health Questionnaire-9 (PHQ-9) total score of 10 or higher.

Exclusion Criteria:

* Any condition identified through TMS safety screening that, in the judgment of a study physician, presents an unacceptable safety risk for TMS. Such conditions may include:
* A history of a serious adverse reaction during TMS treatment.
* A history of seizure.
* A history of stroke.
* A history of serious head injury or neurosurgery.
* Metal in the head outside the mouth, such as shrapnel, surgical clips, or metal fragments.
* An implanted device, such as a cardiac pacemaker, cochlear implant, medical pump, or intracardiac line.
* Frequent or severe headaches.
* Another brain-related condition or an illness that caused brain injury.
* A family history of epilepsy.
* Permanent tattoos on the head or neck.
* Current recreational drug use.
* Current pregnancy or possible pregnancy.
* Use of a medication or combination of medications, a recent medication change, or medication withdrawal that, in the judgment of a study physician, presents an unacceptable safety risk, including a clinically significant increase in seizure risk.
* Current or lifetime diagnosis of bipolar I disorder, bipolar II disorder, a schizophrenia spectrum disorder, or another primary psychotic disorder.
* Active suicidal ideation with intent or plan requiring immediate clinical intervention, or another acute safety concern that cannot be safely managed within the study.

Conditions4

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