Depression, Depressive Disorder, Major Depressive Disorder, Treatment Resistant Depression
Conditions
Keywords
rTMS, mindfulness, depression
Brief summary
Repetitive Transcranial Magnetic stimulation (rTMS) is an FDA-approved therapy for treatment resistant depression (TRD) that involves brief magnetic stimulation pulses on the dorsolateral prefrontal cortex (DLPFC) brain region. But studies of rTMS alone show remission rates of \ 30%. Additionally, rTMS has not been shown to improve cognitive functioning that may be an independent factor predicting treatment success. This study will develop a novel multimodal treatment, which combines intermittent theta burst stimulation (iTBS) - a type of rTMS with digital mindfulness training to engage brain plasticity, enhance cognition and alleviate depression symptoms in individuals with TRD.
Detailed description
This study aims to develop a novel multimodal treatment for treatment resistant depression (TRD), which combines intermittent theta burst stimulation (iTBS), a type of FDA-approved rTMS protocol, with digital mindfulness training. We propose that this multimodal treatment will suppress posterior Default Mode Network (pDMN) brain activity as measured with electroencephalography (primary outcome and neural target), as well as enhance cognition and alleviate depression symptoms in patients with TRD. The study will determine the optimal dose required for neural target engagement by the multimodal iTBS + digital mindfulness training relative to an active control training combined with iTBS.
Interventions
COMBINATION_PRODUCTMedi-TBS
The multimodal intervention involves combining FDA-approved repetitive transcranial magnetic stimulation (rTMS) with digital mindfulness exercises.
Sponsors
University of California, San Diego
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of major depressive episode (MDE, in accordance with the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5), in the context of unipolar major depressive disorder. * At least one failed antidepressant medication trial at level 3 in the Antidepressant Treatment History Form: Short Form (ATHF-SF) classification. * Montgomery-Åsberg Depression Rating Scale (MADRS) Score \>19 (moderate - severe depression). * No increase or initiation of new antidepressant therapy in the four weeks prior to screening. * Demonstrated capacity to give informed consent.
Exclusion criteria
* Inability to provide informed consent. * Medically unstable patients. * Concomitant neurological disorder or a history of a seizure disorder. * Exhibiting current suicidal behavior rating on the Columbia Suicide Severity Rating Scale (C-SSRS) * Patients who are pregnant or breastfeeding. * Any psychotic disorder or current active psychotic symptoms. * Patients who have intracranial implants, other medical device or condition deemed unsafe for TMS. * Contraindication to MRI scanning.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in EEG source localized pDMN alpha activity | 4 weeks | EEG alpha band (8-12 Hz) activity source-localized to the posterior Default Mode Network (pDMN) brain region extracted on distracted trials of the Breath Attention Assessment of Mindfulness task serves as the primary neural target. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Selective Attention | 4 weeks | Processing speed of response to target stimuli on a standard continuous performance task that measures the ability to selectively attend and promptly respond to a goal-relevant target stimulus serves as the secondary cognitive target. |
| Change in Flanker Inhibition | 4 weeks | Efficiency of inhibiting visuo-spatially flanking distractors to target stimuli in the Flanker task serves as the secondary cognitive target. |
| Change in Montgomery Åsberg Depression Rating Scale Scores (MADRS) | 8 weeks | The MADRS will be used to evaluate % depressive symptom response defined as 50% change in the MADRS score from baseline as well as remission defined as MADRS score \<7 at post-intervention. Scale range: 0-54, higher score is worse depression. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJyoti Mishra, PhD
University of California, San Diego
Outcome results
None listed