Treatment Resistant Depression
Conditions
Brief summary
This study evaluates an association between different dosage and the antidepressant efficacy of theta burst stimulation in patients with treatment-resistant depression. In a double-blind design, All patients are randomized to three groups, i.e. standardized dosage intermittent theta-burst stimulation treatment, high dosage intermittent theta-burst stimulation treatment or sham treatment.
Interventions
DEVICEActive standardized iTBS-DMPFC
Participants in the standardized dosage(600 pulse) of intermittent TBS(iTBS) active stimulation group will receive 3-week three-pulse 50-Hz bursts administered every 200 milliseconds (at 5 Hz) at an intensity of 80% active motor threshold (MT) to bilateral DMPF, twice a day. Bilateral side DMPFC will be targeted by MRI-neuronavigation system. Stimulation will be delivered to the DMPFC using a Magstim stimulator.
DEVICEActive high-dosage iTBS-DMPFC
Participants in the standardized dosage(1800pulse) of intermittent TBS(iTBS) active stimulation group will receive 3-week three-pulse 50-Hz bursts administered every 200 milliseconds (at 5 Hz) at an intensity of 80% active motor threshold (MT) to bilateral DMPF, twice a day. Bilateral side DMPFC will be targeted by MRI-neuronavigation system. Stimulation will be delivered to the DMPFC using a Magstim stimulator.
DEVICESham standardized iTBS-DMPFC or high-dosage iTBS-DMPFC
Half of the patients in the sham group received 3-week the same standardized iTBS parameter stimulation (standardized sham-iTBS), and the other half received the same high dosage iTBS parameter stimulation using a sham coil (high dosage sham-rTMS), which also improved the blinding process
Sponsors
Taipei Veterans General Hospital, Taiwan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Male or female, 21 to 70 years of age. * Diagnosed with the recurrent Major depressive disorder (MDD) and currently having a Major Depressive Episode (MDE) * Participants failed to respond to at least one adequate antidepressant treatment in their current episode * Participants have a Clinical Global Impression - Severity score of at least 4 and a total score of at least 18 on the Hamilton Depression Rating Scale (HDRS-17) at both screening and baseline visits ( Day -14 and Day 0) * Participants must discontinue their antidepressant medications at least for one week ( at least two weeks if Fluoxetine) prior to the TMS intervention and keep antidepressant-free during the study duration. * Participants also failed to respond to one complete left-sided DLPFC 10Hz rTMS/piTBS treatment course.
Exclusion criteria
* a lifetime psychiatric history of bipolar disorder, schizophrenia, psychotic disorders, or organic mental disorder including substance abuse and dependence (based on DSM-IV criteria) * Participants with a lifetime medical history of major systemic illness and clinically significantly abnormal screening examination that might affect safety, study participation, or confound interpretation of study results. * Participants with a lifetime medical history of neurological disorder records (e.g., stroke, seizure, traumatic brain injury, post brain surgery), brain implants (neurostimulators), cardiac pacemakers * Women with breastfeeding or pregnancy * Participants with a current strong suicidal risk (i.e., a score of 4 on item 3 of the HDRS-17)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage change in 17-item Hamilton Depression Rating Scale | Baseline, Week 1, Week 2, Week 3, Week 15(three-month after brain stimulation), Week 27(Six-month after brain stimulation) | the altered percentage of 17-item Hamilton Depression Rating Scale (range, 0 to 52, with higher scores indicating more depression) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Remission rate after 3-week treatment | Baseline, Week 1, Week 2, Week 3, Week 15(three-month after brain stimulation), Week 27(Six-month after brain stimulation) | 17-item Hamilton Depression Rating Scale ≤7 (range, 0 to 52, with higher scores indicating more depression) |
| Changes in Clinical Global Index | Baseline, Week 1, Week 2, Week 3 | Clinical Global Index |
| Changes in depression severity, rated by self-reported | Baseline, Week 1, Week 2, Week 3 | Depression and Somatic Symptoms Scale, range from 0 to 66 with higher scores indicating more depressive and somatic symptom. |
| Changes in Young Mania Rating Scale | Baseline, Week 1, Week 2, Week 3 | Young Mania Rating Scale, range from 0 to 60 with higher scores indicating more severe manic symptoms. |
| Baseline treatment refractory level and the further antidepressant efficacy of brain stimulation | Baseline, Week 3 | Maudsley staging method |
| Baseline brain connectivity and the further antidepressant efficacy of brain stimulation | Baseline, Week 3 | baseline functional MRI |
| the change of brain connectivity after 3-week iTBS treatment | Baseline, Week 3 | the change in brain connectivity |
| Response rate after 3-week treatment at the end of iTBS sessions and three and six month after. | Baseline, Week 1, Week 2, Week 3, Week 15(three-month after brain stimulation), Week 27(Six-month after brain stimulation) | improvement \> 50 % of 17-item Hamilton Depression Rating Scale (range, 0 to 52, with higher scores indicating more depression) |
| Changes in EEG band before and after brain stimulation | Day 1(pre-RECT, post RECT, post 1st treatment, pre-30th treatment) | Perform rostral anterior cingulate cortex(rACC)-engaging cognitive task(RECT) before 1-st treatment |
| Baseline single-pulse stimulation and the further antidepressant efficacy of brain stimulation | Baseline, Week 3 | baseline single-pulse stimulation |
| Changes in single-pulse stimulation before and after brain stimulation | Baseline, Week 3 | the change in single-pulse stimulation |
| Baseline paired-pulse stimulation and the further antidepressant efficacy of brain stimulation | Baseline, Week 3 | baseline paired-pulse stimulation |
| Changes in paired-pulse stimulation before and after brain stimulation | Baseline, Week 3 | the change in paired-pulse stimulation |
| Change in anxiosomatic cluster symptoms derived 17-item Hamilton Depression Rating Scale | Baseline, Week 1, Week 2, Week 3 | the altered anxiosomatic cluster symptoms (range, 0 to 26, with higher scores indicating more severe anxiosomatic symptoms).The anxiosomatic cluster symptoms comprised nine items derived from HDRS-17: early insomnia, middle insomnia, slowness or retardation, psychic anxiety, autonomic anxiety, gastrointestinal symptoms, somatic symptoms, genital symptoms, and hypochondriasis. |
| Baseline Life event stress scale and the further antidepressant efficacy of brain stimulation | Baseline, Week 3 | Life event stress scale,range from 0 to 1467 with higher scores indicating more life event stress. |
Countries
Taiwan
Outcome results
None listed