This study investigates the brain-based biomarkers of treatment response to accelerated theta burst stimulation (aTBS) in patients with Major Depressive Disorder resistant to pharmacological treatment(MDD) in an open label design.
Theta burst stimulation (TBS) is a newer form of rTMS which requires less stimulation time and produces longer lasting post-stimulation effects in the cerebral cortex (4). It has been shown to be effective in inducing synaptic plasticity and has similar or better efficacy in treating depression compared to rTMS (4).Newer accelerated TBS (aTBS) protocols that condense stimulation sessions down to several days rather than weeks have shown similar response rates when compared to prolonged TBS protocols, also with similar tolerability and safety. In order to develop aTBS as an effective treatment for MDD, future research should focus on identification of reliable predictors for better outcome to TBS. The main objectives were: 1) To directly compare multiple different brain-based measures (neuroimaging and electrophysiology) to identify which has the most power in accurately predicting response to TBS compared to sham. 2) To track both short and long-term longitudinal electrophysiological (EEG) changes related to the therapeutic effects of TBS.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Participants will receive bilateral TBS, 5 times daily (15 minutes between), over 5 consecutive days (25 sessions total). In each session they will receive intermittent TBS (iTBS) over left dorsolateral prefrontal cortex (DLPFC), followed by continuous TBS (cTBS) over right DLPFC. Stimulation sites will be targeted with the Localite neuronavigation system and Visor2 software, and according to Talairach coordinates in relation to individual MRIs. Intensity will be standardized at 120% of RMT. The MagPro stimulator will deliver iTBS over left DLPFC with 1620 pulses in 54 triplet bursts (5Hz) with train duration of 2 seconds, and intertrain interval of 8 seconds. cTBS over right DLPFC will consist of 1620 pulses in 54 triplet bursts, train duration of 2 seconds, with no intertrain interval.
University of Calgary
Calgary, Alberta, Canada
RECRUITINGHamilton Depression Rating Scale
Clinician administered questionnaire to asses clinical improvement and classify response and remission
Time frame: Change from baseline at 5 days of TBS treatment
1. Montgomery-Åsberg Depression Rating Scale (MADRS)
A ten item clinician administered questionnaire to measure the severity of depressive symptoms on a 0 to 6 severity scale with higher scores indicating more severe depressive symptoms. Cut-off points include: 0 to 6 - symptom absent, 7 to 19 - mild depression, 30 to 34 - moderate, 35 to 60 - severe depression.
Time frame: Change from baseline at 5 days of TBS treatment
2. Hamilton Anxiety rating Scale (HAM-A)
A rating scale to measure the severity of anxiety symptoms. Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where \<17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe.
Time frame: Change from baseline at 5 days of TBS treatment
2. Columbia Suicide Severity Rating Scale ( CSSRS)
A suicidal rating scale devised by researchers at Columbia University. The presence of suicidal ideation score ranges from 1-5 and the intensity of the suicidal ideation ranges from 0-25 with higher scores indicating higher levels of intensity.
Time frame: Change from baseline at 5 days of TBS treatment
MGH Rumination questionnaire
Self administered 9 items scale to measure the severity of rumination. Each item is measured from 0-4 with a total score range of 0-36. Higher scores indicate more severe rumination.
Time frame: Change from baseline at 5 days of TBS treatment
Snaith-Hamilton Pleasure scale-Clinician administered (SHAP-C)
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This is to evaluate the ability to enjoy/experience pleasure. Each item can score 0 or 1 with a total score possibility of 0-14. Higher scores represent higher anhedonia and 3 or over is considered abnormal.
Time frame: Change from baseline at 5 days of TBS treatment
36 item short form survey (SF-36)
This is to evaluate physical and emotional health.
Time frame: Change from baseline at 5 days of TBS treatment
Global Assessment of Functioning (GAF)
This is to evaluate psychological, social and occupational functioning
Time frame: Change from baseline at 5 days of TBS treatment
Resting state functional connectivity-Functional magnetic resonance imaging (rsfMRI)
Temporal correlation of brain signals as measured by BOLD signals
Time frame: Pretreatment baseline
Magnetic resonance spectroscopy (MRS)
To measure glutathione and glutamate concentration in DLPFC and ACC
Time frame: Pretreatment baseline
Electroencephalogram
To measure neuronal oscillations
Time frame: Change from baseline at 5 days of TBS treatment