Depressive Disorder, Treatment-Resistant
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DEVICETheta Burst Stimulation ( Transcranial Magnetic Stimulation)
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.
Sponsors
University of Calgary
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open label study
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Participant must meet the DSM-5 diagnostic criteria for single-episode Major Depressive Disorder (MDD). 2. Participant must have failed to respond to \>1 but \<4 classes of oral antidepressant treatments in the current episode of depression. 3. Participant must have a HAMD total score of at least 18
Exclusion criteria
1. The participant's depressive symptoms have previously demonstrated nonresponse to: * An adequate course of rTMS/TBS over DLPFC in the current major depressive episode, defined as at least 3 weeks of treatment, 5 times weekly * An adequate course of treatment with electroconvulsive therapy (ECT) in the current major depressive episode, defined as at least 7 treatments with unilateral/bilateral ECT. 2. Participant has received vagal nerve stimulation (VNS) or has received deep brain stimulation (DBS) in the current episode of depression. 3. Participant has a current or prior DSM-5 diagnosis of Axis I comorbidities, including psychosis, bipolar disorder, obsessive compulsive disorder, based upon clinical assessment and confirmed by the MINI. 4. Participant has a current or prior DSM-5 diagnosis of Axis II comorbidities, including severe borderline personality disorders, antisocial, schizotypal, schizoid personality disorders based upon clinical assessment and confirmed by the MINI. 5. Participant has severe suicidal ideation/plan/ intent. 6. Participant has a history of moderate or severe substance or alcohol use disorder according to DSM-5 criteria. 7. Participant has a current or past history of seizures and neurological problems, e.g. head injury, stroke, progressive neurological disorder and complicated and unstable medical disorders, e.g. cardiovascular-related conditions, diabetes.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hamilton Depression Rating Scale | Change from baseline at 5 days of TBS treatment | Clinician administered questionnaire to asses clinical improvement and classify response and remission |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 2. Hamilton Anxiety rating Scale (HAM-A) | Change from baseline at 5 days of TBS treatment | 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. |
| 2. Columbia Suicide Severity Rating Scale ( CSSRS) | Change from baseline at 5 days of TBS treatment | 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. |
| MGH Rumination questionnaire | Change from baseline at 5 days of TBS treatment | 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. |
| Snaith-Hamilton Pleasure scale-Clinician administered (SHAP-C) | Change from baseline at 5 days of TBS treatment | 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. |
| 1. Montgomery-Åsberg Depression Rating Scale (MADRS) | Change from baseline at 5 days of TBS treatment | 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. |
| Global Assessment of Functioning (GAF) | Change from baseline at 5 days of TBS treatment | This is to evaluate psychological, social and occupational functioning |
| Resting state functional connectivity-Functional magnetic resonance imaging (rsfMRI) | Pretreatment baseline | Temporal correlation of brain signals as measured by BOLD signals |
| Magnetic resonance spectroscopy (MRS) | Pretreatment baseline | To measure glutathione and glutamate concentration in DLPFC and ACC |
| Electroencephalogram | Change from baseline at 5 days of TBS treatment | To measure neuronal oscillations |
| 36 item short form survey (SF-36) | Change from baseline at 5 days of TBS treatment | This is to evaluate physical and emotional health. |
Countries
Canada
Contacts
Primary ContactRajamannar Ramasubbu, MD,FRCPC,MSc
Backup ContactLaina B McAusland, RN,MSc
Outcome results
None listed