This study evaluates an accelerated schedule of theta-burst stimulation using a transcranial magnetic stimulation device for treatment-resistant depression. In this open label study, all participants will receive accelerated theta-burst stimulation.
Repetitive transcranial magnetic stimulation (rTMS) is an established technology as therapy for treatment-resistant depression. The approved method for treatment is 10Hz stimulation for 40 minutes over the left dorsolateral prefrontal cortex (L-DLPFC) for a 6 week treatment course. This methodology has been successful for many people with treatment-resistant depression. One of the limitations of this approach is the long duration of the treatment course (approximately a 6 weeks per treatment course). Recently, researchers have aggressively pursued modifying the treatment parameters to reduce treatment course time with some preliminary success. This study intends to further modify the parameters to create a more rapid form of the treatment. This study will also look at the change in neuroimaging biomarkers associated with this treatment.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
23
All participants will receive intermittent theta-burst stimulation (iTBS) to the left dorsal lateral prefrontal cortex (L-DLPFC). The L-DLPFC will be targeted utilizing the Localite neuronavigation system. Stimulation intensity will be standardized at 90% of resting motor threshold (adjusted for cortical depth). Stimulation will be delivered to L-DLPFC using the Magventure Magpro X100 and/or the NextStim TMS system.
Nolan Williams, MD
Palo Alto, California, United States
Percent Change in the Montgomery Asberg Depression Rating Scale (MADRS) Score From Pre-treatment to 1-month
A ten item diagnostic questionnaire used to measure the severity of depressive symptoms in patients with mood disorders. Scale range - 0 to 60 with higher score indicative of greater depressive symptomology.
Time frame: Pre-treatment and 1-month post treatment.
Percent Change in the Columbia Suicide Severity Rating Scale (C-SSRS)
A suicidal ideation rating scale created by researchers at Columbia University. The score was calculated by summing the answers to 5 questions. Score range - 0 to 5. Higher score indicate higher suicidal ideation.
Time frame: Pre-treatment to immediately post-treatment (on day 5) and 4 weeks post-treatment
Percent Change in the Hamilton Rating Scale for Depression (HAM-6)
A 6 item questionnaire used to score the severity of depression. Scale range - 0 to 22 with higher score indicative of greater depressive symptomology. Additional collection time points were pre-specified; only those time points for which data were collected are reported.
Time frame: Pre-treatment to immediately post-treatment (on day 5) and 2 weeks,4 weeks and 6 weeks post-treatment
Percent Change in the Hamilton Rating Scale for Depression (HAM-17)
A provider administered questionnaire used to assess remission and recovery from depression. Scale range - 0 to 52 with higher score indicative of greater depressive symptomology. Additional collection time points were pre-specified; only those time points for which data were collected are reported.
Time frame: Pre-treatment to immediately post-treatment (on day 5) and 2 weeks, 4 weeks, 6 weeks and 8 weeks post-treatment
Change From Baseline Functional Connectivity to 1-month Post-treatment
We will assess change in resting state fMRI functional connectivity of the subcallosal cingulate to the default mode network and within the default mode network.
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Time frame: Pre-treatment, immediately post-treatment (on day 5), 1-month post-treatment
Percent Change in the Beck Depression Inventory (BDI-II)
A 21 item Self-report measure of depressive symptoms. Scale range - 0 to 63 with higher score indicative of greater depressive symptomology. Additional collection time points were pre-specified; only those time points for which data were collected are reported.
Time frame: Pretreatment to immediately post-treatment (on day 5) and 2 weeks, 4 weeks, 6 weeks and 8 weeks post treatment.
Percent Change in the Montgomery Asberg Depression Rating Scale (MADRS)
A ten item diagnostic questionnaire used to measure the severity of depressive symptoms in patients with mood disorders. Scale range - 0 to 60 with higher score indicative of greater depressive symptomology. Additional collection time points were pre-specified; only those time points for which data were collected are reported.
Time frame: Pre-treatment to immediately post treatment (on day 5) and 2 weeks, 4 weeks and 8 weeks post-treatment
Change From Baseline Functional Connectivity to Immediately Post-treatment
Within subject changes in resting state functional connectivity of subgenual anterior cingulate cortex (sgACC) to default mode network (DMN). frontal (f)DMN (medial prefrontal cortex), median (m)DMN (posterior cingulate cortex and precuneus), left (l)DMN (left angular gyrus), right (r)DMN (right angular gyrus). T-statistic (T-score): ratio of departure of estimated value from its hypothesized value to its standard error used in a t-test to determine whether to support or reject the null hypothesis. A T-score of ≥ 2.11 or ≤ -2.11 would be considered a statistically significant change if the accompanying p-value (subject to false discovery rate correction of multiple comparisons) was ≤ 0.05. Positive T-score = increased connectivity, negative T-score = decreased connectivity. No established reference range or clinically meaningful threshold exists for this patient population. Higher connectivity between all DMN nodes to sgACC has been found in depressed vs healthy population.
Time frame: Pre-treatment to immediately post treatment (on day 5).