This study is a single-arm, open-label, feasibility trial for the assessment of the clinical effects of a course of accelerated bilateral sequential theta burst stimulation (TBS) for late life depression (LLD). Over approximately 1 year, 30 outpatients at the Centre for Addiction and Mental Health (CAMH) meeting diagnostic criteria for LLD will be recruited and will receive 5 consecutive days (always Monday to Friday) of TBS repetitive transcranial magnetic stimulation (rTMS), administered 8 times daily at approximately 1 hour intervals, with continuous theta-burst stimulation (cTBS) applied to the right dorsolateral prefrontal cortex (DLPFC) followed by left DLPFC intermittent theta-burst stimulation (iTBS). Patients will undergo a series of assessments as well as motor threshold testing to determine the appropriate site and strength of stimulation according to standard methods and then begin treatment.
Repetitive transcranial magnetic stimulation (rTMS) is an evidenced based treatment for medically refractory major depressive disorder (MDD). rTMS involves direct stimulation of cortical neurons using externally applied, powerful, focused magnetic field pulses. Dozens of studies and several meta-analyses over the last 15 years have shown that rTMS of the dorsolateral prefrontal cortex (DLPFC) produces statistically significant improvements in MDD, even when medications have failed. In the most recent generation of randomized controlled trials, rTMS consistently achieves response rates of 50-55% and remission rates of 30-35% in medically refractory MDD patients. rTMS has been shown to be effective and well tolerated for depression in younger and older adults. However, early rTMS studies with older adults were limited by suboptimal stimulation parameters, small sample sizes and insufficient treatment durations. The optimal parameters for rTMS are still in the process of being established, however the most widely-used rTMS protocols apply excitatory, 10 Hz stimulation to the left DLPFC; high frequency left (HFL) or inhibitory, 1 Hz stimulation to the right DLPFC; low frequency right (LFR), or both. Taken together with the reported findings of several other groups, results suggest that accelerated rTMS may be feasible, tolerable, and capable of achieving comparable and potentially better remission rates than longer 20 to 30 day courses. However, all of these studies were small, open-label case series, focused on younger adults.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Subjects will receive 5 consecutive days (always Monday to Friday) of TBS rTMS, administered 8 times daily at 1 hour intervals. Patients will undergo cTBS of the R DLPFC at 110-120% RMT using bursts of 3 pulses at 50 Hz, bursts repeated at 5 Hz for a total of 600 pulses over 40 seconds, followed by iTBS of the L DLPFC at 110-120% resting motor threshold (RMT) using bursts of 3 pulses at 50 Hz, bursts repeated at 5 Hz with a duty cycle of 2 s on, 8 s off for a total of 600 pulses over 3 min 9 s. Participants will be titrated to 110-120% RMT within the first four treatments to aid with tolerability. If patients tolerate the stimulation well, the target will be 120%. Assessments focused on depressive symptoms will be administered at baseline, after final treatment and four weeks post final treatment.
Centre for Addiction and Mental Health
Toronto, Ontario, Canada
RECRUITINGChanges in Montgomery-Asberg Depression Rating Scale (MADRS) score
The investigators will assess the effects of accelerated sequential bilateral TBS based on change on the MADRS using an ANCOVA covarying for baseline differences to measure the change at the final time point for each subject. Higher MADRS scores indicates more severe depression. The overall score ranges from 0 to 60.
Time frame: baseline, last day of treatment (day 5, after the final treatment) and 4 weeks post treatment
Changes in 17 Item Hamilton Rating Scale for Depression (HDRS-17)
The investigators will assess the effects of accelerated sequential bilateral TBS based on change on the HDRS-17 using an ANCOVA covarying for baseline differences to measure the change at the final time point for each subject. Higher HDRS-17 scores indicates more severe depression. The overall score ranges from 0 to 53.
Time frame: baseline, last day of treatment (day 5, after the final treatment) and 4 weeks post treatment
Changes in Beck Depression Inventory (BDI-II)
The investigators will assess the effects of accelerated sequential bilateral TBS based on change on the BDI-II using an ANCOVA covarying for baseline differences to measure the change at the final time point for each subject. Higher BDI-II scores indicates more severe depression. The overall score ranges from 0 to 63.
Time frame: baseline, last day of treatment (day 5, after the final treatment) and 4 weeks post treatment
Changes in Beck Suicide Scale for Suicide Ideation (BSS)
The investigators will assess the effects of accelerated sequential bilateral TBS based on change on the BSS using an ANCOVA covarying for baseline differences to measure the change at the final time point for each subject. Higher BSS scores indicates more severe suicidality. The overall score ranges from 0 to 38.
Time frame: baseline, last day of treatment (day 5, after the final treatment) and 4 weeks post treatment
Changes in General Anxiety Disorder-7 (GAD-7)
The investigators will assess the effects of accelerated sequential bilateral TBS based on change on the GAD-7 using an ANCOVA covarying for baseline differences to measure the change at the final time point for each subject. Higher GAD-7 scores indicates more severe anxiety. The overall score ranges from 0 to 21.
Time frame: baseline, last day of treatment (day 5, after the final treatment) and 4 weeks post treatment
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