Late Life Depression (LLD), Depression - Major Depressive Disorder, Depressive Disorder, Treatment-Resistant, Mood Disorders
Conditions
Keywords
Brain stimulation, rTMS, Theta burst stimulation, Accelerated theta burst stimulation
Brief summary
The purpose of this trial is to compare the treatment efficacy (improvement in depressive symptoms) of accelerated TBS protocol (where participants receive multiple TBS treatments daily) to conventional TBS protocol (where participants receive a single TBS treatment daily) in late life depression. In addition, the study also aims to determine if specific patterns of stimulation are more or less effective. To do this, all participants will receive active treatments, but some of the participants in this study will receive accelerated TBS and some will receive once daily TBS.
Detailed description
The purpose of this trial is to compare the treatment efficacy (change in MADRS scores) of accelerated TBS to conventional TBS in participants with moderate to severe LLD at 4-weeks following accelerated TBS or following 30 once daily treatments of conventional TBS. Accelerated TBS group will receive 5 treatment sessions per day at approximately 1 hour intervals for 4 consecutive days on week 1 and 2 non-consecutive days on week 2. Conventional TBS group will receive 30 once daily treatment (approximately 6 weeks). Each treatment will consist of either 1) cTBS of right DLPFC followed by iTBS of left DLPFC; or 2) iTBS of left DLPFC.
Interventions
DEVICETBS
Repetitive transcranial magnetic stimulation (rTMS) is a form of non-invasive neurostimulation that uses focused magnetic field pulses to directly stimulate cortical neurons. Theta burst stimulation (TBS) is a briefer form of patterned rTMS that has been shown to be effective against major depressive disorder. Each treatment will consist of either 1) cTBS of right DLPFC followed by iTBS of left DLPFC; or 2) iTBS of left DLPFC.
Sponsors
Centre for Addiction and Mental Health
Sunnybrook Health Sciences Centre
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. are voluntary and competent to consent to treatment 2. are an outpatient 3. are ≥ 60 years old 4. have a Mini International Neuropsychiatric Interview (MINI 7.0) confirmed diagnosis of MDD, with a current MDE 5. have failed to achieve a clinical response to an adequate dose of an antidepressant based on an Antidepressant Treatment History Form (ATHF) score of ≥ 3 in the current episode or have failed to tolerate two separate trials of an antidepressant 6. have a score ≥ 10 on the Patient Health Questionnaire (PHQ-9) 7. have had no increase or initiation of any antidepressant or antipsychotic medication in the 4 weeks prior to screening 8. are able to adhere to the treatment schedule 9. pass the TMS adult safety screening (TASS) questionnaire
Exclusion criteria
1. have a Mini International Neuropsychiatric Interview (MINI 7.0) confirmed diagnosis of substance dependence or abuse within the last 3 months 2. have a concomitant major unstable medical illness as determined by one of the study physicians 3. have active suicidal intent 4. have presumed or probable dementia or clinical evidence of dementia as assessed by Short Blessed Test score ≥ 10 5. have a lifetime MINI diagnosis of bipolar I or II disorder, or primary psychotic disorder 6. have current psychotic symptoms 7. have a diagnosis of obsessive compulsive disorder, post-traumatic stress disorder (current or within the last year), anxiety disorder (generalized anxiety disorder, social anxiety disorder, panic disorder), or dysthymia, assessed by a study investigator to be primary and causing greater impairment than MDD 8. have a diagnosis of any personality disorder as assessed by a study investigator to be primary and causing greater impairment than MDD 9. did not respond to a course of ECT in the current depressive episode 10. have received rTMS in the current episode; patients who have had rTMS in a previous episode would be eligible 11. have a history of a primary seizure disorder or a seizure associated with an intracranial lesion 12. have an intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed 13. have an implanted electronic device that is currently in function such as a defibrillator 14. have a non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview) 15. have clinically significant laboratory abnormality, in the opinion of a study investigator 16. currently take more than lorazepam 2 mg daily (or equivalent) or any dose of an anticonvulsant 17. if participating in psychotherapy, must have been in stable treatment for at least 3 months prior to entry into the study, with no anticipation of change in the frequency of therapeutic sessions, or the therapeutic focus over the duration of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Depression severity | 6 weeks | Montgomery Asberg Depression Rating Scale (MADRS) Change |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Depression severity | up to 10 weeks | 17 item Hamilton Depression Rating Scale (HDRS-17) Change |
| Anxiety severity | up to 10 weeks | General Anxiety Disorder-7 (GAD-7) Change |
| Suicidal ideation | up to 10 weeks | The Beck Scale for Suicide Ideation (BSS) Change |
| Global cognition | up to 10 weeks | Montreal Cognitive Assessment (MoCA) Change |
| Executive function | up to 10 weeks | Delis-Kaplan Executive Function System (D-KEFS) Change |
| Memory | up to 10 weeks | California Verbal Learning Test- third edition (CVLT-3) Change |
| Disability and Functional Impairment | up to 10 weeks | Sheehan Disability Scale (SDS) Change |
| Quality of Life Measure | up to 10 weeks | Quality of Life Enjoyment and Satisfaction Scale (Q-LES-Q) change |
| Participant Expectancy of Improvement and Preference | Baseline | Modified Stanford Expectations of Treatment Scale (SETS) |
Countries
Canada
Outcome results
None listed