Overview

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.

Eligibility

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