Accelerated vs. Conventional Theta Burst Stimulation for Late-life Depression

NCT ID: NCT06854367

Last Updated: 2026-01-28

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 280 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-03-27
• Study Completion Date: 2029-12-31

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.

Conditions

Late Life Depression (LLD); Depression - Major Depressive Disorder; Depressive Disorder, Treatment-Resistant; Mood Disorders

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Accelerated TBS

Multiple treatments a day (5 treatments/day) for 4 consecutive days in the first week and 2 non-consecutive days in the second week.

Group Type: ACTIVE_COMPARATOR

TBS

Intervention Type: DEVICE

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.

Conventional TBS

Treatment once a day for 30 days (e.g., 5 days a week for 6 weeks)

Group Type: ACTIVE_COMPARATOR

TBS

Intervention Type: DEVICE

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.

Interventions

TBS

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.

Intervention Type: DEVICE

Eligibility Criteria

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

• Minimum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sunnybrook Health Sciences Centre

OTHER

Sponsor Role: collaborator

Centre for Addiction and Mental Health

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Site Status: RECRUITING

Centre for Addiction and Mental Healh

Toronto, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Facility Contacts

Donguk Jo

Role: primary

donguk.jo@sri.utoronto.ca

416-480-6100 ext. 61518

Elizabeth Clancy

Role: primary

elizabeth.clancy@camh.ca

416-535-8501

Other Identifiers

CTO4933

Identifier Type: -

Identifier Source: org_study_id