Accelerated versus once-daily theta-burst stimulation for late-life depression

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

This test compares multiple theta-burst brain stimulation sessions per day to one session per day to see which better reduces symptoms in people 60 and older with moderate to severe treatment-resistant depression.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 280 (estimated)
• Ages: 60 Years and up
• Sex: All
• Sponsor: Centre for Addiction and Mental Health (other)
• Locations: 2 sites (Toronto, Ontario and 1 other locations)
• Trial ID: NCT06854367 on ClinicalTrials.gov

What this trial studies

This interventional trial enrolls adults aged 60 and over with moderate-to-severe late-life major depressive disorder who have not responded adequately to antidepressants. Participants receive active theta-burst stimulation (TBS) and are assigned to either an accelerated protocol—five TBS sessions per day at about 1-hour intervals for four consecutive days in week 1 plus two non-consecutive days in week 2—or a conventional protocol of 30 once-daily TBS sessions over roughly six weeks. Each treatment session delivers either continuous TBS (cTBS) to the right dorsolateral prefrontal cortex followed by intermittent TBS (iTBS) to the left DLPFC, or iTBS to the left DLPFC alone. The primary outcome is change in MADRS depressive symptom scores measured four weeks after completing the assigned treatment course.

Who should consider this trial

Good fit: Ideal candidates are outpatients aged 60 or older with a current major depressive episode who have failed at least one adequate antidepressant trial or tolerated two unsuccessful trials and can adhere to frequent in-person treatment sessions.

Not a fit: Patients with recent substance dependence, major unstable medical illnesses, or those unable to attend the intensive treatment schedule are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the accelerated protocol could shorten treatment time and produce faster symptom improvement for older adults with treatment-resistant depression.

How similar studies have performed: Standard rTMS and TBS have demonstrated antidepressant benefits and small accelerated-TBS studies in younger adults have shown promise, but accelerated TBS is less well tested in older populations.

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

Where this trial is running

Toronto, Ontario and 1 other locations

• Sunnybrook Health Sciences Centre — Toronto, Ontario, Canada (RECRUITING)
• Centre for Addiction and Mental Healh — Toronto, Ontario, Canada (RECRUITING)

Conditions: Late Life Depression, Depression - Major Depressive Disorder, Depressive Disorder, Treatment-Resistant, Mood Disorders, Brain stimulation, rTMS, Theta burst stimulation, Accelerated theta burst stimulation