NCT04142996

Comparing Uni- and Bi-lateral TBS in Major Depression

A Naturalistic Study Comparing Uni- and Bi-lateral Theta Burst Stimulation in Major Depression

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 256 (estimated)
• Sponsor: The Royal Ottawa Mental Health Centre · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Repetitive transcranial magnetic stimulation (rTMS) is a Health Canada approved treatment for major depression. Theta burst stimulation (TBS) is a very promising new treatment for major depression that allows a 15-fold reduction in duration of daily sessions. However, no large scale naturalistic study has assessed the superiority of bilateral TBS in comparison with unilateral left TBS. In fact, no TBS study thus far has included both unipolar and bipolar depression, or other psychiatric comorbidities such as anxiety. Maintenance has yet to be studied with TBS, along with an effective maintenance protocol to prevent relapse. Our study aims to explore and address these gaps.

Detailed description

Repetitive transcranial magnetic stimulation (rTMS) is a Health Canada approved treatment for major depression. Typical treatments involve 30 to 45 minutes daily session delivered over 4 to 6 weeks. Recent technical advances allowed the development of theta burst stimulation (TBS), a novel rTMS paradigm which reduces daily sessions to 3 to 4 minutes while maintaining the same clinical efficacy. However, it remains to be determined if applying TBS to both sides of the frontal cortex (i.e. bilateral TBS) is more efficient than delivering it to only one side (i.e. unilateral TBS). In addition, it is difficult to predict treatment response as there is a lack of tools to identify potential responders early on in the treatment phase. Finally, the effects of rTMS are known to last up to 12 months after the treatment. To avoid relapse, a maintenance phase is typically introduced after treatment in which treatment sessions are delivered at a gradually decreasing rate. This study proposes to bridge these gaps by conducting a randomized double-blinded naturalistic superiority trial in which the efficacy of bilateral and unilateral TBS will be compared in individuals with a diagnosis of major depressive episodes. Neurobiological markers of response will be assessed at different time points. In people that respond to treatment, a 6-month maintenance phase will be conducted using a flexible schedule. The study has four primary aims: 1. To compare the efficacy of bilateral and unilateral TBS on symptoms of depression, as well as rates of remission and response 2. To investigate how unilateral and bilateral TBS modulates brain activity in the dorsolateral prefrontal cortex (DLPFC) using interleaved TMS-EEG 3. To investigate neural predictors of the clinical response to TBS. 4. To assess the efficacy of a flexible schedule of maintenance on a period of 6 months on symptoms of depression and rate of relapse. TREATMENT PHASE TBS treatment will be administered 5 days/week (on weekdays) over a first phase of 4 weeks (20 sessions). If remission is achieved (Hamilton Rating Scale for Depression-17 score \< 8), treatment will cease and the patient will move on to the maintenance phase. Non-remitters will receive a second phase of treatment, consisting of an additional 2 weeks (10 sessions, for a total of 30). After 6 weeks, all responders may move on to the maintenance phase. MAINTENANCE PHASE The maintenance phase will be of 6 months duration from the end of the randomized treatment. For each TBS condition, responders will be assigned to a flexible maintenance protocol based on symptom emergence. Participants will receive a fixed 2x/week schedule for the month 1. For month 2 and 3, a brief weekly assessment (Hamilton Rating Scale for Depression-17 score) will be conducted in which it will be determined if they will receive 0, 1 or 2 sessions in the week. For month 4 and 5, a bimonthly assessment (Hamilton Rating Scale for Depression-17 score) will be conducted in which it will be determined if they will receive 0, 1 or 2 sessions over the two weeks. For month 6, one brief assessment (Hamilton Rating Scale for Depression-17 score) will be conducted in which it will be determined if they will receive 0, 1 or 2 sessions in the month.

Conditions

• Major Depressive Episode

Interventions

Type	Name	Description
DEVICE	Theta burst stimulation	Cool B70 coil (left DLPFC) and Cool B65 active/placebo coil (right DLPFC), with X100 MagPro rTMS Device (Magventure A/S, Farum, Denmark)

Timeline

• Start date: 2019-12-12
• Primary completion: 2026-09-01
• Completion: 2026-09-01
• First posted: 2019-10-29
• Last updated: 2023-12-04

Locations

1 site across 1 country: Canada