Theta Burst Stimulation for Depression

(CogniTReaD Trial)

Overseen By Adrian I. Espiritu, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Ontario Shores Centre for Mental Health Sciences

Must not be taking: Anticonvulsants, others

Disqualifiers: Substance use disorder, Bipolar, Dementia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 7

Duration: 2 weeks

54 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called accelerated bilateral sequential theta burst stimulation (absTBS) to assist older adults with treatment-resistant depression. The study aims to determine if this stimulation can enhance mood, cognitive functions, anxiety, and overall quality of life. Participants will receive either the active treatment or a sham (inactive) treatment in a specific order without knowing which one they receive. Suitable candidates for this trial are those aged 50 or older with long-term depression that hasn’t improved after trying at least two antidepressants.

As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could lead to new treatment options for depression.

Will I have to stop taking my current medications?

You can continue taking your current medications as long as they are at a stable dose for at least 1 week before the study starts and you are willing to keep them stable during the study. However, if you are taking more than 2 mg of Lorazepam daily or any anticonvulsant, you may not be eligible to participate.

What prior data suggests that this method is safe for treating depression?

Research has shown that accelerated bilateral sequential theta burst stimulation (absTBS) is generally safe for individuals with depression unresponsive to other treatments. Studies have found that patients, including older adults, typically tolerate this treatment well. Reports of serious side effects are rare, indicating it as a reliable option for those who haven't responded to other depression treatments. Some studies compared absTBS to a once-daily treatment schedule and found it equally safe. This finding is encouraging for those considering this treatment, suggesting that absTBS could be a promising option with manageable safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about accelerated bilateral sequential theta burst stimulation (absTBS) for depression because it offers a rapid and non-invasive option compared to traditional treatments like antidepressant medications or regular transcranial magnetic stimulation (rTMS). While typical treatments can take weeks to produce noticeable effects, absTBS has the potential to deliver quicker results in managing depressive symptoms. Additionally, this method targets brain activity more precisely by delivering short, intense bursts of magnetic pulses, which may enhance its effectiveness and patient outcomes.

What evidence suggests that this trial's treatments could be effective for treatment-resistant depression?

Research shows that accelerated bilateral sequential theta burst stimulation (absTBS) might help people with depression unresponsive to other treatments. In this trial, participants will follow different treatment sequences. One group will receive the active absTBS treatment first, followed by a sham treatment. Another group will start with the sham treatment, followed by the active absTBS treatment. Studies have found that absTBS can lessen symptoms of depression, with benefits lasting several weeks. One study found that absTBS was both effective and safe for those who didn't respond to other treatments. Another study showed that absTBS could quickly improve mood and reduce feelings of depression. Overall, these findings suggest that absTBS could be a promising option for difficult-to-treat depression. ^{1 2 4 6 7}

Who Is on the Research Team?

Amer Burhan, MD, MSc

Principal Investigator

Ontario Shores Centre for Mental Health Sciences and University of Toronto

Are You a Good Fit for This Trial?

This trial is for individuals aged 50 or older who have treatment-resistant depression of at least moderate severity. It aims to test if a new therapy, absTBS, can improve mood and cognitive functions in these patients.

Inclusion Criteria

I am 50 years old or older.

Passing the TMS safety screen

I have been diagnosed with major depression without psychosis.

Exclusion Criteria

MINI-confirmed active substance use disorder within the last 3 months

Major unstable medical comorbidities

Cardiac pacemaker or implanted mediation pump

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either active absTBS or sham treatment in a randomized sequence

2 weeks

Multiple visits (in-person)

Post-treatment Acute Effects

Evaluation of acute effects of treatment on dual-task cost, cognitive functions, and depression

1 week

1 visit (in-person)

Post-treatment Delayed Effects

Evaluation of delayed effects of treatment on dual-task cost, cognitive functions, and depression

4 weeks

Visits at Week 6, Week 8, and Week 10 (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Accelerated Bilateral Sequential Theta Burst Stimulation

Trial Overview The study compares active accelerated bilateral sequential theta burst stimulation (absTBS), a potential new treatment for depression, with a sham (inactive) treatment to see which is more effective in improving symptoms of depression and cognitive function.

How Is the Trial Designed?

Group I: absTBS-sham treatment sequence arm Experimental Treatment 1 Intervention

Those assigned to the accelerated bilateral sequential theta burst stimulation (absTBS)-sham arm shall receive the blinded active absTBS treatment at Week 1. At Week 3, they shall receive the blinded sham treatment.

Group II: Sham-absTBS treatment sequence arm Experimental Treatment 1 Intervention

In the sham-absTBS arm, the blinded sham treatment shall be administered at Week 1. The blinded active absTBS treatment shall be given at Week 3.

Who Is Running the Clinical Trial?

Ontario Shores Centre for Mental Health Sciences

Lead Sponsor

Trials

15

Recruited

2,400+

Sunnybrook Health Sciences Centre

Collaborator

Trials

693

Recruited

1,569,000+

Published Research Related to This Trial

In a study of 60 treatment-refractory patients with major depressive disorder, both intermittent and combined theta-burst stimulation showed significantly better antidepressant responses compared to continuous theta-burst stimulation and sham treatment after 2 weeks.

Theta-burst stimulation is well-tolerated and effective, especially in patients with lower levels of treatment refractoriness, indicating that the severity of refractoriness can influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of prefrontal theta-burst stimulation in refractory depression: a randomized sham-controlled study. Li, CT., Chen, MH., Juan, CH., et al.[2022]

In a randomized-controlled trial involving 32 patients with major depression, bilateral theta burst stimulation (TBS) to the dorsolateral prefrontal cortex showed a significant increase in treatment response compared to sham stimulation, with 9 responders in the TBS group versus 4 in the sham group.

The study also indicated a trend towards higher remission rates in the TBS group as measured by the Beck Depression Inventory, suggesting that TBS may enhance the effectiveness of ongoing medication and psychotherapy in treating major depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of major depression with bilateral theta burst stimulation: a randomized controlled pilot trial. Plewnia, C., Pasqualetti, P., Große, S., et al.[2018]

In a randomized, double-blind trial involving 56 patients, intermittent theta burst stimulation (iTBS) over the dorsomedial prefrontal cortex showed a significant reduction in negative symptoms for patients with depression, but not for those with schizophrenia.

The treatment was generally safe and well-tolerated, with serious adverse events occurring only in the sham group, indicating that iTBS may be a promising intervention for depressive symptoms in certain patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dorsomedial prefrontal theta burst stimulation to treat anhedonia, avolition, and blunted affect in schizophrenia or depression - a randomized controlled trial. Bodén, R., Bengtsson, J., Thörnblom, E., et al.[2021]

Intermittent theta-burst stimulation (iTBS) targeting the left visual cortex (VC) was found to be non-inferior to targeting the left dorsolateral prefrontal cortex (DLPFC) in improving depressive symptoms in patients with major depressive disorder (MDD), based on a study of 75 participants over 14 days.

The VC group experienced lower rates of suicidal ideation and fewer adverse events, such as eye discomfort and pain, suggesting that VC-targeted iTBS may be a safer option for treating MDD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-inferiority of intermittent theta burst stimulation over the left V1 vs. classical target for depression: A randomized, double-blind trial. Kong, Y., Zhou, J., Zhao, M., et al.[2023]

In a pilot study of 25 patients with treatment-resistant major depressive disorder, accelerated bilateral theta burst stimulation (TBS) showed significant reductions in depression scores after 5 days and 2 weeks, indicating potential efficacy.

While 60% of patients experienced difficulty tolerating the high-intensity stimulation, no major adverse events were reported, suggesting that accelerated bilateral TBS may be a safe option for some patients with depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated sequential bilateral theta-burst stimulation in major depression: an open trial. Ramasubbu, R., Brown, EC., Selby, B., et al.[2023]

Accelerated intermittent theta burst stimulation (TBS) was found to be safe and well tolerated in 12 suicidal therapy-resistant depressed patients, showing a significant decrease in suicidal ideation over time.

However, the reduction in suicidal thoughts was not definitively linked to the active TBS treatment compared to sham stimulation, indicating that further research is needed to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The acute effects of accelerated repetitive Transcranial Magnetic Stimulation on suicide risk in unipolar depression: preliminary results. Desmyter, S., Duprat, R., Baeken, C., et al.[2022]

Theta burst stimulation (TBS) shows significant efficacy in reducing depression symptoms, with a large effect size (Hedges' g = 1.0) based on a meta-analysis of 5 randomized controlled trials involving 221 subjects.

Active TBS resulted in higher response rates compared to sham TBS (35.6% vs. 17.5%), although there was no significant difference in remission rates, indicating that while TBS is promising, further research is needed to optimize treatment parameters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of theta burst stimulation (TBS) for major depression: An exploratory meta-analysis of randomized and sham-controlled trials. Berlim, MT., McGirr, A., Rodrigues Dos Santos, N., et al.[2018]

Continuous theta burst stimulation (cTBS) was found to be safe and well-tolerated in patients with major depressive disorder (MDD) or bipolar depression (BD), with no significant differences in adverse events compared to sham treatment.

However, the meta-analysis of three randomized controlled trials involving 78 participants showed no significant improvement in depression scores or response rates with cTBS compared to sham, indicating that cTBS may not provide a therapeutic advantage for treating major depressive episodes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjunctive continuous theta burst stimulation for major depressive disorder or bipolar depression: A meta-analysis of randomized controlled studies. Cai, DB., Qin, XD., Qin, ZJ., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37470840/

Accelerated sequential bilateral theta-burst stimulation in ... These preliminary findings suggest that accelerated bilateral TBS may be clinically effective and safe for treatment resistant depression.

2. sciencedirect.com sciencedirect.com/science/article/pii/S3050529125000832

Feasibility and clinical effects of accelerated sequential ... We hypothesized that a course of accelerated bilateral TBS would reduce depressive symptoms, and these improvements would be sustained in the 4 week followup ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04701840

Sequential Bilateral Accelerated Theta Burst Stimulation in ... The investigators hope to learn if this TMS treatment improves suicidal ideation over 10 days and clinical outcomes over 1 year of follow-up. Detailed ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37053246/

Sequential bilateral accelerated theta burst stimulation in ... This is a randomized, double-blind, sham-controlled trial of sequential bilateral aTBS in adolescents with major depressive disorder (MDD) and suicidal ...

5. nature.com nature.com/articles/s41380-024-02630-5

Theta burst stimulation for depression: a systematic review ... The current study outcomes included the response rate (primary), depression symptom improvement, remission rate, all-cause discontinuation rate, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10952126

Accelerated Theta Burst Stimulation (aTBS) The conventional iTBS protocol is FDA-approved to treat otherwise treatment-resistant depression but the 6-week duration limits the applicability of this ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05119699

Study Details | Accelerated TBS in Late Life Depression This study is a single-arm, open-label, feasibility trial for the assessment of the clinical effects of a course of accelerated bilateral sequential theta ...