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

Trial Summary

What is the purpose of this trial?

The CogniTReaD study is a pilot clinical trial that will compare the effects of active accelerated bilateral sequential theta burst stimulation (absTBS) and sham or inactive treatment. The goal is to see if absTBS can help older adults with treatment-resistant depression (TRD) by looking at dual-task cost and mood, as well as other cognitive functions, anxiety levels, quality of life, and physical performance, while also checking for any treatment side effects. The study will recruit participants who will receive different study treatments in a specific order. The study will be double-blinded, meaning neither the participants nor the researchers will know who is receiving which treatment. The study will include people who are 50 years old or older and diagnosed with treatment-resistant depression with at least a moderate severity of depression. This study seeks to discover if absTBS can modify a dementia risk marker (i.e., dual-task cost and depression) in older patients with TRD, and to determine the effect size for larger investigations in the future.

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 data supports the effectiveness of the treatment Accelerated Bilateral Sequential Theta Burst Stimulation for depression?

Research shows that theta burst stimulation (TBS) can significantly improve depression symptoms, with studies indicating better outcomes for certain TBS protocols compared to placebo. Specifically, a combination of continuous and intermittent TBS has shown the highest antidepressant effects, suggesting that TBS is a promising treatment for depression. ^{1 2 3 4 5}

Is theta burst stimulation safe for humans?

Theta burst stimulation (TBS) has been studied for depression and is generally considered safe for humans. Studies have shown it to be well-tolerated, with no major safety concerns reported. ^{1 3 4 6 7}

How is Accelerated Bilateral Sequential Theta Burst Stimulation (absTBS) different from other treatments for depression?

Accelerated Bilateral Sequential Theta Burst Stimulation (absTBS) is unique because it combines multiple daily sessions of theta burst stimulation (TBS) to both sides of the brain, potentially enhancing outcomes compared to traditional once-daily protocols. This approach targets the dorsolateral prefrontal cortex, a brain area involved in mood regulation, and is particularly promising for those who have not responded to other antidepressant treatments. ^{1 3 4 7 8}

Research Team

Amer Burhan, MD, MSc

Principal Investigator

Ontario Shores Centre for Mental Health Sciences and University of Toronto

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Efficacy of prefrontal theta-burst stimulation in refractory depression: a randomized sham-controlled study. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Efficacy of theta burst stimulation (TBS) for major depression: An exploratory meta-analysis of randomized and sham-controlled trials. [2018]

3. Netherlands 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. [2021]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Adjunctive continuous theta burst stimulation for major depressive disorder or bipolar depression: A meta-analysis of randomized controlled studies. [2023]

5. Netherlands 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. [2023]

6. Croatia pubmed.ncbi.nlm.nih.gov

The acute effects of accelerated repetitive Transcranial Magnetic Stimulation on suicide risk in unipolar depression: preliminary results. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Accelerated sequential bilateral theta-burst stimulation in major depression: an open trial. [2023]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Treatment of major depression with bilateral theta burst stimulation: a randomized controlled pilot trial. [2018]