Exercise + TBS for Depression

Overseen By Stacey Shim, MSc

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: The Royal Ottawa Mental Health Centre

Must not be taking: Illegal drugs, Cannabis, Lorazepam

Disqualifiers: Bipolar, Substance abuse, Unstable illness, others

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

Compensation: Varies

Number of Visits: 14

20 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

You need to keep your current psychotropic medication and/or psychotherapy regimen unchanged for at least four weeks before and during the study.

What data supports the effectiveness of the treatment Structured Exercise, Theta Burst Stimulation for depression?

Research shows that theta burst stimulation (TBS), a type of brain stimulation, can significantly improve symptoms of major depression, with studies indicating higher response rates compared to a placebo treatment. Additionally, TBS has shown promise in treating depression symptoms in various trials, suggesting it could be an effective part of the treatment for depression. ^{1 2 3 4 5}

Is theta burst stimulation (TBS) safe for treating depression?

Research on theta burst stimulation (TBS) for depression suggests it is generally safe, with similar dropout rates to sham treatments, indicating no significant safety concerns. ^{1 2 3 6 7}

How does the treatment Theta Burst Stimulation (TBS) for depression differ from other treatments?

Theta Burst Stimulation (TBS) is a unique treatment for depression that uses magnetic pulses to stimulate specific areas of the brain, unlike traditional medications that work through chemical changes. It is a form of repetitive transcranial magnetic stimulation (rTMS) and can be administered in different patterns, such as intermittent or continuous, to potentially improve mood and reduce symptoms of depression. ^{1 2 3 4 8}

What is the purpose of this trial?

The goal of this study is to collect feasibility data on combining structured exercise aimed to improve physical fitness, and intermittent TBS (iTBS) in treating individuals diagnosed with difficult-to-treat depression who are physically inactive. By conducting this trial, we will compare the therapeutic benefits of the combined approach against the standard treatment of iTBS alone (without exercise). These findings will be used to inform future large-scale projects in which we will investigate, in a larger sample size, whether structured exercise aimed to improve fitness as recommended by most public exercise guidelines (i.e., ≥3x/week, moderate-to-vigorous intensity) serves as an active ingredient that amplifies the effectiveness of iTBS. Ultimately, the insights gained from this study will be valuable for clinicians seeking to alleviate depressive symptoms in MDD through neuromodulation techniques such as iTBS.

Research Team

Sara Tremblay, PhD

Principal Investigator

Royal Ottawa Mental Health Centre

Eligibility Criteria

This trial is for individuals with difficult-to-treat depression who are physically inactive. It aims to see if adding structured exercise to a treatment called intermittent Theta Burst Stimulation (iTBS) can help more than iTBS alone.

Inclusion Criteria

Able to provide voluntary informed consent

I have been diagnosed with major depression or persistent depressive disorder, without psychosis.

Able to engage in structured exercise as per the Get Active Questionnaire (GAQ)

Exclusion Criteria

Current or past (<3 months) substance (excluding caffeine or nicotine) or alcohol abuse/dependence, as defined in DSM-5 criteria

Current use of cannabis

Acute suicidality or threat to life from self-neglect

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Priming Phase

Participants in the intervention group undergo 4 weeks of exercise to enhance brain plasticity mechanisms.

4 weeks

3 visits per week (in-person)

Synergetic Phase

Participants in the intervention group continue exercise while receiving iTBS treatment for 6 weeks.

6 weeks

5 visits per week (in-person)

Control Phase

Participants in the control group receive stable treatment for 4 weeks followed by 6 weeks of iTBS alone.

10 weeks

5 visits per week (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment.

6 weeks

1 visit (in-person)

Treatment Details

Interventions

• Structured Exercise
• Theta Burst Stimulation

Trial Overview The study tests whether combining regular, moderate-to-vigorous exercise with iTBS is more effective in treating major depressive disorder than just iTBS on its own. Participants will be compared to see the difference in therapeutic benefits.

Participant Groups

Group I: Standard Group Experimental Treatment 1 Intervention

Standard care of 4 weeks of stable treatment (i.e. no changes to antidepressant regimen or physical activity) followed by 6 weeks of iTBS alone.

Group II: Intervention Group Experimental Treatment 1 Intervention

4-weeks of exercise (moderate-to-vigorous intensity) followed by 6 weeks of iTBS combined with exercise.

Who Is Running the Clinical Trial?

The Royal Ottawa Mental Health Centre

Lead Sponsor

Trials

24

Recruited

2,300+

University of Ottawa

Collaborator

Trials

231

Recruited

267,000+

Findings from Research

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]

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]

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]

Bilateral theta-burst stimulation (TBS) significantly improved depressive symptoms and remission rates in patients with major depressive disorder (MDD), showing a response rate of 55.1% compared to 20.3% for sham stimulation across six randomized controlled trials involving 285 participants.

The treatment was well-tolerated, with similar rates of discontinuation and adverse events (like headache and dizziness) between the TBS and sham groups, indicating its safety as an intervention for mood disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bilateral theta burst stimulation for patients with acute unipolar or bipolar depressive episodes: A systematic review of randomized controlled studies. Qin, ZJ., Huang, SQ., Lan, XJ., et al.[2023]

Theta burst stimulation (TBS) is as effective and safe as standard repetitive transcranial magnetic stimulation (rTMS) for treating depression, based on a meta-analysis of nine randomized controlled trials involving 1124 patients.

The study found no significant differences in response rates or adverse events between TBS and rTMS, suggesting that TBS could be a viable alternative due to its shorter treatment sessions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Theta Burst vs Repetitive Transcranial Magnetic Stimulation for the Treatment of Depression: A Meta-Analysis of Randomized Controlled Trials. Liu, C., Li, L., Li, B., et al.[2023]

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]

References

1. 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]

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

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

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

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

5. England pubmed.ncbi.nlm.nih.gov

iTBS to Relieve Depression and Executive Dysfunction in Older Adults: An Open Label Study. [2021]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Bilateral theta burst stimulation for patients with acute unipolar or bipolar depressive episodes: A systematic review of randomized controlled studies. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Theta Burst vs Repetitive Transcranial Magnetic Stimulation for the Treatment of Depression: A Meta-Analysis of Randomized Controlled Trials. [2023]

8. England pubmed.ncbi.nlm.nih.gov

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