Theta Burst Stimulation for Depression

(ACT-LLD Trial)

Recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Centre for Addiction and Mental Health

Must not be taking: Anticonvulsants

Disqualifiers: Substance abuse, Dementia, Bipolar, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

280 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must not have increased or started any new antidepressant or antipsychotic medications in the 4 weeks before screening. Also, you cannot take more than 2 mg of lorazepam daily or any dose of an anticonvulsant.

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

Research shows that Theta Burst Stimulation (TBS) can significantly improve depression symptoms, with studies indicating a large difference in outcomes favoring active TBS over a placebo. Specifically, active TBS had higher response rates compared to sham TBS, suggesting it can be an effective treatment for major depression. ^{1 2 3 4 5}

Is theta burst stimulation safe for humans?

Research shows that theta burst stimulation (TBS) is generally safe and well-tolerated in humans, with studies reporting no adverse events in patients with depression. It has been tested in various forms, such as continuous and intermittent TBS, and found to be safe even when used multiple times a day. ^{3 4 6 7 8}

How does theta burst stimulation treatment differ from other treatments for depression?

Theta burst stimulation (TBS) is a unique form of repetitive transcranial magnetic stimulation (rTMS) that uses short bursts of magnetic pulses to stimulate specific brain areas, like the prefrontal cortex, to improve depression symptoms. It is considered more efficient and potentially faster-acting than traditional rTMS, with variations like intermittent TBS (iTBS) and continuous TBS (cTBS) showing promise in treating depression, especially in patients who have not responded to other treatments. ^{1 3 4 9 10}

What is the purpose of this trial?

The purpose of this trial is to compare the treatment efficacy (improvement in depressive symptoms) of accelerated TBS protocol (where participants receive multiple TBS treatments daily) to conventional TBS protocol (where participants receive a single TBS treatment daily) in late life depression. In addition, the study also aims to determine if specific patterns of stimulation are more or less effective. To do this, all participants will receive active treatments, but some of the participants in this study will receive accelerated TBS and some will receive once daily TBS.

Eligibility Criteria

This trial is for older adults with late-life depression. Participants should be experiencing depressive symptoms but the specific inclusion and exclusion criteria are not provided in the details given.

Inclusion Criteria

I am willing and able to agree to treatment.

Able to adhere to treatment schedule

PHQ-9 score ≥ 10

Exclusion Criteria

Diagnosis of substance dependence or abuse within the last 3 months

Lifetime diagnosis of bipolar I or II disorder, or primary psychotic disorder

Concomitant major unstable medical illness

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either accelerated TBS (5 treatments/day for 4 consecutive days in week 1 and 2 non-consecutive days in week 2) or conventional TBS (once daily for 30 days over approximately 6 weeks)

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Theta Burst Stimulation

Trial Overview The study tests two different TBS (Theta Burst Stimulation) protocols: an accelerated version with multiple daily treatments versus a conventional approach with one treatment per day, to see which is more effective for depression.

Participant Groups

Group I: Accelerated TBS Active Control 1 Intervention

Multiple treatments a day (5 treatments/day) for 4 consecutive days in the first week and 2 non-consecutive days in the second week.

Group II: Conventional TBS Active Control 1 Intervention

Treatment once a day for 30 days (e.g., 5 days a week for 6 weeks)

Who Is Running the Clinical Trial?

Centre for Addiction and Mental Health

Lead Sponsor

Trials

388

Recruited

84,200+

Sunnybrook Health Sciences Centre

Collaborator

Trials

693

Recruited

1,569,000+

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]

In a study of 50 depressed patients undergoing accelerated intermittent theta burst stimulation (aiTBS), baseline cortical thickness in the right caudal part of the anterior cingulate cortex (cACC) was found to significantly correlate with immediate clinical responses to treatment.

Longitudinal changes in cortical thickness in the right cACC also predicted delayed clinical responses, suggesting that this brain region could serve as a biomarker for determining the effectiveness of aiTBS in treating depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cortical Thickness in the Right Anterior Cingulate Cortex Relates to Clinical Response to Left Prefrontal Accelerated Intermittent Theta Burst Stimulation: An Exploratory Study. Baeken, C., van Beek, V., Vanderhasselt, MA., et al.[2022]

In a study of 26 patients with bipolar depression, active intermittent theta burst stimulation (iTBS) showed a high response rate of 72% and a remission rate of 42%, indicating its potential efficacy in treating this condition.

No adverse events were reported, demonstrating that iTBS is safe and well-tolerated, but further research with larger sample sizes is needed to confirm its superiority over sham treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Twice-daily neuronavigated intermittent theta burst stimulation for bipolar depression: A Randomized Sham-Controlled Pilot Study. Bulteau, S., Beynel, L., Marendaz, C., et al.[2020]

Theta-burst transcranial magnetic stimulation (TBS) is safe and well tolerated in patients with major depression, based on a study involving 33 participants over 10 consecutive days.

The study suggests that TBS may have antidepressant effects, and increasing stimulation parameters does not lead to more side effects, potentially enhancing its therapeutic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability and preliminary evidence for antidepressant efficacy of theta-burst transcranial magnetic stimulation in patients with major depression. Chistyakov, AV., Rubicsek, O., Kaplan, B., et al.[2019]

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 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]

A clinical trial involving 96 outpatients with moderate depression will investigate the effectiveness of intermittent theta burst stimulation (iTBS) on reducing depressive symptoms, comparing it to a sham treatment over ten sessions.

The study will also explore various factors, including genetic and neuropsychological measures, that may influence the response to iTBS, ensuring a thorough safety screening and adherence to ethical guidelines throughout the trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The antidepressant effect of intermittent theta burst stimulation (iTBS): study protocol for a randomized double-blind sham-controlled trial. Ørbo, MC., Grønli, OK., Larsen, C., et al.[2023]

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

Cortical Thickness in the Right Anterior Cingulate Cortex Relates to Clinical Response to Left Prefrontal Accelerated Intermittent Theta Burst Stimulation: An Exploratory Study. [2022]

6. France pubmed.ncbi.nlm.nih.gov

Twice-daily neuronavigated intermittent theta burst stimulation for bipolar depression: A Randomized Sham-Controlled Pilot Study. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Safety, tolerability and preliminary evidence for antidepressant efficacy of theta-burst transcranial magnetic stimulation in patients with major depression. [2019]

8. Germany pubmed.ncbi.nlm.nih.gov

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

9. England pubmed.ncbi.nlm.nih.gov

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

10. England pubmed.ncbi.nlm.nih.gov

The antidepressant effect of intermittent theta burst stimulation (iTBS): study protocol for a randomized double-blind sham-controlled trial. [2023]