Theta Burst Stimulation for Depression

(ACT-LLD Trial)

Not yet 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new application of Theta Burst Stimulation (TBS), a brain stimulation therapy, to aid depression in older adults. It compares two methods: multiple treatments per day versus a single daily treatment, to determine which better alleviates depressive symptoms. Suitable participants have depression unresponsive to antidepressants and can adhere to a strict treatment schedule. All participants will receive active treatments, with some undergoing the accelerated method and others the conventional one. As an unphased trial, this study provides a unique opportunity to explore innovative treatment options for depression.

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 prior data suggests that this Theta Burst Stimulation protocol is safe for treating depression?

Research has shown that both faster and regular Theta Burst Stimulation (TBS) are generally well-tolerated treatments for depression. Studies indicate that faster TBS works well for older patients and has safety and side effects similar to once-daily TBS. Although TBS is considered safe, rare events like seizures can occur, so monitoring remains important.

Additionally, a review of studies found that both repetitive Transcranial Magnetic Stimulation (rTMS) and TBS are similarly safe for reducing depression and anxiety symptoms. The FDA has approved regular TBS for depression that doesn't respond to other treatments, suggesting its high safety.

Overall, research suggests that both faster and regular TBS are safe options for treating depression, with side effects similar to other standard treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for depression, which typically involve medication like SSRIs or therapy sessions, Theta Burst Stimulation (TBS) offers a non-invasive brain stimulation technique that could provide quicker results. Researchers are excited about TBS because it uses rapid bursts of magnetic pulses to target specific areas of the brain associated with mood regulation, potentially leading to faster symptom relief. The Accelerated TBS protocol is particularly noteworthy because it delivers multiple treatments in a very short timeframe, which could significantly reduce the duration needed to see improvement compared to conventional approaches. This could be a game-changer for those seeking quicker relief from depressive symptoms.

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

Research has shown that theta burst stimulation (TBS) can help reduce depression symptoms. In this trial, participants will join one of two treatment arms. The Accelerated TBS arm involves several treatments in one day. Studies have found it has a high success rate, with some trials showing up to 86.4% of participants responding well. This method also shows promise for those whose depression hasn't improved with other treatments. The Conventional TBS arm involves one session per day and is also effective, helping about 50% of participants feel better. Both methods have similar safety levels, causing side effects at about the same rate. Overall, TBS is a promising option for people dealing with depression. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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 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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11841443/

A meta-analysis comparing the effectiveness and safety of ... Both rTMS and TBS are similarly effective in reducing depression and anxiety symptoms, with comparable side effect profiles.

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

Theta burst stimulation for depression: a systematic review ... Theta burst stimulation (TBS) presents as a more efficient and potentially more effective therapeutic modality than conventional repetitive transcranial ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0165178123003797

Accelerated intermittent theta burst stimulation in major ... Cole et al. (2020) assessed depressive symptoms based on the MADRS. The study reported ITT response and remission rates following active treatment of 86.4% [19/ ...

4. medscape.com medscape.com/viewarticle/novel-accelerated-theta-burst-stimulation-protocol-shows-2025a10005ns

Novel Accelerated TBS Promising for Resistant Depression A new accelerated theta-burst stimulation (aTBS) protocol was safe and effective for treatment-resistant depression (TRD) in a randomized controlled trial.

5. psychiatryonline.org psychiatryonline.org/doi/full/10.1176/appi.ajp.2021.21121221

Accelerated Intermittent Theta Burst Stimulation In terms of the primary outcomes, the authors reported an impressive 69.2% response rate and a 46.2% remission rate 4 weeks after treatment, ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38383091/

Accelerated Theta Burst Stimulation: Safety, Efficacy ... - PubMed However, the acceleration of TBS delivery raises questions regarding the relative safety, efficacy, and durability compared with conventional ...

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

Feasibility and clinical effects of accelerated sequential ... Accelerated TBS is feasible in older patients with DTD; its efficacy is comparable to once daily TBS; and it is well-tolerated.

8. jamanetwork.com jamanetwork.com/journals/jamapsychiatry/article-abstract/2830861

Accelerated Theta-Burst Stimulation for Treatment ... The active aTBS group experienced a mean reduction in Hamilton Depression Rating Scale scores of 54.7% compared to 31.87% in the sham group; ...

9. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2024.1504727/full

A meta-analysis comparing the effectiveness and safety of ... Conclusions: Both rTMS and TBS are similarly effective in reducing depression and anxiety symptoms, with comparable side effect profiles. However, TBS is more ...