Theta Burst Stimulation for Depression

Overseen By Jessica Drodge, MSc

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: The Royal Ottawa Mental Health Centre

Must be taking: Antidepressants

Must not be taking: Benzodiazepines

Disqualifiers: Substance abuse, Psychotic disorders, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

22 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called intermittent theta burst stimulation (iTBS), which uses magnetic fields to influence brain activity and may treat depression more effectively than standard methods. Researchers aim to compare changes in brain activity from iTBS to a placebo (a fake treatment) using brain scans. The trial seeks individuals diagnosed with major depression who have not improved after trying at least one antidepressant. Participants should be on a stable dose of their current antidepressant and able to speak and read English. As an unphased trial, this study offers the chance to contribute to groundbreaking research that could lead to more effective depression treatments.

Will I have to stop taking my current medications?

The trial requires participants to have been on a stable antidepressant regimen for at least four weeks before joining, so you will not need to stop taking your current antidepressants.

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

Research has shown that intermittent theta burst stimulation (iTBS) is generally safe and well-tolerated. Studies found that participants experienced no major side effects. Importantly, no serious issues like seizures occurred. This suggests that iTBS could be a safe choice for those considering participation in a clinical trial for depression. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Theta burst stimulation is unique because it offers a non-invasive approach to treating depression by using magnetic pulses to stimulate specific areas of the brain, particularly the left dorsolateral prefrontal cortex (DLPFC). Unlike traditional antidepressants, which often take weeks to show effectiveness, theta burst stimulation has the potential to provide quicker results, possibly within days. Researchers are excited about this technique because it can be precisely targeted and adjusted, offering a personalized treatment option with potentially fewer side effects compared to medication.

What evidence suggests that theta burst stimulation is effective for depression?

Research has shown that intermittent theta burst stimulation (iTBS) can help with depression. In this trial, participants may receive active iTBS, which studies have demonstrated can quickly and safely reduce depression symptoms. One study found that about 42.1% of people responded well to iTBS, comparable to other treatments. Another study showed that intensive iTBS treatment led to a high symptom remission rate of 79%. Overall, iTBS appears to be a promising and effective option for treating depression, potentially more effective than traditional methods. ^{3 6 7 8 9}

Who Is on the Research Team?

Sara Tremblay, PhD

Principal Investigator

The Royal Ottawa Mental Health Centre

Are You a Good Fit for This Trial?

This trial is for adults aged 18-55 with major depressive disorder (MDD) who haven't improved after 2-7 antidepressant treatments. They must have a certain depression score, be on stable medication for four weeks, and not have a history of substance abuse or significant medical conditions. Pregnant women and those with metal implants or severe psychiatric disorders are excluded.

Inclusion Criteria

Mini-International Neuropsychiatric Interview-confirmed diagnosis of MDD, as a single or recurring episode

I have been on a steady antidepressant treatment for over a month.

A baseline score of ≥ 15 on the 17-item Hamilton Rating Scale for Depression (HRSD-17)

Exclusion Criteria

I am currently receiving ECT or rTMS for depression.

Pregnancy (confirmed by urine test) and/or lactation

I do not have any uncontrolled illnesses like diabetes or kidney problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily sessions of intermittent theta burst stimulation (iTBS) on weekdays for 6 weeks

6 weeks

Daily sessions (weekdays)

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 intermittent theta burst stimulation (iTBS), a type of brain stimulation therapy for depression that's quicker than standard treatments. Participants will undergo iTBS compared to sham treatment using PET and MRI scans in a double-blind experiment, followed by six weeks of daily iTBS sessions.

How Is the Trial Designed?

Group I: Active iTBS Active Control 1 Intervention

Intermittent Theta Burst Stimulation (iTBS) will be applied to the left DLPFC. Participants will receive daily sessions (on weekdays) for 6 weeks.

Group II: Sham iTBS/Active iTBS Placebo Group 1 Intervention

Intermittent Theta Burst Stimulation (iTBS) or realistic sham iTBS will be applied to the left DLPFC. Both sessions will be one week apart.

Theta burst stimulation is already approved in United States for the following indications:

Approved in United States as iTBS for:

• Major Depressive Disorder

Who Is Running the Clinical Trial?

The Royal Ottawa Mental Health Centre

Lead Sponsor

Trials

24

Recruited

2,300+

Published Research Related to This Trial

Intermittent theta-burst stimulation (iTBS) and high-frequency rTMS (HF-rTMS) show similar efficacy in treating treatment-resistant depression (TRD), with response rates of 48.0% for iTBS and 45.5% for HF-rTMS based on two high-quality randomized controlled trials involving 474 participants.

Both iTBS and HF-rTMS have comparable safety profiles, with similar rates of discontinuation and adverse events, such as headaches, indicating that iTBS is a safe alternative to HF-rTMS for patients with TRD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of intermittent theta burst stimulation versus high-frequency repetitive transcranial magnetic stimulation for patients with treatment-resistant depression: a systematic review. Lan, XJ., Yang, XH., Qin, ZJ., et al.[2023]

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]

In a study involving 72 patients with major depressive disorder, two daily sessions of prolonged intermittent theta-burst stimulation (piTBS) over two weeks showed significantly more responders compared to a sham treatment, indicating its efficacy as an antidepressant option.

However, the study found no evidence that longer piTBS sessions led to greater improvements in depression scores compared to other treatments, suggesting that while piTBS is effective, increasing treatment duration does not enhance its antidepressant effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The longer, the better ? Longer left-sided prolonged intermittent theta burst stimulation in patients with major depressive disorder: A randomized sham-controlled study. Li, CT., Cheng, CM., Lin, HC., et al.[2023]

In a study of 71 participants with Major Depressive Disorder who had limited response to high-frequency left-sided stimulation, subthreshold intensity intermittent theta-burst stimulation priming (iTBS-P) led to a greater reduction in depressive symptoms compared to suprathreshold intensity stimulation.

The results suggest that iTBS-P may work through homeostatic plasticity mechanisms, indicating that lower intensity stimulation could be more effective for clinical improvement in depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subthreshold stimulation intensity is associated with greater clinical efficacy of intermittent theta-burst stimulation priming for Major Depressive Disorder. Lee, JC., Corlier, J., Wilson, AC., et al.[2021]

Intermittent theta burst stimulation (iTBS) is as effective as standard high-frequency (10 Hz) rTMS for treating treatment-resistant depression, showing non-inferiority in improving depression scores over 4-6 weeks in a study with 414 participants.

Both iTBS and 10 Hz rTMS had similar safety profiles and dropout rates, with headaches being the most common side effect, indicating that iTBS can be a viable alternative that allows for more patients to be treated in a shorter time without losing effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial. Blumberger, DM., Vila-Rodriguez, F., Thorpe, KE., 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]

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, 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 involving 208 participants with treatment-resistant depression, both twice-daily and once-daily intermittent theta burst stimulation (iTBS) protocols showed improvements in depression scores, but there was no significant difference in efficacy between the two schedules after 10 and 30 days.

Response and remission rates were low in both treatment groups, indicating that neither protocol significantly accelerated the improvement of depressive symptoms in patients with treatment-resistant depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized sham controlled comparison of once vs twice-daily intermittent theta burst stimulation in depression: A Canadian rTMS treatment and biomarker network in depression (CARTBIND) study. Blumberger, DM., Vila-Rodriguez, F., Wang, W., et al.[2022]

In a study of 60 patients with treatment-resistant unipolar depression, both intermittent theta burst stimulation (iTBS) and conventional 10 Hz rTMS showed similar efficacy in reducing depression scores and improving quality of life over a 6-month follow-up, with response rates of 36.7% for iTBS and 33.3% for rTMS.

iTBS is highlighted as a more time-efficient and cost-effective option compared to rTMS, suggesting it could be a valuable treatment alternative for patients with severe depression who have not responded to multiple antidepressant trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent theta burst stimulation (iTBS) versus 10 Hz high-frequency repetitive transcranial magnetic stimulation (rTMS) to alleviate treatment-resistant unipolar depression: A randomized controlled trial (THETA-DEP). Bulteau, S., Laurin, A., Pere, M., et al.[2022]

Accelerated, high-dose intermittent theta burst stimulation (iTBS) showed promising results in treating highly treatment-resistant depression, with most patients achieving remission after treatment.

However, the effects were short-lived, as all patients experienced relapse within two weeks, indicating a need for improved treatment strategies that enhance the durability of the therapeutic response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is accelerated, high-dose theta burst stimulation a panacea for treatment-resistant depression? Caulfield, KA.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39761754/

Efficacy study of intermittent theta burst stimulation(iTBS) in ... The current study suggests that two days of active iTBS to the DLPFC region can rapidly, safely, and effectively improve depressive symptoms in adolescents ...

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/S0165032723002604

Outcome of transcranial magnetic intermittent theta-burst ... In this first national register-based cohort study of iTBS for depression we observed a clinician rated response rate of 42.1 %, being on par ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11238064/

Accelerated Intermittent Theta-Burst Stimulation and ... Ten sessions per day for 5 days achieved 79% remission in a sham-controlled randomized clinical trial—substantially better than remission rates ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT07033780

NCT07033780 | Theta-Burst Stimulation to Treat Depression The goal of this clinical trial is to explore the effects of non-invasive brain stimulation protocols using intermittent theta-burst stimulation (iTBS) on ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11609094/

Theta burst stimulation for depression: a systematic review ... A randomized controlled trial (RCT) of SNT demonstrated that iTBS (L-DLPFC) outperformed sham in depressive symptom improvement with a large ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8617062/

A Systematic Review of the Safety and Tolerability of Theta ... All participants tolerated iTBS without significant adverse events. No complications, such as seizures, occurred in any of the participants. One participant ...

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

Accelerated intermittent theta burst stimulation in major ... Four weeks after treatment response rates ranged from 0.0% to 66.7% and remission rates ranged from 0.0% to 57.1%. Three articles described a significant ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006322325013563

Efficacy and Safety of Accelerated Intermittent Theta-burst ... In this trial, a-iTBS, administered five sessions per day for ten days, is effective and safe for adolescents with non-treatment-resistant MDD.