Brain Stimulation for Depression

(LeRNIT Trial)

Recruiting at 1 trial location

Overseen By Fidel Vila-Rodriguez, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of British Columbia

Disqualifiers: Substance use, Unstable illness, Suicidal, Pregnant, Psychotic, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4-6 weeks

420 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two types of brain stimulation treatments to help people with treatment-resistant depression (TRD). It compares a well-known method, intermittent Theta Burst Stimulation (iTBS), with a newer approach, Low Frequency Right (LFR) Repetitive Transcranial Magnetic Stimulation. The researchers aim to determine if LFR can be as effective as iTBS for those who haven't found relief with regular antidepressants. Individuals struggling with major depression, despite trying antidepressants, might be suitable candidates for this trial. As an unphased trial, this study offers a unique opportunity to explore innovative treatments for those seeking new options beyond traditional antidepressants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but you should not have started or increased any psychotropic medications in the 4 weeks before joining. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Intermittent Theta Burst Stimulation (iTBS) is safe and generally well-tolerated for treating depression. Studies have found that iTBS success rates in everyday use match those in clinical trials, making it a dependable option for patients.

Low Frequency Right (LFR) repetitive transcranial magnetic stimulation (rTMS) is also considered safe. A large study found that LFR works as well as some medications for people with treatment-resistant depression. Another study showed that LFR usually has mild side effects and does not harm brain function.

Both treatments have undergone testing in various studies and are generally well-tolerated by patients, indicating a good safety profile. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these brain stimulation treatments for depression because they offer potential alternatives to traditional methods like medication and electroconvulsive therapy. Intermittent Theta Burst Stimulation (iTBS) is unique because it delivers rapid pulses to the left dorsolateral prefrontal cortex (L-DLPFC), potentially accelerating antidepressant effects with shorter session times compared to standard repetitive transcranial magnetic stimulation (rTMS). Meanwhile, Low Frequency Right (LFR) stimulation targets the right dorsolateral prefrontal cortex (R-DLPFC) with a different frequency, which might better suit certain depression profiles. Both approaches provide non-invasive options that could offer quicker symptom relief and different mechanisms of action than existing treatments.

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

Research has shown that Intermittent Theta Burst Stimulation (iTBS), one of the treatments in this trial, helps about 42.1% of people with depression. It offers a quicker and possibly more effective alternative to traditional brain stimulation methods. Meanwhile, Low Frequency Right (LFR) repetitive transcranial magnetic stimulation (rTMS), another treatment option in this trial, has worked as well as some antidepressant medications, such as venlafaxine, for individuals with treatment-resistant depression. Studies also suggest that LFR can significantly reduce depressive symptoms. Both treatments provide promising options for those whose depression doesn't improve with other therapies. ^{1 2 4 5 6}

Who Is on the Research Team?

Fidel Vila-Rodriguez, MD, PhD

Principal Investigator

University of British Columbia

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with treatment-resistant depression, confirmed by specific criteria and interviews. Participants must have tried antidepressants without success or couldn't tolerate them, score ≥18 on a depression scale, not started new psychotropics recently, and can commit to the schedule. Exclusions include suicidal intent, psychotic/bipolar disorders history, recent substance use, pregnancy, metal head implants, significant medical issues or sensory impairments.

Inclusion Criteria

Patients must have a score ≥ 18 on the Hamilton Depression Rating Scale (HDRS-17 item)

I have passed safety screenings for TMS and MRI.

Patients must be able to adhere to the treatment schedule

Exclusion Criteria

I have been in stable psychotherapy for at least 3 months with no expected changes.

Patients with a clinically significant laboratory abnormality, in the opinion of one of the principal investigators

Patients with active suicidal intent

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either iTBS or LFR for 30 sessions

4-6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Intermittent Theta Burst Stimulation (iTBS)
• Low Frequency Right (LFR)
• Repetitive Transcranial Magnetic Stimulation

Trial Overview The study compares two types of rTMS treatments for depression: low-frequency right-sided (LFR) stimulation versus intermittent theta burst stimulation (iTBS). It aims to determine if LFR is as effective as iTBS in patients who haven't responded well to standard antidepressant therapies.

How Is the Trial Designed?

Group I: Intermittent Theta Burst Stimulation (iTBS) Active Control 2 Interventions

iTBS to the L-DLPFC

Group II: Low Frequency Right (LFR) Active Control 2 Interventions

1Hz stimulation to the R-DLPFC

Intermittent Theta Burst Stimulation (iTBS) is already approved in United States, European Union for the following indications:

Approved in United States as rTMS for:

• Major Depressive Disorder (MDD)
• Obsessive-Compulsive Disorder (OCD)
• Migraines
• Smoking Cessation

Approved in European Union as rTMS for:

• Major Depressive Disorder (MDD)

Who Is Running the Clinical Trial?

University of British Columbia

Lead Sponsor

Trials

1,506

Recruited

2,528,000+

Centre for Addiction and Mental Health

Collaborator

Trials

388

Recruited

84,200+

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]

In a study of 54 patients with major depression, the combination of intermittent theta burst stimulation (iTBS) and low-frequency rTMS (LF-rTMS) significantly improved depression and anxiety symptoms more than high-frequency rTMS (HF-rTMS).

The results suggest that iTBS combined with LF-rTMS may be a promising alternative therapy for major depression, offering both efficacy and time-saving benefits compared to traditional methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Left intermittent theta burst stimulation combined with right low-frequency rTMS as an additional treatment for major depression: A retrospective study. Mi, Y., Ji, Y., Lou, Z., et al.[2022]

Intermittent theta burst stimulation (iTBS) and high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) are equally effective and safe for treating patients with treatment-resistant major depressive disorder, based on a comprehensive meta-analysis.

iTBS may be a more practical option in clinical settings because it requires less stimulation intensity and shorter treatment times compared to HF-rTMS, making it potentially more accessible for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent theta burst stimulation vs. high-frequency repetitive transcranial magnetic stimulation for major depressive disorder: A systematic review and meta-analysis. Kishi, T., Sakuma, K., Matsuda, Y., et al.[2023]

Intermittent theta burst stimulation (iTBS) is a cost-effective alternative to conventional 10Hz rTMS for treating depression, with an average treatment cost of $1,108 compared to $1,844 for 10Hz rTMS, resulting in savings of $735 per patient.

iTBS also shows a lower average cost per remission at $3,695, compared to $6,146 for 10Hz rTMS, leading to significant savings of $2,451 per remission, making it a more efficient treatment option in healthcare systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implementation of intermittent theta burst stimulation compared to conventional repetitive transcranial magnetic stimulation in patients with treatment resistant depression: A cost analysis. Mendlowitz, AB., Shanbour, A., Downar, J., et al.[2020]

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]

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 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36841303/

Outcome of transcranial magnetic intermittent theta-burst ... In a clinical setting, iTBS was shown to be safe and tolerable and the response rate was similar to that reported from clinical trials.

2. 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 ...

3. 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 ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35609816/

Intermittent theta burst stimulation (iTBS) versus 10 Hz high ... The aim of our study was to compare the efficacy of 10 Hz rTMS and iTBS in treatment-resistant unipolar depression on response 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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39212556/

Efficacy and Safety of Intermittent Theta Burst Stimulation ... This meta-analysis aimed to evaluate the antidepressant effects and safety profiles of iTBS versus HF-rTMS for MDD. Methods A systematic ...