Brain Stimulation for Depression

(LeRNIT Trial)

Recruiting at 1 trial location

Overseen By Afifa Humaira, BSc

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: University of British Columbia

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

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing two types of brain stimulation therapies to help people with depression that hasn't improved with other treatments. These therapies use magnetic pulses to stimulate brain areas and improve mood.

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.

What data supports the effectiveness of the treatment Intermittent Theta Burst Stimulation (iTBS) for depression?

Research shows that Intermittent Theta Burst Stimulation (iTBS) is as effective as traditional high-frequency repetitive transcranial magnetic stimulation (rTMS) for treating depression, but it can be delivered much faster. Studies also suggest that combining iTBS with low-frequency rTMS may enhance its effectiveness for major depression. ^{1 2 3 4 5}

Is brain stimulation for depression safe?

Research shows that brain stimulation methods like intermittent theta burst stimulation (iTBS) and repetitive transcranial magnetic stimulation (rTMS) are generally safe for treating depression, with similar safety profiles to each other. ^{1 2 3 5 6}

How is intermittent theta burst stimulation (iTBS) different from other treatments for depression?

Intermittent theta burst stimulation (iTBS) is a newer form of repetitive transcranial magnetic stimulation (rTMS) that can be delivered in just 3 minutes, compared to the standard 37.5 minutes for high-frequency rTMS, making it a quicker option for treating depression. It has shown similar effectiveness and safety to traditional rTMS, offering a more time-efficient alternative for patients with treatment-resistant depression. ^{1 2 3 5 7}

Research Team

Fidel Vila-Rodriguez, MD, PhD

Principal Investigator

University of British Columbia

Eligibility Criteria

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

Trial Timeline

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

Treatment Details

Interventions

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

Participant Groups

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

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+

Findings from Research

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 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]

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 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]

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]

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]

References

1. India 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. [2022]

2. Switzerland 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. [2023]

3. England 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. [2022]

4. United States 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). [2022]

5. United States 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. [2022]

6. Ireland 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. [2023]

7. United States 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. [2020]