Brain Stimulation for Depression

(LeRNIT Trial)

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Fidel Vila-Rodriguez, MD, PhD

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.

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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.

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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.

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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

Participant Groups

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.

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)

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Non-Invasive Neurostimulation Therapies Centre, University of British Columbia Vancouver, Canada

Centre for Addiction and Mental Health Toronto, Canada

Who Is Running the Clinical Trial?

University of British Columbia Lead Sponsor

Centre for Addiction and Mental Health Collaborator

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] Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depression (MD). We retrospectively analyzed the efficacy of intermittent theta burst stimulation (iTBS) on the left dorsolateral prefrontal cortex (DLPFC) combined with low-frequency rTMS (LF-rTMS) on the right DLPFC as an additional therapy to standard medication treatment.

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] Intermittent theta-burst stimulation (iTBS), which is a form of repetitive transcranial magnetic stimulation (rTMS), can produce 600 pulses to the left dorsolateral prefrontal cortex (DLPFC) in a stimulation time of just over 3 min. The objective of this systematic review was to compare the safety and efficacy of iTBS and high-frequency (≥ 5 Hz) rTMS (HF-rTMS) for patients with treatment-resistant depression (TRD).

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] Treatment-resistant major depressive disorder is common; repetitive transcranial magnetic stimulation (rTMS) by use of high-frequency (10 Hz) left-side dorsolateral prefrontal cortex stimulation is an evidence-based treatment for this disorder. Intermittent theta burst stimulation (iTBS) is a newer form of rTMS that can be delivered in 3 min, versus 37·5 min for a standard 10 Hz treatment session. We aimed to establish the clinical effectiveness, safety, and tolerability of iTBS compared with standard 10 Hz rTMS in adults with treatment-resistant depression.

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] Recently intermittent theta burst stimulation (iTBS) proved to be non-inferior to conventional repetitive transcranial magnetic stimulation (10 Hz rTMS) in unipolar depression after failure of one antidepressant trial, but to date no randomized control trial assessed the ability of iTBS to improve depression level and quality of life in more resistant features of depression with a long-term (6 month) follow-up in comparison to 10 Hz rTMS.

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] Intermittent theta burst stimulation (iTBS) is a newer form of repetitive transcranial magnetic stimulation (rTMS) for patients with treatment resistant depression (TRD). Applying multiple daily iTBS sessions may enable patients to achieve remission more rapidly.

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] Our meta-analysis demonstrated that intermittent theta burst stimulation (iTBS)/bilateral-TBS (Bi-TBS) and high-frequency repetitive transcranial magnetic stimulation (HF-rTMS)/bilateral-rTMS (Bi-rTMS) had similar efficacy, acceptability, and safety profiles for antidepressant treatment-resistant major depressive disorder (AD-TRD). In our sensitivity analysis that excluded a study that compared Bi-TBS with Bi-rTMS for older adults, all efficacy outcomes were also comparable between iTBS and HF-rTMS. Because iTBS does not require higher stimulation intensity and a longer stimulus time than conventional HF-rTMS protocols, we speculated that for those with AD-TRD, iTBS/Bi-TBS is a more helpful therapeutic modality in clinical practice than HF-rTMS/Bi-rTMS.

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] Repetitive transcranial magnetic stimulation (rTMS) is an evidence-based treatment for depression that is increasingly implemented in healthcare systems across the world. A new form of rTMS called intermittent theta burst stimulation (iTBS) can be delivered in 3 min and has demonstrated comparable effectiveness to the conventional 37.5 min 10Hz rTMS protocol in patients with depression.