Brain Stimulation for Depression and Anxiety

(PORT Trial)

Recruiting in Palo Alto (17 mi)

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: Schizophrenia, Bipolar I, Epilepsy, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial compares intermittent theta-burst stimulation (iTBS) to low frequency repetitive transcranial magnetic stimulation (LFR) in regards to depression and anxiety outcomes in 100 patients with treatment resistant depression (TRD).

Will I have to stop taking my current medications?

The trial requires that if you are taking psychotropic medication, you must be on a stable dose for 4 weeks before starting treatment, and you cannot start any new regular psychotropic medication.

What data supports the effectiveness of the treatment rTMS for depression and anxiety?

Research shows that repetitive transcranial magnetic stimulation (rTMS) is effective in treating depression, with studies indicating it can lead to significant mood improvements. Clinical trials have demonstrated that high-frequency rTMS applied to specific brain areas is more effective than placebo treatments, and it has been confirmed in large-scale studies and meta-analyses. ^{1 2 3 4 5}

Is repetitive transcranial magnetic stimulation (rTMS) safe for humans?

Repetitive transcranial magnetic stimulation (rTMS) is generally considered safe for humans when used within recommended guidelines. Common side effects are usually minor, such as headaches, and there is a low risk of seizures, which can be minimized by screening for risk factors. ^{5 6 7 8 9}

How is the treatment rTMS different from other treatments for depression and anxiety?

rTMS (repetitive transcranial magnetic stimulation) is unique because it uses magnetic fields to stimulate specific areas of the brain, unlike traditional treatments like medication or talk therapy. It is particularly novel for anxiety as it targets brain regions involved in mood regulation, and studies suggest it can reduce anxiety symptoms by altering brain activity. ^{4 10 11 12 13}

Research Team

Fidel Vila-Rodriguez, MD, PhD

Principal Investigator

University of British Columbia

Eligibility Criteria

This trial is for adults over 18 with treatment-resistant depression, scoring ≥26 on the IDS-30-SR. Participants must not have changed or started new psychotropic medications in the last 4 weeks and must be able to follow the treatment schedule. They should pass a safety screening and consent voluntarily.

Inclusion Criteria

able to adhere to the treatment schedule;

pass the TMS adult safety screening (TASS) questionnaire

I haven't started or increased any mental health medications in the last 4 weeks.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either intermittent theta-burst stimulation (iTBS) or low frequency repetitive transcranial magnetic stimulation (LFR) for depression and anxiety outcomes

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

Treatment Details

Interventions

• rTMS (Repetitive Transcranial Magnetic Stimulation)

Trial Overview The study is testing two types of brain stimulation: intermittent theta-burst stimulation (iTBS) versus low frequency repetitive transcranial magnetic stimulation (LFR). It aims to see which is more effective for improving symptoms of depression and anxiety in patients who haven't responded well to other treatments.

Participant Groups

Group I: Low Frequency Right (LFR) Active Control 1 Intervention

1Hz stimulation to the R-DLPFC

Group II: Intermittent Theta Burst Stimulation (iTBS) Active Control 1 Intervention

iTBS to the L-DLPFC

Who Is Running the Clinical Trial?

University of British Columbia

Lead Sponsor

Trials

1,506

Recruited

2,528,000+

Dr. Christopher Haqq

University of British Columbia

Chief Medical Officer since 2019

MD, University of British Columbia

Bekki Bracken Brown

University of British Columbia

Chief Executive Officer since 2023

Bachelor's degree from Duke University

Findings from Research

In a study of 329 subjects with major depressive disorder undergoing 6 weeks of repetitive transcranial magnetic stimulation (rTMS), a lack of early improvement in mood after 1 week was a strong predictor of nonresponse to treatment, especially in those with severe depression.

By 2 weeks, those with very severe depression who showed no improvement in mood were all identified as nonresponders, indicating that early monitoring of mood and sleep can guide treatment adjustments for better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Absence of early mood improvement as a robust predictor of rTMS nonresponse in major depressive disorder. Mirman, AM., Corlier, J., Wilson, AC., et al.[2022]

In a 6-month follow-up study of 31 patients with major depression who completed a 4-week rTMS trial, 63.64% of those who initially did not respond to treatment became late responders, indicating potential for continued improvement after treatment ends.

The study also found a low relapse rate of only 10% among those who initially responded to rTMS, with an overall high rate of maintained response at 90%, suggesting that rTMS can have lasting effects in treating major depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 6-month follow-up study on response and relapse rates following an acute trial of repetitive transcranial magnetic stimulation in patients with major depression. Arici, C., Benatti, B., Cafaro, R., et al.[2022]

In a study of 247 patients with major depressive disorder, repetitive transcranial magnetic stimulation (rTMS) achieved a high clinical remission rate of 72% within an average of 3.1 weeks, indicating its effectiveness in treating severe depression.

The study found that patients treated with the MagVenture rTMS instrument had greater remission rates compared to those treated with the NeuroStar instrument, suggesting that the choice of rTMS device and treatment parameters can influence clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation (rTMS) using different TMS instruments for major depressive disorder at a suburban tertiary clinic. Davila, MC., Ely, B., Manzardo, AM.[2020]

Repetitive transcranial magnetic stimulation (rTMS) has been shown to have antidepressant efficacy, particularly with high-frequency stimulation of the left dorsolateral prefrontal cortex, confirmed by large-scale clinical trials and meta-analyses.

Alternative rTMS methods, such as low-frequency stimulation of the right prefrontal cortex and novel techniques like theta-burst stimulation, show promise but need further research to establish their effectiveness and long-term benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of repetitive transcranial magnetic stimulation in the treatment of depression. Fitzgerald, PB., Daskalakis, ZJ.[2010]

Transcranial Magnetic Stimulation (TMS), particularly repetitive TMS (rTMS) over the frontal cortex, has been shown to be clinically effective in treating depression, with numerous trials supporting its therapeutic potential over the past two decades.

Despite its effectiveness, there is currently no widely accepted 'gold standard' protocol for rTMS treatment, highlighting the need for further research to optimize factors such as localization, frequency, and intensity for better efficacy and tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

UNANSWERED QUESTIONS IN THE TRANSCRANIAL MAGNETIC STIMULATION TREATMENT OF PATIENTS WITH DEPRESSION. Morvai, S., Nagy, A., Kovács, A., et al.[2019]

In a study involving 18 subjects with major depression, repetitive transcranial magnetic stimulation (rTMS) for up to 4 weeks was found to be generally safe, with no significant mean deficits in neuropsychologic function or auditory thresholds.

However, two patients experienced mild high-frequency hearing loss, indicating that while rTMS is safe for most, individual responses may vary and warrant further investigation into long-term safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of a 2- to 4-week course of repetitive transcranial magnetic stimulation (rTMS) on neuropsychologic functioning, electroencephalogram, and auditory threshold in depressed patients. Loo, C., Sachdev, P., Elsayed, H., et al.[2019]

Repetitive transcranial magnetic stimulation (rTMS) has gained popularity for its ability to modulate brain activity, but safety considerations are crucial, especially with the recent updates to safety guidelines published in 2021.

The guidelines emphasize the importance of screening for risks, monitoring for adverse events, and specific safety measures when using rTMS, particularly in patients with conditions like stroke and traumatic brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. Kim, WS., Paik, NJ.[2023]

Repetitive Transcranial Magnetic Stimulation (rTMS) has a good overall safety profile for treating depression, with common side effects like headaches being minor and manageable.

While there is a low incidence of serious side effects such as seizures and hypomania, these are linked to specific risk factors, suggesting that proper screening can enhance patient safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of the safety of repetitive transcranial magnetic stimulation as a clinical treatment for depression. Loo, CK., McFarquhar, TF., Mitchell, PB.[2021]

Repetitive transcranial magnetic stimulation (rTMS) shows potential anxiolytic effects based on a systematic review of existing studies, although many lacked placebo controls and used varied treatment protocols.

Inhibitory rTMS targeting the prefrontal cortex has demonstrated beneficial effects in healthy individuals and patients with conditions like PTSD and panic disorder, suggesting it may help correct imbalances in brain activity associated with anxiety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anxiolytic effects of transcranial magnetic stimulation--an alternative treatment option in anxiety disorders? Zwanzger, P., Fallgatter, AJ., Zavorotnyy, M., et al.[2021]

In a study involving 388 participants, both high-frequency rTMS (10 Hz) and intermittent theta-burst stimulation (iTBS) significantly reduced anxiety symptoms in patients with major depressive disorder, as measured by the Hamilton Depression Rating Scale and the Brief Symptom Inventory.

The results showed no significant difference in anxiety reduction between the two stimulation methods, indicating that both are effective options for treating anxiety symptoms alongside depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of repetitive transcranial magnetic stimulation on anxiety symptoms in patients with major depression: An analysis from the THREE-D trial. Trevizol, AP., Downar, J., Vila-Rodriguez, F., et al.[2021]

Repetitive transcranial magnetic stimulation (rTMS) has been primarily used to treat major depressive disorder (MDD), highlighting its importance in addressing a significant global health challenge.

Recent advancements in rTMS include exploring new stimulation patterns, targets, and personalized treatment approaches, which aim to enhance the effectiveness and response rates of rTMS in treating MDD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation treatment for depressive disorders: current knowledge and future directions. Baeken, C., Brem, AK., Arns, M., et al.[2020]

In a study with 12 participants, slow repetitive transcranial magnetic stimulation (rTMS) applied to the right dorsolateral prefrontal cortex led to a significant increase in EEG theta activity in the left hemisphere, indicating a potential mechanism of action for mood improvement.

Participants experienced a notable decrease in anxiety immediately after rTMS and at 35 and 65 minutes post-treatment, suggesting that this non-invasive intervention may effectively reduce anxiety symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of slow rTMS at the right dorsolateral prefrontal cortex on EEG asymmetry and mood. Schutter, DJ., van Honk, J., d'Alfonso, AA., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Absence of early mood improvement as a robust predictor of rTMS nonresponse in major depressive disorder. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

A 6-month follow-up study on response and relapse rates following an acute trial of repetitive transcranial magnetic stimulation in patients with major depression. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation (rTMS) using different TMS instruments for major depressive disorder at a suburban tertiary clinic. [2020]

4. England pubmed.ncbi.nlm.nih.gov

The effects of repetitive transcranial magnetic stimulation in the treatment of depression. [2010]

5. Hungary pubmed.ncbi.nlm.nih.gov

UNANSWERED QUESTIONS IN THE TRANSCRANIAL MAGNETIC STIMULATION TREATMENT OF PATIENTS WITH DEPRESSION. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation (TMS) safety: a practical guide for psychiatrists. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Effects of a 2- to 4-week course of repetitive transcranial magnetic stimulation (rTMS) on neuropsychologic functioning, electroencephalogram, and auditory threshold in depressed patients. [2019]

8. Korea (South) pubmed.ncbi.nlm.nih.gov

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. [2023]

9. England pubmed.ncbi.nlm.nih.gov

A review of the safety of repetitive transcranial magnetic stimulation as a clinical treatment for depression. [2021]

10. Austria pubmed.ncbi.nlm.nih.gov

Anxiolytic effects of transcranial magnetic stimulation--an alternative treatment option in anxiety disorders? [2021]

11. United States pubmed.ncbi.nlm.nih.gov

Effect of repetitive transcranial magnetic stimulation on anxiety symptoms in patients with major depression: An analysis from the THREE-D trial. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation treatment for depressive disorders: current knowledge and future directions. [2020]

13. England pubmed.ncbi.nlm.nih.gov

Effects of slow rTMS at the right dorsolateral prefrontal cortex on EEG asymmetry and mood. [2019]