TMS for Depression

(T5 Trial)

Overseen By Lauren Sanderson

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Brigham and Women's Hospital

Must not be taking: Ketamine, Esketamine, ECT, others

Disqualifiers: Pregnancy, Autism, Neurological illness, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 11

Duration: 1 week

10 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to test a new brain stimulation treatment target for individuals with depression plus at least one additional psychiatric disorder. The main question is to understand the safety profile of a non-invasive form of brain stimulation called accelerated intermittent theta burst stimulation when it is targeting the posterior parietal cortex. Additional questions focus on whether this stimulation improves symptoms of depression and other psychiatric disorders as well as whether this stimulation changes brain function.

Will I have to stop taking my current medications?

Participants must have a stable psychiatric medication regimen or be medication-free for 4 weeks before starting the trial and must continue this regimen throughout the study until two weeks after treatment.

What data supports the effectiveness of the treatment Transcranial Magnetic Stimulation (TMS) for depression?

Research shows that repetitive transcranial magnetic stimulation (rTMS) is generally well tolerated and more effective than a placebo treatment for depression, with some studies indicating improved outcomes over time. It has been found to be effective in both short-term and some long-term cases, especially in patients who have not responded to other treatments. ^{1 2 3 4 5}

Is Transcranial Magnetic Stimulation (TMS) safe for humans?

TMS, also known as rTMS, is generally considered safe for humans when used within recommended guidelines. Common side effects are minor, like headaches, but there is a low risk of seizures and mood changes, which can be managed by screening for risk factors. ^{6 7 8 9 10}

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

Repetitive transcranial magnetic stimulation (rTMS) is unique because it uses magnetic fields to stimulate nerve cells in the brain, which is different from medications that work chemically. It is a non-invasive procedure, meaning it doesn't require surgery or medication, and is often used when other treatments haven't worked. ^{3 5 11 12 13}

Research Team

Joseph J Taylor, MD, PhD

Principal Investigator

Brigham and Women's Hospital

Eligibility Criteria

This trial is for adults aged 18-65 with depression and another psychiatric disorder like anxiety, OCD, or PTSD. Participants must speak English well enough for consent and treatment, have a stable medication regimen or be medication-free for four weeks prior to the study, and show moderate to severe treatment resistance.

Inclusion Criteria

I have been diagnosed with PTSD.

My condition is hard to treat and has not responded well to treatments.

I am between 18 and 65 years old.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive accelerated intermittent theta burst stimulation (iTBS) targeting the posterior parietal cortex, with 10 sessions per day for 5 consecutive days

1 week

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at multiple intervals

12 months

6 visits (in-person)

Treatment Details

Interventions

• Transcranial Magnetic Stimulation

Trial Overview The trial tests accelerated intermittent theta burst stimulation using transcranial magnetic stimulation (TMS) on the posterior parietal cortex. It aims to assess safety, symptom improvement in depression and other disorders, as well as changes in brain function.

Participant Groups

Group I: Open-label aiTBS to posterior parietal cortex Experimental Treatment 1 Intervention

10 iTBS treatment sessions per day (18,000 pulses/day) for 5 consecutive days (90,000 pulses total). In the unlikely event that a participant is late for an hourly treatment, then the treatment will be delayed accordingly. The minimum gap between treatments will be 25 minutes. Each iTBS treatment will consist of 60 cycles of 10 bursts of three pulses at 50 Hz delivered in 2-second trains (5 Hz) with an 8-second intertrain interval. Stimulation will be delivered at 90% resting motor threshold (rMT), adjusted for depth of the identified functional connectivity target.

Transcranial Magnetic Stimulation is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Transcranial Magnetic Stimulation for:

• Major Depressive Disorder
• Obsessive Compulsive Disorder

Approved in Canada as Transcranial Magnetic Stimulation for:

• Major Depressive Disorder

Approved in European Union as Transcranial Magnetic Stimulation for:

• Major Depressive Disorder

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Findings from Research

Recent studies on repetitive transcranial magnetic stimulation (rTMS) for depression have demonstrated significantly improved clinical outcomes, with a pooled effect size of -0.76 from 5 studies involving 274 patients, compared to -0.35 from earlier studies.

The findings indicate that new parameters of rTMS stimulation may enhance its antidepressant effects, suggesting a potential advancement in treatment strategies for depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Has repetitive transcranial magnetic stimulation (rTMS) treatment for depression improved? A systematic review and meta-analysis comparing the recent vs. the earlier rTMS studies. Gross, M., Nakamura, L., Pascual-Leone, A., et al.[2018]

In a study comparing the effects of electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS) on major depression, both treatments showed similar outcomes at 3 and 6 months, with no significant differences in relapse rates or depression scores among the 41 patients involved.

Both treatment groups maintained low depression scores on the Hamilton Rating Scale and Global Assessment of Functioning, indicating that the benefits of rTMS are comparable to those of ECT over a 6-month period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three and six-month outcome following courses of either ECT or rTMS in a population of severely depressed individuals--preliminary report. Dannon, PN., Dolberg, OT., Schreiber, S., et al.[2019]

In a sham-controlled study involving 29 patients with depression (79% treatment-resistant), fast, left frontal repetitive transcranial magnetic stimulation (rTMS) was found to be more effective than sham treatment, with a response rate of 77% compared to 55% (P<0.05).

The treatment was generally well tolerated, and the improvements in depression symptoms were maintained for up to 12 weeks, suggesting that rTMS could be a valuable addition to existing depression therapies, although further research is needed to optimize treatment parameters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjunctive fast repetitive transcranial magnetic stimulation in depression. Anderson, IM., Delvai, NA., Ashim, B., et al.[2018]

In a study involving 59 patients with major depression, repetitive transcranial magnetic stimulation (rTMS) did not show significant effectiveness compared to sham treatment, with no meaningful differences in depression scores between the two groups.

While there were slightly higher response and remission rates in the real rTMS group (32% and 25%, respectively) compared to the sham group (10% for both), these differences were not statistically significant, indicating that rTMS may not provide a clear benefit over placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized controlled trial with 4-month follow-up of adjunctive repetitive transcranial magnetic stimulation of the left prefrontal cortex for depression. Mogg, A., Pluck, G., Eranti, SV., et al.[2022]

In a study involving 19 patients who had previously responded to rTMS, treatment for 30 episodes of depressive relapse showed significant improvement in symptoms, indicating its effectiveness for recurring depression.

The results suggest that rTMS maintains its efficacy over time, with patients benefiting from both low-frequency right-sided and high-frequency left-sided stimulation during their treatment courses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naturalistic study of the use of transcranial magnetic stimulation in the treatment of depressive relapse. Fitzgerald, PB., Benitez, J., de Castella, AR., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) is generally a well-tolerated treatment for depression, with mild side effects like headaches being the most common, while severe adverse effects are rare.

Special precautions are necessary for certain groups, such as adolescents, pregnant women, and individuals with metal implants, but with proper assessment and monitoring, rTMS can be safely administered to many patients with depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation (TMS) safety: a practical guide for psychiatrists. Taylor, R., Galvez, V., Loo, C.[2019]

A patient with treatment-resistant depression (TRD) showed unexpected improvement after experiencing a seizure during repetitive transcranial magnetic stimulation (rTMS), suggesting a potential link between seizure activity and therapeutic effects in TRD.

While rTMS is generally safe, known adverse events include headaches and seizures; this case highlights an unusual outcome where a seizure may have contributed to the patient's improvement, warranting further investigation into the mechanisms of rTMS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment-Resistant Depression Entering Remission Following a Seizure during the Course of Repetitive Transcranial Magnetic Stimulation. Kim, JW., Bae, KY., Kim, SW., et al.[2020]

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) is generally safe for older adults with late-life depression, with only 12.4% reporting any adverse events and serious adverse events occurring in just 1.5% of cases, based on a review of 11 studies involving 353 patients.

The most common adverse events were mild, such as headaches (6.9%) and discomfort at the stimulation site (2.7%), although some serious adverse events, including psychiatric hospitalization and increased suicidal ideation, were noted in case reports, highlighting the need for further research to ensure safety in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events of repetitive transcranial magnetic stimulation in older adults with depression, a systematic review of the literature. Overvliet, GM., Jansen, RAC., van Balkom, AJLM., et al.[2021]

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]

High-frequency rTMS targeting the left dorsolateral prefrontal cortex is an effective treatment for acute episodes of major depressive disorder, supported by over 20 years of clinical trials.

While rTMS is effective for unipolar and likely bipolar depression, there is limited evidence for its effectiveness in the maintenance phase of treatment, indicating a need for ongoing research and practitioner education.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the clinical use of repetitive transcranial magnetic stimulation in the treatment of depression. Fitzgerald, PB.[2021]

Repetitive transcranial magnetic stimulation (rTMS) is a promising therapy for depression that may selectively modulate neuronal activity with fewer side effects compared to electroconvulsive therapy (ECT).

While rTMS shows potential efficacy similar to ECT in open trials for non-psychotic depression, its benefits in double-blind studies are more modest, indicating that further optimization and research are needed to fully realize its therapeutic potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation in the treatment of mood disorder: a review and comparison with electroconvulsive therapy. Hasey, G.[2017]

High-frequency rTMS targeting the left dorsolateral prefrontal cortex is an effective treatment for major depressive disorder, supported by over 15 years of research and the authors' 10 years of clinical experience.

While other rTMS techniques, such as low-frequency stimulation to the right prefrontal cortex, show potential, they need further evaluation in larger trials to confirm their efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A practical guide to the use of repetitive transcranial magnetic stimulation in the treatment of depression. Fitzgerald, PB., Daskalakis, ZJ.[2022]

References

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

Has repetitive transcranial magnetic stimulation (rTMS) treatment for depression improved? A systematic review and meta-analysis comparing the recent vs. the earlier rTMS studies. [2018]

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

Three and six-month outcome following courses of either ECT or rTMS in a population of severely depressed individuals--preliminary report. [2019]

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

Adjunctive fast repetitive transcranial magnetic stimulation in depression. [2018]

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

A randomized controlled trial with 4-month follow-up of adjunctive repetitive transcranial magnetic stimulation of the left prefrontal cortex for depression. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Naturalistic study of the use of transcranial magnetic stimulation in the treatment of depressive relapse. [2022]

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

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

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

Treatment-Resistant Depression Entering Remission Following a Seizure during the Course of Repetitive Transcranial Magnetic Stimulation. [2020]

8. 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]

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

Adverse events of repetitive transcranial magnetic stimulation in older adults with depression, a systematic review of the literature. [2021]

10. England pubmed.ncbi.nlm.nih.gov

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

11. Netherlands pubmed.ncbi.nlm.nih.gov

An update on the clinical use of repetitive transcranial magnetic stimulation in the treatment of depression. [2021]

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

Transcranial magnetic stimulation in the treatment of mood disorder: a review and comparison with electroconvulsive therapy. [2017]

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

A practical guide to the use of repetitive transcranial magnetic stimulation in the treatment of depression. [2022]