Transcranial Magnetic Stimulation for Depression

Overseen By Susan K Conroy, MD PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Indiana University

Must not be taking: Psychotropics

Disqualifiers: Suicidal, PTSD, OCD, Substance use, 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: 23

Duration: 4 weeks

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not require you to stop taking your current medications, but you must either be off psychotropic medications or on a stable dose for at least 6 weeks before starting the study and be willing to stay on that stable dose throughout the trial.

What data supports the effectiveness of the treatment Transcranial Magnetic Stimulation for Depression?

Research shows that repetitive transcranial magnetic stimulation (rTMS) is effective in treating major depression, especially in patients who have not responded to other treatments. Several studies, including randomized controlled trials, have demonstrated its efficacy in reducing symptoms of depression. ^{1 2 3 4 5}

Is transcranial magnetic stimulation (TMS) safe for humans?

Transcranial magnetic stimulation (TMS), including its repetitive form (rTMS), is generally considered safe for treating depression, though it can cause temporary side effects like headaches, local pain, and in rare cases, seizures. Safety studies have been conducted on both short-term and longer-term use, and expert recommendations exist to ensure its safe application. ^{6 7 8 9 10}

How is the treatment Transcranial Magnetic Stimulation (rTMS) for depression different from other treatments?

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 through chemical changes. It is a non-invasive procedure, meaning it doesn't require surgery or medication, and is typically used when other treatments like antidepressants haven't worked. ^{3 6 11 12 13}

What is the purpose of this trial?

The goal of this clinical trial is to learn if Transcranial Magnetic Stimulation (TMS) to part of the brain called the ventromedial prefrontal cortex (VMPFC) can treat a symptom called rumination in adults with major depression that has not responded to at least one medication trial. The main question it aims to answer are: Does TMS to the VMPFC change brain activity on functional magnetic resonance imaging (fMRI) during a negative self-referential processing task in adults with depression? Does TMS to the VMPFC affect rumination in adults with depression? Researchers will compare brain scans and rumination scores before, during, and immediately after TMS. Participants will: Undergo three functional MRI scans Undergo a course of 20 TMS treatments Respond to clinical questionnaires and complete a computer behavioral task

Research Team

Susan K Conroy, MD PhD

Principal Investigator

Indiana University School of Medicine

Eligibility Criteria

This trial is for adults with major depression that hasn't improved after at least one medication attempt. Participants will undergo brain scans and TMS treatments, and must be able to complete questionnaires and a computer task.

Inclusion Criteria

Ability to safely receive MRI

I am able to understand and agree to the study's requirements.

I am not on psychotropic drugs or have been on a stable dose for 6 weeks.

Exclusion Criteria

I have a history of seizures or take medication that could lower my seizure threshold.

Actively/imminently suicidal, Quick Inventory of Depressive Symptomatology (QIDS) item 12 score >2

Current depressive episode duration > 5 years

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person or virtual)

Baseline Assessment

Participants undergo self-report and clinician-administered assessments, as well as a baseline fMRI scan

1 week

1 visit (in-person or virtual)

Treatment

Participants receive 20 daily sessions of rTMS to the VMPFC along with weekly assessments

4 weeks

20 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including a telephone contact for adverse event assessment

2 weeks

1 contact (telephone)

Treatment Details

Interventions

• Transcranial Magnetic Stimulation

Trial Overview The study tests if Transcranial Magnetic Stimulation (TMS) targeting the VMPFC part of the brain can reduce rumination in treatment-resistant depression. It measures changes in brain activity and rumination through fMRI scans before, during, and after TMS sessions.

Participant Groups

Group I: Active TMS Experimental Treatment 1 Intervention

All participants will receive active TMS to the VMPFC for 20 sessions

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?

Indiana University

Lead Sponsor

Trials

1,063

Recruited

1,182,000+

National Center for Advancing Translational Sciences (NCATS)

Collaborator

Trials

394

Recruited

404,000+

Findings from Research

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]

Repetitive transcranial magnetic stimulation (rTMS) has been shown to have a clear clinical effect in treating major depressive disorder, particularly with left high-frequency rTMS, based on a review of 24 meta-analyses.

The study suggests that rTMS is a justified treatment option for some patients with depression, while also highlighting the need for further research on its efficacy in different stimulation methods and in patients who have not previously received medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A happiness magnet? Reviewing the evidence for repetitive transcranial magnetic stimulation in major depressive disorder. Pridmore, W., Pridmore, S.[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]

In a preliminary study involving four patients with relapsed major depressive disorder, rapid transcranial magnetic stimulation (rTMS) showed significant improvement in depression ratings after treatment.

The results indicated that rTMS can be effectively used again in patients who had previously responded well to this therapy, suggesting its potential for repeated use in managing relapsed depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation is effective in the treatment of relapse of depression. Dannon, PN., Schreiber, S., Dolberg, OT., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) showed a statistically significant but small improvement in depression scores compared to sham treatment, with a weighted mean difference of 2.31 points, which is below the clinically important threshold of 3.5 points.

In comparison to electroconvulsive therapy (ECT), rTMS was less effective, with ECT showing a greater improvement in depression scores and higher rates of remission and response, indicating that ECT may be a more effective option for treatment-resistant depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. [2022]

Repetitive transcranial magnetic stimulation (rTMS) has been shown to be a safe and effective treatment for major depressive disorder (MDD), supported by multiple randomized controlled trials and extensive literature review.

The consensus recommendations from a group of 17 expert clinicians and researchers provide detailed guidance on the clinical application of rTMS, ensuring its safe and effective use in treating MDD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Consensus Recommendations for the Clinical Application of Repetitive Transcranial Magnetic Stimulation (rTMS) in the Treatment of Depression. McClintock, SM., Reti, IM., Carpenter, LL., et al.[2022]

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]

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 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]

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]

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) has shown clinically relevant antidepressant effects, making it a promising treatment option for patients with therapy-resistant depression, who often have limited alternatives.

While rTMS should be introduced into clinical practice, it is essential to continue research and evaluation to ensure its effectiveness and manage patient expectations appropriately.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is it time to introduce repetitive transcranial magnetic stimulation into standard clinical practice for the treatment of depressive disorders? Fitzgerald, P.[2017]

References

1. 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]

2. England pubmed.ncbi.nlm.nih.gov

A happiness magnet? Reviewing the evidence for repetitive transcranial magnetic stimulation in major depressive disorder. [2021]

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

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

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

Transcranial magnetic stimulation is effective in the treatment of relapse of depression. [2022]

5. Canada pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. [2022]

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

Consensus Recommendations for the Clinical Application of Repetitive Transcranial Magnetic Stimulation (rTMS) in the Treatment of Depression. [2022]

7. 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]

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

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

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

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

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

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

12. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

Is it time to introduce repetitive transcranial magnetic stimulation into standard clinical practice for the treatment of depressive disorders? [2017]