Transcranial Magnetic Stimulation for Depression and Anxiety

Overseen By Alma Figueroa

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Pennsylvania

Must not be taking: Psychoactive medications

Disqualifiers: Bipolar, Schizophrenia, Neurological disorder, 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: 9

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial aims to help people who experience negative emotions by using a special treatment to reduce these feelings.

Will I have to stop taking my current medications?

The trial excludes participants who have recently used psychoactive medications or substances, so you may need to stop taking certain medications before joining. The protocol does not specify a washout period, but it's best to discuss your current medications with the study team.

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

Research shows that repetitive transcranial magnetic stimulation (rTMS) is effective for treating major depressive disorder, and there is some evidence suggesting it may also help with anxiety symptoms in patients with 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, with common side effects being mild, such as headaches and local pain. However, there is a small risk of more serious effects like seizures, especially in older adults or those with specific conditions. ^{3 6 7 8 9}

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

Repetitive transcranial magnetic stimulation (rTMS) is unique because it uses magnetic fields to stimulate specific areas of the brain, unlike medications that work through chemical changes. It is non-invasive and typically targets the left dorsolateral prefrontal cortex, showing promise for both depression and anxiety, especially in cases where other treatments have failed. ^{2 10 11 12 13}

Research Team

Desmond Oathes, PhD

Principal Investigator

Assistant Professor of Psychiatry

Eligibility Criteria

This trial is for adults aged 18-65 with moderate to severe depression or anxiety, as indicated by a PHQ-9 score of 10 or higher. Participants must be right-handed, understand English instructions, and can consent and commit to the study duration. Exclusions include bipolar disorder, psychotic disorders, recent psychoactive substance use, neurological issues preventing MRI scans or TMS treatment.

Inclusion Criteria

I understand the study and can follow its procedures.

Availability for the duration of the study

I am between 18 and 65 years old.

Exclusion Criteria

Unable to have an MRI scan, or current or prior medical condition that could interfere with the collection or interpretation of MRI data

I have a history of a serious neurological disorder or traumatic brain injury.

Diagnosis of bipolar disorder, schizophrenia, or other psychotic disorder (at Principal Investigator discretion)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 visit

1 visit (in-person)

Baseline Assessment

Participants undergo MRI scans, facial EMG recordings, cognitive tasks, and complete multiple questionnaires

1 visit

1 visit (in-person)

TMS/fMRI Session

Participants engage in behavioral tasks while receiving interleaved rTMS rounds to determine optimal stimulation frequency

1 visit

1 visit (in-person)

Treatment Phase 1

Participants receive rTMS using either optimal or least optimal frequency, with worry induction or relaxation tasks

3 visits

3 visits (in-person)

Treatment Phase 2

Participants receive rTMS using counterbalanced frequencies from Phase 1, with worry induction or relaxation tasks

3 visits

3 visits (in-person)

Follow-up

Participants are monitored for changes in brain and behavioral responses after neuromodulation sessions

Up to 4 weeks

Treatment Details

Interventions

• Transcranial Magnetic Stimulation

Trial Overview The trial tests personalized brain stimulation using Transcranial Magnetic Stimulation (TMS) to reduce negative emotions in individuals with depression and anxiety. It involves creating unique emotional brain maps via fMRI and muscle activity data then applying tailored TMS sequences over six sessions across three days.

Participant Groups

Group I: Neuromodulation using the optimal rTMS stimulation frequency Experimental Treatment 1 Intervention

Through manipulation of brain state with a negative-affect task and using fMRI as the feedback signal, we aim to fine-tune repetitive Transcranial Magnetic Stimulation (rTMS) delivery to maximally impact the desired brain states in awake behaving study participants in a highly individualized manner (Visit 3: TMS/fMRI). The optimal rTMS stimulation frequency will be tested in a 3-day rTMS neuromodulation intervention.

Group II: Neuromodulation using the least optimal rTMS stimulation frequency Active Control 1 Intervention

We will compare the results of the optimal rTMS frequency neuromodulation with a separate 3-day neuromodulation session using the least optimal rTMS frequency, as determined by Visit 3: TMS/fMRI.

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?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Findings from Research

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]

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 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 a clinically safe and effective treatment for major depressive disorder, particularly for patients who have not responded to at least two antidepressant medications.

In a 3-year cost-effectiveness analysis, rTMS was found to provide greater quality-adjusted life-years (1.25 QALYs) at a lower cost compared to pharmacotherapy (1.18 QALYs), making it a more cost-effective option for treatment-resistant depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness of Repetitive Transcranial Magnetic Stimulation versus Antidepressant Therapy for Treatment-Resistant Depression. Nguyen, KH., Gordon, LG.[2015]

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 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) 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]

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]

In a study of 61 patients with treatment-resistant depression (TRD), repetitive transcranial magnetic stimulation (rTMS) showed significant improvements in anxiety and depression symptoms, with response rates of 17.1% for anxiety and 20.7% for depression.

Post-treatment assessments indicated medium to large effect sizes for anxiety and depression scales, suggesting that rTMS may be a valuable treatment option for patients with TRD, although further randomized controlled trials are needed to solidify clinical guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of repetitive transcranial magnetic stimulation on generalized anxiety disorder in treatment-resistant depression. Griffiths, C., O'Neill-Kerr, A., De Vai, R., et al.[2020]

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]

In a study of 32 adults with treatment-resistant major depressive disorder (MDD), both depression and anxiety symptoms significantly improved after repetitive transcranial magnetic stimulation (rTMS) treatment, indicating its efficacy.

Patients with anxious depression showed similar rates of improvement in depression compared to those without anxious depression, suggesting that anxious depression does not negatively impact the effectiveness of rTMS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating anxious depression using repetitive transcranial magnetic stimulation. Diefenbach, GJ., Bragdon, L., Goethe, JW.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

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

2. 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]

3. 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]

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

Cost-Effectiveness of Repetitive Transcranial Magnetic Stimulation versus Antidepressant Therapy for Treatment-Resistant Depression. [2015]

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

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

6. 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]

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. England pubmed.ncbi.nlm.nih.gov

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

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

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

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

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

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

Impact of repetitive transcranial magnetic stimulation on generalized anxiety disorder in treatment-resistant depression. [2020]

12. 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]

13. Netherlands pubmed.ncbi.nlm.nih.gov

Treating anxious depression using repetitive transcranial magnetic stimulation. [2018]