TMS for Depression and Anxiety

Overseen By Emily Gittle, BS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Jing Jiang

Must not be taking: Opiates, Antihypertensives, Blood flow meds

Disqualifiers: Epilepsy, Metal implants, Heart disease, Pregnancy, 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: 2

97 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to examine the neural mechanisms underlying transcranial magnetic stimulation (TMS) using concurrent functional magnetic resonance imaging (fMRI) in both healthy controls (HCs) and patients with high negative affect symptoms, such as depression and anxiety. Approximately half male and half female participants aged 18-65 will be recruited. The main questions it aims to answer are: 1. Is the acute/transient effect induced by single-pulse TMS related to the long-term modulatory effect induced by repetitive TMS (rTMS)? 2. Do any of these effects predict negative affect symptoms, such as depression and anxiety? Participants will: 1. Complete several tests to assess their cognitive abilities and emotional states 2. Undergo several brain scans, including resting-state fMRI, structural MRI, diffusion tensor imaging (DTI), and task fMRI 3. Have two different types of TMS sequences, single-pulse and repetitive pulses, administered to specific brain regions while undergoing fMRI

Will I have to stop taking my current medications?

The trial requires that you stop taking opiate medications, antihypertensive medications, or any medication that interferes with blood flow, as these can affect the fMRI recordings.

What data supports the effectiveness of the treatment spTMS-TBS-spTMS for depression and anxiety?

Research shows that theta burst stimulation (TBS), a type of repetitive transcranial magnetic stimulation (rTMS), is effective in treating depression. Studies have found that TBS is more efficient in terms of time and energy compared to standard rTMS, and it has been used successfully as an additional therapy to standard treatments for major depression. ^{1 2 3 4 5}

Is TMS generally safe for humans?

There is no relevant safety information about TMS for depression and anxiety in the provided research articles. ^{6 7 8 9 10}

How is the spTMS-TBS-spTMS treatment for depression and anxiety different from other treatments?

The spTMS-TBS-spTMS treatment is unique because it combines single-pulse transcranial magnetic stimulation (spTMS), theta burst stimulation (TBS), and repetitive transcranial magnetic stimulation (rTMS) to potentially offer faster and more efficient relief from depression and anxiety compared to traditional rTMS. TBS, in particular, is a novel pattern that allows for shorter treatment sessions with lower intensity, making it a promising alternative for those who have not responded to other treatments. ^{1 2 11 12 13}

Eligibility Criteria

This trial is for men and women aged 18-65, both healthy individuals and those experiencing symptoms of depression or anxiety. Participants must be able to complete cognitive tests and undergo brain scans. Specific criteria for joining or being excluded from the study are not provided.

Inclusion Criteria

I have been diagnosed with major depression or anxiety.

I understand and agree to participate in research.

Exclusion Criteria

I have been diagnosed with epilepsy or a seizure disorder.

Presence of implanted ferromagnetic equipment in face or skull near the stimulation target

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Baseline Assessment

Participants complete cognitive and emotional tests and undergo initial brain scans to determine TMS locations

1 visit (2 hours)

1 visit (in-person)

TMS-fMRI Sessions

Participants undergo TMS-fMRI sessions including single-pulse and theta-burst stimulation to assess neural mechanisms

1 visit (1 hour)

1 visit (in-person)

Follow-up

Participants are monitored for any changes in cognitive/emotional states and brain connectivity post-intervention

1 week

Treatment Details

Interventions

• spTMS-TBS-spTMS

Trial Overview The study investigates how single-pulse TMS affects the brain immediately and how repetitive TMS can have long-term effects, using fMRI scans. It also explores whether these effects can predict negative emotions like depression or anxiety in participants.

Participant Groups

Group I: spTMS-TBS-spTMS Experimental Treatment 1 Intervention

This is an open-label, single-arm study. The intervention will be delivered in spTMS-TBS-spTMS order to the dorsolateral prefrontal cortex (dlPFC) and vertex for each participant as described in the "Interventions" section. The order of the stimulation sites will be counterbalanced across participants.

spTMS-TBS-spTMS is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Transcranial Magnetic Stimulation (TMS) for:

• Major Depressive Disorder (MDD)
• Anxiety Disorders

Approved in European Union as Transcranial Magnetic Stimulation (TMS) for:

• Major Depressive Disorder (MDD)
• Anxiety Disorders
• Neuropathic Pain

Approved in Canada as Transcranial Magnetic Stimulation (TMS) for:

• Major Depressive Disorder (MDD)
• Anxiety Disorders

Who Is Running the Clinical Trial?

Jing Jiang

Lead Sponsor

Trials

1

Recruited

100+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Findings from Research

In a study involving 300 patients with treatment-resistant depression, accelerated bilateral theta burst stimulation (TBS) was found to be effective and safe, with a treatment response rate of 43.7% and a remission rate of 28.2%.

The study revealed no significant differences in efficacy between different TBS intensities or when compared to traditional unilateral 10 Hz rTMS, indicating that the accelerated TBS does not provide faster antidepressant effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated theta burst stimulation for the treatment of depression: A randomised controlled trial. Chen, L., Thomas, EHX., Kaewpijit, P., et al.[2022]

In a randomized-controlled trial involving 32 patients with major depression, bilateral theta burst stimulation (TBS) to the dorsolateral prefrontal cortex showed a significant increase in treatment response compared to sham stimulation, with 9 responders in the TBS group versus 4 in the sham group.

The study also indicated a trend towards higher remission rates in the TBS group as measured by the Beck Depression Inventory, suggesting that TBS may enhance the effectiveness of ongoing medication and psychotherapy in treating major depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of major depression with bilateral theta burst stimulation: a randomized controlled pilot trial. Plewnia, C., Pasqualetti, P., Große, S., et al.[2018]

In a study of 54 patients with major depression, the combination of intermittent theta burst stimulation (iTBS) and low-frequency rTMS (LF-rTMS) significantly improved depression and anxiety symptoms more than high-frequency rTMS (HF-rTMS).

The results suggest that iTBS combined with LF-rTMS may be a promising alternative therapy for major depression, offering both efficacy and time-saving benefits compared to traditional methods.

NCBI (Pubmed)

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. Mi, Y., Ji, Y., Lou, Z., et al.[2022]

Theta burst stimulation (TBS) is as effective and safe as standard repetitive transcranial magnetic stimulation (rTMS) for treating depression, based on a meta-analysis of nine randomized controlled trials involving 1124 patients.

The study found no significant differences in response rates or adverse events between TBS and rTMS, suggesting that TBS could be a viable alternative due to its shorter treatment sessions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Theta Burst vs Repetitive Transcranial Magnetic Stimulation for the Treatment of Depression: A Meta-Analysis of Randomized Controlled Trials. Liu, C., Li, L., Li, B., et al.[2023]

In a randomized controlled trial involving 56 patients with moderate to severe depression, bilateral theta-burst stimulation (TBS) and repetitive transcranial magnetic stimulation (rTMS) did not show significant improvements in depression scores compared to sham treatment.

However, there was a noted tendency for both active treatments to increase the responder rate, particularly for the TBS group, suggesting that further research may be needed to explore its potential benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bilateral prefrontal rTMS and theta burst TMS as an add-on treatment for depression: a randomized placebo controlled trial. Prasser, J., Schecklmann, M., Poeppl, TB., et al.[2015]

In a meta-analysis of 15 clinical trials involving 2458 patients, serotonin-norepinephrine reuptake inhibitors (SNRIs) demonstrated the highest remission rate for major depressive disorder at 49.0%, outperforming tricyclic antidepressants (TCAs) at 44.1% and selective serotonin-reuptake inhibitors (SSRIs) at 37.7%.

SNRIs also had the lowest dropout rates due to adverse drug reactions (ADRs) and lack of efficacy (LoE), indicating a better safety profile compared to TCAs and SSRIs, which suggests that SNRIs may be a more effective and tolerable treatment option for patients with major depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remission, dropouts, and adverse drug reaction rates in major depressive disorder: a meta-analysis of head-to-head trials. Machado, M., Iskedjian, M., Ruiz, I., et al.[2022]

In a study of 53,042 patients treated with antidepressants, the overall incidence of severe adverse drug reactions (ADRs) was found to be 1.4%, with tricyclic antidepressants (TCAs) showing the highest rates of severe ADRs at 1.0%.

Specific risks associated with TCAs included toxic delirium and seizures, while SSRIs were linked to psychiatric and neurological ADRs, particularly hyponatremia, which occurred in 64% of cases, highlighting the need for monitoring serum sodium levels in high-dose therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe adverse drug reactions of antidepressants: results of the German multicenter drug surveillance program AMSP. Degner, D., Grohmann, R., Kropp, S., et al.[2022]

The AMSP study, involving 29 hospitals and assessing adverse drug reactions (ADRs) in psychiatric inpatients, found that severe ADRs occurred in 1.84% of 48,564 patients, highlighting the importance of continuous drug safety monitoring in psychiatric treatment.

Both tricyclic antidepressants (TCA) and selective serotonin reuptake inhibitors (SSRI) showed similar overall rates of severe ADRs (1.7% for SSRI and 1.5% for TCA), but the types of ADRs differed, with TCAs causing more toxic delirium and liver enzyme increases, while SSRIs were associated with psychic and neurologic issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of adverse drug reactions in psychiatric inpatients with the AMSP drug safety program: methods and first results for tricyclic antidepressants and SSRI. Grohmann, R., Rüther, E., Engel, RR., et al.[2022]

Tandospirone is shown to be safe and effective for treating social anxiety disorder (SAD) in adolescents, demonstrating significant improvements in anxiety scores over 8 weeks of treatment.

The efficacy of tandospirone is comparable to that of sertraline, with response rates of 48.6% for tandospirone and 55.6% for sertraline, indicating that it can be a viable alternative to first-line treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical evaluation of the efficacy and safety of tandospirone versus sertraline monotherapy for social anxiety disorder: a randomized open-label trial. Huang, X., Li, C., Li, WH., et al.[2022]

The study developed a Serotonergic Expanded Bioactivity Matrix (SEBM) to evaluate the role of 71 serotonergic drugs in serotonin syndrome (SS) using data from various public databases, highlighting the need for a systematic approach to assess serotonergic adverse drug events.

Drugs that interact with three different serotonin receptors showed a significantly higher incidence of serotonin syndrome cases, while 5-HT agonists were associated with a lower risk, suggesting that off-target receptor activity may influence the severity and clinical presentation of toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implications of Off-Target Serotoninergic Drug Activity: An Analysis of Serotonin Syndrome Reports Using a Systematic Bioinformatics Approach. Culbertson, VL., Rahman, SE., Bosen, GC., et al.[2020]

Theta burst stimulation (TBS), a novel form of repetitive transcranial magnetic stimulation (rTMS), shows promise as an effective treatment for major depression, with evidence supporting its non-inferiority to traditional rTMS based on a systematic review of studies.

TBS has demonstrated antidepressant effects and is considered a viable alternative for treatment-resistant depression, although further research is needed to fully understand its physiological effects and optimize treatment parameters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is theta burst stimulation ready as a clinical treatment for depression? Chen, L., Chung, SW., Hoy, KE., et al.[2020]

Theta-burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (rTMS), has been shown to be effective in treating major depression, with a response rate effect size of 0.38 and a remission rate effect size of 0.20 based on a meta-analysis of 10 studies involving 591 participants.

TBS is not only effective but also has a favorable safety profile, showing no major adverse events, and is more efficient in terms of time and energy compared to standard rTMS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of theta-burst stimulation for major depression: A systematic review and meta-analysis. Chu, HT., Cheng, CM., Liang, CS., et al.[2021]

In a study involving 74 outpatients with major depressive disorder, intensive theta burst stimulation (TBS) showed similar efficacy to standard repetitive transcranial magnetic stimulation (rTMS) in reducing depressive symptoms, with no significant differences in response or remission rates between the two treatments.

Both treatment methods had limited overall response rates and no significant side effects, indicating that while TBS is a faster method, it does not provide quicker clinical benefits compared to standard rTMS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot investigation of an intensive theta burst stimulation protocol for patients with treatment resistant depression. Fitzgerald, PB., Chen, L., Richardson, K., et al.[2020]

References

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

Accelerated theta burst stimulation for the treatment of depression: A randomised controlled trial. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Treatment of major depression with bilateral theta burst stimulation: a randomized controlled pilot trial. [2018]

3. 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]

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

Efficacy and Safety of Theta Burst vs Repetitive Transcranial Magnetic Stimulation for the Treatment of Depression: A Meta-Analysis of Randomized Controlled Trials. [2023]

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

Bilateral prefrontal rTMS and theta burst TMS as an add-on treatment for depression: a randomized placebo controlled trial. [2015]

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

Remission, dropouts, and adverse drug reaction rates in major depressive disorder: a meta-analysis of head-to-head trials. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Severe adverse drug reactions of antidepressants: results of the German multicenter drug surveillance program AMSP. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

Assessment of adverse drug reactions in psychiatric inpatients with the AMSP drug safety program: methods and first results for tricyclic antidepressants and SSRI. [2022]

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

Clinical evaluation of the efficacy and safety of tandospirone versus sertraline monotherapy for social anxiety disorder: a randomized open-label trial. [2022]

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

Implications of Off-Target Serotoninergic Drug Activity: An Analysis of Serotonin Syndrome Reports Using a Systematic Bioinformatics Approach. [2020]

11. England pubmed.ncbi.nlm.nih.gov

Is theta burst stimulation ready as a clinical treatment for depression? [2020]

12. England pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of theta-burst stimulation for major depression: A systematic review and meta-analysis. [2021]

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

A pilot investigation of an intensive theta burst stimulation protocol for patients with treatment resistant depression. [2020]