rTMS for Anxiety Disorders

Overseen By Christopher T Sege, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Medical University of South Carolina

Must not be taking: Anticholinergics, Neuroleptics, Sedatives, Opiates

Disqualifiers: Substance use disorder, Psychotic disorder, 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: 3

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a device using magnetic pulses to alter brain activity can help individuals manage anxiety-provoking situations. It does not serve as a treatment study but aims to enhance future anxiety treatments. Participants must have begun treatment for anxiety or related issues such as PTSD or OCD and must be able to understand and consent to the study. The trial includes three visits, during which participants will respond to emotional pictures and situations while researchers measure their brain activity. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could shape future anxiety treatments.

Will I have to stop taking my current medications?

The trial requires that you stop taking anticholinergic, neuroleptic, sedative/hypnotic, chronic opiate medications, or naltrexone. However, you can continue taking SSRIs, cholinesterase inhibitors, or NMDA receptor antagonists if you've been on a stable dose for at least four weeks before joining the study.

What prior data suggests that this device is safe for use in anxiety studies?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) is generally safe for people. Studies indicate it can be safely used for those with anxiety disorders. Common side effects are usually minor and manageable, while serious side effects are rare and often preventable.

One study found that rTMS is safe for treating generalized anxiety disorder, with no significant serious side effects reported. Additionally, the FDA has approved rTMS for other conditions like obsessive-compulsive disorder and migraines, suggesting it has a good safety record in various situations.

Overall, evidence suggests that rTMS is well-tolerated and safe for people with anxiety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the use of repetitive transcranial magnetic stimulation (rTMS) for treating anxiety disorders because it offers a novel approach that differs from traditional therapies like medication and talk therapy. Unlike these standard treatments, rTMS targets specific brain regions directly, using magnetic fields to modulate neural activity. This technique could potentially provide quicker relief from anxiety symptoms by directly influencing the ventromedial prefrontal cortex and the pre-supplementary motor area, which are key areas involved in emotion regulation. Additionally, rTMS is non-invasive and may be used when other treatments are ineffective or cause unwanted side effects.

What evidence suggests that rTMS is effective for anxiety?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) can help reduce anxiety symptoms. This technique uses magnetic fields to stimulate brain areas that affect mood and fear. Some studies found that rTMS can lower anxiety in people with depression, including reducing panic-related symptoms. It has also relieved anxiety in people with Parkinson's disease. While most research has focused on its impact on depression, these findings suggest that rTMS might also manage anxiety effectively. Participants in this trial will receive rTMS targeting different brain areas to assess its effectiveness for anxiety disorders. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 who are fluent in English, currently seeking mental health treatment, and diagnosed with an anxiety disorder or related condition. It's not suitable for those on certain medications, pregnant individuals, people with metal implants (due to MRI), history of seizures or severe brain injury, substance abuse issues, psychotic disorders or bipolar mania.

Inclusion Criteria

Is currently seeking mental health treatment

I have been diagnosed with an anxiety disorder or PTSD.

Is able to read consent document and provide informed consent

Exclusion Criteria

Current alcohol or substance use disorder of more than mild severity (as defined by DSM-5 and determined using standardized self-report instruments)

Lifetime diagnosis of psychotic disorder or bipolar mania

I do not have metal implants, am not pregnant, do not have claustrophobia, am not overly sensitive to noise, do not have a low seizure threshold, have never had a severe brain injury, and do not have a history of seizures or epilepsy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants complete interviews, surveys, and tasks involving emotional pictures while brain activation is measured

1 day

1 visit (in-person)

Neurostimulation

Participants receive rTMS and complete tasks before and after stimulation

2 days

2 visits (in-person)

Follow-up

Participants are monitored for changes in anxiety-related measures post-stimulation

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Modulating Anxious Coping

Trial Overview The study tests if repetitive Transcranial Magnetic Stimulation (rTMS) can influence coping mechanisms in anxious situations. Participants will undergo rTMS and perform tasks that measure their reaction to emotional stimuli over three visits lasting up to four hours each at the Medical University of South Carolina.

How Is the Trial Designed?

Group I: Neurostimulation Group Experimental Treatment 1 Intervention

On one study day, participants will complete experimental tasks during functional magnetic resonance imaging. On two other study days, participants will complete tasks before and after receiving repetitive transcranial magnetic stimulation (rTMS). All participants will receive rTMS to ventromedial prefrontal cortex on one study day, and to pre-supplementary motor area on another study day. Two stimulation procedures will be used, one for ventromedial prefrontal cortex and one for pre-supplementary motor area. For both targets, 3 sessions of 600 pulses at 110% of resting motor threshold will be presented over 30 minutes. For ventromedial cortex, a session will involve intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds. For pre-supplementary motor area, a session will involve continuous theta burst presented in 3-pulse bursts with 15 pulses/ sec.

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

A 10-day regimen of repetitive transcranial magnetic stimulation (rTMS) induced anxiety-like behaviors in normal rats, indicating that rTMS can serve as a model for studying anxiety.

Standard anxiolytic medications such as diazepam, alprazolam, and buspirone effectively suppressed the anxiety behaviors induced by rTMS, demonstrating the potential for rTMS to be used in research on anxiety treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anxiolytic suppression of repetitive transcranial magnetic stimulation-induced anxiety in the rats. Isogawa, K., Fujiki, M., Akiyoshi, J., et al.[2013]

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]

In a study involving 102 healthy participants, repetitive transcranial magnetic stimulation (rTMS) applied to the prefrontal cortex did not significantly alter the amygdala's response to emotional stimuli, suggesting limited direct effects on emotional processing.

However, the rTMS intervention showed a trend towards accelerated habituation to emotional stimuli, indicating potential effects on basic learning mechanisms rather than direct modulation of emotional responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emotional processing and rTMS: does inhibitory theta burst stimulation affect the human startle reflex? Vennewald, N., Winter, B., Limburg, K., et al.[2018]

Inhibitory repetitive transcranial magnetic stimulation (rTMS) targeting the intraparietal sulcus (IPS) effectively reduced physiological arousal related to fear and anxiety during shock threat conditions, as evidenced by decreased startle responses in participants.

Although active rTMS did not show a difference in subjective anxiety ratings compared to sham stimulation, the findings suggest that modulating IPS excitability could be a promising approach for developing treatments for clinical anxiety disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-frequency parietal repetitive transcranial magnetic stimulation reduces fear and anxiety. Balderston, NL., Beydler, EM., Goodwin, M., et al.[2022]

In a study of 109 inpatients receiving rTMS for depression, significant reductions in depression, anxiety, and stress were observed from pre-treatment to post-treatment, with large effect sizes particularly noted for depression and stress.

Early improvements in depressive symptoms during rTMS treatment were predictive of better outcomes for depression and stress at the end of treatment, highlighting the importance of monitoring progress throughout the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation: Influence on Stress and Early Responsiveness Outcomes for Depression, Anxiety, and Stress. Badawi, A., Steel, Z., Wijesinghe, N., et al.[2022]

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]

This pilot study suggests that using task-related, connectivity-based rTMS can effectively modulate amygdala activation by targeting its connection with the medial prefrontal cortex, showing significant increases in both areas compared to sham treatment.

The approach of applying rTMS while participants viewed frightening video clips may enhance therapeutic effects by promoting brain plasticity, indicating a potential new method to improve treatment for psychiatric disorders linked to fronto-limbic dysregulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effects of Functionally Guided, Connectivity-Based rTMS on Amygdala Activation. Beynel, L., Campbell, E., Naclerio, M., et al.[2021]

A single session of right prefrontal rTMS significantly improved task performance in patients with acute major depression, suggesting its potential as a therapeutic tool.

The effects of rTMS varied based on the stimulation site and the severity of depression, indicating that personalized treatment approaches may be necessary for optimal outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of low-frequency transcranial magnetic stimulation on an affective go/no-go task in patients with major depression: role of stimulation site and depression severity. Bermpohl, F., Fregni, F., Boggio, PS., et al.[2008]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/18928340/

Repetitive transcranial magnetic stimulation as treatment ... It has been shown to be efficacious in the treatment for depression, but only to a limited degree.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165032725001685

Comorbid anxiety in depression and rTMS treatment ... Unilateral and bilateral rTMS reduced depressive and physical, subjective, and panic-related anxiety symptoms.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11913841/

A naturalistic analysis of rTMS treatment outcomes for ... A 4–7-week course of rTMS significantly reduce symptoms of self-reported depression (42.5% response) and clinician-assessed depression (40.7% response).

4. cochranelibrary.com cochranelibrary.com/cdsr/doi/10.1002/14651858.CD009083.pub2/pdf/full

Repetitive transcranial magnetic stimulation (rTMS) for ... Some studies have investigated the effect of. rTMS on patients with PD and observed a reduction in anxiety levels. The aim of this review was to combine the ...

5. mdpi.com mdpi.com/2076-3425/13/9/1289

A Hospital-Based Study in Oman This study aimed to investigate potential qualitative differences between two modes of repetitive transcranial magnetic stimulation (rTMS) ...

6. academic.oup.com academic.oup.com/ijnp/article/25/2/144/6427794

Repetitive Transcranial Magnetic Stimulation for Generalized ... Our literature search indicates the overall safety of TMS in those with GAD, and no significant serious adverse events were noted to be attributable to TMS ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6802976/

Efficacy and safety of repetitive transcranial magnetic ... The treatment had beneficial effects in the rTMS group compared with the control group in mean anxiety score (SMD=−0.68; 95% CI −0.89 to −0.46).

8. nimh.nih.gov nimh.nih.gov/news/media/2020/sarah-h-lisanby-transcranial-magnetic-stimulation-safety-and-risk

Sarah H. Lisanby: Transcranial Magnetic Stimulation Safety ... The safety profile of TMS is excellent. The common side effects tend to be minor and are easily managed. The serious side effects are rare and can be prevented ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0163834325001793

Effectiveness and safety of repetitive transcranial magnetic ... rTMS treatment can be safely applied in generalized anxiety disorder. •. rTMS combined with other treatments is more effective than single treatment in ...

10. mayoclinic.org mayoclinic.org/tests-procedures/transcranial-magnetic-stimulation/about/pac-20384625

Transcranial magnetic stimulation The FDA also approved TMS for obsessive-compulsive disorder (OCD), migraines and to help people stop smoking when standard treatments haven't ...