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

Trial Summary

What is the purpose of this trial?

This trial is testing if a device called rTMS, which uses magnetic fields to stimulate the brain, can help people cope better with fear and anxiety. The magnetic field increases brain activity, which might improve their responses to anxiety-inducing situations. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive procedure that uses magnetic fields to stimulate nerve cells in the brain and has been explored for treating various psychiatric disorders, including depression and anxiety.

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 data supports the effectiveness of the treatment rTMS for anxiety disorders?

Research shows that repetitive transcranial magnetic stimulation (rTMS) can reduce anxiety and stress levels, as seen in studies where it decreased anxiety in patients with depression and reduced physiological arousal related to fear and anxiety. These findings suggest that rTMS may help manage anxiety disorders by calming overactive brain areas linked to anxiety. ^{1 2 3 4 5}

Is rTMS safe for humans?

Repetitive transcranial magnetic stimulation (rTMS) is generally considered safe for humans, with studies showing it can reduce anxiety and stress in some cases. However, there are reports of rTMS inducing anxiety in some individuals, so it's important to discuss potential risks with a healthcare provider. ^{1 2 4 6 7}

How does rTMS treatment for anxiety disorders differ from other treatments?

rTMS (repetitive transcranial magnetic stimulation) is unique because it is a non-invasive treatment that uses magnetic fields to modulate brain activity, specifically targeting areas like the intraparietal sulcus to reduce anxiety. Unlike traditional medications, it directly influences brain connectivity and excitability, offering a novel approach for those who may not respond well to neuropharmacological treatments. ^{1 2 3 5 8}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 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]

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]

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 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]

References

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

Low-frequency parietal repetitive transcranial magnetic stimulation reduces fear and anxiety. [2022]

2. Austria pubmed.ncbi.nlm.nih.gov

Emotional processing and rTMS: does inhibitory theta burst stimulation affect the human startle reflex? [2018]

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

Effects of slow rTMS at the right dorsolateral prefrontal cortex on EEG asymmetry and mood. [2019]

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

Repetitive Transcranial Magnetic Stimulation: Influence on Stress and Early Responsiveness Outcomes for Depression, Anxiety, and Stress. [2022]

5. Ireland 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. [2008]

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

Anxiolytic suppression of repetitive transcranial magnetic stimulation-induced anxiety in the rats. [2013]

7. 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]

8. Switzerland pubmed.ncbi.nlm.nih.gov

The Effects of Functionally Guided, Connectivity-Based rTMS on Amygdala Activation. [2021]