TMS for PTSD

(rTMS for PTSD Trial)

Overseen By Korie Rice, MPH

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: VA Office of Research and Development

Must not be taking: Clozapine, Bupropion

Disqualifiers: Pregnancy, CNS disorder, Psychosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 6 weeks

91 Participants Needed

Trial Summary

What is the purpose of this trial?

Posttraumatic Stress Disorder (PTSD) is a common and serious condition affecting many Veterans. There are effective treatments for PTSD, but additional treatments are needed in order to better serve Veterans suffering from PTSD. Transcranial magnetic stimulation is one such promising treatment. It involves use of powerful magnet to stimulate the specific brain regions in Veterans with PTSD. Transcranial magnetic stimulation has been shown effective in treating depression, but currently it is unclear if it is an effective treatment for PTSD. This is a randomized clinical trial enrolling 91 Veterans with PTSD comparing the effectiveness of transcranial magnetic stimulation treatment and sham transcranial magnetic stimulation in treating PTSD. The hypothesis is that those who receive transcranial magnetic stimulation will experience improved functioning.

Will I have to stop taking my current medications?

The trial requires that you stop taking clozapine and limit bupropion to 300mg per day. Additionally, you should not have changed your dose of Fluoxetine, Paroxetine, Sertraline, or Venlafaxine in the past 2 months.

What data supports the effectiveness of this treatment for PTSD?

Research shows that repetitive transcranial magnetic stimulation (rTMS) can improve symptoms of PTSD and depression. In one study, both 1 Hz and 10 Hz rTMS led to significant improvements in PTSD and depression scores, although no clear advantage was found between the two frequencies. Another study found that rTMS may help with depression in people with PTSD, but it had minimal impact on core PTSD symptoms. ^{1 2 3 4 5}

Is transcranial magnetic stimulation (TMS) safe for humans?

TMS is generally considered safe for humans, but it can cause seizures, which are rare and often occur when guidelines are not followed or in individuals taking certain medications. Safety guidelines have been developed and updated over the years to minimize risks, and TMS has been used safely in thousands of people with various conditions. ^{3 6 7 8 9}

How does TMS 1 Hz treatment for PTSD differ from other treatments?

TMS 1 Hz is a non-invasive treatment that uses magnetic fields to stimulate the brain, specifically targeting the right prefrontal cortex at a low frequency. Unlike traditional therapies like medication or talk therapy, TMS directly influences brain activity and has shown promise in treating PTSD, especially for those who do not respond to standard treatments. ^{1 10 11 12 13}

Research Team

Bradley V Watts, MD MPH

Principal Investigator

White River Junction VA Medical Center, White River Junction, VT

Eligibility Criteria

This trial is for Veterans aged 19-70 with moderate to severe PTSD, eligible for VA healthcare. Participants must not be using certain medications like high-dose bupropion or clozapine, have no metal in their head (except dental work), no major CNS disorders, unstable medical conditions, recent seizures, or current psychosis. Women of childbearing potential must use birth control.

Inclusion Criteria

You are eligible for VA healthcare.

I am between 19 and 70 years old.

Moderate to severe PTSD as determined by the CAPS within 7 days of randomization

Exclusion Criteria

I do not have a major brain condition like a stroke, tumor, or epilepsy.

You have a problem with alcohol or drugs that affects your ability to take part in the study.

I have previously used TMS therapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive transcranial magnetic stimulation or sham treatment

6 weeks

Multiple visits for TMS sessions

Follow-up

Participants are monitored for PTSD symptoms, functioning, and depressive symptoms

6 months

Assessments at 3 and 6 months post-treatment

Treatment Details

Interventions

• Sham TMS
• TMS 1 hz

Trial Overview The study tests if Transcranial Magnetic Stimulation (TMS), a non-invasive method using magnets to stimulate the brain, can improve functioning in Veterans with PTSD compared to sham TMS. It's randomized and involves 91 participants who either receive real TMS or a placebo-like sham treatment.

Participant Groups

Group I: TMS Experimental Treatment 1 Intervention

transcranial magnetic stimulation delivered to the right dorsolateral prefrontal cortex at 1 Hz

Group II: Sham Placebo Group 1 Intervention

sham transcranial magnetic stimulation delivered to the right dorsolateral prefrontal cortex

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Findings from Research

In a trial involving 44 veterans with PTSD, both 1 Hz and 10 Hz rTMS treatments led to significant improvements in PTSD and depression symptoms after 6 weeks of treatment, but only the 10 Hz group showed notable improvements in functional outcomes.

No significant advantage was found between the two frequencies in terms of overall symptom reduction, suggesting that further research with larger sample sizes is needed to determine the most effective rTMS frequency for treating PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

One hertz versus ten hertz repetitive TMS treatment of PTSD: A randomized clinical trial. Kozel, FA., Van Trees, K., Larson, V., et al.[2019]

In a study of 12 patients with both PTSD and major depression, 75% experienced a significant improvement in depression symptoms after receiving repetitive transcranial magnetic stimulation (rTMS) over 10 days.

While rTMS showed effectiveness in alleviating depression and related symptoms like anxiety and insomnia, it had only minimal impact on the core symptoms of PTSD, suggesting that different treatment approaches may be needed for mood and PTSD symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation treatment of comorbid posttraumatic stress disorder and major depression. Rosenberg, PB., Mehndiratta, RB., Mehndiratta, YP., et al.[2006]

In a study of 770 veterans with major depressive disorder (MDD), TMS treatment led to significant reductions in both MDD and PTSD symptoms, with a response rate of 41.4% and remission rate of 20% for MDD after receiving an adequate dose of 30 sessions.

The treatment was found to be safe, with side effects aligning with the known safety profile of TMS, and 65.3% of veterans with comorbid PTSD experienced clinically meaningful symptom reductions, indicating TMS's effectiveness in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prefrontal transcranial magnetic stimulation for depression in US military veterans - A naturalistic cohort study in the veterans health administration. Madore, MR., Kozel, FA., Williams, LM., et al.[2023]

Bilateral sequential theta-burst stimulation (bsTBS) was well tolerated in a small study of 8 military veterans with treatment-resistant depression (TRD) and comorbid PTSD, showing promising remission rates of 25% and response rates of 38% for depression scores.

The study suggests that bsTBS may be a viable therapeutic option for patients with TRD and PTSD, indicating the need for larger studies to further evaluate its efficacy compared to other rTMS treatment paradigms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bilateral sequential theta burst stimulation in depressed veterans with service related posttraumatic stress disorder: a feasibility study. Vaithianathan, T., Blair, M., Soares, V., et al.[2022]

In a study of 29 individuals with comorbid major depressive disorder (MDD) and posttraumatic stress disorder (PTSD), machine learning analysis of EEG coherence was able to predict clinical outcomes after TMS treatment, with a high area under the curve of 0.83 for MDD and 0.71 for PTSD.

The study demonstrated that EEG coherence could effectively differentiate between pre- and post-TMS treatment states, achieving an accuracy of around 75-78% across different brain wave frequencies, suggesting potential for EEG as a screening tool for TMS candidates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of machine learning in predicting clinical response to transcranial magnetic stimulation in comorbid posttraumatic stress disorder and major depression: A resting state electroencephalography study. Zandvakili, A., Philip, NS., Jones, SR., et al.[2021]

Transcranial magnetic stimulation (TMS) has a very low seizure risk, with only 0.08 seizures reported per 1,000 sessions, and less than 0.02 seizures per 1,000 sessions when guidelines are followed for individuals without known risk factors.

The study found that exceeding safety guidelines increases the risk of seizures, and seizures are more likely to occur during the first few TMS sessions, suggesting that TMS is generally safe when administered properly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Seizures from transcranial magnetic stimulation 2012-2016: Results of a survey of active laboratories and clinics. Lerner, AJ., Wassermann, EM., Tamir, DI.[2021]

Repetitive transcranial magnetic stimulation (rTMS) has gained popularity for its ability to modulate brain activity, but safety considerations are crucial, especially with the recent updates to safety guidelines published in 2021.

The guidelines emphasize the importance of screening for risks, monitoring for adverse events, and specific safety measures when using rTMS, particularly in patients with conditions like stroke and traumatic brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. Kim, WS., Paik, NJ.[2023]

Transcranial magnetic stimulation (TMS) has a strong safety record, with seizures being an extremely rare adverse effect, particularly in patients receiving repetitive TMS (rTMS) under certain conditions.

The updated guidelines provide comprehensive safety recommendations for TMS applications, including risk assessments for new stimulation paradigms and precautions for use in patients with implanted devices or in neuroimaging settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Rossi, S., Hallett, M., Rossini, PM., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) is a powerful tool that can effectively treat clinical depression and potentially other brain disorders, but it carries risks, including the potential to induce seizures, as evidenced by 7 known cases by 1996.

A workshop established safety guidelines for rTMS, emphasizing the importance of monitoring, ethical considerations, and the expertise required for its administration to minimize risks and enhance therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996. Wassermann, EM.[2022]

A study comparing intermittent theta burst stimulation (iTBS) and 5 Hz transcranial magnetic stimulation (TMS) in veterans with PTSD and major depressive disorder (MDD) found that both treatments were safe and effective, but 5 Hz TMS resulted in significantly better symptom improvement.

Veterans receiving 5 Hz TMS showed greater reductions in PTSD and MDD symptoms compared to those receiving iTBS, suggesting that while iTBS is quicker to administer, it may not be as effective for these conditions based on the current data from 20 participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Magnetic Stimulation for Posttraumatic Stress Disorder and Major Depression: Comparing Commonly Used Clinical Protocols. Philip, NS., Doherty, RA., Faucher, C., et al.[2022]

In a rat model of PTSD, high-frequency repetitive transcranial magnetic stimulation (rTMS) effectively prevented anxiety-like behaviors and impaired sensorimotor gating that typically follow stress exposure.

The study suggests that rTMS could be a promising non-pharmacologic treatment for preventing PTSD symptoms, as it mitigated stress-induced increases in cortisol levels and anxiety-related behaviors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation ameliorates anxiety-like behavior and impaired sensorimotor gating in a rat model of post-traumatic stress disorder. Wang, HN., Bai, YH., Chen, YC., et al.[2022]

Transcranial magnetic stimulation (TMS) is a promising noninvasive treatment for PTSD, showing safety and efficacy in numerous studies, including nine randomized controlled trials and various prospective studies.

While TMS has demonstrated positive outcomes for PTSD, there is a need for more standardized approaches and long-term studies to better understand treatment duration and optimize patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation for post-traumatic stress disorder. Petrosino, NJ., Cosmo, C., Berlow, YA., et al.[2022]

Transcranial magnetic stimulation (TMS) is a safe and potentially effective treatment for post-traumatic stress disorder (PTSD) and comorbid major depressive disorder (MDD), but the optimal stimulation techniques are still being researched.

In this study involving TMS treatment over multiple sessions, the individualized alpha frequency (IAF) remained stable and did not predict clinical outcomes, suggesting it may not be a useful marker for guiding TMS therapy in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot Testing of Peak Alpha Frequency Stability During Repetitive Transcranial Magnetic Stimulation. Petrosino, NJ., Zandvakili, A., Carpenter, LL., et al.[2020]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

One hertz versus ten hertz repetitive TMS treatment of PTSD: A randomized clinical trial. [2019]

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

Repetitive transcranial magnetic stimulation treatment of comorbid posttraumatic stress disorder and major depression. [2006]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Prefrontal transcranial magnetic stimulation for depression in US military veterans - A naturalistic cohort study in the veterans health administration. [2023]

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

Bilateral sequential theta burst stimulation in depressed veterans with service related posttraumatic stress disorder: a feasibility study. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Use of machine learning in predicting clinical response to transcranial magnetic stimulation in comorbid posttraumatic stress disorder and major depression: A resting state electroencephalography study. [2021]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Seizures from transcranial magnetic stimulation 2012-2016: Results of a survey of active laboratories and clinics. [2021]

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

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. [2023]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. [2022]

9. Ireland pubmed.ncbi.nlm.nih.gov

Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996. [2022]

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

Transcranial Magnetic Stimulation for Posttraumatic Stress Disorder and Major Depression: Comparing Commonly Used Clinical Protocols. [2022]

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

Repetitive transcranial magnetic stimulation ameliorates anxiety-like behavior and impaired sensorimotor gating in a rat model of post-traumatic stress disorder. [2022]

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

Transcranial magnetic stimulation for post-traumatic stress disorder. [2022]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Pilot Testing of Peak Alpha Frequency Stability During Repetitive Transcranial Magnetic Stimulation. [2020]