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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to help Veterans with PTSD using transcranial magnetic stimulation (TMS). TMS uses a strong magnet to stimulate specific brain areas and has successfully treated depression. The study compares real TMS treatment to a fake version (Sham TMS) to determine its effectiveness in improving PTSD symptoms. Veterans with moderate to severe PTSD who haven't tried TMS before might be suitable candidates for this trial. As an unphased trial, it offers Veterans a unique opportunity to explore an innovative treatment option for PTSD.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that transcranial magnetic stimulation (TMS) is generally safe for patients. Studies have found that using TMS at a low frequency, such as 1 Hz, can significantly improve PTSD symptoms without causing serious side effects. Reports of major negative effects are absent, making it a promising treatment option.

TMS uses magnets to target specific areas of the brain. It has proven effective for treating depression and now shows potential for helping with PTSD. While the focus is on its safety, studies consistently show that patients tolerate TMS well. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for PTSD?

Researchers are excited about transcranial magnetic stimulation (TMS) for PTSD because it offers a non-invasive approach to treatment. Unlike traditional options such as psychotherapy and medication, TMS uses magnetic fields to stimulate nerve cells in the brain, specifically targeting the right dorsolateral prefrontal cortex. This precise mechanism could lead to fewer side effects compared to medications, which often affect the whole body. Additionally, TMS has the potential to provide relief more quickly than therapy, which can take weeks or months to show results. Researchers are hopeful that TMS could become a game-changer in how PTSD is managed.

What evidence suggests that transcranial magnetic stimulation might be an effective treatment for PTSD?

Research has shown that using transcranial magnetic stimulation (TMS) at a low frequency of 1 Hz can greatly help with PTSD symptoms. In this trial, participants will receive either TMS or a sham treatment. One study found that TMS worked better than fake treatments in easing the main symptoms of PTSD. Another review identified TMS as an effective and well-tolerated treatment for PTSD. Although more research is needed, these findings suggest TMS could be a promising option for people with PTSD, including Veterans. ^{1 6 7 8 9}

Who Is on the Research Team?

Bradley V Watts, MD MPH

Principal Investigator

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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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 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]

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]

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]

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]

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 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) 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9193572/

Transcranial Magnetic Stimulation for Post-traumatic Stress ... TMS delivered at 1 Hz to right DLPRC results in statistically and clinically significant improvements in core PTSD symptoms compared with sham treatments.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1935861X13003410

Review of the Effectiveness of Transcranial Magnetic ... TMS for PTSD appears to be an effective and well-tolerated treatment that warrants additional study to further define treatment parameters, course, and side ...

3. nature.com nature.com/articles/s41398-020-0851-5

Non-invasive brain stimulation for posttraumatic stress ... Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) hold promise for the treatment of posttraumatic stress ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32379487/

A Randomized Sham-controlled Trial of 1-Hz and 10 ... Low-frequency rTMS is efficacious in the treatment of civilian PTSD. Our data suggest that high-frequency rTMS of the right DLPFC is worthy of additional ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04207346

Transcranial Magnetic Stimulation to Improve Functioning ... This is a randomized clinical trial enrolling 91 Veterans with PTSD comparing the effectiveness of transcranial magnetic stimulation treatment and sham ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0165178123004833

Effects of intermittent theta-burst transcranial magnetic ... ITBS, with a shorter treatment duration, can effectively improve the symptoms of PTSD, with no significant difference in effect from that of rTMS.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8558793/

Transcranial magnetic stimulation for post-traumatic stress ... Compared with sham, 1 Hz TMS improved PTSD re-experiencing symptoms and total CAPS scores. Avoidance scores trended toward improvement ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06081309

NCT06081309 | EEG Personalized Transcranial Magnetic ... This is an open-label safety pilot study of the Electroencephalogram (EEG) Transcranial Magnetic Stimulation (eTMS) treatment for Post-Traumatic Stress ...

9. dovepress.com dovepress.com/the-effects-of-repetitive-transcranial-magnetic-stimulation-on-post-tr-peer-reviewed-fulltext-article-NDT

The Effects of Repetitive Transcranial Magnetic Stimulation ... Therapeutic TMS is a safe intervention for PTSD patients, with no reports of severe adverse effects. This study demonstrates that therapeutic ...