TMS for Post-Traumatic Stress Disorder

Recruiting at 1 trial location

Overseen By Mohammed Milad, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: The University of Texas Health Science Center, Houston

Must not be taking: Neuroleptics, Antipsychotics, Stimulants, others

Disqualifiers: Seizure, Head trauma, Substance use, 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: 5

250 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to examine how transcranial magnetic stimulation (TMS) affects the brain's fear circuits in individuals with post-traumatic stress disorder (PTSD). Researchers seek to determine the most effective way to use TMS for addressing fear-related memories. Participants will undergo brain scans and TMS over several days. Individuals with PTSD who struggle with fear memories may be suitable candidates for this study. As an unphased trial, this study offers participants the chance to contribute to pioneering research that could lead to new PTSD treatments.

Will I have to stop taking my current medications?

The trial requires that you stop taking medications that lower the seizure threshold, such as antipsychotics, high dose theophylline, or stimulants like methylphenidate. If you are taking bupropion, you must be on a stable dose for the last 3 months and take 300 mg/day or less.

What prior data suggests that transcranial magnetic stimulation (TMS) is safe for treating PTSD?

Research has shown that transcranial magnetic stimulation (TMS) is generally safe. The FDA has approved it for treating depression that doesn't respond to other treatments, indicating it is usually well-tolerated.

Studies examining TMS for PTSD have found no major safety issues. TMS uses magnetic fields to stimulate brain cells, and most people do not experience serious side effects. Some might feel mild discomfort or have minor headaches, but these effects typically resolve quickly.

Overall, evidence suggests that TMS is a safe option for those considering it for PTSD. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Transcranial Magnetic Stimulation (TMS) for treating Post-Traumatic Stress Disorder (PTSD) because it offers a non-invasive approach that directly targets specific brain areas involved in fear and anxiety. Unlike standard treatments like psychotherapy or medication, which can take weeks or months to show effects, TMS potentially offers more immediate relief by modulating neural activity in real time. This technique uses magnetic fields to stimulate nerve cells, providing a unique mechanism of action that could enhance or even transform PTSD treatment by focusing on brain circuits involved in fear learning and extinction.

What evidence suggests that TMS is effective for PTSD?

Research shows that transcranial magnetic stimulation (TMS), which participants in this trial will receive, is a promising treatment for post-traumatic stress disorder (PTSD). Studies have found that TMS can improve mood in people with PTSD. A review of several studies found that TMS therapy led to better mood outcomes for patients. TMS might also help with specific PTSD symptoms, but experts say more research is needed to fully understand its effects on the brain. Overall, TMS is considered a hopeful option for those dealing with PTSD. ^{1 6 7 8 9}

Who Is on the Research Team?

Mohammed Milad, PhD

Principal Investigator

The University of Texas Health Science Center at Houston (UTHealth Houston)

Are You a Good Fit for This Trial?

This trial is for right-handed adults aged 18-70 with primary PTSD, without other major psychiatric disorders or significant neurological issues. Participants must not be on psychotropic medication recently, have no metal implants that affect MRI, and cannot be pregnant. Healthy controls matching in age, gender, education, and ethnicity are also included.

Inclusion Criteria

My participation will help balance the study's diversity in terms of age, gender, education, and race/ethnicity.

Willing and able to provide informed consent

SCID diagnosis consistent with no current or past history of Axis I psychiatric disorders for Healthy Controls (HC)

Exclusion Criteria

I am on stable doses of medications like bupropion (<=300 mg/day) or others that may increase seizure risk.

Implanted devices in subject's head (shunts, cochlear implants); metal in subject's head (other than dental implants)

Pregnancy (to be ruled out by urine ß-HCG)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline

Baseline visits to establish initial conditions and gather preliminary data

1 week

1 visit (in-person)

Experimental

Participants undergo a 3-day experimental paradigm involving TMS and fMRI scans

4 days

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• TMS

Trial Overview The study tests how transcranial magnetic stimulation (TMS) affects fear extinction memory consolidation in PTSD patients. It involves preliminary screenings and experimental visits over four days at NYU Langone Health to optimize TMS parameters for the best therapeutic outcomes.

How Is the Trial Designed?

Group I: Fear Conditioning and Extinction Paradigm, plus Transcranial Magnetic Stimulation (TMS) Experimental Treatment 2 Interventions

Participants will undergo a 3-day experimental paradigm. On day 1, participants will undergo a resting-state and structural scans in the fMRI scanner. The data from this scan will be used to determine the specific location of the TMS target for each participant. And participants will be aversively conditioned to two cues in the fMRI scanner. Task based and resting-state scans will occur on this day. On day 2, subjects will undergo extinction training outside of the scanner where one of the conditioned cues will be paired with TMS in a temporally and anatomically specific manner. A resting-state scan will occur before and after inside the scanner. On day 3, conditioned cues will be presented during the extinction recall phase of the study. This phase will be conducted in the fMRI scanner. Task-based and resting-state scans will occur on this day.

TMS is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Transcranial Magnetic Stimulation for:

• Depression
• Anxiety disorders
• Post-traumatic stress disorder (PTSD)
• Obsessive-compulsive disorder (OCD)

Approved in European Union as Transcranial Magnetic Stimulation for:

• Depression
• Anxiety disorders
• Post-traumatic stress disorder (PTSD)
• Obsessive-compulsive disorder (OCD)

Approved in Canada as Transcranial Magnetic Stimulation for:

• Depression
• Anxiety disorders
• Post-traumatic stress disorder (PTSD)
• Obsessive-compulsive disorder (OCD)

Who Is Running the Clinical Trial?

The University of Texas Health Science Center, Houston

Lead Sponsor

Trials

974

Recruited

361,000+

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

Repetitive transcranial magnetic stimulation (rTMS) has been shown to be effective for treatment-resistant major depressive disorder (trMDD), but there is limited evidence for its use in patients with comorbid posttraumatic stress disorder (PTSD).

In a unique case, a patient with both trMDD and PTSD experienced remission of symptoms after receiving rTMS targeting the left dorsolateral prefrontal cortex, suggesting potential benefits of rTMS in this specific population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case report of a 24-year-old man with resolution of treatment-resistant major depressive disorder and comorbid PTSD using rTMS. Nakama, H., Garcia, A., O'Brien, K., et al.[2015]

Repetitive transcranial magnetic stimulation (rTMS) is a safe treatment option for depression and shows potential for alleviating symptoms of post-traumatic stress disorder (PTSD), particularly when applied to the right dorsolateral prefrontal cortex.

High-frequency rTMS appears to be more effective than low-frequency rTMS in treating PTSD symptoms, possibly by increasing levels of brain-derived neurotrophic factor, which supports brain health and function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Repetitive transcranial magnetic stimulation treatment for post-traumatic stress disorder]. Jensen, BS., Ashkanian, M.[2018]

Repetitive transcranial magnetic stimulation (rTMS) was found to be significantly more effective than sham treatment in reducing PTSD symptoms and depression severity, with a standardized mean difference of -1.13 for PTSD and -0.83 for depression.

While high-frequency (HF) rTMS showed slightly better outcomes compared to low-frequency (LF) rTMS, the overall quality of evidence was rated very low due to factors like small sample sizes and inconsistent results, indicating a need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in repetitive transcranial magnetic stimulation for posttraumatic stress disorder: A systematic review. Belsher, BE., Beech, EH., Reddy, MK., et al.[2021]

In a study involving 24 PTSD patients, high-frequency repetitive transcranial magnetic stimulation (rTMS) at 10 Hz significantly improved core PTSD symptoms and alleviated anxiety over 10 daily sessions.

The results indicate that rTMS targeting the right dorsolateral prefrontal cortex is more effective than low-frequency or sham stimulation, suggesting its potential as a therapeutic intervention for PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation of the right dorsolateral prefrontal cortex in posttraumatic stress disorder: a double-blind, placebo-controlled study. Cohen, H., Kaplan, Z., Kotler, M., et al.[2022]

In a study involving 18 patients with PTSD, low-frequency repetitive transcranial magnetic stimulation (rTMS) to the right prefrontal cortex significantly improved overall PTSD symptoms, particularly in re-experiencing and total scores on the Clinician-Administered PTSD Scale (CAPS).

The results suggest that rTMS is a safe and effective treatment option for PTSD, with a notable impact on specific symptom clusters, indicating potential for further research into optimizing rTMS protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-frequency, Repetitive Transcranial Magnetic Stimulation for the Treatment of Patients with Posttraumatic Stress Disorder: a Double-blind, Sham-controlled Study. Nam, DH., Pae, CU., Chae, JH.[2021]

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 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]

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 been found to be an effective treatment for post-traumatic stress disorder (PTSD), with a meta-analysis of three studies showing a significant reduction in PTSD symptoms.

The treatment is generally well tolerated, and right-sided TMS may be more effective than left-sided, although further research is needed to optimize treatment parameters and understand potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of the effectiveness of transcranial magnetic stimulation for post-traumatic stress disorder. Karsen, EF., Watts, BV., Holtzheimer, PE.[2018]

A study of 77 military patients receiving rTMS treatment showed significant reductions in depression and PTSD symptoms, with over 44% of patients experiencing a notable decrease in depression scores after treatment.

Most patients had previously tried multiple antidepressants (average of 2.7 trials), indicating that rTMS may be an effective alternative for those with treatment-resistant depression and comorbid PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impacts of rTMS on Refractory Depression and Comorbid PTSD Symptoms at a Military Treatment Facility. Wilkes, S., Ona, C., Yang, M., et al.[2021]

In a study of 20 male combat veterans with treatment-resistant PTSD, repetitive transcranial magnetic stimulation (rTMS) significantly reduced hyperarousal symptoms, suggesting its potential effectiveness for this specific symptom.

However, rTMS did not show significant improvements in overall PTSD symptoms or co-occurring depression and anxiety scores, indicating that while it may help with hyperarousal, further research is needed to understand its broader efficacy in PTSD treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is transcranial magnetic stimulation effective in treatment-resistant combat related posttraumatic stress disorder? Oznur, T., Akarsu, S., Celik, C., et al.[2014]

Citations

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Transcranial Magnetic Stimulation for Post-traumatic Stress ... Overall, TMS therapy has been suggested as an effective treatment in PTSD patients. ... A meta-analysis performed looked at PTSD mood outcomes with the use of TMS ...

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The Effects of Repetitive Transcranial Magnetic Stimulation on ... One-year clinical outcomes following theta burst stimulation for post-traumatic stress disorder. Neuropsychopharmacology. 2020;45(6):940–946 ...

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Transcranial magnetic stimulation as a treatment for ... TMS shows potential as a treatment for PTSD, although further research is required to understand the neurological mechanisms of TMS on specific PTSD symptoms.

4. 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 ...

5. mdpi.com mdpi.com/2076-3425/13/9/1274

Repetitive Transcranial Magnetic Stimulation (rTMS) in ... Repetitive Transcranial Magnetic Stimulation (rTMS) in Post-Traumatic Stress Disorder: Study Protocol of a Nationwide Randomized Controlled Clinical Trial of ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39092744/

Repetitive transcranial magnetic stimulation for post- ... Our review suggests that active rTMS probably makes little to no difference to PTSD severity immediately following treatment compared to sham stimulation.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06081309

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

8. sciencedirect.com sciencedirect.com/science/article/pii/S109471592201399X

Repetitive Transcranial Magnetic Stimulation for ... Veterans with mTBI had greater PTSD symptoms, yet neither TBI status nor cumulative head injuries reduced TMS effectiveness.

9. clinicaltrials.gov clinicaltrials.gov/study/NCT00001657

Use of Repetitive Transcranial Magnetic Stimulation (rTMS) ... This study is designed to determine if rTMS stimulation in patients diagnosed with PTSD leads to symptomatic improvement, reductions in blood flow to specific ...