TMS for Post-Traumatic Stress Disorder

Recruiting at 1 trial location

Overseen By Mohammed Milad, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

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

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial uses TMS, a procedure that stimulates brain cells with magnetic fields, to help PTSD patients who struggle with reducing fear responses. The goal is to see if TMS can change brain activity to better manage fear. TMS has been primarily studied for major depression but is increasingly being explored for PTSD treatment.

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 data supports the effectiveness of the treatment TMS for Post-Traumatic Stress Disorder?

Research shows that repetitive transcranial magnetic stimulation (rTMS) can reduce symptoms of PTSD and depression more effectively than a placebo treatment. However, the evidence is considered low quality due to small study sizes and inconsistent results, so more research is needed to confirm its effectiveness. ^{1 2 3 4 5}

Is TMS safe for humans?

TMS (Transcranial Magnetic Stimulation) has been studied for over two decades and is considered safe for treating depression, with safety guidelines established and updated over the years. It has been used in both healthy individuals and those with various neuropsychiatric conditions, with safety protocols in place to minimize risks. ^{3 6 7 8 9}

How is TMS treatment different from other treatments for PTSD?

TMS (Transcranial Magnetic Stimulation) is unique because it uses magnetic fields to stimulate nerve cells in the brain, specifically targeting the right prefrontal cortex, which is different from traditional PTSD treatments like medication or talk therapy. It is non-invasive and does not involve drugs, making it a novel option for those who may not respond to other treatments. ^{2 5 7 10 11}

Research Team

Mohammed Milad, PhD

Principal Investigator

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

Eligibility Criteria

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)

Trial Timeline

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

Treatment Details

Interventions

• TMS (Neuromodulation)

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.

Participant Groups

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 Canada for the following indications:

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+

Findings from Research

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]

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]

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 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]

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]

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]

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 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]

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]

References

1. Saudi Arabia pubmed.ncbi.nlm.nih.gov

Is transcranial magnetic stimulation effective in treatment-resistant combat related posttraumatic stress disorder? [2014]

2. United States 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. [2022]

3. Denmark pubmed.ncbi.nlm.nih.gov

[Repetitive transcranial magnetic stimulation treatment for post-traumatic stress disorder]. [2018]

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

Advances in repetitive transcranial magnetic stimulation for posttraumatic stress disorder: A systematic review. [2021]

5. Korea (South) 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. [2021]

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

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

7. United States 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. [2015]

8. England pubmed.ncbi.nlm.nih.gov

Impacts of rTMS on Refractory Depression and Comorbid PTSD Symptoms at a Military Treatment Facility. [2021]

9. 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]

10. England pubmed.ncbi.nlm.nih.gov

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

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

Review of the effectiveness of transcranial magnetic stimulation for post-traumatic stress disorder. [2018]