rTMS-augmented Written Exposure Therapy for PTSD

Overseen By Crystal M Lantrip

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: VA Office of Research and Development

Disqualifiers: Seizures, Pregnancy, Psychosis, Bipolar, Schizophrenia, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 5 weeks

98 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

You can continue taking your current medications, but you need to be stable on them for at least four weeks before starting the study and throughout the study period.

What data supports the effectiveness of the treatment rTMS-augmented Written Exposure Therapy for PTSD?

Research shows that Written Exposure Therapy (WET) is effective for PTSD, with significant symptom improvement in a short time. Additionally, combining repetitive transcranial magnetic stimulation (rTMS) with exposure therapy has shown promising results in reducing PTSD symptoms, suggesting that the combination of these treatments could be beneficial. ^{1 2 3 4 5}

Is rTMS-augmented Written Exposure Therapy for PTSD safe for humans?

Repetitive Transcranial Magnetic Stimulation (rTMS) has been studied for various conditions, including PTSD and depression, and is generally considered safe with no serious adverse events reported in studies. Safety guidelines for rTMS have been established and updated over the years, ensuring its safe application in clinical settings. ^{3 6 7 8 9}

How is the treatment rTMS-augmented Written Exposure Therapy (WET) for PTSD different from other treatments?

This treatment combines Written Exposure Therapy (WET), which involves writing about traumatic experiences, with repetitive transcranial magnetic stimulation (rTMS), a non-invasive procedure that uses magnetic fields to stimulate nerve cells in the brain. This combination is unique because it aims to enhance the effects of exposure therapy by potentially altering brain activity, which is not a feature of traditional PTSD treatments. ^{3 5 8 10 11}

What is the purpose of this trial?

Post-traumatic stress disorder (PTSD) is prevalent and represents a high healthcare burden among Veterans. Repetitive transcranial magnetic stimulation (rTMS) is a brain-based therapy that may be effective for treating PTSD. The theorized mechanism of rTMS is enhancement of emotional flexibility via the dorsolateral prefrontal cortex node of the brain's cognitive control network. Given this mechanism of action, adding rTMS to an evidence-based psychotherapy (EBP) for PTSD may enhance treatment effects. Written exposure therapy (WET) is a brief EBP for PTSD found to reduce attrition compared to lengthier first line treatments. In this study, the investigators will determine if active rTMS added to WET compared with sham rTMS added to WET results in improved PTSD outcomes. The investigators will also determine if emotional flexibility is a mechanism of symptom improvement. This work will improve upon PTSD intervention and inform the mechanism of treatment effectiveness for Veterans suffering from PTSD.

Research Team

Crystal M Lantrip

Principal Investigator

Central Texas Veterans Health Care System, Temple, TX

Eligibility Criteria

This trial is for English-speaking veterans aged 18-50 with PTSD, who are right-handed and can consent in writing. It's not for those over 50, pregnant women, individuals with seizure history or serious neurological issues, current substance abusers, people at risk of suicide, or those with cognitive impairments.

Inclusion Criteria

I have been diagnosed with PTSD.

I speak English and can sign a consent form.

I am a veteran.

Exclusion Criteria

Current substance use disorder or substance use in the last 12 hours before the rTMS session

I have a history of seizures or serious neurological conditions.

Participants with moderate or severe TBI

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive active or sham rTMS prior to written exposure therapy (WET) for PTSD

5 weeks

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

2 visits (in-person)

Treatment Details

Interventions

• Repetitive Transcranial Magnetic Stimulation
• Written Exposure Therapy

Trial Overview The study tests if adding rTMS (a non-invasive brain stimulation technique) to Written Exposure Therapy (WET), a brief psychotherapy treatment for PTSD, improves outcomes compared to WET with sham rTMS. The focus is on enhancing emotional flexibility as a key mechanism.

Participant Groups

Group I: Active TMS/WET Experimental Treatment 2 Interventions

Active repetitive transcranial magnetic stimulation completed prior to written exposure therapy

Group II: Sham TMS/WET Placebo Group 2 Interventions

Sham repetitive transcranial magnetic stimulation completed prior to written exposure therapy

Written Exposure Therapy is already approved in United States for the following indications:

Approved in United States as Written Exposure Therapy for:

• Post-Traumatic Stress Disorder (PTSD)

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

National Center for PTSD

Collaborator

Trials

13

Recruited

1,200+

Findings from Research

Written exposure therapy (WET) significantly reduced PTSD symptoms in Korean patients, with 60.9% of participants no longer meeting PTSD criteria at 6 weeks, increasing to 77.8% at 24 weeks, demonstrating its efficacy.

The therapy also improved depressive symptoms and global functioning, with a low dropout rate of 8%, indicating that WET is a feasible and effective treatment option for PTSD in diverse populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Open Pilot Trial of Written Exposure Therapy for Patients With Post-Traumatic Stress Disorder in Korea. Park, JE., Choi, KS., Han, YR., et al.[2021]

Written Exposure Therapy (WET) is an effective 5-session treatment for PTSD that shows significant symptom improvement and requires less time from both patients and therapists compared to traditional therapies.

WET has similar efficacy to Cognitive Processing Therapy (CPT) but with a much lower dropout rate (6% for WET vs. 39% for CPT), making it a promising option for diverse populations, including veterans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brief novel therapies for PTSD: Written Exposure Therapy. Thompson-Hollands, J., Marx, BP., Sloan, DM.[2022]

In a study involving 9 subjects with chronic, treatment-refractory PTSD, combining repetitive transcranial magnetic stimulation (rTMS) with exposure therapy resulted in a significant improvement in hyperarousal symptoms compared to a sham treatment, indicating its potential efficacy.

The active rTMS treatment also led to physiological changes, such as increased levels of norepinephrine and T4, and decreased prolactin, suggesting that rTMS may have both symptomatic and biological effects in treating PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive TMS combined with exposure therapy for PTSD: a preliminary study. Osuch, EA., Benson, BE., Luckenbaugh, DA., et al.[2021]

Written Exposure Therapy (WET) is as effective as Cognitive Processing Therapy (CPT) for treating PTSD, maintaining similar outcomes even 60 weeks after treatment, with large effects on PTSD symptoms for both therapies.

Both WET and CPT significantly reduced depressive symptoms over the study period, although CPT showed a quicker reduction; however, the overall difference in effectiveness for depression was small.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term treatment gains of a brief exposure-based treatment for PTSD. Thompson-Hollands, J., Marx, BP., Lee, DJ., et al.[2022]

This pilot study involving 8 veterans with PTSD shows that combining repetitive transcranial magnetic stimulation (rTMS) with prolonged exposure (PE) therapy is safe and feasible, with a dropout rate similar to traditional PE therapy.

While the overall improvement in PTSD symptoms was not statistically significant, veterans with comorbid major depression experienced notable benefits from rTMS, suggesting potential for enhanced treatment outcomes in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exposure Therapy and Simultaneous Repetitive Transcranial Magnetic Stimulation: A Controlled Pilot Trial for the Treatment of Posttraumatic Stress Disorder. Fryml, LD., Pelic, CG., Acierno, R., et al.[2020]

In a pilot study of 10 patients with both PTSD and major depressive disorder, 5-Hz repetitive transcranial magnetic stimulation (rTMS) significantly reduced symptoms of both conditions, with notable effect sizes (1.12 for PTSD and 1.09 for MDD).

The treatment was well tolerated with no serious adverse events reported, suggesting that 5-Hz rTMS could be a safe and effective option for managing these comorbid disorders, although further larger trials are necessary to validate these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

5-Hz Transcranial Magnetic Stimulation for Comorbid Posttraumatic Stress Disorder and Major Depression. Philip, NS., Ridout, SJ., Albright, SE., et al.[2018]

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]

A clinical trial involving 102 patients with refractory PTSD will investigate the effectiveness of high-frequency Transcranial Magnetic Stimulation (HF-rTMS) combined with reactivation therapy over 12 sessions, aiming to improve PTSD symptoms and cognitive functioning.

The primary outcome will be measured using the Clinician-Administered PTSD Scale (CAPS-5) at one month, which could support the approval of HF-rTMS as a viable treatment option for PTSD if successful.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation (rTMS) in Post-Traumatic Stress Disorder: Study Protocol of a Nationwide Randomized Controlled Clinical Trial of Neuro-Enhanced Psychotherapy "TraumaStim". Ferreri, F., Mouchabac, S., Sylvestre, V., et al.[2023]

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]

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 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]

References

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

An Open Pilot Trial of Written Exposure Therapy for Patients With Post-Traumatic Stress Disorder in Korea. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Brief novel therapies for PTSD: Written Exposure Therapy. [2022]

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

Repetitive TMS combined with exposure therapy for PTSD: a preliminary study. [2021]

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

Long-term treatment gains of a brief exposure-based treatment for PTSD. [2022]

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

Exposure Therapy and Simultaneous Repetitive Transcranial Magnetic Stimulation: A Controlled Pilot Trial for the Treatment of Posttraumatic Stress Disorder. [2020]

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

5-Hz Transcranial Magnetic Stimulation for Comorbid Posttraumatic Stress Disorder and Major Depression. [2018]

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

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

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

Repetitive Transcranial Magnetic Stimulation (rTMS) in Post-Traumatic Stress Disorder: Study Protocol of a Nationwide Randomized Controlled Clinical Trial of Neuro-Enhanced Psychotherapy "TraumaStim". [2023]

9. Denmark pubmed.ncbi.nlm.nih.gov

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

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

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

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

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