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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether combining a brain-based therapy called repetitive transcranial magnetic stimulation (rTMS) with written exposure therapy (WET) can better assist veterans with PTSD. The goal is to determine if this combination improves symptoms by enhancing emotional flexibility. Participants will receive either real rTMS or a sham (fake) version, both followed by WET. Veterans diagnosed with PTSD who speak English and have not experienced severe brain injuries may be suitable for this study. As an unphased trial, this study offers veterans the chance to contribute to innovative research that could lead to new PTSD treatments.

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.

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

Previous studies have tested repetitive transcranial magnetic stimulation (rTMS) for treating post-traumatic stress disorder (PTSD). Research shows that patients generally tolerate rTMS well. In one study on PTSD, most participants experienced mild side effects like headaches, but these were temporary and not serious.

Additionally, the FDA has approved rTMS for treating depression, indicating its safety for use in people. This approval confirms that the treatment has undergone thorough testing to ensure it does not cause significant harm.

Overall, evidence from various studies suggests that rTMS is a safe option for many people. However, individual reactions can differ, so participants should discuss potential risks with healthcare providers before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores combining repetitive transcranial magnetic stimulation (rTMS) with Written Exposure Therapy (WET) for PTSD, aiming to enhance the effectiveness of current treatments. Unlike most PTSD therapies that primarily focus on talk therapy or medication, rTMS offers a non-invasive brain stimulation technique that may boost therapy outcomes. By pairing rTMS with WET, this approach could provide faster or more robust relief from PTSD symptoms, potentially offering a new avenue for those who haven’t responded well to traditional treatment options.

What evidence suggests that this trial's treatments could be effective for PTSD?

Research has shown that Written Exposure Therapy (WET), one of the treatments in this trial, effectively treats PTSD. Studies have found that WET can significantly reduce PTSD symptoms and is as effective as longer therapies. In this trial, some participants will receive active repetitive transcranial magnetic stimulation (rTMS) before WET, while others will receive sham rTMS. For rTMS, the evidence is mixed. Some studies suggest it might help by influencing brain areas related to emotional control, but results are not always consistent. High-frequency rTMS appears more promising in some cases, but more research is needed to fully understand its effects. Overall, adding rTMS to WET might enhance the treatment, but the data is still developing. ^{6 7 8 9 10}

Who Is on the Research Team?

Crystal M Lantrip

Principal Investigator

Central Texas Veterans Health Care System, Temple, TX

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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]

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]

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]

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 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]

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]

Citations

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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.

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The Effects of Repetitive Transcranial Magnetic Stimulation on ... rTMS is an effective and noninvasive treatment for PTSD. However, study findings suggest that there are no statistically significant differences ...

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Repetitive Transcranial Magnetic Stimulation (rTMS) in ... Although evidence is limited, HF rTMS may improve PTSD symptoms by modulating the prefrontal cortex activity. The mechanisms by which rTMS might exert its ...

5. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2022.701348/full

Transcranial Magnetic Stimulation for Post-traumatic Stress ... In current studies, high-frequency stimulation has been shown to be more effective in PTSD rating scales posttreatment than low-frequency stimulation. The most ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05149534

rTMS-augmented Written Exposure Therapy for PTSD The overarching goal of this CDA-2 proposal is to use repetitive transcranial magnetic stimulation (rTMS) to augment effectiveness of written exposure therapy ( ...

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Advances in repetitive transcranial magnetic stimulation for ... Repetitive transcranial magnetic stimulation (rTMS) as a treatment for posttraumatic stress disorder (PTSD) has gained interest over the past two decades.

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Clinical Trial to Evaluate the Safety and Efficacy of MeRT ... Concomitant medication use and clinical outcome of repetitive Transcranial Magnetic Stimulation (rTMS) treatment of Major Depressive Disorder. Brain Behav ...