rTMS-augmented Written Exposure Therapy for PTSD

Recruiting in Palo Alto (17 mi)

Overseen by Crystal M Lantrip

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: VA Office of Research and Development

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

No Placebo Group

Approved in 1 Jurisdiction

Trial Summary

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.

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}

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 am between 18 and 50 years old.

I have been diagnosed with PTSD.

I speak English and can sign a consent form.

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

Trial 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 (Other)
• Written Exposure Therapy (Other)

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)

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Central Texas Veterans Health Care System, Temple, TX Temple, TX

Who Is Running the Clinical Trial?

VA Office of Research and Development Lead Sponsor

National Center for PTSD Collaborator

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] Written exposure therapy (WET) is exposure therapy for post-traumatic stress disorder (PTSD). Compared to evidencebased treatments for PTSD, WET requires only five sessions, has a shorter session time, and no between-session assignments. The current study examined the efficacy of WET among Korean patients with PTSD due to various traumatic events on PTSD symptoms, depressive symptoms, and global functioning levels.

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

Brief novel therapies for PTSD: Written Exposure Therapy. [2022] Written Exposure Therapy (WET) is a 5-session exposure-based intervention for the treatment of posttraumatic stress disorder (PTSD). WET was developed through a series of systematic evaluations of the expressive writing procedure. It is an efficient intervention, requiring limited patient and therapist time and no between-session assignments. The treatment results in statistically and clinically significant symptom change among individuals, including veterans, with PTSD.

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

Repetitive TMS combined with exposure therapy for PTSD: a preliminary study. [2021] Treatment for anxiety and post-traumatic stress disorder (PTSD) includes exposure therapy and medications, but some patients are refractory. Few studies of repetitive transcranial magnetic stimulation (rTMS) for anxiety or PTSD exist. In this preliminary report, rTMS was combined with exposure therapy for PTSD. Nine subjects with chronic, treatment-refractory PTSD were studied in a placebo-controlled, crossover design of imaginal exposure therapy with rTMS (1Hz) versus sham. PTSD symptoms, serum and 24h urine were obtained and analyzed. Effect sizes for PTSD symptoms were determined using Cohen's d. Active rTMS showed a larger effect size of improvement for hyperarousal symptoms compared to sham; 24-h urinary norepinephrine and serum T4 increased; serum prolactin decreased. Active rTMS with exposure may have symptomatic and physiological effects. Larger studies are needed to confirm these preliminary findings and verify whether rTMS plus exposure therapy has a role in the treatment of PTSD.

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

Long-term treatment gains of a brief exposure-based treatment for PTSD. [2022] Written exposure therapy (WET) is a 5-session PTSD treatment that may address barriers in treatment for posttraumatic stress disorder (PTSD) given its brevity and tolerability. A recent study found outcomes for WET were non-inferior to outcomes from Cognitive Processing Therapy (CPT) through 36 weeks from first treatment session (Sloan, Marx, Lee, & Resick, 2018); the current study examined whether treatment gains were maintained through 60 weeks from first session, and also evaluated both treatments' effect on depressive symptoms.

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] This is a small preliminary but novel study assessing the feasibility of repetitive transcranial magnetic stimulation (rTMS) delivery to veterans with posttraumatic stress disorder (PTSD) while they simultaneously receive prolonged exposure (PE) therapy.

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

5-Hz Transcranial Magnetic Stimulation for Comorbid Posttraumatic Stress Disorder and Major Depression. [2018] Current treatment options for posttraumatic stress disorder (PTSD) offer modest benefits, underscoring the need for new treatments. Repetitive transcranial magnetic stimulation (rTMS) depolarizes neurons in a targeted brain region with magnetic fields typically pulsed at low (1 Hz) or high (10 Hz) frequency to relieve major depressive disorder (MDD). Prior work suggests an intermediate pulse frequency, 5 Hz, is also efficacious for treating comorbid depressive and anxiety symptoms. In this chart review study, we systematically examined the clinical and safety outcomes in 10 patients with comorbid MDD and PTSD syndromes who received 5-Hz rTMS therapy at the Providence VA Medical Center Neuromodulation Clinic. Self-report scales measured illness severity prior to treatment, after every 5 treatments, and upon completion of treatment. Results showed significant reduction in symptoms of PTSD (p = .003, effect size = 1.12, 8/10 with reliable change) and MDD (p = .005, effect size = 1.09, 6/10 with reliable change). Stimulation was well tolerated and there were no serious adverse events. These data indicate 5-Hz rTMS may be a useful option to treat these comorbid disorders. Larger, controlled trials are needed to confirm the benefits of 5-Hz protocols observed in this pilot study.

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

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. [2023] Studies using repetitive transcranial magnetic stimulation (rTMS) in healthy individuals and those with neuropsychiatric diseases have rapidly increased since the 1990s, due to the potential of rTMS to modulate the cortical excitability in the brain depending on the stimulation parameters; therefore, the safety considerations for rTMS use are expected to become more important. Wassermann published the first safety guidelines for rTMS from the consensus conference held in 1996, and Rossi and colleague then published the second safety guidelines from the multidisciplinary consensus meeting held in Siena, Italy in 2008, on behalf of the International Federation of Clinical Neurophysiology. More than 10 years after the second guidelines, the updated third safety guidelines were recently published in 2021. The general safety guidelines for conventional rTMS have not substantially changed. Because the most frequently used rTMS protocol is conventional (low- and high-frequency) rTMS in research and clinical settings, we focus on reviewing safety issues when applying conventional rTMS with a focal cortical stimulation coil. The following issues will be covered: 1) possible adverse events induced by rTMS; 2) checklists to screen for any precautions and risks before rTMS; 3) safety considerations for dosing conventional rTMS; and 4) safety considerations for using rTMS in stroke and traumatic brain injury.

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] The use of high-frequency Transcranial Magnetic Stimulation (HF-rTMS) of the right dorsolateral prefrontal cortex (DLPFC) in treating Post-traumatic Stress Disorder (PTSD) is currently regarded as a level B intervention (probable effectiveness). HF-rTMS has attracted interest as a neuromodulation therapeutic method for PTSD. Prolonged exposure and reactivation therapy are also regarded as first-line treatments for PTSD. Randomized controlled clinical studies examining the effectiveness of several HF-rTMS sessions coupled with psychotherapy have not yet been completed. In total, 102 patients with refractory PTSD will be randomly assigned (1:1) to reactivation therapy, in addition to either active HF-rTMS (20 Hz) or sham HF-rTMS, for 12 sessions in a nationwide, multicenter, double-blind controlled trial. The impact on PTSD symptoms and neurocognitive functioning will be assessed. The primary outcome is the PTSD severity score measured based on the Clinician-Administered PTSD Scale (CAPS-5) at one month. If this additional therapy is successful, it may strengthen the case for regulatory authorities to approve this additional technique of treating PTSD. Additionally, it expands the field of neurostimulation-assisted psychotherapy.

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

[Repetitive transcranial magnetic stimulation treatment for post-traumatic stress disorder]. [2018] Approximately 10% of combat soldiers and 30% of rape victims develop post-traumatic stress disorder (PTSD). Repetitive transcranial magnetic stimulation (rTMS) is already known to be safe in depression treatment. Research results of the past 15 years indicate that rTMS induced to the right dorsolateral prefrontal cortex may have a potential to treat the symptoms of PTSD. Furthermore, high-frequency rTMS seems to be superior to low-frequency rTMS. The effect of rTMS on PTSD symptoms could be mediated by increasing the level of brain-derived neurotrophic factor.

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

Is transcranial magnetic stimulation effective in treatment-resistant combat related posttraumatic stress disorder? [2014] To examine the effectiveness of repetitive transcranial magnetic stimulation (rTMS) in patients with treatment-resistant posttraumatic stress disorder (PTSD) with co-occurring major depression.

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

Repetitive transcranial magnetic stimulation treatment of comorbid posttraumatic stress disorder and major depression. [2006] Twelve patients with comorbid posttraumatic stress disorder (PTSD) and major depression underwent repetitive transcranial magnetic stimulation (rTMS) to left frontal cortex as an open-label adjunct to current antidepressant medications. rTMS parameters were as follows: 90% of motor threshold, 1 Hz or 5 Hz, 6,000 stimuli over 10 days. Seventy-five percent of the patients had a clinically significant antidepressant response after rTMS, and 50% had sustained response at 2-month follow-up. Comparable improvements were seen in anxiety, hostility, and insomnia, but only minimal improvement in PTSD symptoms. Left frontal cortical rTMS may have promise for treating depression in PTSD, but there may be a dissociation between treating mood and treating core PTSD symptoms.