TMS for Post-Traumatic Stress Disorder

Overseen By Allyson C Rosen, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Allyson Rosen

Must not be taking: Seizure risk, Hemodynamic influencers

Disqualifiers: Significant dementia, Urgent care need, 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: 4

30 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

The trial requires you to maintain a stable medication regimen between the two fMRI sessions. However, if you are currently taking medications that increase the risk of seizure or influence hemodynamic response, you may be excluded from participating.

What data supports the idea that TMS for Post-Traumatic Stress Disorder is an effective treatment?

The available research shows that repetitive transcranial magnetic stimulation (rTMS) can be effective for treating post-traumatic stress disorder (PTSD). Studies have found that rTMS, especially when applied to specific areas of the brain like the prefrontal cortex, can help reduce PTSD symptoms. For example, one study used a double-blind, placebo-controlled method and found that rTMS was more effective than a placebo in relieving PTSD symptoms. Another study compared rTMS to a sham (fake) treatment and found that real rTMS provided more relief from PTSD symptoms. Additionally, rTMS has been shown to help with symptoms of major depression, which often occurs alongside PTSD, suggesting it can be beneficial for people dealing with both conditions. ^{1 2 3 4 5}

What safety data exists for TMS treatment in PTSD?

The safety of transcranial magnetic stimulation (TMS), including repetitive TMS (rTMS), has been evaluated in various populations, including healthy volunteers, adults with neuropsychiatric conditions, and a predominately pediatric cohort. Safety guidelines for rTMS have been established and updated over the years, with the most recent guidelines published in 2021. These guidelines cover potential adverse events, precautions, and dosing considerations. The safety of TMS in PTSD specifically has been studied, with research indicating its application in both PTSD and comorbid conditions like major depressive disorder. ^{1 2 5 6 7}

Is TMS a promising treatment for PTSD?

Yes, TMS is a promising treatment for PTSD. Studies show that it can help reduce symptoms by targeting specific brain areas, like the right prefrontal cortex, which is involved in stress and emotional regulation. TMS can also improve brain connectivity, which is beneficial for people with PTSD and related conditions like depression. ^{2 4 5 8 9}

What is the purpose of this trial?

In post-traumatic stress disorder (PTSD), intrusive, traumatic, autobiographical memories lead to anxiety symptoms. Recent work suggests a new repetitive pulse transcranial magnetic stimulation (rTMS) brain target that might bring relief. Since this proposed target is not well understood, the goal of the study is to use functional magnetic resonance imaging (fMRI) to identify the brain regions and networks that change with rTMS stimulation at this target area in PTSD patients. Ultimately, this would lead to a personalized approach to rTMS treatment of PTSD based on brain imaging that can be used in a future clinical trial. Participants will be asked to complete psychological testing and questionnaires as well as an initial MRI and two separate TMS-fMRI sessions. Total participation time across all visits is estimated to be five to six hours. Research participation will take place at VA Palo Alto as well as at Stanford University.

Research Team

Allyson C Rosen, Ph.D.

Principal Investigator

PAVIR/Palo Alto VAHCS/Stanford University

Eligibility Criteria

This trial is for individuals aged 18-55 with PTSD, who can safely undergo MRI and TMS procedures. Participants must be able to understand and sign the consent form, have a confirmed PTSD diagnosis per DSM 5 criteria, and commit to not changing their medication between two fMRI sessions.

Inclusion Criteria

Able to read, verbalize, understand, and voluntarily sign the Informed Consent Form prior to participating in any study-specific procedures or assessments

Commitment to maintaining a stable medication regimen between the two fMRI sessions

I can safely have an MRI and TMS without discomfort.

Exclusion Criteria

Presence of any other condition that has the potential to prevent study completion and/or have a confounding effect on the interpretation of results

Being in urgent need of care that would make participation impossible

Inability to safely and comfortably undergo an MRI. MRI safety will be determined by the center where MRI's are collected

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 visit

1 visit (in-person)

Baseline Assessment

Participants undergo MRI, psychological, and functional testing to characterize them and confirm eligibility

1 visit

1 visit (in-person)

TMS-fMRI Sessions

Participants undergo simultaneous TMS-fMRI and cTBS and fMRI in two separate sessions

2 visits

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• TMS-fMRI

Trial Overview The study tests whether targeting a new brain area with repetitive pulse transcranial magnetic stimulation (rTMS) while using functional magnetic resonance imaging (fMRI) can help manage PTSD symptoms by altering brain activity. It aims at personalizing rTMS treatment based on brain imaging.

Participant Groups

Group I: TMS-fMRI Experimental Treatment 1 Intervention

Participants will undergo simultaneous TMS-fMRI as part of this study. There will be two locations stimulated: one control region and one target region. Participants will be randomized with respect to the order of receiving stimulation at the locations, but all participants will receive stimulation at both locations as part of the study. All participants will be considered as one group but order effects will be evaluated as an explanatory variable.

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

Approved in United States as Transcranial Magnetic Stimulation for:

• Major Depressive Disorder
• Obsessive-Compulsive Disorder
• Migraines

Approved in European Union as Transcranial Magnetic Stimulation for:

• Major Depressive Disorder
• Obsessive-Compulsive Disorder

Approved in Canada as Transcranial Magnetic Stimulation for:

• Major Depressive Disorder
• Obsessive-Compulsive Disorder

Who Is Running the Clinical Trial?

Allyson Rosen

Lead Sponsor

Trials

1

Recruited

30+

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]

In a study involving 30 patients with PTSD, both left and right dorsolateral prefrontal cortex (DLPFC) stimulation using 20 Hz rTMS significantly reduced PTSD symptoms, with right DLPFC stimulation showing a larger effect.

The treatment was safe, with no cognitive worsening observed, and the benefits lasted for at least three months after the treatment, suggesting that rTMS could be an effective long-term intervention for PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive brain stimulation with high-frequency and low-intensity repetitive transcranial magnetic stimulation treatment for posttraumatic stress disorder. Boggio, PS., Rocha, M., Oliveira, MO., et al.[2021]

In a study of 20 drug-naive PTSD patients and 16 healthy controls, PTSD patients exhibited significant impairments in GABA(A)-ergic function, particularly in the right hemisphere, indicating a potential imbalance in neurotransmitter systems related to their symptoms.

The findings suggest that the altered cortical excitability in PTSD patients, characterized by increased glutamatergic activity and decreased GABA(A)-ergic function, could inform new treatment strategies using neuromodulation techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dysfunctions of cortical excitability in drug-naïve posttraumatic stress disorder patients. Rossi, S., De Capua, A., Tavanti, M., et al.[2021]

In a study of 33 adults with comorbid major depressive disorder and posttraumatic stress disorder, TMS therapy was shown to alter brain connectivity, particularly between the subgenual anterior cingulate cortex and the default mode network, which predicted clinical improvement.

After TMS treatment, reductions in connectivity between specific brain regions were associated with symptom relief, suggesting that these connectivity changes may serve as biomarkers for treatment response in patients with these disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Network Mechanisms of Clinical Response to Transcranial Magnetic Stimulation in Posttraumatic Stress Disorder and Major Depressive Disorder. Philip, NS., Barredo, J., van 't Wout-Frank, M., et al.[2020]

In a study involving 429 pediatric patients undergoing transcranial magnetic stimulation (TMS) for motor and language mapping, most adverse events were benign, with seizures occurring in 5.8% of sessions but not conclusively linked to TMS.

TMS was safely performed in patients with cranial metal, and useful mapping results were achieved in nearly all cases, indicating that TMS is a safe option for functional mapping in pediatric patients with epilepsy or brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Image-guided TMS is safe in a predominately pediatric clinical population. Braden, AA., Weatherspoon, SE., Boardman, T., et al.[2022]

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 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]

Patients with PTSD following minor head trauma showed significantly lower motor evoked potential (MEP) inhibition compared to healthy controls, indicating abnormal motor cortex excitability.

The study, involving 14 PTSD patients and 23 healthy subjects, suggests that PTSD may lead to changes in intracortical inhibition, which could be linked to neuroticism and other psychological conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cortical hyperexcitability in post-traumatic stress disorder secondary to minor accidental head trauma: a neurophysiologic study. Centonze, D., Palmieri, MG., Boffa, L., et al.[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. United States pubmed.ncbi.nlm.nih.gov

Noninvasive brain stimulation with high-frequency and low-intensity repetitive transcranial magnetic stimulation treatment for posttraumatic stress disorder. [2021]

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

Dysfunctions of cortical excitability in drug-naïve posttraumatic stress disorder patients. [2021]

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

Network Mechanisms of Clinical Response to Transcranial Magnetic Stimulation in Posttraumatic Stress Disorder and Major Depressive Disorder. [2020]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Image-guided TMS is safe in a predominately pediatric clinical population. [2022]

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

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

8. 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]

9. Canada pubmed.ncbi.nlm.nih.gov

Cortical hyperexcitability in post-traumatic stress disorder secondary to minor accidental head trauma: a neurophysiologic study. [2018]