Accelerated TMS for PTSD

Overseen By Kevin A Johnson, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Florida State University

Must not be taking: Tricyclics, Clozapine

Disqualifiers: Substance use, Schizophrenia, Pregnancy, 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: 31

132 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will test the clinical efficacy of an accelerated TMS (accel-TMS) protocol that rapidly addresses PTSD symptoms with 1 week (25 sessions over 5 days) of condensed treatment.

Will I have to stop taking my current medications?

The trial requires that you do not change your psychotropic medications (medications affecting mood, perception, or behavior) for 1 month before starting and throughout the trial. If you are taking medications that lower the seizure threshold, you may need to stop them.

What data supports the effectiveness of the treatment Accelerated TMS for PTSD?

Research shows that both intermittent theta-burst stimulation (iTBS) and repetitive transcranial magnetic stimulation (rTMS) can effectively reduce PTSD symptoms. iTBS, a faster form of TMS, has been found to be as effective as traditional rTMS in improving PTSD symptoms, offering a quicker treatment option. ^{1 2 3 4 5}

Is Accelerated TMS safe for humans?

Accelerated TMS, including forms like repetitive TMS (rTMS) and theta-burst stimulation (TBS), has been studied for safety in both healthy individuals and those with conditions like PTSD and depression. Generally, these treatments are considered safe, with established safety guidelines and minimal risk of serious side effects. However, some people may experience mild side effects like headaches or discomfort at the stimulation site. ^{1 2 6 7 8}

How is Accelerated TMS different from other treatments for PTSD?

Accelerated TMS, specifically using intermittent theta burst stimulation (iTBS), is unique because it can be delivered much faster than traditional TMS protocols, offering logistical advantages while still being effective for PTSD and depression. This rapid administration makes it a novel approach compared to other treatments that may require longer sessions. ^{1 2 5 7 9}

Research Team

Frank A Kozel, MD

Principal Investigator

Florida State University

Eligibility Criteria

This trial is for individuals with PTSD or Traumatic Brain Injury who are seeking rapid treatment. Participants should be eligible based on specific criteria set by the study, which aren't detailed here.

Inclusion Criteria

Meets DSM-5 criteria for PTSD with a PCL-5 score > 33

My mental health medication has been stable for the last month.

I understand the study details and can follow its requirements.

Exclusion Criteria

I am fluent in English.

I do not have conditions like metal in my head or seizures that prevent neuromodulation.

OCD cannot be the primary disorder but can have OCD symptoms

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Acute Phase

Participants undergo a three-arm randomized sham-controlled trial with active and sham accel-TMS treatments

1 week

25 sessions over 5 days

Extension Phase

All participants receive active left dl-PFC accel-TMS

1 week

5 sessions over 5 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Assessments at 1-month, 3-months, and 6-months

Treatment Details

Interventions

• Accelerated TMS

Trial Overview The trial tests an accelerated TMS protocol aimed at quickly reducing PTSD symptoms through 25 sessions over a week using different types of brain stimulation coils, some real and some sham (placebo).

Participant Groups

Group I: Arm 1: active left dl-PFC accel-TMS Active Control 1 Intervention

Acute Phase: Eligible participants will be randomized into one of the three treatment groups: active left dl-PFC accel-TMS vs. active dm-PFC accel-TMS vs. sham dl-PFC/dm-PFC accel TMS

Group II: Arm 2:active dm-PFC accel-TMS Active Control 1 Intervention

Acute Phase: Eligible participants will be randomized into one of the three treatment groups: active left dl-PFC accel-TMS vs. active dm-PFC accel-TMS vs. sham dl-PFC/dm-PFC accel TMS

Group III: Arm 5 Active Control 1 Intervention

Extension phase, all participants will receive active left dl-PFC accel-TMS.

Group IV: Arm 3 - sham accel-TMS dl-PFC Placebo Group 1 Intervention

Acute Phase: Eligible participants will be randomized into one of the three treatment groups: active left dl-PFC accel-TMS vs. active dm-PFC accel-TMS vs. sham dl-PFC/dm-PFC accel TMS

Group V: Arm 4: sham accel -TMS dm-PFC Placebo Group 1 Intervention

Acute Phase: Eligible participants will be randomized into one of the three treatment groups: active left dl-PFC accel-TMS vs. active dm-PFC accel-TMS vs. sham dl-PFC/dm-PFC accel TMS

Accelerated TMS is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as rTMS for:

• Major Depressive Disorder
• Obsessive Compulsive Disorder

Approved in European Union as rTMS for:

• Major Depressive Disorder
• Obsessive Compulsive Disorder

Approved in United Kingdom as rTMS for:

• Major Depressive Disorder
• Obsessive Compulsive Disorder
• Post-Traumatic Stress Disorder
• Depersonalization Disorder
• Borderline Personality Disorder
• Addiction

Who Is Running the Clinical Trial?

Florida State University

Lead Sponsor

Trials

234

Recruited

41,100+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Findings from Research

A study comparing intermittent theta burst stimulation (iTBS) and 5 Hz transcranial magnetic stimulation (TMS) in veterans with PTSD and major depressive disorder (MDD) found that both treatments were safe and effective, but 5 Hz TMS resulted in significantly better symptom improvement.

Veterans receiving 5 Hz TMS showed greater reductions in PTSD and MDD symptoms compared to those receiving iTBS, suggesting that while iTBS is quicker to administer, it may not be as effective for these conditions based on the current data from 20 participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Magnetic Stimulation for Posttraumatic Stress Disorder and Major Depression: Comparing Commonly Used Clinical Protocols. Philip, NS., Doherty, RA., Faucher, C., et al.[2022]

A study involving 50 veterans with PTSD showed that intermittent theta-burst stimulation (iTBS) significantly improved social and occupational functioning after 2 weeks, indicating its potential efficacy as a treatment for PTSD.

One month after treatment, iTBS demonstrated significant reductions in both clinician- and self-rated PTSD symptoms, as well as improvements in depression and functioning, suggesting that iTBS could be a promising new approach for managing PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Theta-Burst Transcranial Magnetic Stimulation for Posttraumatic Stress Disorder. Philip, NS., Barredo, J., Aiken, E., 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]

Intermittent theta burst stimulation (iTBS) is an effective treatment for PTSD, showing significant improvement in symptoms compared to a sham treatment, with similar efficacy to the standard 10 Hz rTMS despite shorter session durations.

In a study involving 75 participants, both iTBS and 10 Hz rTMS led to significant reductions in PTSD symptoms, as measured by the PCL-C scale, indicating that iTBS could be a viable alternative to traditional rTMS therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of intermittent theta-burst transcranial magnetic stimulation on post-traumatic stress disorder symptoms: A randomized controlled trial. Yuan, H., Liu, B., Li, F., et al.[2023]

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 165 pediatric participants aged 6 to 18, theta-burst TMS (TBS) demonstrated a similar safety profile to single- and paired-pulse TMS (sp/ppTMS), with no severe adverse effects reported.

The overall rate of adverse effects was 10.5% for TBS and 12.4% for sp/ppTMS, with most effects rated as minimal or mild, indicating that TBS is a safe option for further investigation in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of theta burst stimulation vs. single and paired pulse transcranial magnetic stimulation: a comparative study of 165 pediatric subjects. Hong, YH., Wu, SW., Pedapati, EV., et al.[2020]

In a study of 27 participants, a prolonged intermittent theta burst stimulation (piTBS) protocol using 1,800 pulses showed limited effectiveness for major depressive disorder, with only 18.2% of participants achieving a response and 9.1% reaching remission.

Safety and tolerability were concerns, as 18.5% of participants experienced issues, suggesting that while piTBS is a promising approach, further research is needed to optimize its parameters and improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged intermittent theta burst stimulation in the treatment of major depressive disorder: a case series. Richard, M., Noiseux, C., Desbeaumes Jodoin, V., 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]

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]

References

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

Transcranial Magnetic Stimulation for Posttraumatic Stress Disorder and Major Depression: Comparing Commonly Used Clinical Protocols. [2022]

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

Theta-Burst Transcranial Magnetic Stimulation for Posttraumatic Stress Disorder. [2020]

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

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

4. Ireland pubmed.ncbi.nlm.nih.gov

Effects of intermittent theta-burst transcranial magnetic stimulation on post-traumatic stress disorder symptoms: A randomized controlled trial. [2023]

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

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

6. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and tolerability of theta burst stimulation vs. single and paired pulse transcranial magnetic stimulation: a comparative study of 165 pediatric subjects. [2020]

7. Ireland pubmed.ncbi.nlm.nih.gov

Prolonged intermittent theta burst stimulation in the treatment of major depressive disorder: a case series. [2022]

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

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

9. England pubmed.ncbi.nlm.nih.gov

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