Brain Stimulation for PTSD

Overseen By Lily A Brown, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Pennsylvania

Disqualifiers: Pregnancy, Seizure disorder, Claustrophobia, others

Compensation: Varies

Number of Visits: 4

Duration: 5 weeks

120 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will be the first of its kind to explore the impact of continuous theta burst stimulation (cTBS) to the intraparietal sulcus (IPS) on arousal symptoms among patients with posttraumatic stress disorder (PTSD). The investigators will demonstrate that IPS cTBS results in significant reduction in arousal (measured by startle response) compared to sham cTBS, that IPS cTBS interacts with extinction training to further improve arousal, and that there is a dose/response effect of cTBS on arousal. The investigators will also demonstrate that IPS cTBS significantly improves retention of extinction learning, the experimental analogue of exposure therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those who have had recent medication changes in the past 8 weeks. This might mean you need to be stable on your current medications for at least 8 weeks before joining.

What data supports the effectiveness of the treatment Continuous Theta Burst Stimulation for PTSD?

Research suggests that intermittent theta burst stimulation (iTBS), a form of brain stimulation, has shown promise in improving symptoms of PTSD and depression. Studies indicate that iTBS can change brain connectivity patterns, which may help reduce PTSD symptoms. ^{1 2 3 4 5}

Is theta burst stimulation (TBS) safe for humans?

Theta burst stimulation (TBS) has been studied for various psychiatric conditions and is generally considered safe, with most adverse effects being mild. However, there is a theoretical risk of seizures, so it should be used with caution, and more research is needed to fully understand its long-term safety. ^{1 2 4 6 7}

How is continuous theta burst stimulation different from other PTSD treatments?

Continuous theta burst stimulation (cTBS) is a unique treatment for PTSD that uses magnetic pulses to stimulate specific brain areas, offering a novel approach compared to traditional therapies like medication or talk therapy. It is a form of transcranial magnetic stimulation (TMS) that is faster and has shown promise in improving symptoms of depression and PTSD, especially in cases where other treatments have not been effective. ^{1 2 4 8 9}

Research Team

Lily A Brown, PhD

Principal Investigator

University of Pennsylvania

Eligibility Criteria

This trial is for right-handed adults aged 18-60 with PTSD, as diagnosed by the DSM-5 criteria. Participants must not have any metal implants in their body.

Inclusion Criteria

No metal implants

I am between 18 and 60 years old.

Right-handed

Exclusion Criteria

Any medical condition that increases risk for fMRI or cTBS

Claustrophobia

Non-English speaking

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive continuous theta burst stimulation (cTBS) to the intraparietal sulcus (IPS) and undergo extinction training to reduce arousal symptoms

5 weeks

Multiple visits including Days 4, 5, 34, and 35

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of startle response and subjective distress

4 weeks

Treatment Details

Interventions

• Continuous Theta Burst Stimulation
• Sham Continuous Theta Burst Stimulation

Trial Overview The study tests if a brain stimulation technique called Continuous Theta Burst Stimulation (cTBS) to the Intraparietal Sulcus can reduce arousal symptoms in PTSD patients compared to sham (fake) treatment.

Participant Groups

Group I: Continuous theta burst stimulation to the intraparietal sulcus Experimental Treatment 1 Intervention

Continuous theta burst stimulation will be delivered to the individually targeted intraparietal sulcus site at 100% RMT.

Group II: Sham continuous theta burst stimulation Placebo Group 1 Intervention

We will use the coil's electric stimulation functionality that allows for the delivery of a brief electric pulse to the scalp simultaneous to the pulse to mimic actual stimulation.

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Findings from Research

Intermittent Theta Burst Stimulation (iTBS) was well-tolerated by eight Australian veterans with PTSD, with only mild to moderate side effects reported, such as cranial pain and headaches, which were manageable with analgesics.

Participants showed significant reductions in PTSD and depression symptoms after 20 sessions of iTBS, along with improvements in cognitive functions like working memory and processing speed, suggesting that iTBS could be a promising new treatment for veterans with PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploring Theta Burst Stimulation for Post-traumatic Stress Disorder in Australian Veterans-A Pilot Study. Nursey, J., Sbisa, A., Knight, H., et al.[2021]

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 randomized, double-blind trial involving 56 patients, intermittent theta burst stimulation (iTBS) over the dorsomedial prefrontal cortex showed a significant reduction in negative symptoms for patients with depression, but not for those with schizophrenia.

The treatment was generally safe and well-tolerated, with serious adverse events occurring only in the sham group, indicating that iTBS may be a promising intervention for depressive symptoms in certain patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dorsomedial prefrontal theta burst stimulation to treat anhedonia, avolition, and blunted affect in schizophrenia or depression - a randomized controlled trial. Bodén, R., Bengtsson, J., Thörnblom, E., et al.[2021]

Intermittent theta burst stimulation (iTBS) for PTSD was tested in a randomized controlled trial with 47 participants before treatment and 43 after, showing that EEG can effectively track changes in brain connectivity related to treatment response.

Using machine learning, the study found that EEG data could accurately distinguish between active and sham treatments with 75% accuracy, suggesting that EEG could be a practical tool for personalizing PTSD treatments based on brain activity patterns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in functional connectivity after theta-burst transcranial magnetic stimulation for post-traumatic stress disorder: a machine-learning study. Zandvakili, A., Swearingen, HR., Philip, NS.[2022]

Theta-burst Stimulation (TBS) is a promising form of repetitive transcranial magnetic stimulation that can induce significant and lasting changes in brain activity with lower intensity and shorter duration than traditional methods, making it a potentially more efficient treatment option.

TBS may have therapeutic implications for neuropsychiatric disorders due to its ability to promote synaptic plasticity, although the exact neurobiological mechanisms, including processes like long-term potentiation and GABAergic modulation, are still being researched.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanisms and applications of theta-burst rTMS on the human motor cortex. Cárdenas-Morales, L., Nowak, DA., Kammer, T., et al.[2009]

Theta-burst stimulation (TBS) shows promise as a rapid and effective treatment for psychiatric disorders, particularly treatment-resistant depression and auditory hallucinations, with studies indicating mild adverse effects but no severe complications like seizures or mania.

The current research on TBS is varied in design and outcomes, highlighting the need for more rigorous sham-controlled studies to better assess its long-term safety and efficacy in treating various psychiatric conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Theta-Burst Stimulation in the Treatment of Psychiatric Disorders: A Review of the Literature. Rachid, F.[2019]

Theta burst stimulation (TBS) is a promising technique for altering brain excitability, with a review of studies showing that adverse events were mostly mild and occurred in only 5% of subjects, indicating a generally safe profile.

Despite its safety, TBS carries a theoretical higher risk of seizures compared to other stimulation methods, necessitating cautious application and further research into its dosing parameters to better understand seizure risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of theta burst transcranial magnetic stimulation: a systematic review of the literature. Oberman, L., Edwards, D., Eldaief, M., et al.[2022]

Intermittent theta burst stimulation (iTBS) significantly reduced anger symptoms in veterans with chronic PTSD after just one week of treatment compared to sham stimulation, indicating its potential efficacy in managing anger associated with PTSD.

The reduction in anger was sustained for at least one month after the treatment, suggesting that iTBS may provide lasting benefits for emotional regulation in PTSD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Secondary Analysis on Effects of Theta Burst Transcranial Magnetic Stimulation to Reduce Anger in Veterans With Posttraumatic Stress Disorder. van 't Wout-Frank, M., Shea, MT., Sorensen, DO., et al.[2022]

Continuous theta burst stimulation (cTBS) effectively inhibits synaptic transmission in the primary motor cortex for up to 1 hour, demonstrating its potential as a novel neuromodulation technique.

cTBS applied to the left motor cortex increases local GABA levels, indicating enhanced GABAergic activity, while not significantly affecting glutamate/glutamine levels, suggesting a specific mechanism of action for this stimulation technique.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurochemical effects of theta burst stimulation as assessed by magnetic resonance spectroscopy. Stagg, CJ., Wylezinska, M., Matthews, PM., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Exploring Theta Burst Stimulation for Post-traumatic Stress Disorder in Australian Veterans-A Pilot Study. [2021]

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

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

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

Dorsomedial prefrontal theta burst stimulation to treat anhedonia, avolition, and blunted affect in schizophrenia or depression - a randomized controlled trial. [2021]

4. Germany pubmed.ncbi.nlm.nih.gov

Changes in functional connectivity after theta-burst transcranial magnetic stimulation for post-traumatic stress disorder: a machine-learning study. [2022]

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

Mechanisms and applications of theta-burst rTMS on the human motor cortex. [2009]

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

Safety and Efficacy of Theta-Burst Stimulation in the Treatment of Psychiatric Disorders: A Review of the Literature. [2019]

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

Safety of theta burst transcranial magnetic stimulation: a systematic review of the literature. [2022]

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

A Secondary Analysis on Effects of Theta Burst Transcranial Magnetic Stimulation to Reduce Anger in Veterans With Posttraumatic Stress Disorder. [2022]

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

Neurochemical effects of theta burst stimulation as assessed by magnetic resonance spectroscopy. [2022]