TMS for PTSD
(rTMS for PTSD Trial)
Recruiting in Palo Alto (17 mi)
Overseen byBradley V Watts, MD MPH
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: VA Office of Research and Development
Must not be taking: Clozapine, Bupropion
Disqualifiers: Pregnancy, CNS disorder, Psychosis, others
No Placebo Group
Trial Summary
What is the purpose of this trial?
Posttraumatic Stress Disorder (PTSD) is a common and serious condition affecting many Veterans. There are effective treatments for PTSD, but additional treatments are needed in order to better serve Veterans suffering from PTSD. Transcranial magnetic stimulation is one such promising treatment. It involves use of powerful magnet to stimulate the specific brain regions in Veterans with PTSD. Transcranial magnetic stimulation has been shown effective in treating depression, but currently it is unclear if it is an effective treatment for PTSD. This is a randomized clinical trial enrolling 91 Veterans with PTSD comparing the effectiveness of transcranial magnetic stimulation treatment and sham transcranial magnetic stimulation in treating PTSD. The hypothesis is that those who receive transcranial magnetic stimulation will experience improved functioning.
Will I have to stop taking my current medications?
The trial requires that you stop taking clozapine and limit bupropion to 300mg per day. Additionally, you should not have changed your dose of Fluoxetine, Paroxetine, Sertraline, or Venlafaxine in the past 2 months.
What data supports the effectiveness of this treatment for PTSD?
Research shows that repetitive transcranial magnetic stimulation (rTMS) can improve symptoms of PTSD and depression. In one study, both 1 Hz and 10 Hz rTMS led to significant improvements in PTSD and depression scores, although no clear advantage was found between the two frequencies. Another study found that rTMS may help with depression in people with PTSD, but it had minimal impact on core PTSD symptoms.12345
Is transcranial magnetic stimulation (TMS) safe for humans?
TMS is generally considered safe for humans, but it can cause seizures, which are rare and often occur when guidelines are not followed or in individuals taking certain medications. Safety guidelines have been developed and updated over the years to minimize risks, and TMS has been used safely in thousands of people with various conditions.36789
How does TMS 1 Hz treatment for PTSD differ from other treatments?
TMS 1 Hz is a non-invasive treatment that uses magnetic fields to stimulate the brain, specifically targeting the right prefrontal cortex at a low frequency. Unlike traditional therapies like medication or talk therapy, TMS directly influences brain activity and has shown promise in treating PTSD, especially for those who do not respond to standard treatments.110111213
Eligibility Criteria
This trial is for Veterans aged 19-70 with moderate to severe PTSD, eligible for VA healthcare. Participants must not be using certain medications like high-dose bupropion or clozapine, have no metal in their head (except dental work), no major CNS disorders, unstable medical conditions, recent seizures, or current psychosis. Women of childbearing potential must use birth control.Inclusion Criteria
You are eligible for VA healthcare.
I am between 19 and 70 years old.
Moderate to severe PTSD as determined by the CAPS within 7 days of randomization
See 9 more
Exclusion Criteria
I do not have a major brain condition like a stroke, tumor, or epilepsy.
You have a problem with alcohol or drugs that affects your ability to take part in the study.
I have previously used TMS therapy.
See 10 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive transcranial magnetic stimulation or sham treatment
6 weeks
Multiple visits for TMS sessions
Follow-up
Participants are monitored for PTSD symptoms, functioning, and depressive symptoms
6 months
Assessments at 3 and 6 months post-treatment
Treatment Details
Interventions
- Sham TMS (Behavioural Intervention)
- TMS 1 hz (Behavioural Intervention)
Trial OverviewThe study tests if Transcranial Magnetic Stimulation (TMS), a non-invasive method using magnets to stimulate the brain, can improve functioning in Veterans with PTSD compared to sham TMS. It's randomized and involves 91 participants who either receive real TMS or a placebo-like sham treatment.
Participant Groups
2Treatment groups
Experimental Treatment
Placebo Group
Group I: TMSExperimental Treatment1 Intervention
transcranial magnetic stimulation delivered to the right dorsolateral prefrontal cortex at 1 Hz
Group II: ShamPlacebo Group1 Intervention
sham transcranial magnetic stimulation delivered to the right dorsolateral prefrontal cortex
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
White River Junction VA Medical Center, White River Junction, VTWhite River Junction, VT
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Who Is Running the Clinical Trial?
VA Office of Research and DevelopmentLead Sponsor
References
One hertz versus ten hertz repetitive TMS treatment of PTSD: A randomized clinical trial. [2019]The purpose of this trial was to test whether right prefrontal cortex 1 Hz versus 10 Hz rTMS provides a significantly greater improvement in PTSD symptoms and/or function. Veterans 18 to 50 years of age suffering from PTSD were randomized to right prefrontal 1 Hz rTMS [2400 pulses/session] versus right prefrontal 10 Hz rTMS [2400 pulses/session]. The treatments were performed 5 days a week for 6 weeks with a 3-week taper using the NeuroStar system. There were one month and three months post treatment follow-up evaluations. Forty-four participants were enrolled with 17 being randomized to 1 Hz rTMS and 18 to 10 Hz rTMS. Both groups had significant improvement in PTSD and depression scores from baseline to the end of acute treatment. The 10 Hz group but not the 1 Hz group demonstrated significant improvement in function. Although both groups demonstrated significant improvement in PTSD and depression symptoms, a significant advantage for either the 1 Hz or 10 Hz frequency group on any of the scales acquired was not demonstrated. Further work is required with larger samples sizes to test whether low or high frequency is superior or if individual differences would indicate the more effective frequency.
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.
Prefrontal transcranial magnetic stimulation for depression in US military veterans - A naturalistic cohort study in the veterans health administration. [2023]Repetitive transcranial magnetic stimulation (TMS) is an evidence-based treatment for pharmacoresistant major depressive disorder (MDD), however, the evidence in veterans has been mixed. To this end, VA implemented a nationwide TMS program that included evaluating clinical outcomes within a naturalistic design. TMS was hypothesized to be safe and provide clinically meaningful reductions in MDD and posttraumatic stress disorder (PTSD) symptoms.
Bilateral sequential theta burst stimulation in depressed veterans with service related posttraumatic stress disorder: a feasibility study. [2022]Depression comorbid with posttraumatic stress disorder (PTSD) can be disabling and treatment resistant. Preliminary evidence suggests that repetitive transcranial magnetic stimulation (rTMS), may have a role in helping these patients. There are only few published studies using different rTMS paradigms including bilateral intermittent theta burst (iTBS) and low frequency rTMS.
Use of machine learning in predicting clinical response to transcranial magnetic stimulation in comorbid posttraumatic stress disorder and major depression: A resting state electroencephalography study. [2021]Repetitive transcranial magnetic stimulation (TMS) is clinically effective for major depressive disorder (MDD) and investigational for other conditions including posttraumatic stress disorder (PTSD). Understanding the mechanisms of TMS action and developing biomarkers predicting response remain important goals. We applied a combination of machine learning and electroencephalography (EEG), testing whether machine learning analysis of EEG coherence would (1) predict clinical outcomes in individuals with comorbid MDD and PTSD, and (2) determine whether an individual had received a TMS course.
Seizures from transcranial magnetic stimulation 2012-2016: Results of a survey of active laboratories and clinics. [2021]Transcranial magnetic stimulation (TMS) can cause seizures in healthy individuals and patients. However, the rate at which this occurs is unknown. We estimated the risk of seizure and other adverse events with TMS.
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.
Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. [2022]This article is based on a consensus conference, which took place in Certosa di Pontignano, Siena (Italy) on March 7-9, 2008, intended to update the previous safety guidelines for the application of transcranial magnetic stimulation (TMS) in research and clinical settings. Over the past decade the scientific and medical community has had the opportunity to evaluate the safety record of research studies and clinical applications of TMS and repetitive TMS (rTMS). In these years the number of applications of conventional TMS has grown impressively, new paradigms of stimulation have been developed (e.g., patterned repetitive TMS) and technical advances have led to new device designs and to the real-time integration of TMS with electroencephalography (EEG), positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). Thousands of healthy subjects and patients with various neurological and psychiatric diseases have undergone TMS allowing a better assessment of relative risks. The occurrence of seizures (i.e., the most serious TMS-related acute adverse effect) has been extremely rare, with most of the few new cases receiving rTMS exceeding previous guidelines, often in patients under treatment with drugs which potentially lower the seizure threshold. The present updated guidelines review issues of risk and safety of conventional TMS protocols, address the undesired effects and risks of emerging TMS interventions, the applications of TMS in patients with implanted electrodes in the central nervous system, and safety aspects of TMS in neuroimaging environments. We cover recommended limits of stimulation parameters and other important precautions, monitoring of subjects, expertise of the rTMS team, and ethical issues. While all the recommendations here are expert based, they utilize published data to the extent possible.
Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996. [2022]Single-pulse transcranial magnetic stimulation (TMS) is a safe and useful tool for investigating various aspects of human neurophysiology, particularly corticospinal function, in health and disease. Repetitive TMS (rTMS), however, is a more powerful and potentially dangerous modality, capable of regionally blocking or facilitating cortical processes. Although there is evidence that rTMS is useful for treating clinical depression, and possibly other brain disorders, it had caused 7 known seizures by 1996 and could have other undesirable effects. In June 1996 a workshop was organized to review the available data on the safety of rTMS and to develop guidelines for its safe use. This article summarizes the workshop's deliberations. In addition to issues of risk and safety, it also addresses the principles and applications of rTMS, nomenclature, and potential therapeutic effects of rTMS. The guidelines for the use of rTMS, which are summarized in an appendix, cover the ethical issues, recommended limits on stimulation parameters, monitoring of subjects (both physiologically and neuropsychologically), expertise and function of the rTMS team, medical and psychosocial management of induced seizures, and contra-indications to rTMS.
Transcranial Magnetic Stimulation for Posttraumatic Stress Disorder and Major Depression: Comparing Commonly Used Clinical Protocols. [2022]Transcranial magnetic stimulation (TMS) is increasingly being used to treat posttraumatic stress disorder (PTSD) comorbid with major depressive disorder (MDD). Yet, identifying the most effective stimulation parameters remains an active area of research. We recently reported on the use of 5 Hz TMS to reduce PTSD and MDD symptoms. A recently developed form of TMS, intermittent theta burst stimulation (iTBS), appears noninferior for treating MDD. Because iTBS can be delivered in a fraction of the time, it provides significant logistical advantages; however, evaluations of whether iTBS provides comparable PTSD and MDD symptom reductions are lacking. We performed a retrospective chart review comparing clinical outcomes in veterans with PTSD and MDD who received iTBS (n = 10) with a matched cohort that received 5-Hz TMS (n = 10). Symptoms were evaluated using self-reported rating scales at baseline and every five treatments for up to 30 sessions. Both protocols were safe and reduced symptoms, ps
Repetitive transcranial magnetic stimulation ameliorates anxiety-like behavior and impaired sensorimotor gating in a rat model of post-traumatic stress disorder. [2022]Repetitive transcranial magnetic stimulation (rTMS) has been employed for decades as a non-pharmacologic treatment for post-traumatic stress disorder (PTSD). Although a link has been suggested between PTSD and impaired sensorimotor gating (SG), studies assessing the effects of rTMS against PTSD or PTSD with impaired SG are scarce.
Transcranial magnetic stimulation for post-traumatic stress disorder. [2022]Post-traumatic stress disorder (PTSD) is a debilitating psychiatric disorder. While current treatment options are effective for some, many individuals fail to respond to first-line psychotherapies and pharmacotherapy. Transcranial magnetic stimulation (TMS) has emerged over the past several decades as a noninvasive neuromodulatory intervention for psychiatric disorders including depression, with mounting evidence for its safety, tolerability, and efficacy in treating PTSD. While several meta-analyses of TMS for PTSD have been published to date showing large effect sizes on PTSD overall, there is marked variability between studies, making it difficult to draw simple conclusions about how best to treat patients. The following review summarizes over 20 years of the existing literature on TMS as a PTSD treatment, and includes nine randomized controlled trials and many other prospective studies of TMS monotherapy, as well as five randomized controlled trials investigating TMS combined with psychotherapy. While the majority of studies utilize repetitive TMS targeted to the right dorsolateral prefrontal cortex (DLPFC) at low frequency (1 Hz) or high frequency (10 or 20 Hz), others have used alternative frequencies, targeted other regions (most commonly the left DLPFC), or trialed different stimulation protocols utilizing newer TMS modalities such as synchronized TMS and theta-burst TMS (TBS). Although it is encouraging that positive outcomes have been shown, there is a paucity of studies directly comparing available approaches. Biomarkers, such as functional imaging and electroencephalography, were seldomly incorporated yet remain crucial for advancing our knowledge of how to predict and monitor treatment response and for understanding mechanism of action of TMS in this population. Effects on PTSD are often sustained for up to 2-3 months, but more long-term studies are needed in order to understand and predict duration of response. In short, while TMS appears safe and effective for PTSD, important steps are needed to operationalize optimal approaches for patients suffering from this disorder.
Pilot Testing of Peak Alpha Frequency Stability During Repetitive Transcranial Magnetic Stimulation. [2020]Over half of those diagnosed with post-traumatic stress disorder (PTSD) have comorbid major depressive disorder (MDD), and rates are even higher among military veterans. Transcranial magnetic stimulation (TMS) may be a safe and efficacious treatment for PTSD, both with and without comorbid MDD. Still, the mechanism of action of TMS is not fully understood, and it remains unclear which stimulation techniques (e.g., target regions, pulse strength/frequency, waveform) optimize treatment for these patients. Recent research indicated that a patient's unique individualized alpha frequency (IAF) may be used to guide brain stimulation treatment, and emerging data suggests that stimulation synchronized to the IAF may be efficacious for MDD. However, to our knowledge there are no studies to date that evaluate the stability of IAF over time in patients with comorbid PTSD and MDD. To this end, we used an eight-lead electroencephalography (EEG) system to record IAF before and after a course of TMS. Stimulation parameters were informed by prior studies of TMS for comorbid PTSD and MDD and included 5 Hz TMS to the left dorsolateral prefrontal cortex, at 120% of motor threshold, 3,000-4,000 pulses per session for up to 40 sessions. We tested whether IAF was changed with a course of TMS therapy and evaluated whether IAF predicted clinical outcomes. We observed no significant changes in IAF from baseline to post-treatment, and there was no relationship between IAF and clinical symptom change. These data demonstrate the stability of IAF with TMS and indicate its utility as a trait marker for future brain stimulation studies. This work does not support the use of IAF as predictor of clinical response to TMS as administered.