rTMS for TBI-related Depression

(ADEPT Trial)

Recruiting at 4 trial locations

Overseen by David L Brody, MD, PhD

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Henry M. Jackson Foundation for the Advancement of Military Medicine

Must be taking: Psychotropic medications

Must not be taking: Tricyclics, Neuroleptics

Disqualifiers: Seizure history, Bipolar, Schizophrenia, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

The purpose of this study is to investigate the efficacy, safety, and tolerability of two dorsolateral prefrontal cortex (DLPFC) repetitive transcranial magnetic stimulation (rTMS) protocols to alleviate symptoms of depression in United States (U.S.) military service members and veterans with a history of concussion/mild traumatic brain injury (TBI).

Will I have to stop taking my current medications?

The trial requires participants to have been on a steady psychotropic medication regimen for six weeks before joining, so you may need to continue your current medications. The protocol does not specify if you must stop other medications, but you should discuss this with the study team.

What data supports the effectiveness of the treatment rTMS for TBI-related depression?

Research shows that repetitive transcranial magnetic stimulation (rTMS) can improve depression symptoms in people with traumatic brain injury (TBI), although the effects may not last long. It also appears to help with cognitive functions like memory and thinking skills, and is generally safe and well-tolerated. ^{1 2 3 4 5}

Is rTMS safe for treating depression in people with TBI?

Repetitive transcranial magnetic stimulation (rTMS) is generally considered safe for treating depression, with common side effects being minor, like headaches. However, there is a low risk of seizures, especially in people with traumatic brain injury (TBI), so careful screening and following safety guidelines are important. ^{1 4 6 7 8}

How is rTMS treatment different from other treatments for depression after TBI?

rTMS (repetitive transcranial magnetic stimulation) is a unique treatment for depression after traumatic brain injury (TBI) because it uses magnetic fields to stimulate specific areas of the brain, potentially offering a more targeted approach with fewer side effects compared to traditional medications. Unlike standard treatments, rTMS is non-invasive and does not involve drugs, making it a novel option for those with TBI-related depression, especially since there are no established treatments for this condition. ^{1 4 9 10 11}

Research Team

David L Brody, MD, PhD

Principal Investigator

Uniformed Services University of the Health Sciences

Eligibility Criteria

This trial is for U.S. military service members or veterans aged 18-50 with a history of concussion/mild TBI and depression. They must have stable medication and therapy regimens, be able to consent in English, and have experienced specific short-term memory or consciousness changes due to TBI.

Inclusion Criteria

Baseline MADRS >13 at the time of screening indicating at least mild-moderate depressive symptoms

I am between 18 and 55 years old.

Under the care of a primary care and/or behavioral health provider

Exclusion Criteria

Intracranial lesion compromising the integrity of rsfMRI data

Unable to complete timeline of study

I have a fast-progressing illness like advanced cancer or major organ failure.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive rTMS treatment targeting the dorsolateral prefrontal cortex to alleviate depressive symptoms

Approximately 4 weeks

16 sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• rTMS (Device)
• Sham rTMS (Device)

Trial Overview The study tests the effectiveness of two types of rTMS treatments on alleviating depression symptoms in individuals with a history of mild TBI. Participants will receive either actual rTMS or sham (placebo) treatment targeting the DLPFC area of the brain.

Participant Groups

Group I: Arm 2 Experimental Treatment 1 Intervention

Active rTMS/resting state functional MRI (rsfMRI)-based targeting

Group II: Arm 1 Experimental Treatment 1 Intervention

Active rTMS/Individualized Connectome Targeting (ICT)

Group III: Arm 3 Placebo Group 2 Interventions

Sham rTMS

Who Is Running the Clinical Trial?

Henry M. Jackson Foundation for the Advancement of Military Medicine

Lead Sponsor

Trials

103

Recruited

94,300+

Congressionally Directed Medical Research Programs

Collaborator

Trials

59

Recruited

10,600+

Uniformed Services University of the Health Sciences

Collaborator

Trials

130

Recruited

91,100+

Findings from Research

Repetitive transcranial magnetic stimulation (rTMS) can be safely administered to individuals with traumatic brain injury (TBI) when following specific guidelines, minimizing risks such as seizures.

In a case study of a 48-year-old man with severe TBI, rTMS treatment for post-TBI depression over 6 weeks led to a 49% reduction in depression symptoms, demonstrating its potential efficacy in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary guidelines for safe and effective use of repetitive transcranial magnetic stimulation in moderate to severe traumatic brain injury. Nielson, DM., McKnight, CA., Patel, RN., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) may offer a targeted treatment for depression following traumatic brain injury (TBI) with potentially fewer side effects compared to standard medications, but safety concerns regarding seizure risk must be addressed.

The review suggests that low frequency rTMS could be a safer option for TBI patients, as it is less likely to induce seizures compared to high frequency rTMS, highlighting the need for pilot safety studies before larger trials can be conducted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation: A potential new treatment for depression associated with traumatic brain injury. Reti, IM., Schwarz, N., Bower, A., et al.[2022]

A patient with treatment-resistant depression (TRD) showed unexpected improvement after experiencing a seizure during repetitive transcranial magnetic stimulation (rTMS), suggesting a potential link between seizure activity and therapeutic effects in TRD.

While rTMS is generally safe, known adverse events include headaches and seizures; this case highlights an unusual outcome where a seizure may have contributed to the patient's improvement, warranting further investigation into the mechanisms of rTMS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment-Resistant Depression Entering Remission Following a Seizure during the Course of Repetitive Transcranial Magnetic Stimulation. Kim, JW., Bae, KY., Kim, SW., et al.[2020]

Repetitive Transcranial Magnetic Stimulation (rTMS) has a good overall safety profile for treating depression, with common side effects like headaches being minor and manageable.

While there is a low incidence of serious side effects such as seizures and hypomania, these are linked to specific risk factors, suggesting that proper screening can enhance patient safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of the safety of repetitive transcranial magnetic stimulation as a clinical treatment for depression. Loo, CK., McFarquhar, TF., Mitchell, PB.[2021]

Repetitive transcranial magnetic stimulation (rTMS) is generally a well-tolerated treatment for depression, with mild side effects like headaches being the most common, while severe adverse effects are rare.

Special precautions are necessary for certain groups, such as adolescents, pregnant women, and individuals with metal implants, but with proper assessment and monitoring, rTMS can be safely administered to many patients with depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation (TMS) safety: a practical guide for psychiatrists. Taylor, R., Galvez, V., Loo, C.[2019]

In a safety and efficacy study involving a 26-year-old man with severe traumatic brain injury (TBI), a 6-week rTMS protocol showed no adverse events, indicating it is a safe treatment option for individuals in a minimally conscious state.

The rTMS treatment was associated with a trend toward significant neurobehavioral improvements and enhanced neural conduction, suggesting its potential to facilitate recovery in patients with severe TBI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation-associated neurobehavioral gains during coma recovery. Louise-Bender Pape, T., Rosenow, J., Lewis, G., et al.[2016]

References

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

Preliminary guidelines for safe and effective use of repetitive transcranial magnetic stimulation in moderate to severe traumatic brain injury. [2022]

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

A Pilot Investigation of Repetitive Transcranial Magnetic Stimulation for Post-Traumatic Brain Injury Depression: Safety, Tolerability, and Efficacy. [2020]

3. England pubmed.ncbi.nlm.nih.gov

The use of repetitive transcranial magnetic stimulation (rTMS) following traumatic brain injury (TBI): A scoping review. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation: A potential new treatment for depression associated with traumatic brain injury. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Effect of repetitive transcranial magnetic stimulation on depression and cognition in individuals with traumatic brain injury: a systematic review and meta-analysis. [2021]

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

Treatment-Resistant Depression Entering Remission Following a Seizure during the Course of Repetitive Transcranial Magnetic Stimulation. [2020]

7. England pubmed.ncbi.nlm.nih.gov

A review of the safety of repetitive transcranial magnetic stimulation as a clinical treatment for depression. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation (TMS) safety: a practical guide for psychiatrists. [2019]

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

Repetitive Transcranial Magnetic Stimulation with Resting-State Network Targeting for Treatment-Resistant Depression in Traumatic Brain Injury: A Randomized, Controlled, Double-Blinded Pilot Study. [2020]

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

Transcranial magnetic stimulation for depression after a traumatic brain injury: a case study. [2022]

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

Repetitive transcranial magnetic stimulation-associated neurobehavioral gains during coma recovery. [2016]