rTMS + ACT for Chronic Pain and Depression

Overseen By Erica J Martinez, BA

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: VA Office of Research and Development

Disqualifiers: Cardiovascular disease, Bipolar, Psychotic, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 9 weeks

31 Participants Needed

Trial Summary

What is the purpose of this trial?

Veterans with comorbid chronic pain and depression are highly prevalent, have poor functional status and low quality of life, are at increased risk of suicide and lack access to effective treatments. To address this problem, the proposed research will examine the feasibility of a novel approach that integrates repetitive Transcranial Magnetic Stimulation and Acceptance and Commitment Therapy with the overall goal of maximizing functional improvement in Veterans with chronic pain and depression. This is an important first-step in preparation for a future randomized efficacy trial. The investigators will also include two cognitive control tasks with concurrent electroencephalography to explore as a potential objective indicator of treatment response. This application addresses a critical need within the Veterans Health Administration and is closely aligned with the focus area of developing suicide prevention treatments that influence participation in life roles.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but it does require no changes to your pain or mood treatment for one month before starting the trial.

What data supports the effectiveness of the treatment rTMS + ACT for chronic pain and depression?

Research shows that repetitive transcranial magnetic stimulation (rTMS) is effective in reducing symptoms of depression, and there is evidence that it can also help with pain management. Acceptance and Commitment Therapy (ACT) is known to improve psychological flexibility, which can be beneficial for managing chronic pain and depression. ^{1 2 3 4 5}

Is rTMS generally safe for humans?

Repetitive transcranial magnetic stimulation (rTMS) is generally considered safe when administered according to FDA guidelines, although some patients may find it painful initially. Over time, the painfulness tends to decrease, and serious adverse events are rare. ^{1 2 3 6 7}

How does the rTMS + ACT treatment for chronic pain and depression differ from other treatments?

The rTMS + ACT treatment is unique because it combines repetitive transcranial magnetic stimulation (rTMS), which uses magnetic fields to stimulate the brain, with Acceptance and Commitment Therapy (ACT), a psychological approach that helps patients accept their pain and commit to personal values. This combination targets both the physical and psychological aspects of chronic pain and depression, potentially offering more comprehensive relief than treatments focusing on just one aspect. ^{2 8 9 10 11}

Research Team

Matthew Herbert, PhD

Principal Investigator

VA San Diego Healthcare System, San Diego, CA

Eligibility Criteria

This trial is for veterans with chronic pain (pain most days for at least 6 months) and major depression. Participants must have a pain intensity >4/10, not be undergoing unstable medical treatments or substance abuse, and cannot have tried rTMS before or had no response to electroconvulsive therapy.

Inclusion Criteria

My pain has been over 4/10 and affects my life and activities.

I have been diagnosed with major depression according to DSM5.

I have been in pain most days for at least 6 months.

Exclusion Criteria

I haven't changed my pain or mood treatment in the last month.

I don't have metal implants above the neck, electrical devices like pacemakers, or am not pregnant.

You have had a serious mental health condition like schizophrenia, bipolar disorder, or obsessive-compulsive disorder at any point in your life.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive DLPFC-rTMS or sham-rTMS combined with Acceptance and Commitment Therapy (ACT)

9 weeks

Weekly visits for rTMS and ACT sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Acceptance and Commitment Therapy
• Repetitive Transcranial Magnetic Stimulation

Trial Overview The study tests combining repetitive Transcranial Magnetic Stimulation (rTMS) with Acceptance and Commitment Therapy to improve function in veterans suffering from chronic pain and depression. It's a preliminary step towards a larger efficacy trial.

Participant Groups

Group I: DLPFC-rTMS + ACT Experimental Treatment 2 Interventions

Active DLPFC-rTMS with ACT treatment

Group II: Sham-rTMS + ACT Active Control 1 Intervention

Sham delivered rTMS with ACT treatment

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Findings from Research

In a study of 61 active-duty service members with treatment-resistant depression who underwent at least 20 sessions of repetitive transcranial magnetic stimulation (rTMS), there was a statistically significant reduction in depressive symptoms, as indicated by a decrease in average PHQ-9 scores from 15.8 to 12.6 (P < 0.001).

Approximately 69% of participants experienced a reduction in their depressive ratings, with 20% achieving a level of improvement that placed them in the nondysfunctional range, suggesting that rTMS is a promising treatment option for major depression in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Depression in Active-Duty Service Members Improves Depressive Symptoms. Roach, AE., Hines, C., Stafford, J., et al.[2022]

In a randomized controlled trial involving 142 patients, daily left prefrontal rTMS showed a significant 37% reduction in procedural pain over 15 sessions, indicating that patients may adapt to the treatment's discomfort over time.

The decrease in pain was specific to those receiving active rTMS and suggests that the stimulation itself may contribute to pain reduction, rather than just patient accommodation, which could be linked to improved clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The painfulness of active, but not sham, transcranial magnetic stimulation decreases rapidly over time: results from the double-blind phase of the OPT-TMS Trial. Borckardt, JJ., Nahas, ZH., Teal, J., et al.[2021]

A study of 77 military patients receiving rTMS treatment showed significant reductions in depression and PTSD symptoms, with over 44% of patients experiencing a notable decrease in depression scores after treatment.

Most patients had previously tried multiple antidepressants (average of 2.7 trials), indicating that rTMS may be an effective alternative for those with treatment-resistant depression and comorbid PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impacts of rTMS on Refractory Depression and Comorbid PTSD Symptoms at a Military Treatment Facility. Wilkes, S., Ona, C., Yang, M., et al.[2021]

High-frequency repetitive transcranial magnetic stimulation (rTMS) applied to the primary motor cortex is definitively effective for pain relief, while high-frequency rTMS targeting the left dorsolateral prefrontal cortex is effective for treating depression, based on a review of evidence up to March 2014.

Low-frequency rTMS of the right dorsolateral prefrontal cortex shows probable efficacy for depression, and high-frequency rTMS of the left dorsolateral prefrontal cortex may help with negative symptoms of schizophrenia, indicating that rTMS can be a valuable treatment option for various mental health conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Lefaucheur, JP., André-Obadia, N., Antal, A., et al.[2022]

Accelerated transcranial magnetic stimulation (aTMS) has been shown to significantly improve depressive symptoms, with a cumulative effect size of 0.39 from randomized control trials and an even higher effect size of 1.27 when including open-label trials.

The review analyzed 18 articles from 11 distinct studies, indicating that while the methodologies were generally acceptable, there is room for improvement in sham techniques and blinding to enhance the reliability of future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated TMS for Depression: A systematic review and meta-analysis. Sonmez, AI., Camsari, DD., Nandakumar, AL., et al.[2020]

Repetitive transcranial magnetic stimulation (rTMS) is generally safe for older adults with late-life depression, with only 12.4% reporting any adverse events and serious adverse events occurring in just 1.5% of cases, based on a review of 11 studies involving 353 patients.

The most common adverse events were mild, such as headaches (6.9%) and discomfort at the stimulation site (2.7%), although some serious adverse events, including psychiatric hospitalization and increased suicidal ideation, were noted in case reports, highlighting the need for further research to ensure safety in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events of repetitive transcranial magnetic stimulation in older adults with depression, a systematic review of the literature. Overvliet, GM., Jansen, RAC., van Balkom, AJLM., et al.[2021]

Transcranial magnetic stimulation (TMS) was effective in treating treatment-resistant depression, with a response rate of 50.6% and a remission rate of 24.7% after 6 weeks of treatment in a cohort of 100 patients.

TMS was well tolerated, showing a low discontinuation rate of 3% and no serious adverse events, indicating its safety as an adjunctive treatment for patients who have not responded to other antidepressant therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of transcranial magnetic stimulation in clinical practice post-FDA approval in the United States: results observed with the first 100 consecutive cases of depression at an academic medical center. Connolly, KR., Helmer, A., Cristancho, MA., et al.[2022]

High-frequency repetitive transcranial magnetic stimulation (rTMS) on the left dorsolateral prefrontal cortex (DLPFC) shows significant long-term analgesic effects on chronic pain, with improvements noted over mid-term and long-term periods.

HF rTMS also effectively alleviates depressive symptoms in patients suffering from chronic pain, indicating its potential as a dual treatment for both pain and depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review and Meta-Analysis of High-Frequency rTMS over the Dorsolateral Prefrontal Cortex .on Chronic Pain and Chronic-Pain-Accompanied Depression. Zhu, Y., Li, D., Zhou, Y., et al.[2023]

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive treatment that can provide partial and temporary relief from severe chronic pain, particularly in conditions like neuropathic pain and fibromyalgia.

While rTMS effects are generally short-lived, daily sessions over several weeks can lead to longer-lasting pain relief, and for patients who respond but later relapse, surgical options like implanted electrodes may help maintain the benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of repetitive transcranial magnetic stimulation in pain relief. Lefaucheur, JP.[2022]

In a study involving 18 patients with chronic neurogenic pain, non-invasive repetitive transcranial magnetic stimulation (rTMS) at 10 Hz significantly reduced pain levels, demonstrating its potential as a treatment for medication-resistant pain.

The study indicates that while 0.5 Hz and sham rTMS did not produce significant pain relief, the 10 Hz stimulation can provide transient pain relief, suggesting a targeted approach to managing chronic pain through cortical stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pain relief induced by repetitive transcranial magnetic stimulation of precentral cortex. Lefaucheur, JP., Drouot, X., Keravel, Y., et al.[2019]

High-frequency repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex is definitively effective for treating neuropathic pain, while high-frequency rTMS of the left dorsolateral prefrontal cortex is effective for depression, based on a comprehensive review of literature up to 2018 involving multiple studies.

Low-frequency rTMS has probable efficacy for various conditions, including improving motor recovery in stroke and quality of life in fibromyalgia, but the overall clinical relevance of rTMS benefits may vary and is not guaranteed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): An update (2014-2018). Lefaucheur, JP., Aleman, A., Baeken, C., et al.[2020]

References

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

Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Depression in Active-Duty Service Members Improves Depressive Symptoms. [2022]

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

The painfulness of active, but not sham, transcranial magnetic stimulation decreases rapidly over time: results from the double-blind phase of the OPT-TMS Trial. [2021]

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

Impacts of rTMS on Refractory Depression and Comorbid PTSD Symptoms at a Military Treatment Facility. [2021]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). [2022]

5. Ireland pubmed.ncbi.nlm.nih.gov

Accelerated TMS for Depression: A systematic review and meta-analysis. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Adverse events of repetitive transcranial magnetic stimulation in older adults with depression, a systematic review of the literature. [2021]

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

Effectiveness of transcranial magnetic stimulation in clinical practice post-FDA approval in the United States: results observed with the first 100 consecutive cases of depression at an academic medical center. [2022]

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

Systematic Review and Meta-Analysis of High-Frequency rTMS over the Dorsolateral Prefrontal Cortex .on Chronic Pain and Chronic-Pain-Accompanied Depression. [2023]

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

Use of repetitive transcranial magnetic stimulation in pain relief. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Pain relief induced by repetitive transcranial magnetic stimulation of precentral cortex. [2019]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): An update (2014-2018). [2020]