Brain Stimulation for Depression

Overseen By Doan Ngo, BS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, Los Angeles

Must be taking: Antidepressants, Augmentation therapies

Must not be taking: Seizure-inducing medications

Disqualifiers: Pregnancy, Suicidal intent, Psychotic disorders, Neurological conditions, others

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

Compensation: Varies

Number of Visits: 30

Duration: 6 weeks

54 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will examine the effects of brain stimulation on pain symptoms associated with Major depressive disorder. This study will enroll 54 Subjects. Study subjects will be asked to complete surveys about their mood and well-being, 2 blood draws, 2 MRIs, 3 electroencephalograms, and receive 30 treatments of blinded transcranial magnetic stimulation. There is no control group as all subjects will receive some form of active treatment. Subjects are required to participate in 30-33 study visits and volunteer 40 hours of their time. Compensation for this study is $150 for completing all study activities.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it mentions that participants must have failed to respond to at least two different classes of antidepressant medications and augmentation therapies, which suggests that you may continue your current medications.

What data supports the effectiveness of the treatment Brain Stimulation for Depression?

Research shows that repetitive transcranial magnetic stimulation (rTMS) and intermittent theta burst stimulation (iTBS) are effective treatments for depression, with high-frequency rTMS of the left dorsolateral prefrontal cortex (DLPFC) having definite efficacy for depression. These treatments are well-tolerated and have been shown to improve symptoms in patients with major depressive disorder. ^{1 2 3 4 5}

Is brain stimulation for depression generally safe for humans?

Repetitive transcranial magnetic stimulation (rTMS) is generally considered safe when used according to established guidelines, with the most serious risk being seizures, which are rare and often linked to not following safety recommendations. Most people tolerate the treatment well, although some may experience pain that usually decreases over time. ^{1 6 7 8 9}

How is the treatment of rTMS/iTBS for depression different from other treatments?

This treatment uses magnetic pulses to stimulate specific areas of the brain, offering a non-drug option for depression. The iTBS protocol is unique because it can be delivered in just 3 minutes, compared to the longer sessions required for traditional rTMS, while maintaining similar effectiveness. ^{1 2 4 10 11}

Eligibility Criteria

This trial is for adults aged 18-75 with chronic pain and moderate Major Depressive Disorder who haven't improved after at least two different antidepressant medications and psychotherapy. Participants must speak English, be right-handed, have a specific depression score, and not respond to other treatments including psychotherapy.

Inclusion Criteria

I am receiving two or more approved additional treatments (not including Benzodiazepines).

I have been experiencing pain for at least 3 months.

I have been diagnosed with moderate depression and scored at least 17 on the HAM-D17.

Exclusion Criteria

Are pregnant

I have undergone Transcranial Magnetic Stimulation treatment.

I have a neurological condition like epilepsy or severe head trauma.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 30 sessions of neuro-navigated rTMS treatment targeting depression and pain symptoms

6 weeks

30-33 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Active rTMS/Active iTBS
• Active rTMS/Active iTBS DFPLC/Sham Pain M1
• Sham rTMS/ Active iTBS Pain

Trial Overview The study tests the effects of brain stimulation (rTMS/iTBS) on pain in those with depression. All participants receive active treatment over approximately 30 sessions. They'll complete surveys, undergo blood draws, MRIs, EEGs, and dedicate about 40 hours across up to 33 visits.

Participant Groups

Group I: Active rTMS/Active iTBS DFPLC/Sham Pain M1 Experimental Treatment 1 Intervention

Group II: Active rTMS/Active iTBS Experimental Treatment 1 Intervention

Active rTMS/Active iTBS is already approved in United States, European Union for the following indications:

Approved in United States as rTMS for:

• Major Depressive Disorder
• Obsessive-Compulsive Disorder
• Migraines
• Smoking Cessation

Approved in European Union as rTMS for:

• Major Depressive Disorder
• Obsessive-Compulsive Disorder

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

Findings from Research

In a study involving 414 patients with treatment-resistant depression, both High-Frequency Left (HFL) and intermittent theta burst stimulation (iTBS) showed similar pain profiles, although iTBS was reported to be more uncomfortable.

Pain severity decreased significantly over the course of treatment, with less pain associated with better clinical outcomes, indicating a potential link between mood improvement and pain reduction in rTMS therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A patient-oriented analysis of pain side effect: A step to improve the patient's experience during rTMS? Humaira, A., Gao, S., Gregory, E., et al.[2021]

Patients receiving intermittent theta burst stimulation (iTBS) for depression reported higher scalp pain compared to those receiving sham treatment, particularly on the first and fifth days of treatment.

However, pain levels decreased significantly over time, suggesting that patients may experience habituation or an analgesic effect, which can help set realistic expectations for pain during iTBS treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pain trajectories of dorsomedial prefrontal intermittent theta burst stimulation versus sham treatment in depression. Malm, E., Struckmann, W., Persson, J., et al.[2020]

In a case study of a 77-year-old woman with chronic neuropathic pain, high-frequency repetitive transcranial magnetic stimulation (rTMS) improved her quality of life, anxiety, depression, and walking ability, despite no change in pain intensity.

The results suggest that rTMS may enhance daily functioning in chronic pain patients by influencing brain circuits, indicating its potential therapeutic benefits beyond just pain relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic impact of motor cortex rTMS in patients with chronic neuropathic pain even in the absence of an analgesic response. A case report. Hodaj, H., Payen, JF., Lefaucheur, JP.[2018]

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]

Prolonged continuous theta burst stimulation (pcTBS) over the primary motor cortex was found to be significantly more effective in providing analgesic effects compared to traditional high frequency rTMS (10 Hz), suggesting a promising new treatment for pain management.

The study involved 14 healthy volunteers and demonstrated that pcTBS not only has stronger analgesic effects but also requires a shorter treatment duration, making it a potentially more efficient option for clinical use, although further studies in patients are needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged continuous theta-burst stimulation is more analgesic than 'classical' high frequency repetitive transcranial magnetic stimulation. Moisset, X., Goudeau, S., Poindessous-Jazat, F., et al.[2018]

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]

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]

Transcranial magnetic stimulation (TMS) has been shown to have a very low incidence of side effects, with the most serious being seizures, which often occurred when stimulation parameters were not followed or when combined with medications that lower seizure thresholds.

The expert consensus indicates that repetitive TMS (rTMS) is effective for treating chronic neuropathic pain, major depressive episodes, and auditory hallucinations, suggesting it has a strong therapeutic indication in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[French guidelines on the use of repetitive transcranial magnetic stimulation (rTMS): safety and therapeutic indications]. Lefaucheur, JP., André-Obadia, N., Poulet, E., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) is a powerful tool that can effectively treat clinical depression and potentially other brain disorders, but it carries risks, including the potential to induce seizures, as evidenced by 7 known cases by 1996.

A workshop established safety guidelines for rTMS, emphasizing the importance of monitoring, ethical considerations, and the expertise required for its administration to minimize risks and enhance therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Wassermann, EM.[2022]

Intermittent theta burst stimulation (iTBS) is a cost-effective alternative to conventional 10Hz rTMS for treating depression, with an average treatment cost of $1,108 compared to $1,844 for 10Hz rTMS, resulting in savings of $735 per patient.

iTBS also shows a lower average cost per remission at $3,695, compared to $6,146 for 10Hz rTMS, leading to significant savings of $2,451 per remission, making it a more efficient treatment option in healthcare systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implementation of intermittent theta burst stimulation compared to conventional repetitive transcranial magnetic stimulation in patients with treatment resistant depression: A cost analysis. Mendlowitz, AB., Shanbour, A., Downar, J., et al.[2020]

Deep Transcranial Magnetic Stimulation (dTMS) is a safe and effective treatment for Major Depressive Disorder (MDD), with FDA approval for use in patients resistant to other therapies, and it may also help reduce chronic low back pain.

The mechanism of action for dTMS involves enhancing brain connectivity in areas that regulate mood, which could explain its dual benefits in treating both depression and chronic pain, as demonstrated in two case studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep Transcranial Magnetic Stimulation: A Promising Drug-Free Treatment Modality in the Treatment of Chronic Low Back Pain. Yates, E., Balu, G.[2016]

References

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

A patient-oriented analysis of pain side effect: A step to improve the patient's experience during rTMS? [2021]

2. England pubmed.ncbi.nlm.nih.gov

Pain trajectories of dorsomedial prefrontal intermittent theta burst stimulation versus sham treatment in depression. [2020]

3. France pubmed.ncbi.nlm.nih.gov

Therapeutic impact of motor cortex rTMS in patients with chronic neuropathic pain even in the absence of an analgesic response. A case report. [2018]

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

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

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

Prolonged continuous theta-burst stimulation is more analgesic than 'classical' high frequency repetitive transcranial magnetic stimulation. [2018]

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

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

7. 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]

8. France pubmed.ncbi.nlm.nih.gov

[French guidelines on the use of repetitive transcranial magnetic stimulation (rTMS): safety and therapeutic indications]. [2022]

9. Ireland pubmed.ncbi.nlm.nih.gov

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]

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

Implementation of intermittent theta burst stimulation compared to conventional repetitive transcranial magnetic stimulation in patients with treatment resistant depression: A cost analysis. [2020]

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

Deep Transcranial Magnetic Stimulation: A Promising Drug-Free Treatment Modality in the Treatment of Chronic Low Back Pain. [2016]