Transcranial Magnetic Stimulation for Major Depression

(Maitr-De Trial)

Recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, San Diego

Must not be taking: Rapid-acting antidepressants, Benzodiazepines

Disqualifiers: Pregnancy, Psychotic disorder, Substance use, others

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

75 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you require a benzodiazepine dose higher than lorazepam 2 mg/day or any anticonvulsant, except Gabapentin.

What data supports the effectiveness of the treatment Transcranial Magnetic Stimulation for Major Depression?

Research shows that repetitive transcranial magnetic stimulation (rTMS) is a safe and effective treatment for major depression, with studies indicating significant improvements in depression symptoms. Additionally, rTMS targeting specific brain areas, like the visual cortex, has shown therapeutic potential and good tolerance in patients with major depressive disorder. ^{1 2 3 4 5}

Is transcranial magnetic stimulation (TMS) safe for humans?

Transcranial magnetic stimulation (TMS) is considered a safe treatment for major depression, as supported by multiple studies. It is a noninvasive procedure that has been shown to be safe in clinical trials. ^{4 5 6 7 8}

How does transcranial magnetic stimulation treatment differ from other treatments for major depression?

Transcranial magnetic stimulation (TMS) is unique because it uses magnetic fields to stimulate nerve cells in the brain, specifically targeting the left prefrontal cortex, which is different from medications that work chemically. It is a non-invasive procedure, meaning it doesn't require surgery or medication, and is often considered when other treatments haven't worked. ^{2 9 10 11 12}

What is the purpose of this trial?

Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising intervention for treatment-resistant depression (TRD), yet substantial uncertainties persist regarding its efficacy as a maintenance treatment. This prospective study seeks to investigate the efficacy of maintenance rTMS in individuals with TRD who have previously responded to an acute course of rTMS. In the R61 phase of the study, we will recruit 75 participants across three study sites, the University of California San Diego, Weill Cornell Medicine, and Australian National University, into a double-blind, three-arm maintenance treatment trial. In this trial, participants will be randomized to receive either standard maintenance rTMS, clustered maintenance rTMS, or sham maintenance rTMS for a duration of 6 months. Our primary aim is to examine the efficacy of maintenance rTMS on sustaining connectivity between the dorsolateral prefrontal cortex (DLPFC) and subgenual cingulate cortex (SGC) measured through concurrent TMS and electroencephalography (TMS-EEG) at baseline and every six weeks throughout the 6-month treatment period. We will also assess changes in depressive symptom severity using clinical scales, including the Montgomery-Asberg Depression Rating Scale (MADRS) as a secondary outcome measure. It is hypothesized that stimulation with clustered maintenance rTMS will demonstrate superiority in sustaining DLPFC-SGC connectivity compared with standard maintenance rTMS and sham maintenance rTMS

Eligibility Criteria

This trial is for individuals with treatment-resistant depression who've had a positive response to an initial rTMS treatment. Participants will be recruited from three study sites and must have maintained their depressive symptoms despite previous treatments.

Inclusion Criteria

Participants must be in good general health, as evidenced by medical history

If a person of child-bearing potential, must take a pregnancy test at the screening visit with results confirmed as negative by study staff

Participants must be able to read, understand, and provide written, dated informed consent prior to screening

Exclusion Criteria

Severe borderline personality disorder based on clinical assessment

Treatment with an investigational drug or other intervention within the study period

I have a hormone disorder that is not fully treated.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive maintenance rTMS, either standard, clustered, or sham, for 6 months

6 months

Baseline and every six weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Clustered maintenance rTMS
• Sham maintenance rTMS
• Standard maintenance rTMS

Trial Overview The study tests the effectiveness of maintenance rTMS in sustaining brain connectivity related to mood regulation. It compares standard, clustered, and sham (placebo) maintenance rTMS over six months, measuring brain activity and depression severity.

Participant Groups

Group I: Clustered maintenance rTMS Experimental Treatment 1 Intervention

Clustered maintenance treatment involves administering four sessions of rTMS over a two-day span, conducted once per month for six months.

Group II: Standard maintenance rTMS: Active Control 1 Intervention

Standard maintenance rTMS involves a course of rTMS with once-weekly sessions for 6 months.

Group III: sham maintenance rTMS Placebo Group 1 Intervention

Somatosensory-matched placebo rTMS is delivered according to either standard or clustered maintenance schedules over a six-month period (50/50% allotment). Patient's maintenance protocol parameters will otherwise mirror those used during their acute treatment with identical cortical targets, stimulation intensity, frequency, and duration. Sham TMS-EEG will be conducted by rotating the coil 90 degrees while maintaining contact with the scalp. This standard practice prevents current induction while replicating the auditory click associated with TMS, ensuring comparable EEG recordings

Who Is Running the Clinical Trial?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Findings from Research

A meta-analysis of 24 studies involving 911 patients found that maintenance rTMS can help stabilize mood symptoms for up to 5 months after an initial acute rTMS treatment for depression.

Patients receiving monthly or more frequent maintenance rTMS experienced sustained benefits for up to 6-12 months, while those without maintenance showed only minor changes in mood symptoms over the same period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trajectory of changes in depressive symptoms after acute repetitive transcranial magnetic stimulation: A meta-analysis of follow-up effects. Brian Chen, YC., Chou, PH., Tu, YK., et al.[2023]

Repetitive transcranial magnetic stimulation (rTMS) is a clinically safe and effective treatment for major depressive disorder, particularly for patients who have not responded to at least two antidepressant medications.

In a 3-year cost-effectiveness analysis, rTMS was found to provide greater quality-adjusted life-years (1.25 QALYs) at a lower cost compared to pharmacotherapy (1.18 QALYs), making it a more cost-effective option for treatment-resistant depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness of Repetitive Transcranial Magnetic Stimulation versus Antidepressant Therapy for Treatment-Resistant Depression. Nguyen, KH., Gordon, LG.[2015]

In a pilot study involving 19 medication-resistant depressed subjects, bilateral prefrontal repetitive transcranial magnetic stimulation (rTMS) did not show superior efficacy compared to sham treatment over 3 weeks, as both groups experienced similar improvements in mood.

Despite the lack of significant differences in mood improvement, rTMS was found to be safe, with no neuropsychological impairments reported in either the active or sham treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blind controlled investigation of bilateral prefrontal transcranial magnetic stimulation for the treatment of resistant major depression. Loo, CK., Mitchell, PB., Croker, VM., et al.[2019]

In a study of 301 medication-free patients with treatment-resistant major depression, transcranial magnetic stimulation (TMS) significantly improved quality of life (QOL) and functional status compared to sham treatment during a 6-week trial.

The benefits of TMS were not only observed during the acute treatment phase but also sustained over a 24-week follow-up, indicating that TMS provides durable improvements in patients' overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvement in quality of life with left prefrontal transcranial magnetic stimulation in patients with pharmacoresistant major depression: acute and six month outcomes. Solvason, HB., Husain, M., Fitzgerald, PB., et al.[2018]

In a study involving 59 patients with major depression, repetitive transcranial magnetic stimulation (rTMS) did not show significant effectiveness compared to sham treatment, with no meaningful differences in depression scores between the two groups.

While there were slightly higher response and remission rates in the real rTMS group (32% and 25%, respectively) compared to the sham group (10% for both), these differences were not statistically significant, indicating that rTMS may not provide a clear benefit over placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized controlled trial with 4-month follow-up of adjunctive repetitive transcranial magnetic stimulation of the left prefrontal cortex for depression. Mogg, A., Pluck, G., Eranti, SV., et al.[2022]

In a study involving 10 adults with major depressive disorder, long-term maintenance therapy using repetitive transcranial magnetic stimulation (rTMS) showed that 7 participants experienced significant benefits, with some maintaining improvement without additional antidepressant medications.

The treatment was found to be safe, with no serious adverse events reported and a zero seizure rate across 1831 rTMS sessions, suggesting that rTMS could be a viable long-term option for managing depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term maintenance therapy for major depressive disorder with rTMS. O'Reardon, JP., Blumner, KH., Peshek, AD., et al.[2022]

In a 6-month follow-up study of 31 patients with major depression who completed a 4-week rTMS trial, 63.64% of those who initially did not respond to treatment became late responders, indicating potential for continued improvement after treatment ends.

The study also found a low relapse rate of only 10% among those who initially responded to rTMS, with an overall high rate of maintained response at 90%, suggesting that rTMS can have lasting effects in treating major depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 6-month follow-up study on response and relapse rates following an acute trial of repetitive transcranial magnetic stimulation in patients with major depression. Arici, C., Benatti, B., Cafaro, R., et al.[2022]

References

1. China pubmed.ncbi.nlm.nih.gov

Task-related functional magnetic resonance imaging-based neuronavigation for the treatment of depression by individualized repetitive transcranial magnetic stimulation of the visual cortex. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Trajectory of changes in depressive symptoms after acute repetitive transcranial magnetic stimulation: A meta-analysis of follow-up effects. [2023]

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

Efficacy of adjunctive high frequency repetitive transcranial magnetic stimulation of left prefrontal cortex in depression: a randomized sham controlled study. [2022]

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

Cost-Effectiveness of Repetitive Transcranial Magnetic Stimulation versus Antidepressant Therapy for Treatment-Resistant Depression. [2015]

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

Blinding integrity in randomized sham-controlled trials of repetitive transcranial magnetic stimulation for major depression: a systematic review and meta-analysis. [2018]

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

Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial. [2022]

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

Double-blind controlled investigation of bilateral prefrontal transcranial magnetic stimulation for the treatment of resistant major depression. [2019]

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

Improvement in quality of life with left prefrontal transcranial magnetic stimulation in patients with pharmacoresistant major depression: acute and six month outcomes. [2018]

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

A randomized controlled trial with 4-month follow-up of adjunctive repetitive transcranial magnetic stimulation of the left prefrontal cortex for depression. [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation (rTMS) in combination with escitalopram in patients with treatment-resistant major depression: a double-blind, randomised, sham-controlled trial. [2021]

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

Long-term maintenance therapy for major depressive disorder with rTMS. [2022]

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

A 6-month follow-up study on response and relapse rates following an acute trial of repetitive transcranial magnetic stimulation in patients with major depression. [2022]