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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of repetitive transcranial magnetic stimulation (rTMS) as a long-term treatment for individuals with major depression who have responded well to an initial round of rTMS. The study tests three approaches: standard maintenance rTMS, clustered maintenance rTMS, and a placebo-like version called sham rTMS. The goal is to determine which method best maintains brain activity related to mood regulation. Participants should have experienced a major depressive episode and shown improvement from initial rTMS treatment. As an unphased trial, this study offers participants the chance to contribute to understanding long-term treatment strategies for depression.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) is a safe and well-tolerated treatment for major depressive disorder. This method uses magnetic fields to stimulate brain cells. Studies have found that rTMS is a noninvasive and effective way to manage depression symptoms.

For clustered maintenance rTMS, research suggests it can effectively treat depression without increasing the risk of serious side effects. It may also help prevent depression from returning after treatment.

Both types of rTMS are considered safe, but like any treatment, some side effects can occur. These may include headaches or mild discomfort where the treatment is applied. However, these side effects are usually mild and tend to resolve on their own. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the different approaches to transcranial magnetic stimulation (rTMS) for major depression because they offer unique maintenance strategies. Unlike standard care options like antidepressants or electroconvulsive therapy, Clustered maintenance rTMS involves intensive sessions over two days each month, potentially offering a more efficient and time-saving schedule. Standard maintenance rTMS provides consistent weekly sessions, which some patients might find more manageable. Both active treatments are contrasted with the sham maintenance rTMS, a placebo method ensuring rigorous testing and clear results. These variations in treatment delivery aim to enhance patient outcomes and provide more tailored approaches to managing major depression.

What evidence suggests that this trial's treatments could be effective for major depression?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) can help prevent depression from returning. In this trial, participants may receive clustered maintenance rTMS, which studies suggest might delay relapse in those who responded well to initial treatment. Alternatively, participants might receive standard maintenance rTMS. One study found this approach was about 85% successful in preventing relapse after 24 weeks. Another large study reported response rates between 58% and 83%, with up to 28% of participants experiencing complete remission. These findings suggest that both clustered and standard rTMS could help maintain improvements in individuals with treatment-resistant depression. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5802466/

Clustered repetitive transcranial magnetic stimulation for ... We concluded that TMS, whether as a mono- or additional therapy, is superior to antidepressants in preventing depressive relapse/recurrence, ...

2. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2835319

Repetitive Transcranial Magnetic Stimulation as ... This randomized clinical trial of 75 participants with TRD showed that rTMS and lithium had comparable efficacy in preventing TRD relapse.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1935861X1200085X

An Open Label Trial of Clustered Maintenance rTMS for ... Although preliminary, this study suggests that clustered maintenance rTMS has the potential to substantially delay the occurrence of relapse following a ...

4. bmcpsychiatry.biomedcentral.com bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-023-04944-0

Maintenance repetitive transcranial magnetic stimulation ... We hypothesize that maintenance rTMS therapy could be an effective and safe treatment for preventing depressive relapse/recurrence. Considering ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT01370733

Synchronized Transcranial Magnetic Stimulation (sTMS) in ... Preliminary study results using sTMS have shown improvements in depressive symptoms with minimal side effects. This multicenter study is designed to evaluate ...

6. cms.gov cms.gov/medicare-coverage-database/view/lcd.aspx?LCDId=34998

Transcranial Magnetic Stimulation (TMS) in the Treatment ... McClintock et al17 provided a consensus statement concluding that "Repetitive transcranial magnetic stimulation (rTMS) is a safe, noninvasive neuromodulation ...