TMS for Depression

(TMS-LLD Trial)

Overseen By Davin Quinn, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of New Mexico

Disqualifiers: Bipolar, Schizophrenia, Substance use, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 30

Duration: 6 weeks

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to enhance the effectiveness of transcranial magnetic stimulation (TMS) for treating depression in older adults by using fMRI, a type of brain imaging. TMS, already FDA-approved, uses magnetic fields to stimulate nerve cells in the brain. The study targets individuals currently experiencing major depression, diagnosed for at least six months. Ideal participants are aged 60 to 79 and have not previously undergone TMS treatment. As an unphased trial, it offers participants the chance to contribute to advancing treatment options for depression in older adults.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What prior data suggests that rTMS is safe for treating depression?

Research shows that repetitive transcranial magnetic stimulation (rTMS) is a safe treatment for depression. Studies have found that it can improve symptoms of major depression by using magnetic fields to stimulate brain cells.

A review of several studies found that rTMS, when combined with antidepressants, can further enhance depressive symptoms. This indicates the treatment is generally well-tolerated. Additionally, the FDA has approved rTMS for treating depression, confirming it has passed numerous safety checks.

Some people might experience mild side effects like headaches or scalp discomfort, but serious side effects are rare. Overall, rTMS maintains a strong safety record for treating depression. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about rTMS (repetitive Transcranial Magnetic Stimulation) for depression because it offers a non-invasive alternative that specifically targets brain regions differently than medications or talk therapy. Unlike traditional antidepressants, which can take weeks to show effects and often have side effects, rTMS uses magnetic fields to stimulate the dorsolateral prefrontal cortex (DLPFC), a brain area involved in mood regulation. This technique is especially promising because it targets the DLPFC area most anticorrelated with the anterior cingulate cortex (ACC), potentially offering more rapid relief from depressive symptoms with fewer side effects.

What is the effectiveness track record for rTMS in treating depression?

Research has shown that repetitive transcranial magnetic stimulation (rTMS), which participants in this trial will receive, can help treat depression. In one study, 35.71% of patients experienced significant improvement in their depression symptoms. Another study found that 85% of patients who used rTMS alone did not experience a return of symptoms after 24 weeks. Additional research suggests that patients with treatment-resistant depression are more likely to benefit from rTMS if they have positive expectations before starting. Overall, rTMS may reduce the need for hospital visits and lower healthcare costs for these patients. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for English-speaking individuals aged 60-79 with major depressive disorder diagnosed by a psychiatrist, currently experiencing a depressive episode. Excluded are pregnant women, those with bipolar or psychotic disorders, recent hospitalization, neurosurgery history, ECT in the last three months, MRI contraindications, substance abuse within three months, seizure history or neurological disorders.

Inclusion Criteria

Participant must be fluent in English

Must show evidence of being in a current major depressive episode, as indicated by score on QIDS-C of 10 or higher

Participant must not have any conditions listed in the exclusion criteria

Exclusion Criteria

I have had TMS treatment before.

I have not had ECT treatment in the last 3 months.

I have been diagnosed with a neurological or neurocognitive disorder.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Treatment Assessment

Participants undergo sfMRI and cognitive/behavioral assessment prior to TMS treatment

1-2 weeks

Treatment

Participants receive 30 sessions of TMS targeted to the DLPFC

6 weeks

30 visits (in-person)

Post-Treatment Assessment

Clinical and imaging assessments are repeated following the 15th and 30th TMS sessions

1 week

Follow-up

Participants are monitored for changes in depressive symptoms and connectivity

3 weeks

What Are the Treatments Tested in This Trial?

Interventions

• rTMS

Trial Overview The study tests how to improve transcranial magnetic stimulation (TMS), an existing treatment for late-life depression. It uses fMRI to personalize TMS targeting and assess its effectiveness in an open-label setting where all participants receive the intervention.

How Is the Trial Designed?

Group I: rTMS Experimental Treatment 1 Intervention

Subjects will receive rTMS to the area of the DLPFC most anticorrelated with the ACC.

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

Approved in United States as rTMS for:

• Obsessive-Compulsive Disorder (OCD)
• Major Depressive Disorder
• Migraines
• Smoking cessation

Approved in European Union as rTMS for:

• Obsessive-Compulsive Disorder (OCD)
• Major Depressive Disorder

Who Is Running the Clinical Trial?

University of New Mexico

Lead Sponsor

Trials

393

Recruited

3,526,000+

The Mind Research Network

Collaborator

Trials

27

Recruited

2,300+

Published Research Related to This Trial

Repetitive transcranial magnetic stimulation (rTMS) is a promising therapy for depression that may selectively modulate neuronal activity with fewer side effects compared to electroconvulsive therapy (ECT).

While rTMS shows potential efficacy similar to ECT in open trials for non-psychotic depression, its benefits in double-blind studies are more modest, indicating that further optimization and research are needed to fully realize its therapeutic potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation in the treatment of mood disorder: a review and comparison with electroconvulsive therapy. Hasey, G.[2017]

In a study involving 18 subjects with major depression, repetitive transcranial magnetic stimulation (rTMS) for up to 4 weeks was found to be generally safe, with no significant mean deficits in neuropsychologic function or auditory thresholds.

However, two patients experienced mild high-frequency hearing loss, indicating that while rTMS is safe for most, individual responses may vary and warrant further investigation into long-term safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of a 2- to 4-week course of repetitive transcranial magnetic stimulation (rTMS) on neuropsychologic functioning, electroencephalogram, and auditory threshold in depressed patients. Loo, C., Sachdev, P., Elsayed, H., et al.[2019]

In a study involving 232 depressive patients, high-frequency repetitive transcranial magnetic stimulation (rTMS) was found to be a feasible and safe treatment option, with no severe side effects reported and only four patients discontinuing due to side effects.

Patients showed an average improvement of 9.0 points on the Hamilton Depression Rating Scale after receiving an average of 13 rTMS sessions, with 53 patients experiencing a 50% or greater reduction in their depression scores, indicating significant efficacy in a real-world clinical setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation for the treatment of depression: feasibility and results under naturalistic conditions: a retrospective analysis. Frank, E., Eichhammer, P., Burger, J., et al.[2021]

Repetitive transcranial magnetic stimulation (rTMS) has been primarily used to treat major depressive disorder (MDD), highlighting its importance in addressing a significant global health challenge.

Recent advancements in rTMS include exploring new stimulation patterns, targets, and personalized treatment approaches, which aim to enhance the effectiveness and response rates of rTMS in treating MDD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation treatment for depressive disorders: current knowledge and future directions. Baeken, C., Brem, AK., Arns, M., et al.[2020]

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]

High-frequency rTMS targeting the left dorsolateral prefrontal cortex is an effective treatment for acute episodes of major depressive disorder, supported by over 20 years of clinical trials.

While rTMS is effective for unipolar and likely bipolar depression, there is limited evidence for its effectiveness in the maintenance phase of treatment, indicating a need for ongoing research and practitioner education.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the clinical use of repetitive transcranial magnetic stimulation in the treatment of depression. Fitzgerald, PB.[2021]

Repetitive transcranial magnetic stimulation (rTMS) has been shown to have a clear clinical effect in treating major depressive disorder, particularly with left high-frequency rTMS, based on a review of 24 meta-analyses.

The study suggests that rTMS is a justified treatment option for some patients with depression, while also highlighting the need for further research on its efficacy in different stimulation methods and in patients who have not previously received medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A happiness magnet? Reviewing the evidence for repetitive transcranial magnetic stimulation in major depressive disorder. Pridmore, W., Pridmore, S.[2021]

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]

In a preliminary study of 24 drug-resistant patients with bipolar disorder or recurrent major depressive disorder, deep transcranial magnetic stimulation (dTMS) significantly reduced depressive symptoms after 4 weeks of treatment, as measured by the Hamilton Depression Rating Scale (HDRS).

Patients who received maintenance dTMS sessions showed stable HDRS scores over 12 months, while those who did not receive maintenance experienced a significant increase in depressive symptoms, suggesting that ongoing dTMS may help prevent relapses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintenance Deep Transcranial Magnetic Stimulation Sessions are Associated with Reduced Depressive Relapses in Patients with Unipolar or Bipolar Depression. Rapinesi, C., Bersani, FS., Kotzalidis, GD., et al.[2020]

In a study of 40 patients with major depressive disorder (MDD), electroconvulsive therapy (ECT) was found to be more effective than repetitive transcranial magnetic stimulation (rTMS), especially in patients with MDD and psychosis.

For patients with MDD without psychosis, rTMS showed similar efficacy to ECT, suggesting that rTMS could be a viable treatment option for this subgroup, but further blinded studies are needed to clarify its role.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation is as effective as electroconvulsive therapy in the treatment of nondelusional major depressive disorder: an open study. Grunhaus, L., Dannon, PN., Schreiber, S., et al.[2021]

Recent studies on repetitive transcranial magnetic stimulation (rTMS) for depression have demonstrated significantly improved clinical outcomes, with a pooled effect size of -0.76 from 5 studies involving 274 patients, compared to -0.35 from earlier studies.

The findings indicate that new parameters of rTMS stimulation may enhance its antidepressant effects, suggesting a potential advancement in treatment strategies for depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Has repetitive transcranial magnetic stimulation (rTMS) treatment for depression improved? A systematic review and meta-analysis comparing the recent vs. the earlier rTMS studies. Gross, M., Nakamura, L., Pascual-Leone, A., 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]

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) 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10375664/

Efficacy of repetitive transcranial magnetic stimulation ... Data on remission rates were available from 9 studies. The overall remission rate was 35.71% (120/336) in the active rTMS group and 8.37% (18/ ...

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

Repetitive Transcranial Magnetic Stimulation as ... The relapse prevention success rate at 24 weeks in the rTMS monotherapy group was approximately 85%, whereas prior literature indicates that the ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X24001128

Treatment expectations and clinical outcomes following ... Positive pre-treatment expectancy boosts remission odds in Treatment-Resistant Depression (TRD) after acute rTMS.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12224075/

Resource utilization and economic outcomes following ... This study suggests that patients who receive rTMS for treatment-resistant depression required fewer high acuity hospital visits and incurred less expensive ...

5. uclahealth.org uclahealth.org/news/release/study-finds-possible-early-predictor-successful-transcranial

Study finds possible early predictor of successful ... The effectiveness of rTMS has previously been observed as quite variable, with reported response rates ranging from 30-60%. Researchers at UCLA ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4329899/

Efficacy and safety of deep transcranial magnetic ... Conventional rTMS procedures have been investigated in several psychiatric disorders, including unipolar depression, schizophrenia and bipolar disorder (16–18).

7. mayoclinic.org mayoclinic.org/tests-procedures/transcranial-magnetic-stimulation/about/pac-20384625

Transcranial magnetic stimulation Transcranial magnetic stimulation (TMS) is a procedure that uses magnetic fields to stimulate nerve cells in the brain to improve symptoms of major depression.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5925584/

Meta-analysis of the Efficacy and Safety of Repetitive ... After Meta-analysis, we found that treatment combined rTMS with antidepressants improves depressive symptoms in patients with depression.

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1876201824001254

Deep transcranial magnetic stimulation for treatment ... Active dTMS can be a safe and effective treatment for patients with TRD. The active dTMS group showed notably higher antidepressant response rates and ...