TMS for Depression

(TMS-LLD Trial)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: University of New Mexico

Disqualifiers: Bipolar, Schizophrenia, Substance use, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial aims to improve the effectiveness of a non-invasive brain stimulation technique for elderly patients with late-life depression by using imaging technology to precisely target brain areas involved in mood regulation. The goal is to provide a safer and more effective treatment option for those who have not responded well to traditional therapies. This brain stimulation technique has been studied for many years as a treatment for depression, showing potential benefits especially in older patients.

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 data supports the effectiveness of the treatment rTMS for depression?

Research shows that repetitive transcranial magnetic stimulation (rTMS) has been studied for over three decades and is primarily used for major depressive disorder, with ongoing efforts to improve its effectiveness. Some studies suggest that new parameters in rTMS treatment have shown improved clinical results for depression. ^{1 2 3 4 5}

Is repetitive transcranial magnetic stimulation (rTMS) safe for humans?

Repetitive transcranial magnetic stimulation (rTMS) is generally considered safe when used within recommended guidelines. Common side effects are minor, like headaches, but there is a low risk of seizures and mood changes, which can be managed by screening for risk factors. ^{6 7 8 9 10}

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

Repetitive transcranial magnetic stimulation (rTMS) is unique because it uses magnetic fields to stimulate specific areas of the brain, unlike medications that work through chemical changes. It is non-invasive and can be as effective as electroconvulsive therapy (ECT) for major depressive disorder, but without the need for anesthesia or inducing seizures. ^{2 11 12 13 14}

Research Team

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• rTMS (Neuromodulation)

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.

Participant Groups

Group I: rTMS Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

University of New Mexico

Lead Sponsor

Trials

393

Recruited

3,526,000+

Lisa Kuuttila

University of New Mexico

Chief Executive Officer since 2013

PhD in Pharmaceutical Sciences

David L. Perkins

University of New Mexico

Chief Medical Officer since 2015

MD, PhD

The Mind Research Network

Collaborator

Trials

27

Recruited

2,300+

Findings from Research

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]

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 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 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]

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) 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]

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]

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) 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]

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]

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]

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]

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]

References

1. United States 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. [2018]

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

Repetitive transcranial magnetic stimulation treatment for depressive disorders: current knowledge and future directions. [2020]

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

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

4. 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]

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

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

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

Transcranial magnetic stimulation (TMS) safety: a practical guide for psychiatrists. [2019]

7. United States 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. [2019]

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

Treatment-Resistant Depression Entering Remission Following a Seizure during the Course of Repetitive Transcranial Magnetic Stimulation. [2020]

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

A review of the safety of repetitive transcranial magnetic stimulation as a clinical treatment for depression. [2021]

10. 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]

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

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

12. Germany pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation for the treatment of depression: feasibility and results under naturalistic conditions: a retrospective analysis. [2021]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Maintenance Deep Transcranial Magnetic Stimulation Sessions are Associated with Reduced Depressive Relapses in Patients with Unipolar or Bipolar Depression. [2020]

14. United States 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. [2021]