rTMS for Depression

Overseen By Nadine Obeid, MPH

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Baylor College of Medicine

Disqualifiers: Unstable medical condition, pregnant, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 20

Duration: 3 weeks

50 Participants Needed

Trial Summary

What is the purpose of this trial?

Major depressive disorder (MDD) is a leading cause of disability worldwide with a 19% lifetime prevalence in the United States. Dysfunctional reward processing (e.g., the loss of pleasure) is one of the core features of MDD. Common treatments of MDD include psychological therapies (e.g., cognitive behavioral therapy), medication (e.g., bupropion, sertraline), and psychological therapies and medication combined, but they may not address the function of the reward circuit in MDD. These treatments often do not improve depressive symptoms in MDD patients who are classified as having treatment-resistant depression, and they may be unlikely to respond to further medication trials. Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation that enables us to selectively excite or inhibit neural activity. Multiple TMS pulses given consecutively are known as repetitive TMS (rTMS), and the primary clinical location for applying rTMS is the left dorsolateral prefrontal cortex (dlPFC) for treatment of MDD. Many of these studies have shown that rTMS to the dlPFC may result in decreased depressive symptoms, but is only partially effective (response and remission rates of 41.2 and 35.3%, respectively). This evidence supports the importance of evaluating the efficacy of rTMS in other brain regions, such as the orbitofrontal cortex (OFC), in the treatment of MDD rather than in the dlPFC.

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 is best to discuss this with the research team to get a clear answer.

What data supports the effectiveness of the treatment rTMS for depression?

Research shows that repetitive transcranial magnetic stimulation (rTMS) has been used for over 20 years in treating depression, with studies indicating it is more effective than a placebo (fake treatment) and generally well tolerated by patients. ^{1 2 3 4 5}

Is repetitive transcranial magnetic stimulation (rTMS) safe for treating depression?

Repetitive transcranial magnetic stimulation (rTMS) is generally considered safe for treating depression, with common side effects being minor, such as headaches. There is a low risk of more serious effects like seizures, but these are rare and usually linked to specific risk factors. Overall, when used according to guidelines, rTMS has a good safety profile. ^{6 7 8 9 10}

How is rTMS treatment different from other treatments for depression?

Repetitive transcranial magnetic stimulation (rTMS) is unique because it uses magnetic fields to stimulate nerve cells in the brain, which can help improve symptoms of depression. Unlike medications, it is non-invasive and does not involve taking drugs, making it a novel option for those who haven't responded to traditional treatments. ^{1 3 11 12 13}

Eligibility Criteria

This trial is for adults aged 18-60 with Major Depressive Disorder, as indicated by specific depression scales. Participants must understand and consent to the study's procedures, not be pregnant or nursing if female, and have no metal implants that interfere with MRI or TMS.

Inclusion Criteria

Able to verbalize understanding of consent form, provide written informed consent, and verbalize willingness to complete study procedures

I am not pregnant or breastfeeding during the fMRI and TMS treatment periods.

I have been diagnosed with Major Depressive Disorder.

Exclusion Criteria

I cannot tolerate TMS treatment.

Contraindications to MRI (pacemaker, cochlear implants, metal in the eye, other metal implants, etc.): Do not meet the pre-screening MRI questions provided by the CAMRI at BCM

Contraindications to TMS (any types of non-removable metal in their head except the mouth, or within 12 inches of the coil, etc.): Do not meet the pre-screening TMS safety questionnaire (TASS). Additional exclusion criteria for the TMS experiments are based on the recommendations described by the international consensus panel on brain stimulation

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 20 sessions of rTMS targeting the orbitofrontal cortex (OFC) over 20 days

3 weeks

20 visits (in-person)

Follow-up

Participants are monitored for changes in functional connectivity and clinical outcomes after treatment

4 weeks

Treatment Details

Interventions

• Repetitive Transcranial Magnetic Stimulation

Trial Overview The trial tests repetitive Transcranial Magnetic Stimulation (rTMS) on a brain area called the orbitofrontal cortex in people with depression who haven't fully responded to other treatments. It aims to see if rTMS can better alleviate depressive symptoms.

Participant Groups

Group I: rTMS Experimental Treatment 1 Intervention

20 sessions of rTMS

Repetitive Transcranial Magnetic Stimulation is already approved in United States, European Union, Canada for the following indications:

Approved in United States as rTMS for:

• Major depressive disorder
• Obsessive-compulsive disorder
• Migraines

Approved in European Union as rTMS for:

• Major depressive disorder
• Obsessive-compulsive disorder
• Anxiety disorders

Approved in Canada as rTMS for:

• Major depressive disorder
• Obsessive-compulsive disorder

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Findings from Research

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]

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 19 patients who had previously responded to rTMS, treatment for 30 episodes of depressive relapse showed significant improvement in symptoms, indicating its effectiveness for recurring depression.

The results suggest that rTMS maintains its efficacy over time, with patients benefiting from both low-frequency right-sided and high-frequency left-sided stimulation during their treatment courses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naturalistic study of the use of transcranial magnetic stimulation in the treatment of depressive relapse. Fitzgerald, PB., Benitez, J., de Castella, AR., 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]

In a sham-controlled study involving 29 patients with depression (79% treatment-resistant), fast, left frontal repetitive transcranial magnetic stimulation (rTMS) was found to be more effective than sham treatment, with a response rate of 77% compared to 55% (P<0.05).

The treatment was generally well tolerated, and the improvements in depression symptoms were maintained for up to 12 weeks, suggesting that rTMS could be a valuable addition to existing depression therapies, although further research is needed to optimize treatment parameters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjunctive fast repetitive transcranial magnetic stimulation in depression. Anderson, IM., Delvai, NA., Ashim, B., et al.[2018]

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]

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]

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]

High-frequency rTMS targeting the left dorsolateral prefrontal cortex is an effective treatment for major depressive disorder, supported by over 15 years of research and the authors' 10 years of clinical experience.

While other rTMS techniques, such as low-frequency stimulation to the right prefrontal cortex, show potential, they need further evaluation in larger trials to confirm their efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A practical guide to the use of repetitive transcranial magnetic stimulation in the treatment of depression. Fitzgerald, PB., Daskalakis, ZJ.[2022]

Repetitive transcranial magnetic stimulation (rTMS) has shown statistically significant effects in treating major depression, with 29 studies reviewed indicating that factors like high treatment resistance and advanced age negatively predict treatment response.

Effective rTMS treatment parameters include using stimulation intensity above 100% of the motor threshold and more than 1000 stimulations per session, with older patients requiring higher intensity due to cortical atrophy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Repetitive transcranial magnetic stimulation in major depression: response factor]. Dumas, R., Padovani, R., Richieri, R., et al.[2012]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

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

2. 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]

3. England pubmed.ncbi.nlm.nih.gov

Naturalistic study of the use of transcranial magnetic stimulation in the treatment of depressive relapse. [2022]

4. 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]

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

Adjunctive fast repetitive transcranial magnetic stimulation in depression. [2018]

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

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

7. 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]

8. 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]

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

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

10. England pubmed.ncbi.nlm.nih.gov

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

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

A practical guide to the use of repetitive transcranial magnetic stimulation in the treatment of depression. [2022]

12. France pubmed.ncbi.nlm.nih.gov

[Repetitive transcranial magnetic stimulation in major depression: response factor]. [2012]

13. Thailand pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation for treatment resistant depression: six case reports and review. [2010]