Brain Stimulation for Depression

Overseen By Benjamin Pace, M.S.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Krystal Parker, PhD

Disqualifiers: Seizures, Epilepsy, Substance use, 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: 8

Duration: 1 week

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether targeting the cerebellum (a part of the brain that helps control movement and balance) with repetitive transcranial magnetic stimulation (rTMS) can improve mood and cognitive issues in individuals with conditions like schizophrenia, autism, bipolar disorder, Parkinson's disease, and major depression. Participants will receive either real rTMS or a sham (fake) version to compare effects. Suitable candidates include those diagnosed with one of these conditions and without a history of seizures, substance use issues, or significant heart or kidney problems. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could lead to new treatment options.

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 trial coordinators or your doctor.

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 generally safe for treating depression. In past studies, patients using rTMS experienced significant improvements in their depression symptoms. Some studies suggest that combining rTMS with antidepressants can enhance these improvements.

Most people tolerate rTMS well, and studies do not report any serious side effects. Some individuals might experience mild side effects like headaches or discomfort at the treatment site, but these usually resolve quickly. Overall, rTMS is considered a safe option for people with depression and has a good track record of improving mood over time. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about repetitive Transcranial Magnetic Stimulation (rTMS) for depression because it offers a non-invasive alternative that targets the brain directly, unlike typical antidepressants that alter brain chemistry systemically. rTMS specifically focuses on stimulating the cerebellum, which is a different target area compared to traditional rTMS treatments that usually aim at the prefrontal cortex. This could lead to more precise and potentially faster relief from depressive symptoms. Additionally, rTMS can be administered daily, providing more immediate feedback and allowing for a potentially quicker adjustment to treatment plans compared to oral medications that can take weeks to show results.

What evidence suggests that this trial's treatments could be effective for improving cognitive deficits and mood in patients with schizophrenia, autism, bipolar disorder, Parkinson's disease, and major depression?

Research has shown that repetitive Transcranial Magnetic Stimulation (rTMS), which participants in this trial may receive, can help treat major depression. Studies indicate that about 35.71% of patients who received rTMS experienced significant symptom improvement. In everyday settings, about 40% to 50% of people respond well to this treatment, demonstrating its real-life effectiveness. Additionally, rTMS has shown promise for those with depression that hasn't improved with other treatments, especially if their symptoms are less severe. Overall, rTMS is considered a helpful option for managing depression. Participants in this trial may also receive Sham rTMS, which serves as a control to evaluate the effectiveness of the active treatment. ^{6 7 8 9 10}

Who Is on the Research Team?

Krystal L Parker, Ph.D

Principal Investigator

Univeristy of Iowa

Are You a Good Fit for This Trial?

This trial is for individuals with schizophrenia, autism, bipolar disorder, Parkinson's disease, or major depression. Participants must be able to consent and not have a recent substance use disorder (except tobacco), uncontrolled high blood pressure, significant heart disease, kidney disease, seizures/epilepsy or certain other medical conditions.

Inclusion Criteria

A clinical diagnosis consistent with enrollment

Exclusion Criteria

I have a history of seizures or epilepsy.

I have atrial fibrillation.

I have a serious heart condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cerebellar or sham TMS stimulation twice per day for 5 days

1 week

5-6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 months

3 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Repetitive Transcranial Magnetic Stimulation (rTMS)
• Sham Repetitive Transcranial Magnetic Stimulation (rTMS)

Trial Overview The study tests if cerebellar stimulation using Repetitive Transcranial Magnetic Stimulation (rTMS) can improve cognitive function and mood in patients. Some will receive real rTMS while others get a sham treatment to compare outcomes.

How Is the Trial Designed?

Group I: patient active rTMS Experimental Treatment 1 Intervention

Subjects will receive 5 days of 2x daily rTMS targeted over the cerebellum.

Group II: Control active rTMS Active Control 1 Intervention

Group III: Control sham rTMS Placebo Group 1 Intervention

Group IV: patient sham rTMS Placebo Group 1 Intervention

Subjects will receive 5 days of 2x daily sham stimulation of the cerebellum.

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

Approved in United States as rTMS for:

• Depression
• Smoking cessation

Approved in European Union as rTMS for:

• Depression

Approved in Canada as rTMS for:

• Depression

Approved in Japan as rTMS for:

• Depression

Who Is Running the Clinical Trial?

Krystal Parker, PhD

Lead Sponsor

Trials

1

Recruited

200+

Published Research Related to This Trial

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]

Intermittent theta burst stimulation (iTBS) is a cost-effective alternative to conventional 10Hz rTMS for treating depression, with an average treatment cost of $1,108 compared to $1,844 for 10Hz rTMS, resulting in savings of $735 per patient.

iTBS also shows a lower average cost per remission at $3,695, compared to $6,146 for 10Hz rTMS, leading to significant savings of $2,451 per remission, making it a more efficient treatment option in healthcare systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implementation of intermittent theta burst stimulation compared to conventional repetitive transcranial magnetic stimulation in patients with treatment resistant depression: A cost analysis. Mendlowitz, AB., Shanbour, A., Downar, J., et al.[2020]

Repetitive transcranial magnetic stimulation (rTMS) has been shown to be a safe and effective treatment for major depressive disorder (MDD), supported by multiple randomized controlled trials and extensive literature review.

The consensus recommendations from a group of 17 expert clinicians and researchers provide detailed guidance on the clinical application of rTMS, ensuring its safe and effective use in treating MDD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Consensus Recommendations for the Clinical Application of Repetitive Transcranial Magnetic Stimulation (rTMS) in the Treatment of Depression. McClintock, SM., Reti, IM., Carpenter, LL., et al.[2022]

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]

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]

In a study comparing the effects of electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS) on major depression, both treatments showed similar outcomes at 3 and 6 months, with no significant differences in relapse rates or depression scores among the 41 patients involved.

Both treatment groups maintained low depression scores on the Hamilton Rating Scale and Global Assessment of Functioning, indicating that the benefits of rTMS are comparable to those of ECT over a 6-month period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three and six-month outcome following courses of either ECT or rTMS in a population of severely depressed individuals--preliminary report. Dannon, PN., Dolberg, OT., Schreiber, S., et al.[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]

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]

A study involving 145 first-time patients with treatment-resistant depression found that 15-minute rTMS sessions were as effective as 30-minute sessions in achieving response and remission rates over 6 weeks.

Both treatment durations resulted in similar outcomes, with the 15-minute sessions showing a partial response rate of 28.2% and a remission rate of 21.8%, indicating that shorter sessions could allow for more patients to be treated with the same resources.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of 15 minute vs 30 minute repetitive transcranial magnetic stimulation sessions for treatment resistant depression - are longer treatment sessions more effective? Ford, H., Hahn, L., Clarke, P., et al.[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]

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]

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8474312/

Repetitive transcranial magnetic stimulation for major ... Real world data has also confirmed the effectiveness of rTMS for MDD in clinical practice, with the most recent literature indicating response rates of 40–50% ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0165178124005481

A multisite observational real-world study on the ... In addition, the study also suggested that rTMS therapy may be more effective for patients with TRD, especially those with milder levels of depression severity.

4. sciencedirect.com sciencedirect.com/science/article/pii/S0165032720325933

Clinical outcomes in a large registry of patients with major ... Randomized clinical trials have demonstrated that Transcranial Magnetic Stimulation (TMS) is an effective treatment for episodes of major depressive disorder ( ...

5. jamanetwork.com jamanetwork.com/journals/jamapsychiatry/fullarticle/210744

Daily Left Prefrontal Transcranial Magnetic Stimulation ... Results Patients, treaters, and raters were effectively masked. Minimal adverse effects did not differ by treatment arm, with an 88% retention rate (90% sham ...

6. 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.

7. sciencedirect.com sciencedirect.com/science/article/pii/S2667174325001727

Efficacy, effectiveness and safety of transcranial magnetic ... TMS is efficacious and safe in BDep, with response and remission rates on par with unipolar depression. High and low frequency protocols on left ...

8. 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 ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11234753/

Utilization and outcomes of transcranial magnetic ... In this real-world study of a large sample of patients with MDD, TMS patients experienced statistically significant improvements in depression ...

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

Transcranial magnetic stimulation Results. If rTMS works for you, your depression symptoms may improve or go away completely. Symptom relief may take a few weeks of treatment.