Brain Stimulation for Depression

Overseen by Krystal L Parker, Ph.D

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Krystal Parker, PhD

Disqualifiers: Seizures, Epilepsy, Substance use, others

No Placebo Group

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

The purpose of this study is to examine whether cerebellar stimulation can be used to improve cognitive deficits and mood in patients with schizophrenia, autism, bipolar disorder, Parkinson's disease, and major depression.

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.

What data supports the effectiveness of the treatment Repetitive Transcranial Magnetic Stimulation (rTMS) for depression?

Repetitive transcranial magnetic stimulation (rTMS) has been shown to be an effective treatment for depression, supported by over 20 years of clinical trials and recent studies that highlight its effectiveness in treating major depression. Additionally, a randomized controlled trial found that rTMS had positive effects compared to a placebo, with follow-up studies indicating sustained benefits. ^{1 2 3 4 5}

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

Repetitive transcranial magnetic stimulation (rTMS) is generally considered safe for humans, with common side effects including temporary headaches and local pain. Rarely, it can cause more serious effects like seizures, but these are uncommon. ^{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 nerve cells in the brain, which is different from medications or talk therapy. It is non-invasive and can be delivered in shorter sessions, like the 3-minute intermittent theta burst stimulation (iTBS), making it a convenient option for patients with depression. ^{1 2 11 12 13}

Research Team

Krystal L Parker, Ph.D

Principal Investigator

Univeristy of Iowa

Eligibility Criteria

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.

Trial Timeline

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)

Treatment Details

Interventions

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

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.

Participant Groups

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 Canada, Japan for the following indications:

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+

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]

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 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 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 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 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 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]

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 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]

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]

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]

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]

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

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

3. United States 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. [2019]

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

A randomized controlled trial with 4-month follow-up of adjunctive repetitive transcranial magnetic stimulation of the left prefrontal cortex for depression. [2022]

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

Consensus Recommendations for the Clinical Application of Repetitive Transcranial Magnetic Stimulation (rTMS) in the Treatment of Depression. [2022]

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. 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

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

10. 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]

11. United States 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. [2020]

12. Netherlands 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? [2021]

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

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