rTMS for Treatment-Resistant Depression

(BioTMS Trial)

Recruiting at 2 trial locations

Overseen By Lindsay Victoria, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Trial Phase: Phase 3

Sponsor: Weill Medical College of Cornell University

Must not be taking: Bupropion, Tricyclic antidepressants

Disqualifiers: Suicide risk, Long depressive episode, PTSD, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 2

Duration: 8-10 weeks

348 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a magnetic brain stimulation treatment for people with depression who don't respond to standard medications. The treatment uses magnetic pulses to target brain areas involved in mood regulation, aiming to improve symptoms. The method has been studied for its effectiveness in treating major depression.

Do I have to stop taking my current medications for the trial?

You must either stop or maintain the same daily dose of any depression medication for at least 4 weeks before joining the trial and throughout its duration.

What data supports the idea that rTMS for Treatment-Resistant Depression is an effective treatment?

The available research shows that rTMS is more effective than a placebo treatment for people with treatment-resistant depression. In one study, 77% of patients responded positively to rTMS compared to 55% who received a sham treatment. Another study found that increasing the number of rTMS sessions and adjusting the treatment location can improve its effectiveness. These findings suggest that rTMS can be a beneficial option for those who haven't found relief with other treatments. ^{1 2 3 4 5}

What safety data is available for rTMS in treating depression?

Existing safety data for rTMS in treating depression includes reports of transient headaches, local pain, syncope, seizure induction, and hypomania induction. Studies and reviews have been conducted to assess these safety issues, providing recommendations for clinical practice to ensure safe application of rTMS in treating depression. ^{6 7 8 9 10}

Is repetitive transcranial magnetic stimulation (rTMS) a promising treatment for treatment-resistant depression?

Yes, rTMS is a promising treatment for treatment-resistant depression. Studies show it is effective in reducing depressive symptoms and is generally well-tolerated. It offers a non-drug option for those who haven't responded to other treatments. ^{3 4 11 12 13}

Research Team

Conor Liston, MD, PhD

Principal Investigator

Weill Medical College of Cornell University

Eligibility Criteria

Adults aged 22-65 with moderate to severe depression, who haven't improved after trying at least one antidepressant, can join this trial. They must be fluent in English and able to have an MRI safely. Participants should not change their antidepressant dose during the study and must consent to team communication with their clinicians.

Inclusion Criteria

I can safely undergo an MRI scan.

Fluent in English

Major Depressive Disorder (by M.I.N.I., Diagnostic Statistical Manual V (DSM-V criteria)); Verification by evaluation by licensed study psychiatrist or psychologist

Exclusion Criteria

Participated in any clinical trial with an investigational drug or device within the past 6 weeks prior to screening

I have had brain surgery for a neurological or mental health issue.

I have major depression and Vagus Nerve Stimulation didn't work for me.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive biotype-guided or standard-of-care rTMS treatment targeting the DLPFC or DMPFC

8-10 weeks

Multiple sessions per week

Follow-up

Participants are monitored for changes in depression severity and resting state fMRI connectivity

1 week

1 visit (in-person)

Treatment Details

Interventions

• Repetitive Transcranial Magnetic Stimulation

Trial Overview The trial is testing whether brain scans (fMRI) can help optimize rTMS treatment for depression. It explores how rTMS affects brain networks by using these scans before and after therapy sessions.

Participant Groups

Group I: Targeted Side Arm Experimental Treatment 1 Intervention

iTBS rTMS targeting the area of the brain (DLPFC or dorsomedial prefrontal cortex DMPFC)) that we hypothesize will be most effective for that subject's biotype (confirmation arm).

Group II: Standard of Care Active Control 1 Intervention

FDA-cleared, standard-of-care iTBS repetitive Transcranial Magnetic Stimulation targeting the left dorsolateral prefrontal cortex (DLPFC), regardless of the depression subtype (biotype) determined by a magnetic resonance imaging (MRI) scan.

Group III: Opposite Side Arm Active Control 1 Intervention

iTBS rTMS targeting the opposite site (DLPFC or DMPFC) than the one we hypothesize will be most effective for that subject's biotype (disconfirmation arm).

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?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Stanford University

Collaborator

Trials

2,527

Recruited

17,430,000+

Findings from Research

In a study involving 18 medication-resistant depressed subjects, both real and sham rTMS treatments led to significant mood improvements over 2 weeks, but there was no notable difference in effectiveness between the two groups.

The 4-week course of rTMS was found to be safe, indicating that while it may not be more effective than sham treatment, it does not pose additional risks to patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blind controlled investigation of transcranial magnetic stimulation for the treatment of resistant major depression. Loo, C., Mitchell, P., Sachdev, P., et al.[2021]

In a study of 58 patients with treatment-resistant depression (TRD), increased connectivity between the left dorsolateral prefrontal cortex (DLPFC) and the right cerebellum was found to predict a positive response to repetitive transcranial magnetic stimulation (rTMS).

The predictive model based on SPECT connectivity showed a significant ability to forecast rTMS response, with an area under the curve of 0.756, indicating that brain connectivity patterns can help identify which patients are more likely to benefit from rTMS treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictive value of dorso-lateral prefrontal connectivity for rTMS response in treatment-resistant depression: A brain perfusion SPECT study. Richieri, R., Verger, A., Boyer, L., et al.[2019]

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]

In a study involving 141 patients with treatment-resistant depression, 30.5% achieved remission after receiving an average of 26 fast left rTMS treatments, indicating that a higher number of stimulations may be necessary for effective treatment.

Additionally, 26% of patients who did not respond to fast left rTMS found remission when switched to slow right rTMS, suggesting that alternative rTMS protocols can be beneficial for those who initially fail to respond.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving the antidepressant efficacy of transcranial magnetic stimulation: maximizing the number of stimulations and treatment location in treatment-resistant depression. McDonald, WM., Durkalski, V., Ball, ER., et al.[2022]

In a pilot study involving 19 medication-resistant depressed subjects, bilateral prefrontal repetitive transcranial magnetic stimulation (rTMS) did not show superior efficacy compared to sham treatment over 3 weeks, as both groups experienced similar improvements in mood.

Despite the lack of significant differences in mood improvement, rTMS was found to be safe, with no neuropsychological impairments reported in either the active or sham treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blind controlled investigation of bilateral prefrontal transcranial magnetic stimulation for the treatment of resistant major depression. Loo, CK., Mitchell, PB., Croker, VM., et al.[2019]

In a study of 22 outpatients with treatment-resistant depression, repetitive transcranial magnetic stimulation (rTMS) was found to be safe and effective, with 50% of participants responding positively and 40.9% achieving remission after 4 weeks of treatment.

The treatment led to a significant reduction in depression scores, with no major side effects reported, indicating that rTMS could be a viable option for patients who have not responded to traditional antidepressant medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation (5 and 10 Hz) With Modified Parameters in the Treatment of Resistant Unipolar and Bipolar Depression in a Private Practice Setting. Rachid, F., Moeglin, C., Sentissi, O.[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) 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) 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) has shown statistical superiority over sham therapy for treating depression, particularly with left-prefrontal high frequency stimulation, but the actual clinical benefits are often marginal.

Factors such as younger age, absence of treatment-resistant depression, and no psychotic features are associated with a better response to rTMS, highlighting the need for further research to optimize treatment parameters and confirm its clinical utility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation for depression. Mitchell, PB., Loo, CK.[2017]

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) has been shown to be an effective and safe treatment for treatment-resistant depression (TRD), with 16 out of 17 studies indicating positive outcomes in reducing depressive symptoms.

The review included 17 randomized controlled trials published in the last five years, highlighting the need for further research to establish standardized protocols for rTMS application, including factors like frequency and intensity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation for the Treatment of Resistant Depression: A Scoping Review. Adu, MK., Shalaby, R., Chue, P., et al.[2022]

This study is a large-scale, multicenter clinical trial involving 360 Veterans with treatment-resistant major depression (TRMD) to evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) compared to sham treatment over 30 sessions.

The trial uniquely includes Veterans with posttraumatic stress disorder (PTSD) and substance abuse histories, aiming to assess a wide range of predictors for treatment response, with the primary outcome being the remission rate measured by the Hamilton Rating Scale for Depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant major depression (TRMD) Veteran patients: study protocol for a randomized controlled trial. Mi, Z., Biswas, K., Fairchild, JK., et al.[2018]

References

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

Double-blind controlled investigation of transcranial magnetic stimulation for the treatment of resistant major depression. [2021]

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

Predictive value of dorso-lateral prefrontal connectivity for rTMS response in treatment-resistant depression: A brain perfusion SPECT study. [2019]

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

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

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

Improving the antidepressant efficacy of transcranial magnetic stimulation: maximizing the number of stimulations and treatment location in treatment-resistant depression. [2022]

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

Double-blind controlled investigation of bilateral prefrontal transcranial magnetic stimulation for the treatment of resistant major depression. [2019]

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

Repetitive Transcranial Magnetic Stimulation (5 and 10 Hz) With Modified Parameters in the Treatment of Resistant Unipolar and Bipolar Depression in a Private Practice Setting. [2019]

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

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

8. England pubmed.ncbi.nlm.nih.gov

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

9. 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]

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

Transcranial magnetic stimulation for depression. [2017]

11. 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]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation for the Treatment of Resistant Depression: A Scoping Review. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant major depression (TRMD) Veteran patients: study protocol for a randomized controlled trial. [2018]