rTMS for Depression and Substance Use Disorder

Overseen By Teresa Slettebo, B.A.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: Alcohol, Benzodiazepines, Sedatives

Disqualifiers: Seizures, Brain lesions, Pregnancy, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 3 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to help individuals struggling with both depression and stimulant use, such as meth or cocaine. The treatment employs repetitive transcranial magnetic stimulation (rTMS) to determine its effectiveness in improving depression symptoms and reducing drug use. Suitable candidates for this trial have experienced issues with meth or cocaine in the past year and have felt down or depressed. Participants will provide urine samples and undergo brain and heart activity monitoring through EEGs and ECGs. As an unphased trial, this study offers a unique opportunity to contribute to pioneering research that could lead to new treatment options.

Do I need to stop my current medications for the trial?

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 to understand any specific requirements.

What prior data suggests that this rTMS is safe for individuals with depression and stimulant use disorder?

Research shows that accelerated repetitive transcranial magnetic stimulation (rTMS) is generally safe and well-tolerated. Studies have found that it has very few side effects, so most people handle the treatment well. One study found that rTMS effectively treats depression, improving mood without causing many side effects. For those considering joining a trial, current research suggests that rTMS is a safe option. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike standard treatments for depression and substance use disorder, which often involve medication and therapy, Accelerated Repetitive Transcranial Magnetic Stimulation (rTMS) offers a non-invasive, brain-targeting approach. This technique uses magnetic fields to stimulate nerve cells, potentially offering faster relief from symptoms with fewer side effects. Researchers are excited because it targets brain areas linked to these conditions more directly, which could lead to quicker and more effective outcomes compared to traditional methods.

What evidence suggests that accelerated rTMS is effective for depression and stimulant use disorder?

Research has shown that accelerated repetitive transcranial magnetic stimulation (rTMS), which participants in this trial will receive, holds promise for treating depression. Studies have found that this treatment can work faster and more effectively than the standard version in alleviating major depression. With more treatment sessions, accelerated rTMS can provide quicker relief from depression symptoms. This approach also reduces the overall treatment time and may enhance efficiency. Although information on its effects on substance use disorder is limited, the positive results for depression are encouraging for addressing both conditions together. ^{1 2 4 5 6}

Who Is on the Research Team?

Manish Jha, M.B.B.S

Principal Investigator

UT Southwestern Medical Center

Are You a Good Fit for This Trial?

This trial is for individuals who are struggling with both depression and stimulant use disorder, which includes problems with drugs like methamphetamine or cocaine. Participants should be suitable candidates for the rTMS treatment.

Inclusion Criteria

Have a PHQ9 of greater than or equal to five (5)

Be able to sufficiently understand, speak, and read English to provide informed consent and ask relevant questions, and be willing to comply with all study procedure instructions

Be willing to use appropriate birth control method during the treatment phase of the study, if individual is of childbearing potential

Exclusion Criteria

Current pregnancy as determined by a urine screening

Current or lifetime manic or hypomanic episode, defined by MINI diagnostic interview

I have a documented history of brain lesions or tumors.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive an accelerated course of repetitive Transcranial Magnetic Stimulation (rTMS) with up to four sessions per day, five days a week, for a total of 50 sessions over three weeks

3 weeks

Daily visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of craving, substance use, and mood symptoms

1 week

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Accelerated Repetitive Transcranial Magnetic Stimulation

Trial Overview

The study is testing an accelerated course of repetitive transcranial magnetic stimulation (rTMS), a non-invasive procedure that uses magnetic fields to stimulate nerve cells in the brain, on people with depression and stimulant abuse issues.

How Is the Trial Designed?

Group I: rTMS Intervention Experimental Treatment 1 Intervention

Eligible participants who are enrolled will receive an accelerated course of repetitive Transcranial Magnetic Stimulation.

Accelerated 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
• Smoking cessation

Approved in European Union as rTMS for:

• Major Depressive Disorder
• Obsessive Compulsive Disorder

Approved in Canada as rTMS for:

• Major Depressive Disorder
• Obsessive Compulsive Disorder

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Published Research Related to This Trial

In a case series of 9 patients with major depressive disorder and bipolar disorder, accelerated theta-burst rTMS treatment over 8 days led to significant reductions in depression symptoms, as measured by the CES-D and CGI scales.

The treatment was well tolerated, with mild headaches being the most common side effect, and five patients achieving at least a 50% reduction in symptoms by the end of the treatment period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated theta-burst repetitive transcranial magnetic stimulation for depression in South Africa. Bröcker, E., van den Heuvel, L., Seedat, S.[2020]

Repetitive transcranial magnetic stimulation (rTMS) is an established treatment for major depressive disorder (MDD), but its effect sizes are modest compared to standard treatments.

Accelerated high-frequency rTMS (arTMS) and accelerated intermittent theta burst stimulation (aiTBS) showed similar clinical efficacy, but both methods have the potential to significantly reduce the time it takes for patients to move from a depressed state to a response state, which is beneficial for patient recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated rTMS: A Potential Treatment to Alleviate Refractory Depression. Baeken, C.[2020]

In a study of 27 participants, a prolonged intermittent theta burst stimulation (piTBS) protocol using 1,800 pulses showed limited effectiveness for major depressive disorder, with only 18.2% of participants achieving a response and 9.1% reaching remission.

Safety and tolerability were concerns, as 18.5% of participants experienced issues, suggesting that while piTBS is a promising approach, further research is needed to optimize its parameters and improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged intermittent theta burst stimulation in the treatment of major depressive disorder: a case series. Richard, M., Noiseux, C., Desbeaumes Jodoin, V., et al.[2022]

Intermittent theta burst stimulation (iTBS) is as effective as standard high-frequency (10 Hz) rTMS for treating treatment-resistant depression, showing non-inferiority in improving depression scores over 4-6 weeks in a study with 414 participants.

Both iTBS and 10 Hz rTMS had similar safety profiles and dropout rates, with headaches being the most common side effect, indicating that iTBS can be a viable alternative that allows for more patients to be treated in a shorter time without losing effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial. Blumberger, DM., Vila-Rodriguez, F., Thorpe, KE., et al.[2022]

In a study of 54 patients with major depression, the combination of intermittent theta burst stimulation (iTBS) and low-frequency rTMS (LF-rTMS) significantly improved depression and anxiety symptoms more than high-frequency rTMS (HF-rTMS).

The results suggest that iTBS combined with LF-rTMS may be a promising alternative therapy for major depression, offering both efficacy and time-saving benefits compared to traditional methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Left intermittent theta burst stimulation combined with right low-frequency rTMS as an additional treatment for major depression: A retrospective study. Mi, Y., Ji, Y., Lou, Z., et al.[2022]

In a study of 105 patients with major depressive disorder, higher baseline cognition-modulated frontal theta activity (Δfrontalθ) was found to predict the antidepressant response to repetitive transcranial magnetic stimulation (rTMS), but not to prolonged intermittent theta-burst stimulation (piTBS).

Both rTMS and piTBS are effective treatments for depression, but they may operate through different neurobiological mechanisms, as indicated by the differing predictive values of Δfrontalθ for each treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Task-Modulated Brain Activity Predicts Antidepressant Responses of Prefrontal Repetitive Transcranial Magnetic Stimulation: A Randomized Sham-Control Study. Li, CT., Cheng, CM., Juan, CH., et al.[2022]

A proof-of-concept study involving 19 individuals with cocaine use disorder showed that administering intermittent theta-burst stimulation (iTBS) to the left dorsolateral prefrontal cortex was well-tolerated and safe, even in participants actively using cocaine.

Participants who completed at least 26 of the 30 iTBS sessions reduced their weekly cocaine use by 78% in spending and 70% in frequency, indicating that iTBS may effectively modulate addiction-related circuits and reduce substance use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated Intermittent Theta-Burst Stimulation as a Treatment for Cocaine Use Disorder: A Proof-of-Concept Study. Steele, VR., Maxwell, AM., Ross, TJ., et al.[2020]

Intermittent theta burst stimulation (iTBS) of the prefrontal cortex has shown effects on reducing cocaine craving and consumption that are comparable to traditional high-frequency rTMS (15 Hz) in a study of 25 treatment-seeking cocaine addicts.

Both iTBS and 15 Hz rTMS demonstrated similar safety and tolerability profiles, with low dropout rates, suggesting that iTBS could be a more efficient treatment option due to its shorter duration (3 minutes) compared to the 15-minute standard protocol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent Theta Burst Stimulation of the Prefrontal Cortex in Cocaine Use Disorder: A Pilot Study. Sanna, A., Fattore, L., Badas, P., et al.[2020]

In a study of 45 antidepressant-free patients with medication-resistant depression, accelerated intermittent Theta Burst Stimulation (aiTBS) led to significant changes in brain perfusion, particularly increasing blood flow in areas like the ventromedial prefrontal cortex, which are linked to mood regulation.

The findings suggest that active aiTBS not only improves depressive symptoms but also alters brain activity in regions associated with depression, while sham treatment showed different effects, indicating that the clinical benefits of aiTBS may be due to both direct stimulation and potential placebo responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated iTBS changes perfusion patterns in medication resistant depression. Wu, GR., Duprat, R., Baeken, C.[2022]

Intermittent theta burst stimulation (iTBS) and high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) are equally effective and safe for treating patients with treatment-resistant major depressive disorder, based on a comprehensive meta-analysis.

iTBS may be a more practical option in clinical settings because it requires less stimulation intensity and shorter treatment times compared to HF-rTMS, making it potentially more accessible for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent theta burst stimulation vs. high-frequency repetitive transcranial magnetic stimulation for major depressive disorder: A systematic review and meta-analysis. Kishi, T., Sakuma, K., Matsuda, Y., et al.[2023]

A clinical trial involving 96 outpatients with moderate depression will investigate the effectiveness of intermittent theta burst stimulation (iTBS) on reducing depressive symptoms, comparing it to a sham treatment over ten sessions.

The study will also explore various factors, including genetic and neuropsychological measures, that may influence the response to iTBS, ensuring a thorough safety screening and adherence to ethical guidelines throughout the trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The antidepressant effect of intermittent theta burst stimulation (iTBS): study protocol for a randomized double-blind sham-controlled trial. Ørbo, MC., Grønli, OK., Larsen, C., et al.[2023]

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