Sleep TMS for Depression

Overseen By Jade T Truong, BS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Stanford University

Must be taking: Antidepressants

Disqualifiers: Intellectual disability, Neurological disorder, Pregnancy, others

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

Compensation: Varies

Number of Visits: 2

Duration: 3 hours per session

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a special type of brain stimulation, called sleep-state transcranial magnetic stimulation (TMS), can help treat depression. Researchers seek to evaluate its effectiveness and gather patient feedback. Participants will receive either the real or a placebo version of TMS while awake, before sleep, or during specific sleep stages. This trial targets individuals with major depressive disorder who have not found success with at least one antidepressant and are experiencing moderate to severe depression. As an unphased trial, it offers a unique opportunity to explore a novel treatment approach for depression.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators.

What prior data suggests that sleep-state TMS is safe for depression treatment?

Research has shown that Transcranial Magnetic Stimulation (TMS) is generally safe. The FDA has approved TMS for treating depression, migraines, and obsessive-compulsive disorder (OCD), indicating it is usually well-tolerated for these conditions. Studies have also found that TMS can improve sleep and reduce insomnia. Specifically, one study found that TMS significantly improved sleep quality in patients with depression unresponsive to other treatments.

Most people using TMS do not experience serious side effects, though some might have mild headaches or feel discomfort where the treatment is applied. These effects usually resolve quickly. Overall, TMS appears to be a safe option for many, including those managing symptoms of depression. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Sleep TMS for depression because it offers a unique approach by delivering Transcranial Magnetic Stimulation (TMS) during sleep. Unlike traditional treatments that are typically administered while patients are awake, this method targets brain activity during specific sleep stages, potentially enhancing treatment effectiveness. Additionally, this trial uses a non-invasive method with intermittent theta-burst stimulation (iTBS), which is different from many pharmacological treatments for depression. By incorporating EEG monitoring, researchers hope to better understand how sleep and brain stimulation interact to improve mood and cognitive functions.

What evidence suggests that Sleep TMS might be an effective treatment for depression?

Research shows that sleep-state transcranial magnetic stimulation (TMS) might alleviate depression symptoms. In this trial, participants will receive either active or sham TMS during pre-sleep wakefulness or NREM sleep stages. Studies have found that TMS can enhance sleep quality, which correlates with reduced depression symptoms. Specifically, improved sleep following TMS was linked to fewer depression symptoms. Additionally, evidence suggests that TMS can aid individuals with treatment-resistant depression by improving sleep and reducing insomnia. This indicates that TMS could be beneficial for enhancing sleep and mood in depression treatment. ^{5 6 7 8 9}

Who Is on the Research Team?

Corey J Keller, MD, PhD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

This trial is for individuals with Major Depressive Disorder (MDD) who have not had success with at least one antidepressant medication and are experiencing moderate-to-severe depression. Specific details on who cannot participate were not provided.

Inclusion Criteria

* Current Major Depressive Disorder (MDD) diagnosis

* Failed \>= 1 antidepressant medication

* Moderate-to-severe depression

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 2 sessions of Transcranial Magnetic Stimulation (TMS) with either active or sham iTBS during pre-sleep wakefulness or NREM sleep stages, while performing cognitive tasks.

3 hours per session

2 sessions

Follow-up

Participants are monitored for changes in sleep quality, treatment tolerability, and cognitive performance after each session.

3 hours after each session

What Are the Treatments Tested in This Trial?

Interventions

• Sleep TMS

Trial Overview The study is testing the use of sleep-state transcranial magnetic stimulation (TMS), a non-invasive brain stimulation technique, to see if it can improve symptoms in people suffering from depression by enhancing brain plasticity during sleep.

How Is the Trial Designed?

Group I: Sham TMS, Active TMS Experimental Treatment 1 Intervention

Participants will receive 2 sessions of Transcranial Magnetic Stimulation (TMS) delivered during using standard intermittent theta-burst (iTBS) parameters (600 pulses, 3 min, 120% rMT). Participants will receive, on separate sessions, either active or sham iTBS delivered during pre-sleep wakefulness or NREM sleep stages while recording with Electroencephalography (EEG). Participants will perform the N-back task and Multi-source Interference Task (MSIT) during each session to measure working memory and cognitive control performance.

Group II: Active TMS, Sham TMS Experimental Treatment 1 Intervention

Participants will receive 2 sessions of Transcranial Magnetic Stimulation (TMS) delivered using standard intermittent theta-burst (iTBS) parameters (600 pulses, 3 min, 120% rMT). Participants will receive, on separate sessions, either active or sham iTBS delivered during pre-sleep wakefulness or NREM sleep stages while recording with Electroencephalography (EEG). Participants will perform the N-back task and Multi-source Interference Task (MSIT) during each session to measure working memory and cognitive control performance.

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

National Center for Advancing Translational Sciences (NCATS)

Collaborator

Trials

394

Recruited

404,000+

Published Research Related to This Trial

Transcranial magnetic stimulation (TMS) is an effective and safe treatment for major depressive disorder (MDD), showing significant improvements in quality of life (QOL) and functional status in 307 outpatients after an acute treatment course.

Patients reported statistically significant enhancements in mental and physical health across various domains, indicating that TMS not only alleviates depressive symptoms but also leads to meaningful improvements in overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation (TMS) for major depression: a multisite, naturalistic, observational study of quality of life outcome measures in clinical practice. Janicak, PG., Dunner, DL., Aaronson, ST., 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]

In a study of 329 subjects with major depressive disorder undergoing 6 weeks of repetitive transcranial magnetic stimulation (rTMS), a lack of early improvement in mood after 1 week was a strong predictor of nonresponse to treatment, especially in those with severe depression.

By 2 weeks, those with very severe depression who showed no improvement in mood were all identified as nonresponders, indicating that early monitoring of mood and sleep can guide treatment adjustments for better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Absence of early mood improvement as a robust predictor of rTMS nonresponse in major depressive disorder. Mirman, AM., Corlier, J., Wilson, AC., et al.[2022]

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 of 301 medication-free patients with treatment-resistant major depression, transcranial magnetic stimulation (TMS) significantly improved quality of life (QOL) and functional status compared to sham treatment during a 6-week trial.

The benefits of TMS were not only observed during the acute treatment phase but also sustained over a 24-week follow-up, indicating that TMS provides durable improvements in patients' overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvement in quality of life with left prefrontal transcranial magnetic stimulation in patients with pharmacoresistant major depression: acute and six month outcomes. Solvason, HB., Husain, M., Fitzgerald, PB., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11456523/

Effect of sleep quality on repetitive transcranial magnetic ... We found that sleep quality improves after TMS (p<.001) and correlates with improvement in non-insomnia related depression symptoms (r= .318, p<.001).

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165032724010097

Sleep as a predictor of improved response to transcranial ... This study examined the association between sleep dysfunction and improvement in depression symptoms with TMS treatment for TRD.

3. jcsm.aasm.org jcsm.aasm.org/doi/10.5664/jcsm.10954

Impact of deep transcranial magnetic stimulation on insomnia ... Our results suggest that dTMS holds promise to improve insomnia outcomes in patients with TRD. However, the study's limitations, including its ...

4. sleepmedres.org sleepmedres.org/journal/view.php?doi=10.17241/smr.2024.02607

The Effect of Accelerated Transcranial Magnetic ... Conclusions. aTMS significantly alleviated insomnia severity and enhanced sleep quality in patients with TRD within just two weeks. Key words: ...

5. frontiersin.org frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1646383/full

Effectiveness of different repetitive transcranial magnetic ... Our results revealed that low-frequency rTMS targeting the r-DLPFC and b-DLPFC significantly improved PSQI scores, sleep efficiency, and HAMD-17 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7732158/

Transcranial Magnetic Stimulation (TMS) Safety with ... Transcranial Magnetic Stimulation (TMS) is FDA approved for depression, migraines, and OCD, with other symptoms and disorders being aggressively ...

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

Transcranial magnetic stimulation Transcranial magnetic stimulation (TMS) is a procedure that uses magnetic fields to stimulate nerve cells in the brain to improve symptoms of major depression.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9094636/

Safety and recommendations for TMS use in healthy subjects ... Safety and recommendations for TMS use in healthy subjects and patient populations, with updates on training, ethical and regulatory issues: Expert Guidelines

9. sciencedirect.com sciencedirect.com/science/article/pii/S1389945725001868

The effects of transcranial magnetic stimulation on patients ... Repetitive transcranial magnetic stimulation noninvasively modulates brain synaptic plasticity, showing therapeutic potential for insomnia.