Brain Stimulation for Depression

Overseen By Jade Truong

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Stanford University

Disqualifiers: Unstable condition, Substance abuse, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

49 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how brain stimulation can better treat depression by examining the brain's response to repeated doses of transcranial magnetic stimulation (TMS). Researchers aim to identify specific brain markers that indicate TMS effectiveness. The study includes several groups, with participants receiving either real or sham (fake) treatments using magnetic or direct electrical stimulation. Suitable candidates have epilepsy that is difficult to treat with medication and do not have other major neurological disorders. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research in brain stimulation therapies.

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

The trial protocol does not specify whether you need to stop taking your current medications. However, since the trial involves participants with medication-refractory epilepsy, it might be expected that you continue your current epilepsy medications.

What prior data suggests that this brain stimulation technique is safe for treating depression?

Research shows that both types of theta burst stimulation (TBS) under study are generally safe and well-tolerated for treating depression. Studies have found that TBS using direct electrical stimulation is safe, with no major side effects reported. One study confirmed its safety even at higher doses for conditions like stroke recovery.

For TBS using transcranial magnetic stimulation, research indicates it balances benefits and risks well. It effectively treats depression with manageable side effects and is considered as safe as other common depression treatments, like repetitive TMS (rTMS).

Overall, both treatments have been studied and found safe for most people, with minimal side effects similar to other depression treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the use of repetitive brain stimulation for depression because it offers a novel approach compared to traditional treatments like antidepressants or psychotherapy. Unlike medications that affect neurotransmitter levels, this method directly targets brain activity through electrical or magnetic stimulation. Specifically, transcranial magnetic stimulation (TMS) and direct electrical stimulation aim to modulate neural circuits involved in mood regulation, potentially providing faster and more targeted relief for patients. This approach could reduce side effects associated with medications and offer an option for those who do not respond well to standard treatments. By providing both active and sham (placebo) comparisons, researchers hope to better understand the effectiveness and mechanisms of these brain stimulation techniques.

What evidence suggests that this trial's treatments could be effective for depression?

Research has shown that theta burst stimulation (TBS) may help treat depression. This trial will compare different methods of TBS application. One group of participants will receive TBS through direct electrical stimulation, which studies suggest can strongly activate the brain and improve depression symptoms, leading to high recovery rates. Another group will receive TBS via transcranial magnetic stimulation, found to be an effective, safe, and manageable treatment. Both methods offer potential benefits for people with depression, providing options for those seeking relief. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for men and women aged 18 to 65 who have medication-resistant epilepsy needing detailed monitoring, and are able to understand the study's risks to give informed consent. It excludes those with major neurological disorders besides epilepsy.

Inclusion Criteria

My epilepsy does not improve with medication and needs special monitoring.

I understand the study and its risks well enough to give informed consent.

I have epilepsy but no other major neurological disorders.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive repetitive transcranial magnetic stimulation (rTMS) sessions to study neural mechanisms and brain markers

6 weeks

Daily sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Repetitive Brain Stimulation

Trial Overview The study tests how repetitive brain stimulation affects the brain using TMS (a noninvasive treatment for depression) and intracranial electrodes. It aims to identify precise brain activity markers that can enhance TMS effectiveness for treating depression.

How Is the Trial Designed?

Group I: TBS via direct electrical stimulation Active Control 1 Intervention

Group II: TBS via transcranial magnetic stimulation Active Control 1 Intervention

Group III: Sham TBS via direct electrical stimulation Placebo Group 1 Intervention

Group IV: Sham TBS via transcranial magnetic stimulation Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

University of Iowa

Collaborator

Trials

486

Recruited

934,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

This study presents the first case of safely administering electroconvulsive therapy (ECT) to a patient with deep brain stimulation (DBS) by temporarily interrupting DBS only during the ECT sessions.

Previous reports indicated no adverse events when DBS was withheld for the entire ECT course, but this case suggests that short interruptions during ECT may be a safe approach, warranting further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temporary interruption of deep brain stimulation for Parkinson's disease during outpatient electroconvulsive therapy for major depression: a novel treatment strategy. Ducharme, S., Flaherty, AW., Seiner, SJ., et al.[2011]

In a study of 200 patients undergoing deep brain stimulation (DBS) procedures over a follow-up period of approximately 43 months, 20% experienced surgical or hardware-related adverse events (AEs), but all resolved without permanent effects.

The most common AEs were surgical site infections (9.95%) and wire tethering (2.49%), indicating that while AEs can occur, major complications requiring further surgery are rare, highlighting the overall safety of DBS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical and Hardware-Related Adverse Events of Deep Brain Stimulation: A Ten-Year Single-Center Experience. Bouwens van der Vlis, TAM., van de Veerdonk, MMGH., Ackermans, L., et al.[2022]

Deep brain stimulation (DBS) has shown a significant increase in response rates and reduction in depressive symptoms compared to sham treatment, based on a meta-analysis of 190 participants from nine studies.

Despite its promise for treatment-resistant depression, DBS is still considered experimental due to potential publication bias and the occurrence of serious adverse effects in some patients, indicating the need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review and meta-analysis of deep brain stimulation for depression. Kisely, S., Li, A., Warren, N., et al.[2019]

Electroconvulsive therapy (ECT) remains the most effective treatment for acute depression in patients who do not respond to medications, highlighting its importance in the landscape of depression treatments.

Repeated daily repetitive transcranial magnetic stimulation (rTMS) of the prefrontal cortex has become an established clinical treatment for acute depressive episodes after nearly 20 years of research, although the efficacy of other brain stimulation methods is still being evaluated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating the depressions with superficial brain stimulation methods. George, MS., Taylor, JJ., Short, B.[2021]

Deep brain stimulation (DBS) shows promise as a treatment for patients with major depression who do not respond to conventional therapies, with about 50% of patients experiencing long-term antidepressant effects and improved social functioning.

While cognitive safety regarding attention, learning, and memory has been reported, there are potential adverse events such as wound infection and suicide, highlighting the need for larger studies to confirm safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for major depression. Schlaepfer, TE., Bewernick, BH.[2013]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11609094/

Theta burst stimulation for depression: a systematic review ... The current study outcomes included the response rate (primary), depression symptom improvement, remission rate, all-cause discontinuation rate, ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0022395616306392

Efficacy of theta burst stimulation (TBS) for major depression Theta burst stimulation (TBS) has been proposed as a novel treatment for major depression (MD). However, randomized and sham-controlled trials (RCTs) ...

3. nature.com nature.com/articles/s41467-024-51443-1

Theta-burst direct electrical stimulation remodels human ... Here we show that individual bursts of direct electrical TBS at 29 frontal and temporal sites evoked strong neural responses spanning broad cortical regions.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10427506/

Electric field distribution predicts efficacy of accelerated ... Electric field distribution predicts efficacy of accelerated intermittent theta burst stimulation for late-life depression. Davin K Quinn ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S3050529124000849

Clinical and electrophysiological predictors of treatment ... Effectiveness of theta burst versus high-frequency ... Accelerated theta burst stimulation for the treatment of depression: A randomised controlled trial.

6. nature.com nature.com/articles/s41380-024-02630-5

Theta burst stimulation for depression: a systematic review ... Approximately 69.57% of the trials included individuals with an exclusive diagnosis of major depressive disorder. The following six TBS ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X25000403

Efficacy and safety of high-dose and personalized TBS on ... This study highlights the efficacy and safety of high-dose iTBS targeting the individualized FCN for post-stroke cognitive recovery.

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006322323017614

Accelerated Theta Burst Stimulation: Safety, Efficacy, and ... In this review paper, we present the data from accelerated TBS trials to date that support the safety and effectiveness of accelerated protocols ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8555652/

an umbrella review of meta-analyses of randomized ... Appraising the effectiveness of electrical and magnetic brain stimulation techniques in acute major depressive episodes: an umbrella review of meta-analyses.