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

Trial Summary

What is the purpose of this trial?

Transcranial magnetic stimulation (TMS) is an effective treatment for depression, but clinical outcome is suboptimal, partially because investigators are missing biologically-grounded brain markers which show that TMS is modifying activity at the intended target in the brain. The goal of this proposal is to characterize the key markers of the brain's response to repeated doses of TMS with high resolution using invasive brain recordings in humans, and relate these brain markers to noninvasive recordings. These markers will improve the understanding of TMS and can be used to optimize and enhance clinical efficacy for depression and other psychiatric disorders.

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 data supports the effectiveness of the treatment Repetitive Brain Stimulation for depression?

Research shows that various forms of brain stimulation, like cranial electrotherapy stimulation, have been used as alternative treatments for depression, with growing evidence supporting their effectiveness. Additionally, deep brain stimulation, another type of brain stimulation, has shown promise in treating depression, especially when traditional treatments fail. ^{1 2 3 4 5}

Is brain stimulation safe for treating depression?

Brain stimulation, like deep brain stimulation (DBS), has been studied for depression and other conditions. While it can be effective, there are some risks, such as wound infections and mood changes. However, cognitive safety regarding attention, learning, and memory has been reported, and larger studies are ongoing to better understand its safety. ^{4 6 7 8 9}

How does repetitive brain stimulation differ from other treatments for depression?

Repetitive brain stimulation, like repetitive transcranial magnetic stimulation (rTMS), is unique because it uses magnetic fields to stimulate specific brain areas, offering an alternative for those who don't respond to medications or talk therapy. Unlike traditional treatments, it directly targets brain activity and is non-invasive, making it a promising option for treatment-resistant depression. ^{2 4 10 11 12}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Comparative efficacy and acceptability of non-surgical brain stimulation for the acute treatment of major depressive episodes in adults: systematic review and network meta-analysis. [2020]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Closing the Loop on Deep Brain Stimulation for Treatment-Resistant Depression. [2020]

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

A systematic review and meta-analysis of deep brain stimulation for depression. [2019]

4. England pubmed.ncbi.nlm.nih.gov

A meta-analysis of cranial electrotherapy stimulation in the treatment of depression. [2021]

5. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[The effect of multichannel electrostimulation of neck nervous structures on the brain connectivity of patients with depressive disorders]. [2020]

6. United States 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. [2011]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for major depression. [2013]

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

Surgical and Hardware-Related Adverse Events of Deep Brain Stimulation: A Ten-Year Single-Center Experience. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Long versus short pulse width subcallosal cingulate stimulation for treatment-resistant depression: a randomised, double-blind, crossover trial. [2020]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Treating the depressions with superficial brain stimulation methods. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Brain stimulation treatments in bipolar disorder: A review of the current literature. [2017]

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

Low-frequency rTMS over right dorsolateral prefrontal cortex in the treatment of resistant depression: cognitive improvement is independent from clinical response, resting motor threshold is related to clinical response. [2012]