Intracranial Electrodes for Depression

Overseen By Jade Truong

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Stanford University

Disqualifiers: Diffuse epilepsy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 5 minutes per session

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to discover new methods to measure mood in individuals with depression using advanced technology. Researchers examine how facial expressions and speech patterns reflect mood changes and their connections to brain activity. The study involves using implanted electrodes in the brain to test whether these technologies can provide reliable mood estimates. Individuals with major depressive disorder who are currently experiencing depression may qualify, provided they do not have epilepsy affecting multiple brain areas. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could revolutionize the monitoring and treatment of depression.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What prior data suggests that intracranial electrodes are safe for depression treatment?

Research has shown that using electrodes in the brain to treat depression is generally safe. One study found that only 4.9% of participants experienced complications, with just 3.1% of these being serious. Most people handle the procedure well.

These results are encouraging for those considering joining trials for this treatment. Although some risks exist, current research indicates a low chance of serious problems. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using intracranial electrodes for depression because this approach targets the brain more directly than traditional treatments like antidepressants or psychotherapy. Unlike standard treatments that often take weeks to show effects, this method may offer quicker relief by delivering direct electrical stimulation to specific brain areas involved in mood regulation. Additionally, by using a combination of active and sham stimulation, researchers aim to better understand which specific patterns of brain activity are most effective in alleviating depressive symptoms. This could pave the way for more personalized and efficient treatment options for depression in the future.

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

Research has shown that electrical brain stimulation, such as Direct Electrical Stimulation (DES), can help treat depression. In this trial, participants will join one of two groups: one receiving Active DES and the other receiving Sham DES. A review of several studies has found that various types of electrical brain stimulation positively affect people with major depression. Another similar method, cranial electrotherapy stimulation, has shown small benefits for depression. A review of many studies suggests these techniques are promising for treating sudden episodes of depression. However, some studies indicate they might not work as well as traditional antidepressants for everyone. Overall, DES offers a hopeful way to improve mood in depression, but results can vary. ^{1 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with Major Depressive Disorder currently experiencing a depressive episode. Participants must understand the study and consent independently, without medical or surgical reasons preventing electrode implantation. It's not suitable for those with diffuse epilepsy affecting multiple brain lobes.

Inclusion Criteria

I understand the study's details and can sign the consent form by myself.

I have been diagnosed with major depression currently.

I have no health issues preventing me from getting an electrode implant.

Exclusion Criteria

My epilepsy affects multiple areas of my brain.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo direct electrical stimulation and audio-facial behavior monitoring

5 minutes per session

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• N/A

Trial Overview The study tests if audio-facial behaviors captured on video can reliably indicate mood states by correlating them with neural activity via intracranial electrodes. This could lead to better remote monitoring of mood in clinical and home settings.

How Is the Trial Designed?

Group I: Active Direct electrical stimulation (DES) Active Control 1 Intervention

Intracranial electrodes will be used for the delivery of invasive brain stimulation.

Group II: Sham Direct electrical stimulation (DES) Placebo Group 1 Intervention

Intracranial electrodes will be used for the delivery of invasive brain stimulation.

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

Neurosurgery for depression has evolved from early invasive techniques to more precise methods like frequency-dependent chronic electric stimulation, which is favored for its nondestructive nature and effectiveness in treating severe depression.

Future advancements in neurosurgery may include combining chronic electric stimulation with techniques like microdialysis and imaging technologies, necessitating a new classification system for depression based on current neurobiological understanding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Depression and neurosurgery: past, present, and future. Nicolaidis, S.[2005]

In a study of 163 intracranial electrode implantation procedures for drug-resistant focal epilepsy, the overall complication rate was low at 4.9%, with no permanent morbidity or mortality reported, indicating a favorable safety profile for this intervention.

Major complications were more likely in patients with MRI-negative cases, suggesting that careful patient selection may further enhance safety when considering invasive exploration for epilepsy treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of intracranial electrode implantation for video-EEG recordings in drug-resistant focal epilepsy. Mathon, B., Clemenceau, S., Hasboun, D., et al.[2018]

This study is the first to use high-frequency measurements of depressive severity through a computerized adaptive test (CAT) during deep-brain stimulation (DBS) treatment, showing that daily monitoring is feasible and can capture significant fluctuations in mood.

The patient experienced a notable improvement in depression severity, with scores decreasing from severe to mild, highlighting the potential effectiveness of DBS, although traditional clinician ratings (HAM-D) did not fully reflect the detailed changes observed through daily assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-frequency measurement of depressive severity in a patient treated for severe treatment-resistant depression with deep-brain stimulation. Sani, S., Busnello, J., Kochanski, R., et al.[2018]

Ketamine and esketamine demonstrate rapid antidepressant effects, with improvements in clinical response observed within 40 minutes to 1 week for ketamine and 2 hours to 4 weeks for esketamine, along with reductions in depression scores and suicidality.

Despite their effectiveness, the long-term safety and efficacy of ketamine and esketamine remain uncertain, and the overall quality of the studies reviewed was critically low, highlighting the need for more rigorous research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of ketamine and esketamine for depression: an overview of systematic reviews with meta-analyses. Lima, TM., Visacri, MB., Aguiar, PM.[2022]

In a study of 9016 patients receiving ketamine intravenous therapy (KIT) for depression, 53.6% showed a significant response (≥50% reduction in depression scores) within 14-31 days, indicating KIT's efficacy in real-world settings.

While most patients benefited from KIT, a small percentage (8.4%) experienced worsening depressive symptoms, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective analysis of ketamine intravenous therapy for depression in real-world care settings. McInnes, LA., Qian, JJ., Gargeya, RS., et al.[2023]

A single case study of a 55-year-old man with treatment-resistant depression showed that intravenous ketamine significantly improved depression symptoms, with the most substantial effects observed two days after the first infusion, but these effects began to fade by day 7 and returned to baseline by day 35.

The second ketamine infusion was less effective, indicating that while repeated treatments can provide benefits, the efficacy may diminish over time, suggesting a need for further research into optimal dosing and scheduling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repeated intravenous ketamine therapy in a patient with treatment-resistant major depression. Liebrenz, M., Stohler, R., Borgeat, A.[2013]

A review of 11 studies, including 7 on humans with major depressive disorder (MDD), found that intravenous ketamine can reduce brain activation related to depression and improve cognitive flexibility without causing significant cognitive impairments in most patients.

Some studies indicated that ketamine may enhance cognitive functions such as processing speed, verbal learning, and attention, suggesting it has a normalizing effect on brain functions involved in emotional processing for MDD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurocognitive impact of ketamine treatment in major depressive disorder: A review on human and animal studies. Crisanti, C., Enrico, P., Fiorentini, A., et al.[2021]

Cranial electrical stimulation (CES) has been suggested as a treatment for acute depression with minimal adverse effects, but this systematic review found no studies that met the criteria for rigorous evaluation.

The authors concluded that there is a significant lack of methodologically sound research on CES for depression, highlighting the need for more double-blind randomized controlled trials to assess its efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alternating current cranial electrotherapy stimulation (CES) for depression. Kavirajan, HC., Lueck, K., Chuang, K.[2023]

Non-invasive brain stimulation (NIBS) combined with psychosocial intervention significantly alleviates moderate to severe depressive symptoms, as shown in a meta-analysis of 17 studies involving 660 participants.

However, the combination treatment did not show a significant advantage over sham NIBS or psychosocial intervention alone for minimal to mild depression, indicating that the effectiveness may vary based on the severity of depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-invasive brain stimulation combined with psychosocial intervention for depression: a systematic review and meta-analysis. He, J., Tang, Y., Lin, J., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) is an established and safe treatment for major depression, showing promising efficacy, while transcranial direct current stimulation (tDCS) is easier to administer but has less robust evidence supporting its effectiveness.

Both NIBS techniques are generally safe and well-tolerated, but further research is needed to enhance their efficacy, especially for tDCS, which has shown to be less effective than traditional antidepressant medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive brain stimulation in psychiatric disorders: a primer. Brunoni, AR., Sampaio-Junior, B., Moffa, AH., et al.[2019]

Deep brain stimulation (DBS) targeting the subcallosal cingulate white matter is confirmed to be safe for patients with treatment-resistant depression, with only a few serious adverse events related to the device or surgery.

However, the study did not find a statistically significant difference in antidepressant efficacy between active DBS and sham stimulation over a 6-month period, indicating that while DBS is feasible, its effectiveness needs further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcallosal cingulate deep brain stimulation for treatment-resistant depression: a multisite, randomised, sham-controlled trial. Holtzheimer, PE., Husain, MM., Lisanby, SH., et al.[2019]

In a study of 30 subjects with treatment-resistant major depressive disorder, cranial electrical stimulation (CES) did not show significant differences in depression improvement compared to a sham treatment, with both groups experiencing similar reductions in Hamilton Depression Rating Scale scores.

CES was found to be safe and well-tolerated, with only minor adverse effects reported, but the lack of significant efficacy suggests that further research is needed to explore different settings and compare CES against other active treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of a form of cranial electrical stimulation (CES) as an add-on intervention for treatment-resistant major depressive disorder: A three week double blind pilot study. Mischoulon, D., De Jong, MF., Vitolo, OV., et al.[2015]

In a study of 30 outpatients with severe major depressive disorder, adding a single dose of intravenous ketamine to escitalopram treatment significantly improved response rates (92.3% vs. 57.1%) and remission rates (76.9% vs. 14.3%) over 4 weeks, indicating enhanced efficacy.

The combination treatment led to a faster reduction in depressive symptoms, with significant improvements observed as early as 2 hours after administration, while maintaining a good safety profile, as only mild increases in manic symptoms were noted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single i.v. ketamine augmentation of newly initiated escitalopram for major depression: results from a randomized, placebo-controlled 4-week study. Hu, YD., Xiang, YT., Fang, JX., et al.[2022]

In a study of 123 patients undergoing deep brain stimulation (DBS) surgery, adverse events (AEs) occurred in 14.6% of cases, but all resolved without permanent effects, indicating a relatively safe profile for the procedure.

The study found that rates of complications such as infections and lead revisions were comparable to existing literature, suggesting that the proposed categories for assessing AEs are effective for evaluating DBS safety and can help in benchmarking against other studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Towards unambiguous reporting of complications related to deep brain stimulation surgery: A retrospective single-center analysis and systematic review of the literature. Engel, K., Huckhagel, T., Gulberti, A., et al.[2019]

Citations

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Transcranial Electrical Stimulation in Treatment of Depression This systematic review and meta-analysis evaluates outcomes of various transcranial electrical stimulation treatments in patients with major depressive disorder

2. nature.com nature.com/articles/s41591-024-03305-y

Home-based transcranial direct current stimulation ... Efficacy and acceptability of transcranial direct current stimulation (tDCS) for major depressive disorder: an individual patient data meta- ...

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Efficacy of cranial electrotherapy stimulation for treating ... CES, a safe adjunctive therapy, demonstrates small effect in the treatment of depression. Future research should explore long-term effects of CES for treating ...

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an umbrella review of meta-analyses of randomized ... Electrical and magnetic brain stimulation techniques present distinct mechanisms and efficacy in the acute treatment of depression.

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa1612999

Trial of Electrical Direct-Current Therapy versus ... In a single-center trial, tDCS for the treatment of depression did not show noninferiority to escitalopram over a 10-week period and was associated with more ...

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Safety of transcranial Direct Current Stimulation: Evidence ... This review updates and consolidates evidence on the safety of transcranial Direct Current Stimulation (tDCS). Safety is here operationally defined by, ...

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A comparative analysis of technical data: At-home vs. in- ... This study investigates tDCS quality based on its technical parameters as well as safety of at-home and in-clinic tDCS applications comparing the data from two ...

8. withpower.com withpower.com/trial/phase-depressive-disorder-11-2023-bcc15

Intracranial Electrodes for Depression Intracranial electrode implantation has a favorable safety profile, with a low overall complication rate of 4.9%, including 3.1% major complications, but no ...