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

Trial Summary

What is the purpose of this trial?

Optimizing treatments in mental health requires an easy to obtain, continuous, and objective measure of internal mood. Unfortunately, current standard-of-care clinical scales are sparsely sampled, subject to recency bias, underutilized, and are not validated for acute mood monitoring. The recent shift to remote care also requires novel methods to measure internal mood. Recent advances in computer vision have allowed the accurate quantification of observable speech patterns and facial representations. The continuous and objective nature of these audio-facial behavioral outputs also enable the study of their neural correlates. Here, the investigators hypothesize that video-derived audio-facial behaviors have discrete neural representations in the limbic network and can provide a critical set of reliable longitudinal estimates of mood at low cost across home and clinic settings.

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 data supports the effectiveness of the treatment involving intracranial electrodes for depression?

Research on deep-brain stimulation (DBS), a similar treatment involving electrodes, shows it can reduce depression severity in patients with treatment-resistant depression, as seen in a case study where a patient's symptoms improved from severe to mild. ^{1 2 3 4 5}

Is the use of intracranial electrodes generally safe in humans?

Intracranial electrode implantation has a favorable safety profile, with a low overall complication rate of 4.9%, including 3.1% major complications, but no permanent harm or deaths were reported. Infections occurred in 1.2% and bleeding in 3.7% of patients, with no complications from microelectrodes. ^{6 7 8 9 10}

How does the intracranial electrodes treatment for depression differ from other treatments?

Intracranial electrodes for depression involve a unique approach by using frequency-dependent chronic electric stimulation directly in the brain, which is different from non-invasive methods like transcranial magnetic stimulation or cranial electrotherapy. This method is more targeted and potentially more effective for severe cases, as it directly stimulates specific brain areas involved in mood regulation. ^{1 11 12 13 14}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

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]

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]

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]

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]

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]

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]

References

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

Non-invasive brain stimulation combined with psychosocial intervention for depression: a systematic review and meta-analysis. [2022]

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

High-frequency measurement of depressive severity in a patient treated for severe treatment-resistant depression with deep-brain stimulation. [2018]

3. Netherlands pubmed.ncbi.nlm.nih.gov

A retrospective analysis of ketamine intravenous therapy for depression in real-world care settings. [2023]

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

Repeated intravenous ketamine therapy in a patient with treatment-resistant major depression. [2013]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Neurocognitive impact of ketamine treatment in major depressive disorder: A review on human and animal studies. [2021]

6. Germany pubmed.ncbi.nlm.nih.gov

Use of ketamine and esketamine for depression: an overview of systematic reviews with meta-analyses. [2022]

7. England 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. [2022]

8. United States 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. [2019]

9. Germany pubmed.ncbi.nlm.nih.gov

Safety profile of intracranial electrode implantation for video-EEG recordings in drug-resistant focal epilepsy. [2018]

10. England 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. [2015]

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

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

12. Brazil pubmed.ncbi.nlm.nih.gov

Noninvasive brain stimulation in psychiatric disorders: a primer. [2019]

13. England pubmed.ncbi.nlm.nih.gov

Alternating current cranial electrotherapy stimulation (CES) for depression. [2023]

14. England pubmed.ncbi.nlm.nih.gov

Subcallosal cingulate deep brain stimulation for treatment-resistant depression: a multisite, randomised, sham-controlled trial. [2019]