tDCS Brain-Stimulation for Depression

Overseen By Mayank A Jog, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of California, Los Angeles

Must be taking: Antidepressants

Must not be taking: Anticonvulsants, Lithium, Psychostimulants, others

Disqualifiers: Pregnancy, Substance use disorder, Neurological conditions, others

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

Compensation: Varies

Number of Visits: 3

Duration: 1 day

144 Participants Needed

Trial Summary

What is the purpose of this trial?

Patients, physicians, and those who fund depression research are keenly interested in depression treatments that do not involve taking medications. One promising candidate treatment is transcranial direct current stimulation (tDCS), a low-cost technique that involves placing electrodes on specific scalp locations and using a 9-volt battery to cause a small amount of electricity to pass through parts of the brain. Depending on the direction of electrical flow, tDCS can make brain cells (neurons) more likely or less likely to generate their own electrical signals. When evaluated as a treatment, tDCS is typically done in daily sessions over a period of two weeks. One of the challenges of tDCS is to work out the best possible positioning of electrodes and direction of electricity flow to gradually cause lasting changes in brain activity in ways that might be expected to improve depression. To address this challenge, the investigators are using MRI to take pictures of the brain during tDCS. This data will help us better understand the short-term effects of tDCS in depression and help us learn how to customize future treatments to cause a lasting beneficial response. Patients with depression between the ages of 20-55 years are eligible to take part in this research. Potential participants will undergo: 1. An assessment to confirm eligibility. This will take place over a secure videoconference call lasting no more than 3 hours. 2. Two in-person study visits lasting 30 min and 2-1/2 hours respectively. In the first visit, the investigators will use the MRI to take a picture of the brain and head structure to determine appropriate locations for placing the tDCS electrodes at the start of the second visit. Following electrode placement, an MRI scan will be performed to take pictures of the brain during tDCS. Depending on the study arm, 1. Participants may receive 'active' or 'sham' tDCS. The 'sham' condition is identical to the 'active' tDCS in every way except that it involves minimal tDCS and is designed to help rule out effects unrelated to the administered tDCS electricity. 2. Participants may also be asked to perform a mental task during MRI. All participants will be compensated $150 + parking upon completion of all study-visits.

Will I have to stop taking my current medications?

If you are on a stable antidepressant regimen, you can continue taking it as long as there has been no change in your treatment for 6 weeks before and during the trial. However, if you are taking anticonvulsants, lithium, psychostimulants, or certain other medications, you may need to stop them before participating.

What data supports the effectiveness of the treatment tDCS Brain-Stimulation for Depression?

Research shows that transcranial direct current stimulation (tDCS) targeting the left dorsolateral prefrontal cortex (DLPFC) can engage and modulate brain areas related to depression, with some studies indicating improvements in symptoms like anhedonia (loss of interest or pleasure). Additionally, combining tDCS with positive psychotherapy has shown greater improvements in mood and optimism over time. ^{1 2 3 4 5}

Is transcranial direct current stimulation (tDCS) safe for humans?

Research shows that tDCS is generally safe for humans, with no reports of serious adverse effects or irreversible injury in over 33,200 sessions across various populations, including potentially vulnerable groups like children and the elderly. ^{4 5 6 7 8}

How is tDCS treatment for depression different from other treatments?

Transcranial Direct Current Stimulation (tDCS) is unique because it is a non-invasive treatment that uses mild electrical currents to stimulate specific areas of the brain, like the left dorsolateral prefrontal cortex (DLPFC), which is involved in mood regulation. Unlike medications, tDCS directly targets brain circuits and can be administered at home under supervision, offering an alternative for those with treatment-resistant depression. ^{1 4 5 9 10}

Research Team

Mayank A Jog, PhD

Principal Investigator

University of California, Los Angeles

Eligibility Criteria

This trial is for adults aged 20-55 with depression who can consent, are either treatment-naive or on a stable antidepressant regimen without changes in the past 6 weeks. They must live near UCLA and have moderate depression scores. Excluded are pregnant individuals, non-English speakers, those with skin conditions affecting electrode placement, metal implants, severe depression, recent psychotherapy or neuromodulation therapy.

Inclusion Criteria

My gender does not affect my eligibility.

I understand the information given to me and can make decisions about my health care.

I am between 20 and 55 years old.

Exclusion Criteria

I cannot stop taking my benzodiazepine medication for 2 weeks.

Actively suicidal as defined by a score of 4 on item 3 of HAMD

I have depression linked to my serious health condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (virtual)

Baseline Assessment

Initial MRI scan to determine electrode placement for tDCS

1 day

1 visit (in-person)

Treatment

Participants receive tDCS with MRI monitoring, potentially performing a mental task

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Cognitive task
• Left DLPFC tDCS
• Right DLPFC tDCS

Trial Overview The study tests tDCS brain stimulation's effect on depression by placing electrodes on the scalp to alter neuron activity. MRI scans will monitor these effects during sessions over two weeks. Participants may receive real or sham tDCS and might perform cognitive tasks during MRI to see how this technique could be tailored for treating depression.

Participant Groups

Group I: Right DLPFC tDCS + task Experimental Treatment 2 Interventions

Participants randomized to this arm will receive tDCS at the right DLPFC brain region. Additionally, participants will be asked to perform a mental task (2-back working memory) at the same time.

Group II: Right DLPFC tDCS Experimental Treatment 1 Intervention

Participants randomized to this arm will receive tDCS at the right DLPFC brain region.

Group III: Left DLPFC tDCS + task Experimental Treatment 2 Interventions

Participants randomized to this arm will receive tDCS at the left DLPFC brain region. Additionally, participants will be asked to perform a mental task (2-back working memory) at the same time.

Group IV: Left DLPFC tDCS Experimental Treatment 1 Intervention

Participants randomized to this arm will receive tDCS at the left DLPFC brain region.

Left DLPFC tDCS is already approved in European Union for the following indications:

Approved in European Union as Transcranial Direct Current Stimulation for:

• Depression

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Findings from Research

In a study involving 24 subjects with treatment-resistant major depression (TRD), transcranial direct current stimulation (tDCS) using anodal stimulation to the left dorsolateral prefrontal cortex (DLPFC) and cathodal stimulation to the right DLPFC did not show a significant difference in remission rates compared to sham tDCS.

The treatment was well tolerated with no significant differences in side effects between the active and sham groups, but methodological limitations suggest caution in interpreting the results and highlight the need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized double-blind sham-controlled study of transcranial direct current stimulation for treatment-resistant major depression. Blumberger, DM., Tran, LC., Fitzgerald, PB., et al.[2021]

Transcranial direct current stimulation (tDCS) targeting the left dorsolateral prefrontal cortex (lDLPFC) and medial prefrontal cortex (MPFC) shows comparable electric field strengths, suggesting both areas may play a role in treating major depressive disorder (MDD).

The study utilized computational modeling on 38 head models from 19 healthy adults and 19 MDD patients, indicating that individual modeling of tDCS can enhance targeting effectiveness, although the exact relationship between electric field strength and clinical outcomes remains to be explored.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of transcranial direct current stimulation for treating depression: A modeling study. Csifcsák, G., Boayue, NM., Puonti, O., et al.[2018]

Transcranial direct current stimulation (tDCS) combined with positive psychotherapy significantly improved mood, hope, and optimism in patients with clinical depression, showing greater benefits than either treatment alone after 4 weeks and at a 3-month follow-up.

The study utilized standardized scales to measure outcomes in participants, indicating that the combination of tDCS and positive psychology may have a synergistic effect in enhancing treatment efficacy for depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation based on quantitative electroencephalogram combining positive psychotherapy for major depression. Khayyer, Z., Ngaosuvan, L., Sikström, S., et al.[2018]

The pilot study involving 14 depressed participants found that both alternative electrode montages (Fronto-Occipital and Fronto-Cerebellar) for transcranial direct current stimulation (tDCS) were safe and feasible, with no significant adverse effects reported.

The Fronto-Occipital montage showed a promising mood improvement rate of 43.8% after four weeks, suggesting potential efficacy in treating depression, while the Fronto-Cerebellar montage had a lower improvement rate of 15.9%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study of alternative transcranial direct current stimulation electrode montages for the treatment of major depression. Ho, KA., Bai, S., Martin, D., et al.[2018]

Transcranial direct current stimulation (tDCS) effectively targets and modulates depression-related brain areas, specifically the left dorsolateral prefrontal cortex (DLPFC), as confirmed by significant changes in cerebral blood flow and induced magnetic fields during treatment in a study of 66 depressed participants.

High-definition (HD) tDCS showed stronger effects on brain network modulation compared to conventional tDCS, and while both active treatments improved symptoms of anhedonia, there were no significant differences in overall depression scores between the two stimulation methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In-vivo imaging of targeting and modulation of depression-relevant circuitry by transcranial direct current stimulation: a randomized clinical trial. Jog, MS., Kim, E., Anderson, C., et al.[2021]

Transcranial Direct Current Stimulation (tDCS) has been shown to be safe, with no reports of Serious Adverse Effects or irreversible injuries across over 33,200 sessions involving more than 1,000 subjects, including vulnerable populations.

Safety assessments indicate that the current densities used in conventional tDCS (≤4 milliamperes) are significantly lower than those that could potentially cause brain injury, suggesting that tDCS protocols are well within safe limits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. Bikson, M., Grossman, P., Thomas, C., et al.[2022]

Transcranial Direct Current Stimulation (tDCS) is generally considered safe, but there are concerns that it could lead to significant negative effects in healthy individuals.

The scientific community needs to be alerted about the potential risks of tDCS, emphasizing the importance of protecting healthy volunteers from possible harm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of transcranial direct current stimulation in healthy participants. Boccard-Binet, S., Sen, A.[2021]

The study found that fronto-extracephalic (F-EX) transcranial direct current stimulation (tDCS) is safe and well tolerated, showing significant improvement in depression severity after treatment in 11 participants with Major Depressive Episode.

F-EX tDCS resulted in a greater initial treatment response compared to the bifrontal (BF) montage, suggesting it may lead to faster antidepressant effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fronto-extracephalic transcranial direct current stimulation as a treatment for major depression: an open-label pilot study. Martin, DM., Alonzo, A., Mitchell, PB., et al.[2018]

In a clinical trial with 59 participants suffering from depression, high-definition transcranial direct current stimulation (HD-tDCS) was found to induce significant gray matter changes in the left dorso-lateral prefrontal cortex (DLPFC) compared to sham stimulation, indicating its potential efficacy in altering brain structure.

The study also revealed that HD-tDCS led to increases in gray matter in other brain regions connected to the DLPFC, suggesting that the effects of this treatment may extend beyond the immediate stimulation site, promoting broader neuroplasticity in the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation (tDCS) in depression induces structural plasticity. Jog, MA., Anderson, C., Kubicki, A., et al.[2023]

In a case series of 16 treatment-resistant depression patients, home-administered transcranial direct current stimulation (HA-tDCS) showed clinical benefits, with 5 out of 12 patients responding within 6 weeks and 9 maintaining improvements after 12 weeks of treatment.

HA-tDCS was found to be safe and well-tolerated, with no significant cognitive impairments reported over up to 2 years of treatment, although two patients experienced mild side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Clinical Case Series of Acute and Maintenance Home Administered Transcranial Direct Current Stimulation in Treatment-Resistant Depression. Le, B., Alonzo, A., Bull, M., et al.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

A randomized double-blind sham-controlled study of transcranial direct current stimulation for treatment-resistant major depression. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of transcranial direct current stimulation for treating depression: A modeling study. [2018]

3. Singapore pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation based on quantitative electroencephalogram combining positive psychotherapy for major depression. [2018]

4. Netherlands pubmed.ncbi.nlm.nih.gov

A pilot study of alternative transcranial direct current stimulation electrode montages for the treatment of major depression. [2018]

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

In-vivo imaging of targeting and modulation of depression-relevant circuitry by transcranial direct current stimulation: a randomized clinical trial. [2021]

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

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. [2022]

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

Safety of transcranial direct current stimulation in healthy participants. [2021]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Fronto-extracephalic transcranial direct current stimulation as a treatment for major depression: an open-label pilot study. [2018]

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

Transcranial direct current stimulation (tDCS) in depression induces structural plasticity. [2023]

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

A Clinical Case Series of Acute and Maintenance Home Administered Transcranial Direct Current Stimulation in Treatment-Resistant Depression. [2023]