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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a non-drug treatment for depression called transcranial direct current stimulation (tDCS). tDCS uses small electrical currents to potentially alter brain activity and improve depression symptoms. The trial tests various electrode placements and directions of electrical flow on the scalp to determine the most effective setup. Participants with depression who have been stable on their current medications for at least six weeks and live near UCLA might be suitable candidates.

As an unphased trial, this study provides a unique opportunity to contribute to innovative research in depression treatment.

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

Studies have shown that transcranial direct current stimulation (tDCS) is safe for treating depression. Research indicates that applying tDCS to both the left and right sides of the brain's frontal area is well-tolerated. Reported side effects are usually mild, such as slight scalp discomfort, and they don't last long.

Several studies found no significant differences in side effects between those who received real tDCS and those who received a fake (inactive) version. This indicates that the treatment doesn't cause more unwanted effects than the fake version.

Additionally, the safety of tDCS is supported by its use at home, demonstrating its practicality and manageable side effects. Overall, this suggests that tDCS is a low-risk option for those considering it as a treatment for depression. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about tDCS brain stimulation for depression because it offers a non-invasive way to potentially improve mood by targeting specific brain areas. Unlike traditional antidepressants that alter brain chemistry, tDCS uses electrical currents to stimulate the dorsolateral prefrontal cortex (DLPFC), a brain region linked to mood regulation. This technique has the potential to provide faster results and fewer side effects compared to medications. Moreover, the trial explores both left and right DLPFC stimulation, with some groups performing a mental task during treatment, which could enhance the therapy's effectiveness. This unique approach could offer new hope for those who haven't responded well to existing treatments.

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

This trial will compare the effects of transcranial direct current stimulation (tDCS) on different brain regions for treating depression. Participants may receive tDCS on the left side of the dorsolateral prefrontal cortex (DLPFC). Studies have shown that this can significantly improve depression symptoms for a month or longer. Specifically, research found that people with moderate to severe depression felt better after just 12 days of this treatment. Additionally, home-based tDCS treatments have been linked to even greater improvements over a 10-week period.

Other participants will receive tDCS on the right side of the DLPFC. Studies found a significant drop in depression symptoms, with one study showing a 48.65% reduction. Another analysis highlighted the strong positive effect of right DLPFC tDCS on depression, demonstrating its potential effectiveness. Overall, both left and right DLPFC tDCS show promise in reducing symptoms of depression. ^{1 3 4 6 7}

Who Is on the Research Team?

Mayank A Jog, PhD

Principal Investigator

University of California, Los Angeles

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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) 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]

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]

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) 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9195619/

Transcranial Direct Current Stimulation of the Dorsolateral ... Majority of these studies have shown that tDCS targeting at DLPFC (mostly the left DLPFC) can significantly improve depression symptoms for a month or longer.

2. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2838763

Personalized High-Definition Transcranial Direct Current ... In this randomized clinical trial, mood in participants with moderate to severe depression significantly improved after 12 days of left DLPFC ...

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

Home-based transcranial direct current stimulation ... In summary, a 10-week course of home-based active tDCS was associated with greater improvements in depressive symptoms, clinical response and ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2666915325000320

Home-use transcranial direct current stimulation (tDCS) as ... The results of our study demonstrate that home-use tDCS is feasible, safe and might be effective for patients with depression.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11258305/

Evaluating the effects of tDCS on depressive and anxiety ... tDCS over the left DLPFC is effective in reducing depressive symptoms and shows promising effects in alleviating anxiety symptoms among individuals with ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11549028/

Effects of Transcranial Direct Current Stimulation Targeting ... In conclusion, the tDCS targeting DLPFC may be a potentially effective therapeutic target for alleviating somatic symptoms in patients with MDD.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11464394/

Efficacy and Safety of Transcranial Direct Current ... Regarding safety, active tDCS was well tolerated and all the adverse reactions reported were mild and limited to transient scalp discomfort.