tDCS for Depression

Overseen By Shayna Pehel

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: NYU Langone Health

Must not be taking: Antidepressants, Antipsychotics, Anxiolytics, Stimulants

Disqualifiers: Neurologic, Psychiatric, Cardiac, Pregnancy, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 10

Duration: 2-4 weeks

100 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

Yes, you will need to stop taking certain medications, including antidepressants, antipsychotics, anxiolytics (anti-anxiety medications), stimulants, and medications that affect heart rate variability like beta-blockers and calcium channel blockers.

What data supports the effectiveness of the treatment Transcranial Direct Current Stimulation (tDCS) for depression?

Research shows that tDCS is a promising non-drug therapy for major depression, effective for acute episodes and potentially beneficial in treatment-resistant cases. Some studies also explore its use in combination with other therapies, although results can vary. ^{1 2 3 4 5}

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

tDCS is generally considered safe for humans, with no serious adverse effects reported in over 33,200 sessions across various studies, including those involving potentially vulnerable groups like children and the elderly. However, some studies suggest caution as it could potentially cause harm, and more research is needed to fully understand its safety, especially in specific conditions like major depressive disorder. ^{6 7 8 9 10}

How does the treatment tDCS for depression differ from other treatments?

Transcranial Direct Current Stimulation (tDCS) is unique because it involves applying a low electrical current to the scalp to modulate brain activity, which is different from traditional depression treatments like medication or talk therapy. This non-invasive method aims to alter brain function directly, offering a novel approach for those who may not respond well to other treatments. ^{11 12 13 14 15}

What is the purpose of this trial?

This trial tests a new treatment where a small electrical current is applied to the brain using a special headset, done under remote supervision. It targets people with mild to moderate depression to see if it can help improve their mood. The treatment aims to 'reset' brain activity in areas linked to mood regulation.

Research Team

Giuseppina Pilloni, PhD

Principal Investigator

NYU Langone Health

Eligibility Criteria

This trial is for 100 people with mild to moderate depression. Participants will use a special headset at home for 10 days, following a remotely supervised protocol. They must not have certain conditions that would exclude them from the study, but specific exclusion criteria are not listed here.

Inclusion Criteria

I have mild to moderate depression.

Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-V-TR) Depressive episode

Wide Range Achievement Test (WRAT)-4th Reading Recognition subtest standard score >85

Exclusion Criteria

I have skin conditions or sensitive skin near where a medical device would be placed.

Active or high suicidality risk (Columbia-Suicide Severity Rating Scale, C-SSRS), or otherwise judged as inappropriate by the study clinicians

History of a heart transplant, presence of permanent pacemaker implant or Left Ventricular Assist Device

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 10 days of 30-minute tDCS sessions using the RS-tDCS protocol, with HR and impedance-based HRV data collection

2-4 weeks

10 sessions (remote)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Transcranial Direct Current Stimulation (tDCS)

Trial Overview The study tests if Transcranial Direct Current Stimulation (tDCS) can help with depression by comparing active tDCs against sham (fake) treatment. It's double-blinded, meaning neither participants nor researchers know who gets real or sham treatment until after the results are collected.

Participant Groups

Group I: Active tDCS Experimental Treatment 1 Intervention

Participants randomized to the Active tDCS arm will complete 10 sessions of 30-minute active remotely supervised (RS)-tDCS with chest strap and impedance-based HRV data collection over the course of approximately 2-4 weeks.

Group II: Sham tDCS Placebo Group 1 Intervention

Participants randomized to the Active tDCS arm will complete 10 sessions of 30-minute sham RS-tDCS with chest strap and impedance-based HRV data collection over the course of approximately 2-4 weeks.

Transcranial Direct Current Stimulation (tDCS) is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Transcranial Direct Current Stimulation for:

• Depression
• Stroke rehabilitation
• Chronic pain management
• Research use for various neurological and psychiatric conditions including autism spectrum disorder

Approved in European Union as Transcranial Direct Current Stimulation for:

• Depression
• Stroke rehabilitation
• Chronic pain management
• Research use for various neurological and psychiatric conditions including autism spectrum disorder

Approved in Canada as Transcranial Direct Current Stimulation for:

• Depression
• Stroke rehabilitation
• Chronic pain management
• Research use for various neurological and psychiatric conditions including autism spectrum disorder

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

National Institute for Biomedical Imaging and Bioengineering (NIBIB)

Collaborator

Trials

102

Recruited

21,600+

Findings from Research

In the SELECT-TDCS trial, transcranial direct current stimulation (tDCS) was effective in treating major depression, with 52% of participants responding positively during the crossover phase after previously receiving sham treatment.

During the follow-up phase, the average duration of response to tDCS was 11.7 weeks, but patients with treatment-resistant depression had a significantly lower survival rate (10%) compared to non-refractory patients (77%), highlighting the need for optimized continuation protocols to prevent relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The sertraline versus electrical current therapy for treating depression clinical study (select-TDCS): results of the crossover and follow-up phases. Valiengo, L., Benseñor, IM., Goulart, AC., et al.[2014]

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]

Transcranial direct current stimulation (tDCS) significantly reduced depression scores compared to sham treatment, with the most effective results seen when tDCS was combined with medication, particularly selective serotonin re-uptake inhibitors (SSRIs).

The study included 12 randomized, sham-controlled trials with 251 participants receiving active tDCS and 204 receiving sham, showing that while tDCS alone or combined with psychotherapy did not significantly improve outcomes, the combination with medication led to a higher response rate and a greater reduction in depression scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is transcranial direct current stimulation, alone or in combination with antidepressant medications or psychotherapies, effective in treating major depressive disorder? A systematic review and meta-analysis. Wang, J., Luo, H., Schülke, R., et al.[2022]

In a study involving 22 patients with treatment-resistant major depression, anodal transcranial direct current stimulation (tDCS) did not show a significant improvement in depression scores compared to placebo after 2 weeks of treatment.

Despite the lack of overall efficacy in reducing depression scores, tDCS was associated with increased positive emotions, suggesting potential benefits that warrant further investigation with improved protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation in treatment resistant depression: a randomized double-blind, placebo-controlled study. Palm, U., Schiller, C., Fintescu, Z., et al.[2022]

Transcranial direct current stimulation (tDCS) significantly improved depressive symptoms in patients who had not responded to previous pharmacological treatments, with a notable reduction in scores on the Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HDRS) after just five days of treatment.

The study found that the effectiveness of tDCS was influenced by prior medication use; specifically, benzodiazepines were linked to poorer outcomes, while dual-reuptake inhibitors showed a positive interaction with tDCS effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interactions between transcranial direct current stimulation (tDCS) and pharmacological interventions in the Major Depressive Episode: findings from a naturalistic study. Brunoni, AR., Ferrucci, R., Bortolomasi, M., et al.[2020]

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]

A study involving 64 participants with bipolar disorder assessed the efficacy and safety of home-based transcranial direct current stimulation (tDCS) over 6 weeks, but found no significant improvement in depression scores compared to a sham treatment.

While tDCS did not show efficacy in reducing depression symptoms, it was deemed safe and tolerable, with some participants reporting higher pain scores associated with the active treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of daily home-based transcranial direct current stimulation as adjunct treatment for bipolar depressive episodes: Double-blind sham-controlled randomized clinical trial. Lee, J., Lee, CW., Jang, Y., et al.[2022]

A systematic review of 64 studies involving 2262 participants found that transcranial direct current stimulation (tDCS) has a low dropout rate (6% for active and 7.2% for sham), indicating good acceptability among participants.

Despite the low dropout rates, many studies inadequately reported adverse events (AEs), highlighting a need for improved guidelines to standardize AE reporting in tDCS research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review on the Acceptability and Tolerability of Transcranial Direct Current Stimulation Treatment in Neuropsychiatry Trials. Aparício, LVM., Guarienti, F., Razza, LB., et al.[2018]

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 shown to be as safe and acceptable as sham treatment in patients with major depressive disorder (MDD), with dropout rates of 8.8% for active tDCS and 12% for sham, indicating no significant difference.

The study analyzed data from 6 randomized clinical trials, revealing that while adverse event rates were slightly higher in the active tDCS group (73.5%) compared to sham (68.3%), the difference was not statistically significant, suggesting that tDCS is well-tolerated in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and acceptability of transcranial direct current stimulation for the acute treatment of major depressive episodes: Analysis of individual patient data. Moffa, AH., Brunoni, AR., Fregni, F., et al.[2019]

The combination of dichloroacetate (DCA) with talaporfin sodium (TS) significantly enhances the effectiveness of photodynamic therapy (PDT) in treating U251 human astrocytoma cells, allowing for potentially lower doses of TS to be used without losing anti-cancer efficacy.

DCA not only boosts the anti-cancer effects of TS-PDT but also suggests a promising avenue for drug repositioning in cancer therapy, improving treatment outcomes while potentially reducing costs and side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synergistic effect of dichloroacetate on talaporfin sodium-based photodynamic therapy on U251 human astrocytoma cells. Shinoda, Y., Aoki, K., Shinkai, A., et al.[2021]

Dichloroacetate (DCA) activates pyruvate dehydrogenase, which helps reduce harmful lactic acidosis in the brain during ischaemia, showing substantial efficacy in various models of stroke and head injury.

DCA has been clinically shown to lower lactate levels in patients with brain injuries and is well-tolerated, making it a promising candidate for treating conditions like stroke and head injury, where elevated brain lactate is linked to worse outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dichloroacetate and cerebral ischaemia therapeutics. Marangos, PJ., Turkel, CC., Dziewanowska, ZE., et al.[2019]

Chronic administration of dichloroacetate (DCA) for 9.7 to 16.5 years in 8 patients with metabolic deficiencies was generally well-tolerated and effectively maintained normal blood lactate levels, even in children not on strict ketogenic diets.

Despite some modest changes in nerve conduction in a few patients, there were no significant symptoms of peripheral neuropathy, indicating that DCA can be a safe long-term treatment for congenital lactic acidosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety of dichloroacetate in congenital lactic acidosis. Abdelmalak, M., Lew, A., Ramezani, R., et al.[2022]

Dichloroacetate (DCA) effectively activates the pyruvate dehydrogenase complex, leading to improved recovery of brain energy markers like ATP and lactate after ischemia in animal models.

In a study with rats, a higher dose of NaDCA (100 mg/kg) significantly reduced neuronal injury in critical brain regions after induced ischemia, while a lower dose (10 mg/kg) did not show the same protective effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protective effect of dichloroacetate in a rat model of forebrain ischemia. Peeling, J., Sutherland, G., Brown, RA., et al.[2019]

In a 17-month trial involving a 13-year-old girl with complex I deficiency, the combination of polyvitamins and dichloroacetate (DCA) did not lead to any clinical improvement, despite DCA successfully lowering lactate levels in the blood and central nervous system.

DCA treatment resulted in a reversible peripheral polyneuropathy after 20 weeks, indicating a potential toxic effect on the peripheral nervous system, even with thiamine co-medication, but no abnormalities were found in cerebral MRI studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapy of complex I deficiency: peripheral neuropathy during dichloroacetate therapy. Kurlemann, G., Paetzke, I., Möller, H., et al.[2022]

References

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

The sertraline versus electrical current therapy for treating depression clinical study (select-TDCS): results of the crossover and follow-up phases. [2014]

2. 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]

3. England pubmed.ncbi.nlm.nih.gov

Is transcranial direct current stimulation, alone or in combination with antidepressant medications or psychotherapies, effective in treating major depressive disorder? A systematic review and meta-analysis. [2022]

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

Transcranial direct current stimulation in treatment resistant depression: a randomized double-blind, placebo-controlled study. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Interactions between transcranial direct current stimulation (tDCS) and pharmacological interventions in the Major Depressive Episode: findings from a naturalistic study. [2020]

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

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

7. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of daily home-based transcranial direct current stimulation as adjunct treatment for bipolar depressive episodes: Double-blind sham-controlled randomized clinical trial. [2022]

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

A Systematic Review on the Acceptability and Tolerability of Transcranial Direct Current Stimulation Treatment in Neuropsychiatry Trials. [2018]

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

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

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

Safety and acceptability of transcranial direct current stimulation for the acute treatment of major depressive episodes: Analysis of individual patient data. [2019]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Synergistic effect of dichloroacetate on talaporfin sodium-based photodynamic therapy on U251 human astrocytoma cells. [2021]

12. England pubmed.ncbi.nlm.nih.gov

Dichloroacetate and cerebral ischaemia therapeutics. [2019]

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

Long-term safety of dichloroacetate in congenital lactic acidosis. [2022]

14. Ireland pubmed.ncbi.nlm.nih.gov

Protective effect of dichloroacetate in a rat model of forebrain ischemia. [2019]

15. Germany pubmed.ncbi.nlm.nih.gov

Therapy of complex I deficiency: peripheral neuropathy during dichloroacetate therapy. [2022]