Transcranial Direct Current Stimulation for Depression

Recruiting in Palo Alto (17 mi)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Northwestern University

Must be taking: Antidepressants

Must not be taking: Decongestants, Antihistamines, Benzodiazepines, Antipsychotics

Disqualifiers: Bipolar, Anxiety, PTSD, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial studies how tDCS, a technique using mild electrical currents, affects brain function and depressive symptoms in adults with major depression. The goal is to see if this method can improve brain activity and reduce depression after a short period of treatment. Transcranial direct current stimulation (tDCS) has been investigated for the treatment of depression since 2006.

Will I have to stop taking my current medications?

The trial requires that your antidepressant medication has been stable for at least 6 weeks before starting. However, you cannot take medications that might affect brain function, like decongestants, antihistamines, or certain other drugs.

What data supports the effectiveness of the treatment Transcranial Direct Current Stimulation for Depression?

Research shows that transcranial direct current stimulation (tDCS) is a promising non-drug therapy for major depression, with studies indicating it can be effective for acute episodes and may have antidepressant effects. ^{1 2 3 4 5}

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

Transcranial direct current stimulation (tDCS) is generally considered safe for humans, with studies showing no serious adverse effects across thousands of sessions. Common side effects are mild and include itching, tingling, and headaches, which are similar to those experienced with placebo treatments. ^{6 7 8 9 10}

How is transcranial direct current stimulation (tDCS) different from other treatments for depression?

Transcranial direct current stimulation (tDCS) is unique because it is a non-invasive brain stimulation technique that uses a low electrical current to modulate brain activity, unlike medications or more invasive procedures. It can be administered at home under remote supervision, making it more accessible and convenient compared to other treatments like deep brain stimulation or transcranial magnetic stimulation. ^{4 11 12 13 14}

Research Team

Eligibility Criteria

Adults aged 18-65 with a confirmed diagnosis of Major Depressive Disorder for at least one year, currently experiencing symptoms of depression, and under a stable antidepressant regimen can participate. They must be able to consent and not have any MRI contraindications like metal implants or claustrophobia.

Inclusion Criteria

I am currently experiencing symptoms of depression.

I am currently seeing a professional for depression.

I was diagnosed with Major Depressive Disorder over a year ago.

Exclusion Criteria

I am over 65 years old.

You have been thinking about hurting yourself or have made plans to hurt yourself in the past month.

I haven't changed my antidepressant medication in the last 6 weeks.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive MRI-guided high-definition transcranial direct current stimulation (tDCS) for five consecutive days

1 week

5 visits (in-person)

Follow-up

Participants are monitored for changes in depressive symptoms using Hamilton Depression Rating Scale and Beck Depression Inventory

1 month

3 visits (in-person)

Treatment Details

Interventions

• Sham Transcranial Direct Current Stimulation (Behavioural Intervention)
• Transcranial Direct Current Stimulation (Transcranial Electrical Stimulation)

Trial Overview The trial is testing the effects of transcranial direct current stimulation (tDCS), which involves passing mild electrical currents through the scalp, on brain function in depressed adults using fMRI imaging. Some participants will receive sham treatment as a comparison.

Participant Groups

Group I: Active Experimental Treatment 1 Intervention

Group II: Sham Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

Dr. Jeffrey Sherman

Northwestern University

Chief Medical Officer

MD from Northwestern University

Dr. Alicia Löffler

Northwestern University

Chief Executive Officer since 2010

PhD from the University of Massachusetts at Amherst, post-doctoral training at Caltech

Findings from Research

Transcranial direct current stimulation (tDCS) was found to be significantly more effective than sham treatment in reducing depression severity, with a moderate effect size (Hedges' g=0.743) based on a meta-analysis of 6 randomized controlled trials involving 176 participants.

The study highlights the need for larger and more representative trials to better evaluate the efficacy of tDCS in treating major depression, as the current analysis was limited by the small number of studies and their sample sizes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation in the treatment of major depression: a meta-analysis. Kalu, UG., Sexton, CE., Loo, CK., et al.[2021]

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) showed significant antidepressant effects in a study of 64 participants with depression, with improved mood after active treatment compared to sham treatment.

While tDCS was generally safe, there was a cautionary note regarding mood switching in individuals with bipolar disorder, as one participant experienced hypomania after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation for depression: 3-week, randomised, sham-controlled trial. Loo, CK., Alonzo, A., Martin, D., 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]

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]

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]

Transcranial direct current stimulation (tDCS) is generally considered a safe treatment for major depressive disorder, with very low side effects reported, making it a viable option for patients.

While meta-analyses indicate some efficacy of tDCS for acute depression with a moderate effect size, its effectiveness is reduced in treatment-resistant cases, suggesting that more research is needed to establish its overall therapeutic value.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

tDCS for the treatment of depression: a comprehensive review. Palm, U., Hasan, A., Strube, W., et al.[2018]

In a follow-up study of 23 patients with major depressive disorder or bipolar disorder, the antidepressant effects of transcranial direct current stimulation (tDCS) persisted for up to 3 months in nearly half of the participants after the initial treatment, indicating potential long-term benefits.

No significant side effects were reported during the follow-up period, suggesting that tDCS is a safe option for treating mood disorders, although the study highlighted a high dropout rate, emphasizing the need for further controlled research to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Augmentative transcranial direct current stimulation (tDCS) in poor responder depressed patients: a follow-up study. Dell'Osso, B., Dobrea, C., Arici, C., et al.[2014]

Transcranial direct current stimulation (tDCS) is generally considered safe, with mild and transient adverse effects reported in clinical trials, but the frequency and relationship of these effects with clinical variables remain unclear due to selective reporting bias.

Out of 209 studies reviewed, 117 mentioned adverse effects, with common issues like itching and tingling reported more frequently in the active tDCS group, although these differences were not statistically significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review on reporting and assessment of adverse effects associated with transcranial direct current stimulation. Brunoni, AR., Amadera, J., Berbel, B., 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 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) is a promising noninvasive treatment for major depression, showing potential for significant clinical gains in recent studies, although past trials had mixed results due to varied methodologies.

Current evidence is not yet sufficient to fully endorse tDCS as a standard treatment for depression, but optimizing stimulation parameters, such as individualization and longer sessions, could enhance its effectiveness and warrant further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation as a therapeutic tool for the treatment of major depression: insights from past and recent clinical studies. Murphy, DN., Boggio, P., Fregni, F.[2009]

References

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

Transcranial direct current stimulation in the treatment of major depression: a meta-analysis. [2021]

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

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

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

Transcranial direct current stimulation for depression: 3-week, randomised, sham-controlled trial. [2022]

4. 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]

5. 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]

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. Germany pubmed.ncbi.nlm.nih.gov

tDCS for the treatment of depression: a comprehensive review. [2018]

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

Augmentative transcranial direct current stimulation (tDCS) in poor responder depressed patients: a follow-up study. [2014]

10. England pubmed.ncbi.nlm.nih.gov

A systematic review on reporting and assessment of adverse effects associated with transcranial direct current stimulation. [2022]

11. 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]

12. 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]

13. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

Transcranial direct current stimulation as a therapeutic tool for the treatment of major depression: insights from past and recent clinical studies. [2009]