Transcranial Direct Current Stimulation for Depression

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Northwestern University

Must be taking: Antidepressants

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

Disqualifiers: Bipolar, Anxiety, PTSD, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a gentle brain stimulation technique, Transcranial Direct Current Stimulation (tDCS), might help adults with major depression. The technique applies a mild current to the scalp, and researchers will use brain scans to observe its effects on brain activity. Participants will receive either the actual stimulation or a placebo version. This trial is open to individuals diagnosed with major depression for at least a year, who are currently experiencing symptoms, and have not changed their depression medication in the last six weeks. As an unphased trial, this study offers a unique opportunity to contribute to pioneering research in depression treatment.

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 prior data suggests that this neurostimulation technique is safe for adults with major depression?

Research has shown that transcranial direct current stimulation (tDCS) is generally safe for people with depression. Studies demonstrate that tDCS is safe and easy to use, even at home. One study found that using tDCS at home for ten weeks under supervision was safe and acceptable. Another study found it caused only minor side effects when treating depression with suicidal thoughts. Overall, evidence suggests that tDCS is well-tolerated, with few side effects reported. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Transcranial Direct Current Stimulation (tDCS) is unique because it offers a non-invasive approach to treating depression by applying a mild electrical current to the scalp. Unlike traditional antidepressants that can take weeks to show results and often come with side effects, tDCS has the potential to provide quicker relief with fewer side effects. Researchers are excited about this treatment because it targets brain activity directly and can be easily administered, possibly even at home, making it a promising option for individuals seeking alternative therapies for depression.

What evidence suggests that transcranial direct current stimulation is effective for depression?

Studies have shown that transcranial direct current stimulation (tDCS), which participants in this trial may receive, can help reduce symptoms of depression. One analysis found a significant positive effect, with a measure of improvement showing a moderate to strong impact on reducing depressive symptoms. Another study noted that a 10-week course of home-based tDCS led to greater improvements in depressive symptoms compared to a sham treatment. In this trial, some participants will receive active tDCS, while others will receive a sham treatment. Additionally, using tDCS with traditional antidepressants proved effective in reducing symptoms within three weeks. Overall, these findings suggest tDCS could be a promising option for treating depression. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

Interventions

• Sham Transcranial Direct Current Stimulation
• Transcranial Direct Current 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.

How Is the Trial Designed?

Group I: Active Experimental Treatment 1 Intervention

Group II: Sham Placebo Group 1 Intervention

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

Approved in United States as Transcranial Direct Current Stimulation for:

• Chronic pain management
• Depression
• Anxiety

Approved in European Union as Transcranial Direct Current Stimulation for:

• Chronic pain management
• Neurological rehabilitation

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

Published Research Related to This Trial

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]

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) 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) 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]

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) 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]

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]

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]

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) 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]

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]

Citations

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Transcranial Electrical Stimulation in Treatment of Depression This systematic review and meta-analysis evaluates outcomes of various transcranial electrical stimulation treatments in patients with major depressive disorder

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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 ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0165032725000011

Transcranial direct current stimulation in patients with ... Our analysis found a significant effect of tDCS on depression, with a Hedge's g = 0.66 (95 % CI: 0.565 to 0.767). Although studies aimed to ...

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A meta-analysis of randomized controlled trials Efficacy and acceptability of transcranial direct current stimulation for treating depression: A meta-analysis of randomized controlled trials.

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Transcranial direct current stimulation as an adjuvant in the ... We conclude that tDCS proved to be effective as an adjunct to antidepressant treatment in reducing depressive symptoms after three weeks of ...

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An open-label, single-arm feasibility study with long term ... Attrition rate was 7.7%. There was a significant improvement in depressive symptoms following treatment (mean HAMD 5.33 ± 2.33), which was ...

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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.

8. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2835422

Transcranial Electrical Stimulation in Treatment of ... Transcranial direct current stimulation and transcranial alternating current stimulation was associated with positive outcomes among patients with MDD and DPC ...

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Efficacy and Safety of Transcranial Direct Current ... The tDCS was effective as an antisuicide treatment for acute bipolar depression patients with suicidal ideation, with minimal side effects reported.