tDCS for Depression

Overseen By Sarah M Williams

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Mayo Clinic

Disqualifiers: Bipolar, Psychotic, Neurological, 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: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called transcranial Direct Current Stimulation (tDCS) to determine its effectiveness for people with Treatment Resistant Depression (TRD) in the hospital. tDCS is a non-invasive method that uses a small electric current on the head to improve mood and thinking skills. The researchers aim to assess whether this treatment is feasible and acceptable for patients and if it might alleviate depression and cognitive symptoms. Suitable candidates include those hospitalized for depression that hasn't improved after at least two different treatments lasting four weeks each. As an unphased trial, this study offers patients the chance to explore a novel treatment option that could potentially improve their condition.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it does exclude those who have had certain neuromodulation therapies in the last 3 months.

What prior data suggests that transcranial Direct Current Stimulation (tDCS) is safe for treating depression?

Research has shown that transcranial Direct Current Stimulation (tDCS) is generally safe for treating depression. Several studies have examined its safety. For instance, one study found that using tDCS at home was both practical and safe for people with depression. Another study demonstrated that a 10-week home-based tDCS treatment was very safe, and participants were comfortable with it.

In another study, researchers used tDCS to treat sudden episodes of bipolar depression, reporting only minor side effects. This suggests that most patients tolerate tDCS well. Overall, research indicates that tDCS is a safe option for many people dealing with depression. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Transcranial Direct Current Stimulation (tDCS) for depression because it offers a non-invasive approach that can potentially speed up the onset of relief compared to traditional treatments like antidepressants and psychotherapy. Unlike medications that often take weeks to work and come with side effects, tDCS involves a mild electrical current to stimulate specific areas of the brain, possibly leading to quicker mood improvements. Additionally, tDCS can be administered at home under guidance, making it a convenient option for patients.

What evidence suggests that transcranial Direct Current Stimulation (tDCS) might be an effective treatment for depression?

Research has shown that transcranial Direct Current Stimulation (tDCS) can help reduce depression symptoms. Studies found that a 10-week tDCS treatment led to noticeable improvements. Another study showed that people with major depressive disorder (MDD) found tDCS effective and safe. However, the long-term effects remain uncertain, as some studies did not observe significant changes in symptoms after six months. Overall, tDCS appears promising for treating depression, with evidence supporting its short-term benefits. Participants in this trial will receive a 30-minute tDCS treatment at 2 mA twice daily over 5 days. ^{3 4 6 7 8}

Who Is on the Research Team?

Maria I Lapid, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for adults hospitalized with Treatment Resistant Depression (TRD), which means their depression hasn't improved after trying at least two different treatments. Participants should be able to give informed consent and follow the study procedures.

Inclusion Criteria

I am capable of understanding and giving my consent for the trial.

Ability to adhere to protocol

Voluntary admission status

Exclusion Criteria

Active primary psychotic or substance use disorders (except nicotine dependence) within the past year

I have bipolar disorder.

I haven't had any brain stimulation treatments in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive transcranial Direct Current Stimulation (tDCS) treatments twice daily for 5 days

1 week

10 sessions (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Transcranial Direct Current Stimulation (tDCS)

Trial Overview

The study is testing transcranial Direct Current Stimulation (tDCS) as an additional treatment for TRD. It aims to see if tDCS is a feasible and acceptable option, whether it can improve depressive symptoms and thinking processes, and if certain biomarkers can predict how well someone will respond to this therapy.

How Is the Trial Designed?

Group I: tDCS interventional arm Experimental Treatment 1 Intervention

Participants will receive a 30-minute tDCS treatments at 2 mA twice daily over the course of 5 days.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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 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) 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]

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]

Citations

1.

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 ...

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39433921/

a fully remote phase 2 randomized sham-controlled trial

A 10-week home-based tDCS treatment with remote supervision in MDD showed high efficacy, acceptability and safety.

3.

jamanetwork.com

jamanetwork.com/journals/jamanetworkopen/fullarticle/2835422

Transcranial Electrical Stimulation in Treatment of ...

Among tES modalities, tDCS was associated with a significant improvement in depressive symptoms among patients with DMC (SMD = −1.05; 95% CI, − ...

4.

sciencedirect.com

sciencedirect.com/science/article/pii/S0022395625002018

6-month follow-up from randomised sham-controlled trial ...

No significant differences were found in depressive symptoms between those who had continued tDCS with those who had not in the long term. Over half of ...

5.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/30637889/

Transcranial direct current stimulation (tDCS) for ...

Conclusion: An intensive tDCS treatment regimen consisting of sessions twice a week achieved relatively low relapse rates after a 6-month follow up of tDCS ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/35839661/

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 ...

7.

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.

8.

pmc.ncbi.nlm.nih.gov

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

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.