tDCS for Major Depressive Disorder

(NESBID Trial)

Overseen By Michael L Demas, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Alberta

Must be taking: Antidepressants

Must not be taking: Herbal compounds, NMDA agents

Disqualifiers: Psychosis, Addiction, Neurological, 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: 31

Duration: 6 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to help people with major depressive disorder (MDD) who haven't found relief from other treatments. It compares real and sham sessions of transcranial direct current stimulation (tDCS), which uses mild electrical currents to potentially improve mood. Participants continue their usual treatment while receiving up to 30 sessions of either active or sham tDCS. This trial suits those whose depression hasn't improved after trying at least five different antidepressants, electroconvulsive therapy (ECT), or ketamine. As an unphased trial, it offers a unique opportunity to explore innovative treatments for those seeking new options.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it mentions that participants will receive the treatment in addition to their usual treatment. However, you cannot participate if you are using a herbal compound or certain agents that affect brain function.

What prior data suggests that transcranial direct current stimulation is safe for treating Major Depressive Disorder?

Research has shown that transcranial direct current stimulation (tDCS) is generally safe for people with major depressive disorder (MDD). Studies have found that both real and sham tDCS are well-tolerated, meaning people usually handle the treatment without serious problems.

For instance, one study found no major differences in the number of people who stopped the treatment or in the side effects between real and sham tDCS. This suggests that the treatment does not cause more issues than the fake version. Another study noted that tDCS was safe and easy to use even at home, indicating its safety in different settings.

While researchers continue to study the safety of tDCS, current evidence is promising. Higher doses of tDCS did not lead to more side effects, suggesting it is safe even at stronger levels. This should help ease concerns about trying this treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about transcranial direct current stimulation (tDCS) for major depressive disorder because it offers a non-invasive approach that might complement existing treatments like antidepressants and psychotherapy. Unlike medications, which can have various side effects, tDCS uses a gentle electrical current applied to the scalp to potentially modulate brain activity linked to mood regulation. This method could offer a new option for patients who don't respond well to traditional treatments or are looking for alternatives with fewer side effects. Additionally, tDCS can be administered alongside current therapies, possibly enhancing their effectiveness without the need for additional drugs.

What evidence suggests that transcranial direct current stimulation is effective for major depressive disorder?

Research has shown that transcranial direct current stimulation (tDCS) can reduce symptoms of depression in individuals with Major Depressive Disorder (MDD). More than half of the patients in studies have experienced a full recovery after using tDCS. In this trial, participants will receive either active tDCS or sham tDCS. One study demonstrated that using tDCS at home for 10 weeks significantly improved depression symptoms. Another study found tDCS to be both effective and safe for people with MDD. While tDCS might not enhance thinking skills, it is associated with a noticeable decrease in depression for many patients. ^{2 4 5 6 7}

Who Is on the Research Team?

Serdar M Dursun, MD, PhD

Principal Investigator

University of Alberta

Are You a Good Fit for This Trial?

This trial is for adults with severe depression who haven't improved after trying at least five different antidepressants, ECT, or ketamine. It's not suitable for pregnant women, those using certain herbal compounds or NMDA-modulating agents, people with psychosis or specific personality disorders, and individuals with electronic implants or certain neurological conditions.

Inclusion Criteria

I am currently experiencing severe depression.

My depression hasn't improved after trying five different antidepressants, ECT, or ketamine.

Exclusion Criteria

Are pregnant, as tDCS has not been adequately studied in this population

I am not taking any herbal compounds or NMDA-modulating agents.

You have been diagnosed with a mental illness like psychosis, addiction (except for nicotine), borderline personality disorder, or antisocial personality disorder. These conditions could make it difficult for you to follow the study rules.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either active or sham transcranial direct current stimulation for 30 sessions over 6 weeks

6 weeks

30 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Transcranial Direct Current Stimulation

Trial Overview The NESBID trial tests if brain stimulation (transcranial direct current stimulation) helps people with ultra treatment-resistant major depressive disorder. Participants will get either real or sham stimulation over several weeks to see if it improves their depression symptoms compared to usual treatments.

How Is the Trial Designed?

Group I: Active transcranial direct current stimulation Experimental Treatment 1 Intervention

Active transcranial direct current stimulation (tDCS), delivered at 2 mA and for 30 minutes, on sequential weekdays, for a total of 30 sessions. Participants will continue to receive their usual pharmacotherapy and psychotherapy.

Group II: Sham transcranial direct current stimulation Placebo Group 1 Intervention

Sham transcranial direct current stimulation (tDCS), which will ramp up to 2 mA over 17 s, and then ramp down to and remain at 0.3 mA for the remainder of the 30 minute session. The short period of active stimulation is included to stimulate the somatic sensations of active therapy. The trickle current at 0.3 mA is necessary to measure electrode contact and prevent investigators from deducing that the device is no longer active. Participants will receive the sham therapy on sequential weekdays for a total of 30 sessions. Participants will continue to receive their usual pharmacotherapy and psychotherapy.

Who Is Running the Clinical Trial?

University of Alberta

Lead Sponsor

Trials

957

Recruited

437,000+

Alberta Health services

Collaborator

Trials

168

Recruited

658,000+

Published Research Related to This Trial

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) 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 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) 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]

In a clinical trial with 40 medication-free patients suffering from major depression, transcranial direct current stimulation (tDCS) targeting the left dorsolateral prefrontal cortex (DLPFC) resulted in a significant 40.4% reduction in depression scores, indicating its potential efficacy as a treatment.

The treatment was well tolerated with minimal side effects, and the positive effects on mood persisted for one month after the treatment ended, suggesting that tDCS could be a promising therapeutic option for major depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, double-blind clinical trial on the efficacy of cortical direct current stimulation for the treatment of major depression. Boggio, PS., Rigonatti, SP., Ribeiro, RB., 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) 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) 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) 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]

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. sciencedirect.com sciencedirect.com/science/article/pii/S2666915322000403

Reduction of symptoms in patients with major depressive ... Highlights. Depressive symptoms reduced after transcranial direct current stimulation (tDCS). Complete clinical response was achieved by >50% of the patients. ...

4. 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, − ...

5. frontiersin.org frontiersin.org/journals/human-neuroscience/articles/10.3389/fnhum.2024.1458295/full

Cognitive potency and safety of tDCS treatment for major ... (2018) found no significant cognitive enhancement following active tDCS compared to sham for 12 cognitive outcomes across 478 MDD patients.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35185515/

Safety and Feasibility of Tele-Supervised Home-Based ... We found that the home-based, remotely-supervised, study companion administered, multi-channel tDCS protocol for older adults with MDD was feasible and safe.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165032717304937

Safety and acceptability of transcranial direct current ... Active tDCS is as acceptable and safe as sham in randomized clinical trials of MDD. · Higher tDCS doses did not affect the overall acceptability.