Transcranial Direct Current Stimulation for Depression

(DOS Trial)

Overseen By Interventional Psychiatry

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, San Diego

Must be taking: Antidepressants

Must not be taking: Benzodiazepines, Investigational drugs

Disqualifiers: Pregnancy, Psychotic disorder, Substance use, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for Major Depressive Disorder (MDD) in individuals who haven't found relief with standard treatments. The study tests whether a dose-optimized and spaced form of transcranial direct current stimulation (a method using mild electrical currents through the scalp) can reduce depression symptoms. Participants will join one of three groups: one will receive the new treatment, another will get a standard version, and the last will receive a placebo. Individuals diagnosed with major depression who haven't responded well to at least two different antidepressants might be suitable for this trial. As an unphased trial, this study offers a unique opportunity to explore innovative treatment options for those seeking alternatives to traditional therapies.

Do I have to stop taking my current medications for the trial?

No, you do not have to stop taking your current medications. The trial requires that you stay on a stable antidepressant regimen or not receive treatment for 4 weeks before enrolling and continue this regimen throughout the study.

What prior data suggests that this transcranial direct current stimulation protocol is safe for treating depression?

Research has shown that spaced transcranial direct current stimulation (tDCS) is generally safe and well-tolerated. One study found no serious side effects, with minor issues like mild skin irritation being rare. Patients in that study adhered to the treatment and experienced significant reductions in depression symptoms.

For the dose-optimized and spaced tDCS treatment, less direct safety data is available. However, tDCS is non-invasive and usually considered safe. This treatment adjusts intensity and frequency to aim for better results, but more research is needed to fully understand its safety. So far, evidence suggests that this type of brain stimulation is promising for people with depression that hasn't improved with other treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the use of transcranial direct current stimulation (tDCS) for depression because it offers a non-invasive and potentially quick-acting alternative to traditional treatments like antidepressants and therapy. Unlike medications that can take weeks to show effects and may have side effects, tDCS involves applying a mild electrical current to the brain, which can modulate neural activity more rapidly. The dose-optimized and spaced tDCS (DOS-tDCS) is particularly promising because it uses a higher intensity (up to 4 mA) and a structured schedule of multiple sessions a day, which may enhance its efficacy compared to the standard 2 mA dose. These features could make tDCS a flexible and accessible option for patients who don't respond well to conventional treatments.

What evidence suggests that this trial's treatments could be effective for depression?

Research has shown that transcranial direct current stimulation (tDCS) can help reduce symptoms of depression. Studies have found that spacing out tDCS sessions over time can lead to significant improvements, with about a 30% to 40% reduction in depression scores. In this trial, participants may receive the dose-optimized and spaced tDCS (DOS-tDCS) method, which uses a stronger and more frequent application, believed to enhance these effects. Alternatively, participants may receive the standard spaced tDCS or a sham tDCS as part of the trial's different arms. Overall, tDCS is considered a promising non-invasive option for people who haven't responded to traditional treatments. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for individuals with Major Depressive Disorder (MDD) who haven't had success with traditional treatments. Participants will be involved in a study over six weeks to test an innovative electrical stimulation therapy.

Inclusion Criteria

I have been diagnosed with Major Depressive Disorder.

MADRS score of ≥20 at screening (Visit 1)

I have been on a stable antidepressant regimen for 4 weeks or haven't been treated.

Exclusion Criteria

Has started a new psychotherapeutic process in the past 3 months from screening

I don't have metal implants, seizures, or known brain lesions.

I do not have skin conditions on my face or scalp that would interfere with treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either DOS-tDCS, spaced tDCS, or sham tDCS treatment over a period of six weeks

6 weeks

5 sessions per day, each lasting 20 minutes, with a 20-minute intersession interval

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dose-Optimized and Spaced Transcranial Direct Current Stimulation

Trial Overview The study tests a new approach called Dose-Optimized and Spaced Transcranial Direct Current Stimulation (DOS-tDCS), comparing it against standard spaced tDCS and sham treatment in a randomized controlled trial.

How Is the Trial Designed?

Group I: DOS-tDCS: A dose-optimized and spaced form of tDCS Active Control 1 Intervention

On each treatment day, participants will receive 5 tDCS sessions, each lasting 20 minutes, with a 20-minute intersession interval. The dose-optimized and spaced tDCS (DOS-tDCS) group will be treated using a stimulation intensity of up to 4 mA.

Group II: Spaced tDCS: A spaced form of tDCS only Active Control 1 Intervention

On each treatment day, participants will receive 5 tDCS sessions, each lasting 20 minutes, with a 20-minute intersession interval. The spaced tDCS only group will receive stimulation at the standard 2 mA dose.

Group III: Sham tDCS Placebo Group 1 Intervention

On each treatment day, participants will receive 5 sham tDCS sessions, each lasting 20 minutes, with a 20-minute intersession interval.

Dose-Optimized and Spaced Transcranial Direct Current Stimulation is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Transcranial Direct Current Stimulation for:

• Major Depressive Disorder
• Treatment-Resistant Depression

Approved in United States as Transcranial Direct Current Stimulation for:

• Major Depressive Disorder
• Treatment-Resistant Depression

Approved in Canada as Transcranial Direct Current Stimulation for:

• Major Depressive Disorder
• Treatment-Resistant Depression

Who Is Running the Clinical Trial?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

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]

A randomized controlled trial (HomeDC) on the use of transcranial direct current stimulation (tDCS) at home for major depressive disorder was prematurely terminated due to safety concerns, specifically skin lesions in patients, highlighting the need for better safety monitoring.

Although the study showed significant reductions in depression scales over time, active tDCS did not demonstrate superior efficacy compared to sham tDCS, indicating that further high-quality research is necessary to explore the potential of tDCS for treating depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TDCS at home for depressive disorders: an updated systematic review and lessons learned from a prematurely terminated randomized controlled pilot study. Kumpf, U., Palm, U., Eder, J., et al.[2023]

A review of 15 studies on transcranial direct current stimulation (tDCS) before 1998 found that most trials (about 83%) focused on treating psychiatric conditions like depression and schizophrenia, with 12 out of 15 studies showing positive outcomes.

While the stimulation intensities used in older studies were lower than modern standards, the longer session durations and higher current densities suggest that these factors may have contributed to the encouraging results and mild side effects reported, such as headaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Notes on Human Trials of Transcranial Direct Current Stimulation between 1960 and 1998. Esmaeilpour, Z., Schestatsky, P., Bikson, M., et al.[2022]

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]

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]

Microdermabrasion significantly reduced skin resistance by about 32%, allowing for higher doses of transcranial direct current stimulation (tDCS) without increasing skin sensations or device limitations.

The study found that while microdermabrasion increased perceived sensations slightly when not combined with sonication, overall, it enabled safer and more effective delivery of tDCS by lowering the voltage needed to achieve the same current.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microdermabrasion facilitates direct current stimulation by lowering skin resistance. Chhatbar, PY., Liu, S., Ramakrishnan, V., et al.[2023]

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 for improving response rates (30.9% vs. 18.9%) and achieving remission (19.9% vs. 11.7%) in patients with acute depressive episodes, based on a systematic review of 9 studies involving 572 participants.

The study showed that tDCS not only provided immediate benefits but also led to continuous clinical improvement after treatment, although the overall clinical effects were considered moderate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and acceptability of transcranial direct current stimulation (tDCS) for major depressive disorder: An individual patient data meta-analysis. Moffa, AH., Martin, D., Alonzo, A., et al.[2021]

Transcranial direct current stimulation (tDCS) effectively targets and modulates depression-related brain areas, specifically the left dorsolateral prefrontal cortex (DLPFC), as confirmed by significant changes in cerebral blood flow and induced magnetic fields during treatment in a study of 66 depressed participants.

High-definition (HD) tDCS showed stronger effects on brain network modulation compared to conventional tDCS, and while both active treatments improved symptoms of anhedonia, there were no significant differences in overall depression scores between the two stimulation methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In-vivo imaging of targeting and modulation of depression-relevant circuitry by transcranial direct current stimulation: a randomized clinical trial. Jog, MS., Kim, E., Anderson, C., et al.[2021]

Transcranial direct current stimulation (tDCS) shows potential as a treatment for depression, but current evidence is inconclusive and based on small studies, highlighting the need for larger, controlled trials to assess its safety and efficacy.

Establishing a standardized method for reporting stimulation 'dosage' is crucial for future research, as it will help create evidence-based guidelines for the clinical use of tDCS in treating psychiatric conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation for major depression: a general system for quantifying transcranial electrotherapy dosage. Bikson, M., Bulow, P., Stiller, JW., et al.[2021]

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. clinicaltrials.gov clinicaltrials.gov/study/NCT06730841

Dose-Optimized and Spaced Transcranial Direct Current ... This study aims to evaluate the feasibility, safety, and tolerability of an innovative approach to treating Major Depressive Disorder (MDD), ...

2. clinicaltrials.ucsd.edu clinicaltrials.ucsd.edu/trial/NCT06730841

Dose-Optimized and Spaced Transcranial Direct Current ... This approach is hypothesized to lead to a significant reduction in depressive symptoms. Participants in the study will be randomly assigned to ...

3. psychiatryonline.org psychiatryonline.org/doi/10.1176/appi.ajp.20241088

Spaced Transcranial Direct Current Stimulation for ... In terms of clinical efficacy, the effects of tDCS were only modest, with improvements of approximately 30% and 40% in depression scores 3 and 6 ...

4. 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 ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11524011/

Machine learning-optimized non-invasive brain stimulation ... Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation intervention that shows promise as a potential treatment for depression.