Brain Stimulation for Depression

(DBA Trial)

Overseen By Justin Riddle, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Florida State University

Disqualifiers: ADHD, Neurological disorders, Severe substance use, others

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

Compensation: Varies

Number of Visits: 8

Duration: 5 days

72 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore a new method to help people with depression who struggle with anhedonia, the inability to feel pleasure. Researchers are testing different types of brain stimulation to determine if they can boost mood and motivation. Participants will receive either delta-beta tACS (transcranial alternating current stimulation), theta-gamma tACS, or a sham (fake) treatment for comparison. Individuals who may qualify have major depressive disorder and difficulty enjoying activities. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could lead to new treatments for depression.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are currently being treated for ADHD, you would be excluded from participating.

What prior data suggests that this brain stimulation technique is safe for treating depression?

Research has shown that transcranial alternating current stimulation (tACS) is generally well-tolerated by patients in clinical trials. For delta-beta tACS, studies have found that this type of stimulation can reduce symptoms of depression without causing serious side effects. Participants usually report minor sensations like itching or tingling at the stimulation site, which are not serious.

Regarding theta-gamma tACS, research indicates it can improve symptoms of major depressive disorder (MDD) and enhance motor skills. Like delta-beta tACS, most people experience only mild skin sensations, which are expected and not harmful.

In summary, both delta-beta and theta-gamma tACS have demonstrated promising safety in studies, with no significant adverse events reported. This suggests these treatments are generally safe, with only minor and manageable side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these brain stimulation approaches for depression because they offer a non-invasive way to potentially improve mood. Unlike traditional treatments like antidepressants and therapy, Delta-beta and Theta-gamma tACS use transcranial alternating current stimulation (tACS) to target specific brain wave patterns linked to depression. This method is unique because it directly influences brain activity with electrical currents, aiming for quicker results with fewer side effects. Additionally, the sham comparator helps ensure the study's findings are robust by mimicking the physical sensations without the full treatment. This innovative approach could pave the way for new, effective treatments for depression.

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

This trial will compare different types of brain stimulation for depression. Research has shown that delta-beta tACS, one of the treatments participants may receive, can reduce symptoms of depression and anhedonia. One study found that just one session of this treatment significantly lessened these symptoms in patients. Another study showed that tACS helped ease depression in people with major depressive disorder (MDD).

Theta-gamma tACS, another treatment option in this trial, has also shown promise. Research indicates improvements in depression symptoms, with one study finding it boosted motor skills, suggesting a positive effect on brain function. Further research showed that tACS greatly reduced depression scores, with some patients experiencing significant improvements. These findings suggest that both delta-beta and theta-gamma tACS could be promising treatments for depression-related anhedonia. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with major depressive disorder and anhedonia, who score high on specific depression scales. Participants must speak English, have good vision (with correction if needed), and be at low suicide risk. Exclusions include traumatic brain injury, certain medical conditions, metal implants or ferrous body materials, pregnancy, claustrophobia, prior brain surgery, current ADHD treatment or severe substance use disorders.

Inclusion Criteria

Able to provide informed consent

Your score on the Patient Health Questionnaire (PHQ-8) is 8 or higher before the first session.

You have been diagnosed with major depressive disorder using a specific interview.

Exclusion Criteria

Any brain devices/implants including cochlear implants and aneurysm clips, cardiac pacemaker, or any other implanted electronic device

Pregnancy (for females)

I have had brain surgery before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 session

1 visit (in-person)

Baseline Assessment

Participants complete a functional MRI session with reward-based decision-making tasks

1 session

1 visit (in-person)

Treatment

Participants receive five consecutive days of CF-tACS with goal-setting and action planning worksheets

5 days

5 visits (in-person)

Follow-up

Participants return for an in-person session including self-report clinical assessments and EEG

2 weeks after treatment

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Delta-beta tACS
• Sham tACS
• Theta-gamma tACS

Trial Overview The study tests the effects of five consecutive days of transcranial alternating current stimulation (tACS) using a Neurocare stimulator to improve goal-directed behavior in people with anhedonic depression. It compares different tACS frequencies: Delta-beta coupling versus Theta-gamma coupling against a sham (fake) treatment.

How Is the Trial Designed?

Group I: Delta-beta tACS Experimental Treatment 1 Intervention

The study is investigating the use of transcranial alternating current stimulation (tACS). The stimulation is delivered at 1 milliampere (mA) zero-to-peak amplitude at the target electrodes and 2 mA zero to-peak amplitude at the return electrode. For the experimental arm, the tACS will be delivered using the cross-frequency stimulation waveform delta-beta (3-20Hz).

Group II: Theta-gamma tACS Active Control 1 Intervention

This arm serves as an active control where tACS will be delivered using the cross-frequency stimulation waveform theta-gamma (5-50Hz).

Group III: Active-sham tACS Placebo Group 1 Intervention

For active sham stimulation, either delta-beta or theta-gamma stimulation is delivered for 15 seconds only at the beginning and end of the stimulation period. This is intended to mimic the skin sensations (e.g., itching, burning, tingling) that are experienced at the onset and offest of stimulation, assisting with blinding the participant's assignment.

Who Is Running the Clinical Trial?

Florida State University

Lead Sponsor

Trials

234

Recruited

41,100+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

This study is the first double-blind controlled trial comparing the efficacy and safety of transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), and the antidepressant escitalopram in treating moderate-to-severe depression, involving outpatient subjects with a Hamilton Rating Scale for Depression score of 17 or higher.

The study aims to assess response rates and safety over 6 weeks, with tDCS and tACS being evaluated for their potential as effective antidepressant treatments alongside standard medication, providing valuable insights for future clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of tDCS and tACS in Treatment of Major Depressive Disorder: A Randomized, Double-Blind, Factorial Placebo-Controlled Study Design. Huang, Y., Shen, L., Huang, J., et al.[2022]

In a case series of six patients with major depression, transcranial Alternating Current Stimulation (tACS) at a gamma frequency (40 Hz) led to significant reductions in depression scores, with an 85% decrease in the Hamilton Depression Rating Scale for one group and a 62% decrease for another group.

The treatment also improved cognitive functions, suggesting that gamma tACS may help restore neural connectivity in the brain, which is often disrupted in psychiatric disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gamma transcranial alternating current stimulation improves mood and cognition in patients with major depression. Haller, N., Senner, F., Brunoni, AR., et al.[2021]

The study evaluates the efficacy and safety of transcranial alternating current stimulation (tACS) in treating major depressive disorder (MDD) over 8 weeks, involving 92 drug-naive patients who received either active or sham stimulation.

The primary outcome is the remission rate measured by the Hamilton depression rating scale, with the study aiming to demonstrate that tACS can effectively reduce depression symptoms with minimal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protocol on transcranial alternating current stimulation for the treatment of major depressive disorder: a randomized controlled trial. Wang, HX., Wang, K., Zhang, WR., et al.[2023]

Transcranial alternating current stimulation (tACS) is a promising non-invasive treatment for major depressive disorder (MDD), particularly for patients who do not respond to medications, as it manipulates brain oscillations to potentially alleviate symptoms.

Recent studies highlight two effective tACS techniques—high-definition tACS and bifocal tACS—that target specific brain areas and their connections, showing positive results in reducing MDD symptoms, although challenges remain in optimizing treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial alternating current stimulation for the treatment of major depressive disorder: from basic mechanisms toward clinical applications. Pan, R., Ye, S., Zhong, Y., et al.[2023]

In a pilot study involving 30 drug-naive adults with major depressive disorder, transcranial alternating current stimulation (tACS) at 77.5 Hz and 15 mA showed a significant remission rate of 10 out of 15 patients at week 8, compared to only 3 out of 15 in the sham group.

The tACS treatment was well-tolerated with no severe adverse events reported, indicating it is a safe and acceptable intervention for treating depressive symptoms in adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A pilot study of transcranial alternating current stimulation in the treatment of drug-naive adult patients with major depressive disorder]. Wang, HX., Wang, K., Sun, ZC., et al.[2020]

Transcranial alternating current stimulation (TACS) has demonstrated significant efficacy in improving symptoms of depression, with a standardized mean difference (SMD) of 1.14, indicating a strong positive effect compared to sham stimulation in patients.

TACS also showed a notable improvement in cognitive function among patients with psychiatric disorders, with an SMD of 0.60, suggesting it may enhance cognitive abilities in both patients and healthy individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial alternating current stimulation and its effects on cognition and the treatment of psychiatric disorders: a systematic review and meta-analysis. Lee, ARYB., Yau, CE., Mai, AS., et al.[2022]

In a randomized crossover study involving 43 participants (22 with major depression and 21 healthy volunteers), gamma transcranial alternating current stimulation (tACS) did not improve working memory performance during a computerized task, regardless of whether the stimulation was active or sham.

The study highlights the need for standardized methodologies in gamma tACS research, as the lack of cognitive improvement aligns with previous inconsistent findings in the field.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single session gamma transcranial alternating stimulation does not modulate working memory in depressed patients and healthy controls. Palm, U., Baumgartner, C., Hoffmann, L., et al.[2022]

Transcranial alternating current stimulation (tACS) showed a significant improvement in depressive symptoms for patients with major depressive disorder (MDD) compared to sham treatment, based on a meta-analysis of 4 randomized controlled trials involving 224 participants.

The treatment was found to be safe, with similar discontinuation rates between the active tACS and sham groups, indicating that tACS could be a viable option for managing MDD symptoms, although more research is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjunctive transcranial alternating current stimulation for patients with major depressive disorder: A systematic review and meta-analysis. Zheng, W., Cai, DB., Nie, S., et al.[2023]

In a study of 32 participants with major depressive disorder (MDD), 10 Hz transcranial alternating current stimulation (tACS) showed potential efficacy, with more responders observed 2 weeks after treatment compared to 40 Hz tACS and sham groups.

The 10 Hz tACS group also demonstrated a significant reduction in alpha power in the left frontal regions, suggesting that this method may help normalize brain activity associated with depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blind, randomized pilot clinical trial targeting alpha oscillations with transcranial alternating current stimulation (tACS) for the treatment of major depressive disorder (MDD). Alexander, ML., Alagapan, S., Lugo, CE., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12244068/

Augmenting single-session behavioral activation for ... A single-session of concurrent BA and tACS significantly reduces depression and anhedonia. · A single-session of concurrent BA and tACS significantly enhances ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X24001025

Effect of add-on transcranial alternating current stimulation ... A study examining tACS's role in treating MDD revealed that tACS with 15 mA and 77.5 Hz was effective in alleviating depressive symptoms in MDD [8]. However, ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05693922?term=AREA%5BBasicSearch%5D(eefrt)&rank=7&tab=results

Augmenting Single-session Behavioral Activation (BA) ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10507344/

Transcranial alternating current stimulation for the treatment of ... Recent studies have indicated that the effect of tACS is influenced by the state of the ongoing brain oscillations (Krause et al., 2022). However, currently, ...

5. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/22/NCT05693922/Prot_SAP_000.pdf

Augmenting single-session behavioral activation (BA) with ... Explore the effects of delta-beta transcranial alternating current stimulation (tACS) on anhedonia symptom severity from pre- to post-treatment.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7867505/

Transcranial alternating current stimulation (tACS): from basic ... In conclusion, the initial results may support the feasibility of tACS in clinical psychiatric populations without serious adverse events. Moreover, these ...

7. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2024.1419243/full

a systematic review of treatment parameters and outcomes Across studies that published results on tACS outcome measures, tACS resulted in enhanced symptoms and/or improvements in overall psychopathology for ...