Cognitive Training + tDCS for Depression

Overseen By Sarah M Szymkowicz, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Vanderbilt University Medical Center

Must not be taking: Sodium channel blockers, anticonvulsants

Disqualifiers: Other Axis I, Neurological disorders, others

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

Compensation: Varies

Number of Visits: 3

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a gentle brain stimulation technique, transcranial direct current stimulation (tDCS), can enhance the effects of brain exercises on depression in older adults. It targets individuals who have experienced depression at least twice, with one episode occurring in the last three years. Participants may receive either real or sham brain stimulation during cognitive training sessions. This trial suits those over 60 who have had depression and face memory or thinking challenges in daily life. As an unphased trial, it provides an opportunity to contribute to innovative research that could improve depression treatments for older adults.

Will I have to stop taking my current medications?

The trial requires that participants either have a stable antidepressant regimen for at least 6 weeks or not be on any current antidepressant treatment. However, you cannot participate if you are taking medications that significantly interact with tDCS, like sodium channel blockers or anticonvulsants.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that transcranial direct current stimulation (tDCS) combined with cognitive training is safe for individuals with various mental health conditions. Studies have found that this combination enhances thinking skills and is generally well-tolerated.

For example, one study found that a 10-week tDCS treatment for major depression was both effective and safe, with participants reporting high satisfaction. Another study demonstrated that this method did not cause any major side effects and remained safe even when conducted remotely.

Overall, existing research suggests that tDCS with cognitive training is safe for individuals. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for depression because they combine cognitive training with transcranial direct current stimulation (tDCS), offering a potentially new way to enhance brain function. Unlike traditional antidepressants, which often target chemical imbalances, this approach may help in rewiring brain networks through non-invasive electrical stimulation. The study features two arms: one uses active tDCS, which could directly influence brain activity, and the other uses sham stimulation to help determine the effectiveness of the active approach. This combination could offer a novel, non-pharmaceutical option for those who haven't responded well to existing therapies.

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

In this trial, participants will be divided into two groups. One group will receive Cognitive Training combined with active transcranial direct current stimulation (tDCS). A previous study showed that combining brain exercises with active tDCS improved mental skills like attention and processing speed. Another study found that a 10-week course of active tDCS significantly reduced symptoms of depression. These findings suggest that adding active tDCS to brain exercises might enhance its effectiveness in treating depression. However, the improvements observed in these studies were small, so participants should maintain realistic expectations.

The other group will receive Cognitive Training combined with sham tDCS. For this group, the benefits primarily come from the brain exercises alone, which have been shown to improve mental skills. ^{1 2 3 5 6}

Who Is on the Research Team?

Sarah M Szymkowicz, PhD

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

This trial is for adults aged 60 and over who have been diagnosed with Major Depressive Disorder, as per DSM-5 criteria. They should be experiencing cognitive complaints and a depression severity of 15+ on the MADRS scale. Participants must speak English fluently and either be on a stable antidepressant regimen for at least six weeks or not taking any antidepressants.

Inclusion Criteria

You have reported problems with memory and thinking on a specific questionnaire.

My depression is severe, scoring 15 or more on a scale.

I have been on the same antidepressant for at least 6 weeks or am not taking any.

Exclusion Criteria

You have a significant memory problem compared to other people your age, even though your overall thinking skills seem normal.

I have a neurological disorder such as dementia, stroke, or Parkinson's.

Current involvement in other research studies (including but not limited to: neuromodulation [TMS or tDCS] or investigational drug studies)

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 tDCS combined with daily computerized cognitive remediation over 4 weeks

4 weeks

Daily visits for treatment

Follow-up

Participants are monitored for cognitive and psychiatric outcomes post-intervention

3 months

Cognitive assessments at 3 months post-intervention

What Are the Treatments Tested in This Trial?

Interventions

• Cognitive Training
• tDCS (active stimulation)
• tDCS (sham stimulation)

Trial Overview The study examines if transcranial direct current stimulation (tDCS), which uses mild electrical currents applied to the head, can improve cognitive function when combined with cognitive training in older adults suffering from depression.

How Is the Trial Designed?

Group I: Cognitive Training + Sham Stimulation Experimental Treatment 2 Interventions

This arm receives cognitive training combined with sham tDCS.

Group II: Cognitive Training + Active Stimulation Experimental Treatment 2 Interventions

This arm receives cognitive training combined with active tDCS.

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

American Academy of Neurology

Collaborator

Trials

12

Recruited

370+

Published Research Related to This Trial

A home-based protocol for transcranial direct current stimulation (tDCS) was tested on 26 participants with major depressive disorder (MDD) over 6 weeks, showing significant improvement in depressive symptoms that persisted for at least 6 months.

The treatment was highly acceptable to participants, with 92.3% completing the study, indicating that tDCS could be a feasible and effective option for managing MDD outside of clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjunctive home-based transcranial direct current stimulation treatment for major depression with real-time remote supervision: An open-label, single-arm feasibility study with long term outcomes. Woodham, RD., Rimmer, RM., Young, AH., et al.[2022]

Transcranial direct current stimulation (tDCS) shows potential for reducing symptoms of major depression, particularly when applied to frontal brain regions, but results have been inconsistent across studies.

Currently, no tDCS devices are FDA-cleared for clinical use, and while older systems have some regulatory approval, they lack demonstrated efficacy in rigorous trials, highlighting the need for more research and education in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Direct Current Stimulation in Psychiatry: What Psychiatrists Need to Know. Zandvakili, A., Berlow, YA., Carpenter, LL., et al.[2020]

In a study involving 75 severely depressed psychiatric inpatients, metacognitive training for depression (D-MCT) did not show a significant added benefit over standard cognitive-behavioral therapy (CBT) in reducing overall depression severity, but it was particularly effective for patients with major depressive disorder (MDD) without comorbidities, leading to greater improvements in depressive cognition.

Patients reported higher satisfaction, motivation, and treatment preference for D-MCT, indicating it is a well-accepted and feasible intervention in acute psychiatric care, although further research is needed to assess its long-term effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of metacognitive training for depression as add-on intervention for patients with depression in acute intensive psychiatric inpatient care: A randomized controlled trial. Hauschildt, M., Arlt, S., Moritz, S., 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]

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]

A randomized controlled trial with 112 participants showed that cognitive and emotional remediation training (CERT-D) significantly improved psychosocial function and reduced symptom severity in individuals with Major Depressive Disorder (MDD).

The training focused on enhancing cognitive, emotional, and social-cognitive skills through repeated exercises, suggesting that this approach could be a cost-effective alternative to traditional psychological therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychological training to improve psychosocial function in patients with major depressive disorder: A randomised clinical trial. Knight, MJ., Lyrtzis, E., Fourrier, C., et al.[2023]

Cognitive Control Training (CCT) significantly reduced negative mood in participants with high depression scores, showing a large effect size (d = 0.73) compared to a control group that received Peripheral Vision Training (PVT).

The study involved 48 participants over a 2-week period, and results indicated that better performance in CCT was associated with improved mood, suggesting that enhancing cognitive focus can positively impact emotional well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effects of Computerized Cognitive Control Training on Community Adults with Depressed Mood. Calkins, AW., McMorran, KE., Siegle, GJ., et al.[2022]

In a study involving 46 young adults with mild depressive symptoms, executive functioning and processing speed (EF/PS)-focused computerized cognitive training (CCT) led to greater improvements in those specific cognitive areas compared to verbal ability-focused CCT.

Both types of CCT resulted in significant improvements in mood and everyday functioning, but the EF/PS group achieved similar mood benefits with only half the training time, suggesting that the content of CCT may not be as crucial as the engagement in the training itself.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Computerized cognitive training in young adults with depressive symptoms: Effects on mood, cognition, and everyday functioning. Motter, JN., Grinberg, A., Lieberman, DH., et al.[2019]

This study aims to systematically review and analyze the efficacy of computerized cognitive training (CCT) in improving cognitive performance in adults with depression, focusing on randomized controlled trials.

The research will explore how CCT affects not only cognitive outcomes but also mood and daily functioning, making it the first comprehensive analysis of its kind in this specific clinical population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Computerized cognitive training in people with depression: a protocol for a systematic review and meta-analysis. Lampit, A., Launder, NH., Minkov, R., et al.[2022]

Computerized cognitive training (CCT) using Brain HQ showed significant cognitive improvements in psychiatric rehabilitation clients, with an average increase of 4.4 points in BACS t-scores after about 17 days of training.

Higher engagement in training (measured by levels completed per day) was positively correlated with cognitive gains, suggesting that monitoring engagement can help identify patients who may need additional support to benefit from CCT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Training engagement, baseline cognitive functioning, and cognitive gains with computerized cognitive training: A cross-diagnostic study. Harvey, PD., Balzer, AM., Kotwicki, RJ.[2020]

A 2-year follow-up study involving 42 participants with major depressive disorder showed that Goal Management Training (GMT) led to long-term reductions in depressive symptoms and rumination, while drill-and-practice cognitive training (CCT) did not show significant differences in outcomes.

Despite improvements in mental health from GMT, everyday executive functions did not show sustained improvement, suggesting that additional treatment may be necessary to maintain these cognitive benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Goal Management Training and Computerized Cognitive Training in Depression-a 2-Year Follow-Up of a Randomized Controlled Trial. Hagen, BI., Stubberud, J.[2021]

In a pilot study involving 31 patients with drug-resistant depression, combining transcranial direct current stimulation (tDCS) with mindfulness-based cognitive therapy (MBCT) showed better long-term maintenance of clinical improvements compared to tDCS with relaxation.

Both treatment conditions improved symptoms of depression, but the tDCS and MBCT combination was more effective in sustaining reductions in depression and cognitive symptoms two weeks after treatment, suggesting a promising multi-disciplinary approach for resistant depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Resistant Depression: A Pilot Study Assessing the Efficacy of a tDCS-Mindfulness Program Compared With a tDCS-Relaxation Program. Monnart, A., Vanderhasselt, MA., Schroder, E., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10823589/

Combined Cognitive Training and Transcranial Direct Current ... Retained studies included cognitive training combined with active or sham tDCS in a neuropsychiatric population and reported a post-treatment cognitive outcome.

2. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X25003110

A randomized, double-blind, sham-controlled trial In a doubleblind, sham-controlled trial, tDCS+CT improved inhibitory control, processing speed, and divided attention, although the effects were small. •.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5892209/

Cognitive Training and Transcranial Direct Current ... Participants with PD-MCI receiving cognitive training (standard or tailored) or tDCS demonstrated significant improvements on cognitive and functional outcomes, ...

4. jamanetwork.com jamanetwork.com/journals/jamapsychiatry/fullarticle/2791248

Efficacy of Augmentation of Cognitive Behavioral Therapy ... In this randomized clinical trial including 148 patients, a 6-week CBT group intervention augmented by tDCS was not found to be superior to CBT plus sham-tDCS ...

5. 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 ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2666915325001039

Effect of combined transcranial direct current stimulation ... Our results demonstrated that cognitive training led to significantly improved overall white matter integrity, with no additional benefits ...