Brain Stimulation + Cognitive Behavioral Therapy for Depression

Overseen By Eun Hyung Choi

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Manitoba

Disqualifiers: Metallic implants, Claustrophobia, 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: Unknown

Duration: 5 months

30 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of the proposed study is to examine if a repeated treatment of High Definition Transcranial Direct Current Stimulation (HD-tDCS) can increase the functional connectivity between the left ventrolateral prefrontal cortex and posterior cingulate, which may further enhance the effects of cognitive behavioral therapy with mindfulness classes.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment HD-tDCS for depression?

Research shows that transcranial direct current stimulation (tDCS), a part of HD-tDCS, can help improve symptoms of depression, especially when combined with other therapies like positive psychotherapy. Studies have found that people receiving combined treatments often experience greater mood improvements and increased hope and optimism. ^{1 2 3 4 5}

Is brain stimulation with tDCS safe for humans?

Transcranial direct current stimulation (tDCS) is generally considered safe for humans, with very low and minor side effects reported. However, there are warnings that it could potentially cause serious conditions in healthy individuals, so caution is advised. ^{6 7 8 9 10}

How does the Brain Stimulation + Cognitive Behavioral Therapy treatment for depression differ from other treatments?

This treatment is unique because it combines transcranial direct current stimulation (tDCS), a non-invasive method that uses electrical currents to stimulate specific brain areas, with cognitive behavioral therapy (CBT), a type of talk therapy. This combination aims to enhance the effects of each component, potentially offering a more effective approach for those who do not respond to standard treatments like medication or CBT alone. ^{1 4 6 11 12}

Eligibility Criteria

This trial is for individuals in Manitoba enrolled in virtual mental health programs, such as CBT or DBT, or those who provide these services. It's not suitable for people with MRI contraindications like metallic implants or claustrophobia.

Inclusion Criteria

I am enrolled in mental health programs like CBT or group therapy.

Patients who have agreed to participate in virtual mental health treatment at health care sites throughout Manitoba

Must be located within Manitoba

Exclusion Criteria

Contraindication for MRI (e.g., metallic implants and claustrophobia)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive repeated treatment of High Definition Transcranial Direct Current Stimulation (HD-tDCS) combined with cognitive behavioral therapy and mindfulness classes

5 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• HD-tDCS

Trial Overview The study tests if brain stimulation using the MxN-9 HD-tES device can boost the effects of cognitive behavioral therapy and mindfulness classes by improving brain connectivity.

Participant Groups

Group I: Active Stimulation Active Control 1 Intervention

MxN-9 HD-tES Stimulator (Soterix Inc.) will be used to deliver direct current (High-Definition Transcranial Direct Current Stimulation) to the target brain areas via electrodes and conducive gels. A constant current will be applied for 20 minutes with peak current of 2 mA. The 9 electrodes (8 channels + 1 ground) positions and current intensity have been determined based on computer simulation using HDTargets software (Soterix Inc.) that results in maximum focal current on the left VLPFC (x=-50, y=+26, z=+8) and the PCC (x=1, y=-61, z=38) with inward field orientation.

Group II: Inactive Stimulation Placebo Group 1 Intervention

The current will be applied for 30 seconds ramp-up followed by 30 seconds ramp-down, and thus no active stimulation will be administered except for the initial and last 1 minutes of 20 minute stimulation duration.

Who Is Running the Clinical Trial?

University of Manitoba

Lead Sponsor

Trials

628

Recruited

209,000+

Winnipeg Foundation

Collaborator

Trials

2

Recruited

90+

Findings from Research

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 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]

In a randomized study of 57 participants, both transcranial direct-current stimulation (tDCS) and venlafaxine ER (VNF) showed similar efficacy in reducing depression symptoms, with no significant differences in the Montgomery-Åsberg Depression Rating Scale scores after 4 weeks.

The response and remission rates were also comparable between tDCS (24% response, 17% remission) and VNF (43% response, 32% remission), suggesting that tDCS may be a viable alternative treatment for depression, although further research is needed to confirm its clinical effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Direct-Current Stimulation (tDCS) Versus Venlafaxine ER In The Treatment Of Depression: A Randomized, Double-Blind, Single-Center Study With Open-Label, Follow-Up. Bares, M., Brunovsky, M., Stopkova, P., et al.[2022]

Transcranial direct current stimulation (tDCS) combined with positive psychotherapy significantly improved mood, hope, and optimism in patients with clinical depression, showing greater benefits than either treatment alone after 4 weeks and at a 3-month follow-up.

The study utilized standardized scales to measure outcomes in participants, indicating that the combination of tDCS and positive psychology may have a synergistic effect in enhancing treatment efficacy for depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation based on quantitative electroencephalogram combining positive psychotherapy for major depression. Khayyer, Z., Ngaosuvan, L., Sikström, S., et al.[2018]

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]

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 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]

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]

High-Definition transcranial Direct Current Stimulation (HD-tDCS) at amplitudes up to 4 mA was well tolerated by 292 older adults, with no safety-related adverse events reported and mostly mild sensations experienced during sessions.

The study demonstrated effective blinding for both participants and researchers, indicating that the sham stimulation was convincing, which supports the use of higher amplitudes for potentially greater therapeutic effects in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability and blinding of high-definition transcranial direct current stimulation among older adults at intensities of up to 4 mA per electrode. El Jamal, C., Harrie, A., Rahman-Filipiak, A., 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]

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]

Transcranial direct current stimulation (tDCS) is being tested as a safe and noninvasive treatment for patients with ultraresistant major depressive disorder (MDD) in a trial involving 60 participants, aiming to improve depressive symptoms compared to a sham treatment.

The study will assess various outcomes, including changes in depression ratings and cognitive function, over 30 sessions of stimulation, with the goal of determining the efficacy of tDCS in patients who have not responded to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Neurostimulation of the Brain in Depression Trial: Protocol for a Randomized Controlled Trial of Transcranial Direct Current Stimulation in Treatment-Resistant Depression. Suleman, R., Tucker, BV., Dursun, SM., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

A Clinical Case Series of Acute and Maintenance Home Administered Transcranial Direct Current Stimulation in Treatment-Resistant Depression. [2023]

2. England 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. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Transcranial Direct-Current Stimulation (tDCS) Versus Venlafaxine ER In The Treatment Of Depression: A Randomized, Double-Blind, Single-Center Study With Open-Label, Follow-Up. [2022]

4. Singapore pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation based on quantitative electroencephalogram combining positive psychotherapy for major depression. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation in treatment resistant depression: a randomized double-blind, placebo-controlled study. [2022]

6. Netherlands 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. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Safety of transcranial direct current stimulation in healthy participants. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

A Systematic Review on the Acceptability and Tolerability of Transcranial Direct Current Stimulation Treatment in Neuropsychiatry Trials. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Tolerability and blinding of high-definition transcranial direct current stimulation among older adults at intensities of up to 4 mA per electrode. [2023]

10. Germany pubmed.ncbi.nlm.nih.gov

tDCS for the treatment of depression: a comprehensive review. [2018]

11. United States 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. [2009]

12. Canada pubmed.ncbi.nlm.nih.gov

The Neurostimulation of the Brain in Depression Trial: Protocol for a Randomized Controlled Trial of Transcranial Direct Current Stimulation in Treatment-Resistant Depression. [2021]