Neurofeedback for Depression

Overseen By Adar Shani, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: GrayMatters Health Ltd.

Must be taking: Antidepressants

Must not be taking: Benzodiazepines, Psychotropics, others

Disqualifiers: Schizophrenia, Bipolar, Substance use, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 13

80 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this interventional double-blind study is to demonstrate the safety and efficacy of PRISM neurofeedback training within an MDD Anhedonia sample. The goals of this study include: 1. Demonstrating the safety and efficacy of Prism Neurofeedback training within an MDD Anhedonia sample; 2. Identifying clinical profile/symptoms-based biomarkers (e.g., Hamilton Depression Rating Scale - HDRS-21, Dimensional Anhedonia Rating Scale - DARS, Snaith-Hamilton Pleasure Scale for Clinicians SHAPS) scores that can be used by clinics to administer Prism therapy in conjunction with standard of care (SOC) therapy; 3. Producing initial guidelines for integrating Prism neurofeedback training for MDD therapy with MDD Anhedonia (SOC). Participants will be randomly assigned to one of two arms, Active, or Sham.

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

Participants may need to stop taking certain medications, such as benzodiazepines, which require a 2-week washout period (time without taking the medication) before starting the trial. However, stable doses of antidepressants like SSRIs, SNRIs, and bupropion are allowed. It's important not to change or start new psychiatric medications during the study.

What data supports the effectiveness of the treatment PRISM Neurofeedback Training for depression?

Research shows that neurofeedback, a type of brain training, can help reduce symptoms of depression. Studies have found that neurofeedback can lead to improvements in mood and cognitive function, and it is considered a promising supplementary treatment for depression, especially for those who do not respond well to traditional therapies. ^{1 2 3 4 5}

Is neurofeedback generally safe for humans?

The safety of neurofeedback treatment has not been thoroughly investigated in youth or adults, but clinical experience suggests it is reasonably safe. ^{5 6 7 8 9}

How is PRISM Neurofeedback Training different from other treatments for depression?

PRISM Neurofeedback Training is unique because it is a non-invasive treatment that uses brain activity feedback to help improve symptoms of depression, unlike traditional treatments like medication or talk therapy. It offers minimal side effects and can be used alongside standard treatments for those who do not fully respond to medication. ^{1 2 3 4 10}

Research Team

Diego Pizzagalli, PhD

Principal Investigator

Mclean Hospital

Eligibility Criteria

This trial is for adults aged 22-65 with Major Depressive Disorder (MDD) and Anhedonia, who can complete questionnaires in English and adhere to the study schedule. Participants must have specific scores on depression scales and be right-handed. Exclusions include certain mental health disorders, recent substance abuse, unstable medical conditions, use of excluded medications including benzodiazepines or dopamine-affecting drugs, recent psychotherapy initiation, pregnancy, MRI contraindications like metal implants or claustrophobia.

Inclusion Criteria

You are right-handed according to Chapman and Chapman's method from 1987.

My vision and hearing are normal, or corrected to be normal.

I have been diagnosed with major depression and experience a lack of pleasure in most activities.

Exclusion Criteria

Your hairstyle makes it difficult to place the EEG net, such as braids, dreadlocks, cornrows, or recently dyed hair.

I haven't changed or started any SSRIs or SNRIs in the last 4 weeks and don't plan to change my depression treatment during the study.

I cannot stop or switch my Benzodiazepine medication for the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Assessment

Participants complete clinical assessments using questionnaires, an MRI scan, and tasks that probe reward responsivity, learning, and motivation

1 week

1 visit (in-person)

Neurofeedback Training

Participants perform at least 10 sessions but optimally 15 (+/-3) neurofeedback training sessions, performed twice a week on nonconsecutive days

5-8 weeks

10-15 visits (in-person)

Post-Treatment Assessment

Participants complete the same clinical assessments, post-NF training MRI scan, and tasks as in the baseline stage

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Treatment Details

Interventions

• PRISM Neurofeedback Training

Trial Overview The PRISM neurofeedback training study tests if this therapy can reduce symptoms of MDD with Anhedonia when added to standard care. It's a double-blind trial where participants are randomly assigned to receive either active neurofeedback or a sham (placebo) version over approximately two months while undergoing clinical assessments and MRIs before and after the sessions.

Participant Groups

Group I: Active Arm Experimental Treatment 1 Intervention

Subjects randomized into the Active arm will receive RS-EFP-NF Prism training as an adjunct to standard of care.

Group II: Control Arm Placebo Group 1 Intervention

Subjects randomized into the Control arm will receive a Sham-EFP-NF training with the same schedule as the active arm, adjunct to standard of care.

PRISM Neurofeedback Training is already approved in United States for the following indications:

Approved in United States as PRISM Neurofeedback Training for:

• Posttraumatic Stress Disorder (PTSD)

Who Is Running the Clinical Trial?

GrayMatters Health Ltd.

Lead Sponsor

Trials

4

Recruited

460+

Findings from Research

In a study of 20 drug-free patients with mild to moderate depression, both real-time fMRI neurofeedback and cognitive behavioral therapy (CBT) were effective in reducing depressive symptoms, but neurofeedback was not found to be superior to CBT.

The neurofeedback group showed a continuous improvement in self-regulation skills over the treatment sessions, indicating a potential learning effect, while a trend suggested that CBT might lead to greater overall improvement in depression symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-time fMRI neurofeedback compared to cognitive behavioral therapy in a pilot study for the treatment of mild and moderate depression. Mel'nikov, MY., Bezmaternykh, DD., Savelov, AA., et al.[2023]

Neurofeedback has shown clinical efficacy in treating children with ADHD, outperforming computerized attention training in a randomized controlled trial with a medium effect size.

The benefits of neurofeedback training appear to be stable for at least six months, with different training protocols (theta/beta and slow cortical potentials) demonstrating distinct neurophysiological mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The usage of neurofeedback in children with ADHD: the method and its evaluation]. Gevensleben, H., Moll, GH., Rothenberger, A., et al.[2019]

Heart rate variability (HRV) biofeedback shows moderate support as a treatment for major depressive disorder (MDD), with evidence rated as 'probably efficacious' based on subjective measures like the Beck Depression Inventory.

Various neurofeedback protocols, including EEG methods and real-time fMRI targeting the amygdala and frontal cortices, are considered 'possibly efficacious' for treating depression, but their effectiveness is limited by a lack of controlled studies and replication issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Current Evidence Levels for Biofeedback and Neurofeedback Interventions in Treating Depression: A Narrative Review. Melnikov, MY.[2021]

EEG-neurofeedback (EEG-NF) training has shown significant cognitive, clinical, and neural improvements in patients with depression across 12 studies, suggesting it can be an effective non-invasive treatment option.

Due to its low cost and minimal side effects, EEG-NF could serve as a supplementary tool for patients who are already on standard medications but still experience symptoms of depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of EEG-based neurofeedback as a therapeutic intervention to treat depression. Patil, AU., Lin, C., Lee, SH., et al.[2023]

Neurofeedback is a noninvasive treatment that uses brainwave analysis to help patients with central nervous system issues, especially when traditional therapies like medication and psychotherapy are ineffective.

While there are many clinical case studies supporting the efficacy of neurofeedback, there is still a need for more controlled studies in peer-reviewed journals to further validate its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurofeedback: an emerging technology for treating central nervous system dysregulation. Larsen, S., Sherlin, L.[2013]

Neurofeedback training has shown promise as an additional treatment for major depressive disorder (MDD), with 24 studies involving 480 patients indicating that participants experienced greater symptom improvement compared to control groups.

Despite the positive findings, many studies lacked adherence to high-quality research standards, highlighting the need for better experimental designs and reporting practices in future neurofeedback research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurofeedback training in major depressive disorder: A systematic review of clinical efficacy, study quality and reporting practices. Trambaiolli, LR., Kohl, SH., Linden, DEJ., et al.[2021]

The study provides a real-time fMRI dataset from three participants, allowing researchers to test the Open NeuroFeedback Training (OpenNFT) framework without needing an MR scanner.

The dataset includes various types of neurofeedback, such as activation-based feedback and effective connectivity feedback, which can help in exploring the software's functionality and measuring data processing times.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-time fMRI data for testing OpenNFT functionality. Koush, Y., Ashburner, J., Prilepin, E., et al.[2020]

Neurofeedback (NF) has been explored as a treatment for various child psychiatric disorders, including ADHD, autism, learning disorders, and epilepsy, by providing real-time feedback on brain activity.

However, many studies on NF have methodological limitations, such as not using proper blinding or sham controls, and while clinical experience suggests NF is reasonably safe, its safety has not been rigorously studied in youth or adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative EEG neurofeedback for the treatment of pediatric attention-deficit/hyperactivity disorder, autism spectrum disorders, learning disorders, and epilepsy. Hurt, E., Arnold, LE., Lofthouse, N.[2019]

The study developed a new EEG-based neurofeedback method targeting the right inferior frontal gyrus (rIFG), which showed successful engagement of the intended brain region during training, as confirmed by fMRI results from a small group of 14 participants.

After two sessions of this EEG neurofeedback training with 41 participants, individuals demonstrated improved cognitive control by reducing their risk-taking behavior, indicating the method's potential efficacy for enhancing cognitive functions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neural and functional validation of fMRI-informed EEG model of right inferior frontal gyrus activity. Or-Borichev, A., Gurevitch, G., Klovatch, I., et al.[2023]

Neurofeedback training significantly improved working memory performance and processing speed in patients with major depressive disorder (MDD), as evidenced by a study involving 40 participants undergoing eight training sessions compared to a control group of 20.

The training led to increased upper alpha power in the brain, particularly in the subgenual anterior cingulate cortex, indicating a specific brain area involved in the cognitive improvements observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A controlled study on the cognitive effect of alpha neurofeedback training in patients with major depressive disorder. Escolano, C., Navarro-Gil, M., Garcia-Campayo, J., et al.[2022]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Real-time fMRI neurofeedback compared to cognitive behavioral therapy in a pilot study for the treatment of mild and moderate depression. [2023]

2. Germany pubmed.ncbi.nlm.nih.gov

[The usage of neurofeedback in children with ADHD: the method and its evaluation]. [2019]

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

The Current Evidence Levels for Biofeedback and Neurofeedback Interventions in Treating Depression: A Narrative Review. [2021]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Review of EEG-based neurofeedback as a therapeutic intervention to treat depression. [2023]

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

Neurofeedback: an emerging technology for treating central nervous system dysregulation. [2013]

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

Neurofeedback training in major depressive disorder: A systematic review of clinical efficacy, study quality and reporting practices. [2021]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Real-time fMRI data for testing OpenNFT functionality. [2020]

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

Quantitative EEG neurofeedback for the treatment of pediatric attention-deficit/hyperactivity disorder, autism spectrum disorders, learning disorders, and epilepsy. [2019]

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

Neural and functional validation of fMRI-informed EEG model of right inferior frontal gyrus activity. [2023]

10. Switzerland pubmed.ncbi.nlm.nih.gov

A controlled study on the cognitive effect of alpha neurofeedback training in patients with major depressive disorder. [2022]