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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for individuals with Major Depressive Disorder (MDD) who experience Anhedonia (a loss of interest or pleasure in activities). Researchers aim to determine if PRISM neurofeedback training—a therapy using real-time brain activity displays to teach self-regulation of brain function—is safe and effective alongside standard treatments. Participants will be randomly assigned to receive either active neurofeedback training or a sham (placebo) version, both in addition to their usual care. The trial seeks individuals diagnosed with MDD who experience Anhedonia and can commit to the study schedule.

As an unphased trial, this study provides a unique opportunity to contribute to pioneering research in understanding and potentially improving treatments for MDD.

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 prior data suggests that PRISM neurofeedback training is safe for treating MDD Anhedonia?

Research has shown that PRISM neurofeedback training is being tested for safety and effectiveness in treating major depressive disorder (MDD) with anhedonia, a loss of interest or pleasure. Studies with similar neurofeedback systems indicate that participants generally tolerate the treatments well. Reports of serious side effects are few, with most being mild and temporary, such as slight headaches or fatigue.

As this treatment remains under investigation, researchers continue to collect detailed safety information. However, neurofeedback is a non-invasive therapy, typically safer than treatments involving surgery or other invasive methods. While side effects can occur, they are usually not severe.

Prospective clinical trial participants should consult their healthcare provider about potential risks and benefits to make an informed decision. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about PRISM Neurofeedback Training for depression because it offers a unique approach compared to standard treatments like antidepressants or psychotherapy. Unlike typical treatments that primarily focus on altering brain chemistry or thought patterns, PRISM Neurofeedback directly targets brain activity. This method involves training the brain to self-regulate by providing real-time feedback on its activity, which could lead to more personalized and potentially faster improvements in mood. Additionally, this non-invasive technique might have fewer side effects, making it a promising alternative or adjunct to existing therapies.

What evidence suggests that PRISM Neurofeedback Training might be an effective treatment for depression?

Research has shown that PRISM neurofeedback training, which participants in the active arm of this trial will receive, may help treat depression, particularly for those who have lost interest or pleasure in activities. In an initial study, patients with this type of depression showed positive results after PRISM sessions. Another study found that 76% of patients with depression experienced significant improvement in their symptoms following PRISM neurofeedback sessions. These findings suggest that PRISM neurofeedback could be a useful tool for managing depression symptoms. ^{1 2 3 5 6}

Who Is on the Research Team?

Diego Pizzagalli, PhD

Principal Investigator

Mclean Hospital

Are You a Good Fit for This Trial?

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.

Any unstable medical condition, as per the clinical judgment of the investigator

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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 (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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05869708

PRISM Neurofeedback Training for MDD Anhedonic ... The goal of this interventional double-blind study is to demonstrate the safety and efficacy of PRISM neurofeedback training within an MDD Anhedonia sample.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12110136/

Reward System EEG–fMRI-Pattern Neurofeedback for ... The pilot study of the Prism for Depression™ sessions in patients with anhedonic MDD demonstrated favorable outcomes across the following ...

3. meetradial.com meetradial.com/prism

Prism Neurofeedback - For PTSD & Depression For PTSD, clinical studies show that 67% of patients had significant symptom improvement, including better sleep. For depression, 76% of patients experienced ...

4. withpower.com withpower.com/trial/neurofeedback-for-depression-bf4b6

Neurofeedback for Depression · Info for Participants The goal of this interventional double-blind study is to demonstrate the safety and efficacy of PRISM neurofeedback training within an MDD Anhedonia sample.

5. adaa.trialstoday.org adaa.trialstoday.org/trial/NCT05869708

PRISM Neurofeedback Training for MDD Anhedonic Patients The goal of this interventional double-blind study is to demonstrate the safety and efficacy of PRISM neurofeedback training within an MDD ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06770998

A Study of a Novel EEG Neurofeedback System for PTSD ... The goal of this clinical trial is to learn if training with the Prism system can reduce PTSD symptoms in US military Veterans and civilians with PTSD.