Transcranial Photobiomodulation for Depression

(TRIADE-R33 Trial)

Recruiting at 2 trial locations

Overseen By Anna Peterson

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: NYU Langone Health

Must be taking: SSRIs, SNRIs, Wellbutrin

Must not be taking: Antidepressants, others

Disqualifiers: Bipolar, Substance use, Neurological, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 19

Duration: 10 weeks

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether applying near-infrared energy to the forehead can improve blood flow in the brains of people with depression. It involves two groups: one receiving the actual treatment, called Transcranial Photobiomodulator, and another receiving a placebo-like version for comparison. The trial seeks participants who have experienced significant symptoms of major depressive disorder and have been stable on their current depression treatment for at least 8 weeks. As an unphased trial, this study offers a unique opportunity to contribute to innovative research that could lead to new treatment options for depression.

Will I have to stop taking my current medications?

The trial requires that participants taking medications for depression must be stable on their current medications for at least 8 weeks before screening. If you are taking medications other than SSRIs, SNRIs, or Wellbutrin (bupropion), you may need to stop them.

What prior data suggests that transcranial photobiomodulation is safe for treating depression?

Research has shown that transcranial photobiomodulation (tPBM), which uses near-infrared light, is generally well-tolerated by people with depression. One study found that tPBM did not harm brain structure or function and did not affect thinking skills. Another study found that patients could safely use wearable tPBM devices, reporting them as practical and well-tolerated.

These findings suggest that tPBM is a safe treatment option with no major safety concerns reported. However, more studies are needed to confirm these results. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Transcranial Photobiomodulation (tPBM) is unique because it uses light to stimulate brain activity, offering a non-invasive approach to treating depression. Unlike traditional treatments like antidepressants or psychotherapy, tPBM directly targets the brain's activity patterns using specific wavelengths of light. This method may provide faster relief from depressive symptoms with fewer side effects. Researchers are excited because tPBM could revolutionize how we address depression, offering a novel option for those who might not respond well to current treatments.

What evidence suggests that transcranial photobiomodulation might be an effective treatment for depression?

Research has shown that transcranial photobiomodulation (t-PBM), a treatment participants in this trial may receive, may help with depression. Studies have found that it can significantly reduce symptoms, with many people feeling noticeably better. Other research has also found it helps with anxiety and depression, with benefits lasting at least a month after treatment. Importantly, t-PBM is safe and does not harm the brain. Although few studies exist, early results are promising for those considering this treatment. ^{1 4 5 6 7}

Who Is on the Research Team?

Dan Iosifescu, MD, MSc

Principal Investigator

NYU Langone Health

Are You a Good Fit for This Trial?

Adults aged 18-65 with Major Depressive Disorder, stable on current medications or psychotherapy for at least 8 weeks, and not in immediate crisis. They must score ≥23 on the IDS-C for depression severity and be able to consent to study procedures. Excludes those with certain psychiatric disorders, substance abuse issues, significant medical conditions, or using specific depression treatments.

Inclusion Criteria

I have been on a stable treatment for depression for at least 8 weeks.

Inventory for Depressive Symptomatology Clinician-rated (IDS-C) total score ≥23 at screening

Participants must have major depressive disorder; all the following conditions need to be met to ensure presence of significant depression symptoms: Meeting diagnostic criteria for Major Depressive Disorder (MDD) in the past two weeks, at the DSM-5 Mini-International Neuropsychiatric Interview (MINI) Inventory for Depressive Symptomatology Clinician-rated (IDS-C) total score ≥23 at screening Depression symptoms are the primary target of treatment or treatment-seeking. Women of child-bearing potential must agree to use adequate contraception Participants taking medications or psychotherapy approved for the treatment of major depressive disorder will need to be stable for at least 8 weeks prior to screen.

Exclusion Criteria

I haven't had ECT in the past year, VNS ever, or been resistant to device-based depression treatments.

My thyroid condition is stable, and I've been on medication for at least a month.

Pregnant (as confirmed by pregnancy test at screen) or nursing

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo a 16-session course of transcranial Photobiomodulation (tPBM) or sham treatment

10 weeks

19 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Sham
• Transcranial Photobiomodulator

Trial Overview The trial is testing if near infrared energy applied to the forehead can alter brain blood flow in depressed individuals. Participants will either receive the actual Transcranial Photobiomodulator treatment or a sham (placebo) procedure to compare effects.

How Is the Trial Designed?

Group I: tPBM Group Experimental Treatment 2 Interventions

Visit 1: t-PBM at irradiance dose of 291.7 mW/cm2 (333s) Visit 2 - 18: randomized to receive active t-PBM of 291.7 mW/cm2 (333s) Visit 19: t-PBM at irradiance dose of 291.7 mW/cm2 (333s)

Group II: Sham Group Active Control 2 Interventions

Visit 1: t-PBM at irradiance does of 291.7 mW/cm2 (333s) Visit 2 - 18: randomized to receive Sham of 0 mW/cm2 (333s) Visit 19: t-PBM at irradiance dose of 291.7 mW/cm2 (333s)

Transcranial Photobiomodulator is already approved in United States, European Union for the following indications:

Approved in United States as Transcranial Photobiomodulation Therapy for:

• Depression (investigational)
• Traumatic Brain Injury (investigational)
• Stroke (investigational)
• Breast Cancer Related Lymphedema (investigational)

Approved in European Union as Transcranial Photobiomodulation Therapy for:

• No specific approvals listed; various investigational uses

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

Photobiomodulation (PBM) using red and near-infrared light shows promise as a low-risk treatment for major depressive disorder (MDD), with studies indicating significant antidepressant effects comparable to traditional medications.

The proposed mechanism of action involves enhancing mitochondrial metabolism in brain cells, suggesting that PBM could improve brain function, although more research is needed to determine optimal treatment parameters and confirm its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial and systemic photobiomodulation for major depressive disorder: A systematic review of efficacy, tolerability and biological mechanisms. Caldieraro, MA., Cassano, P.[2019]

Transcranial photobiomodulation (tPBM) shows promise in reducing depressive symptoms, with a significant effect size found in a meta-analysis of eight studies, indicating its potential as a treatment for major depressive disorder (MDD).

However, the evidence from double-blind, sham-controlled studies did not show a significant advantage of tPBM over sham treatment, suggesting that further research with larger sample sizes and optimized treatment parameters is necessary to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Transcranial Photobiomodulation on Depressive Symptoms: A Meta-Analysis. Cho, Y., Tural, U., Iosifescu, DV.[2023]

In a study involving 49 participants with major depressive disorder (MDD), transcranial photobiomodulation (t-PBM) using low irradiance and low energy did not show significant efficacy compared to sham treatment, indicating that the current dosing may be insufficient for therapeutic effects.

The results suggest that a minimal dose threshold is necessary for t-PBM to be effective in treating MDD, similar to other neuromodulation techniques, highlighting the need for further research to determine optimal dosing parameters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Very Low-Level Transcranial Photobiomodulation for Major Depressive Disorder: The ELATED-3 Multicenter, Randomized, Sham-Controlled Trial. Iosifescu, DV., Norton, RJ., Tural, U., et al.[2022]

Transcranial photobiomodulation (tPBM) is a safe and non-invasive treatment that effectively enhances higher electrophysiological oscillations in the brain, based on a review of 10 studies involving healthy individuals aged 18-80.

While tPBM shows promise in improving brain activity, the evidence regarding its effects on lower oscillatory frequencies remains inconclusive.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of transcranial photobiomodulation on electrophysiological activity of brain in healthy individuals: A scoping review. Shetty, SJ., Shetty, S., Shettigar, D., et al.[2023]

In a study involving 20 individuals, those receiving near-infrared transcranial photobiomodulation (NIR t-PBM) showed a significant improvement in sexual function compared to those receiving sham therapy, indicating its potential efficacy for treating sexual dysfunction.

The improvements in sexual function were not linked to the antidepressant effects of t-PBM, suggesting that NIR t-PBM may have a distinct therapeutic action specifically for sexual dysfunction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of transcranial photobiomodulation with near-infrared light on sexual dysfunction. Cassano, P., Dording, C., Thomas, G., et al.[2020]

In a study involving 18 participants with major depressive disorder, repeated sessions of near-infrared transcranial photobiomodulation (t-PBM) showed a trend towards more side effects compared to a sham treatment, but these were generally mild and resolved during the study.

The treatment did not lead to significant changes in weight or blood pressure, although a slight increase in diastolic blood pressure was noted, indicating that the overall safety profile of repeated t-PBM sessions appears to be benign.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reported Side Effects, Weight and Blood Pressure, After Repeated Sessions of Transcranial Photobiomodulation. Cassano, P., Caldieraro, MA., Norton, R., et al.[2020]

Transcranial photobiomodulation (t-PBM) using near-infrared light showed significant antidepressant effects in patients with major depressive disorder (MDD), with effect sizes ranging from 0.90 to 1.5 based on different analysis methods over an 8-week treatment period.

The treatment was well tolerated with no serious adverse events reported, suggesting it is a safe adjunct therapy for MDD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Photobiomodulation for the Treatment of Major Depressive Disorder. The ELATED-2 Pilot Trial. Cassano, P., Petrie, SR., Mischoulon, D., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7864111/

Transcranial Photobiomodulation for the Treatment of ... Conclusions: t-PBM with NIR light demonstrated antidepressant properties with a medium to large effect size in patients with MDD. Replication is warranted, ...

2. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2023.1267415/full

Photobiomodulation improves depression symptoms We conclude that PBM is effective in reducing depression symptoms in patients. However, the current number of studies is small, and further studies are needed.

3. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X24001955

Transcranial low-level laser stimulation in the near-infrared ... Our data indicate that 1064 nm laser tPBM does not induce adverse effects on brain structure or function, nor does it impair cognitive abilities.

4. bmcpsychiatry.biomedcentral.com bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-025-06555-3

The effectiveness of Transcranial Photobiomodulation therapy ... tPBMT led to significant improvements in anxiety, depression, and opioid craving among individuals in MMT, and these improvements were sustained at one month ...

5. mdpi.com mdpi.com/2304-6732/10/1/90

Grant Report on the Transcranial near Infrared Radiation ... tPBM with near-infrared radiation (NIR) has shown promising early results for the treatment of neuropsychiatric disorders [8].

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39706483/

A randomized, double blind, sham-controlled trial Conclusions: Self-administered wearable tPBM appears to be a feasible and well-tolerated in MDD patients. The low-level dosimetry appeared ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06934135?locStr=Peru&country=Peru&rank=8

NCT06934135 | Trial of Transcranial Photobiomodulation ... The primary outcome is change in depressive symptom severity in patients with Major Depressive Disorder (MDD), comparing three active doses of near-infrared ...