Transcranial Photobiomodulation (tPBM) for Somatic Symptoms in Treatment-Resistant Depression

April 24, 2026 updated by: Taipei Veterans General Hospital, Taiwan

The Clinical Efficacy of Prefrontal Transcranial Photobiomodulation (tPBM) in Patients With Treatment-Resistant Major Depressive Disorder: A Subgroup Analysis Focusing on Somatic Symptoms

The primary objective of this study is to evaluate the clinical efficacy of moderate-dose transcranial photobiomodulation (t-PBM) at different frequencies (10 Hz and 40 Hz) in patients with treatment-resistant depression (TRD). It further aims to explore the differential efficacy across various symptom subtypes, with a particular focus on the somatic symptom-dominant subtype. Additionally, this study will collect paired-pulse neurophysiological parameters (e.g., the ratio of cortical inhibition to excitation) to preliminarily explore the neural mechanisms underlying the modulation of cortical excitability by t-PBM intervention, and to analyze their correlation with the magnitude of clinical symptom improvement.

The specific aims of this study are as follows:

To evaluate the differential efficacy of t-PBM at varying frequencies (10 Hz vs. 40 Hz) in improving clinical depressive symptoms (as measured by scales such as HAM-D and MADRS).

To investigate the therapeutic response to t-PBM in patients with the somatic symptom-dominant depression subtype, analyzing its potential suitability for targeting specific symptoms.

To explore the changes in paired-pulse TMS parameters (e.g., SICI, ICF, and LICI) before and after t-PBM treatment, gaining preliminary insights into the potential association between its cortical modulatory effects and clinical outcomes.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This study aims to investigate the potential efficacy of transcranial photobiomodulation (tPBM) as an adjunctive antidepressant treatment in patients with treatment-resistant depression (TRD), with a specific focus on the subtype predominantly presenting with somatic symptoms. tPBM is a non-invasive neuromodulation technique that utilizes near-infrared light to stimulate the prefrontal cortex. It potentially improves energy metabolism and neural function while offering advantages such as high safety and minimal side effects. Although preliminary studies support its antidepressant potential, evidence regarding the relationship between treatment parameters, stimulation frequencies, and subtype-specific efficacy remains limited.

This prospective, randomized controlled trial expects to enroll 40 TRD subjects, who will be randomly assigned to either a 10 Hz or a 40 Hz group. Both groups will receive tPBM treatment twice a week for four consecutive weeks. Pre- and post-treatment clinical assessments will evaluate depressive symptoms (HDRS-17, MADRS), somatic symptoms (PHQ-15, DSSS), sleep quality, and overall functioning. Additionally, paired-pulse transcranial magnetic stimulation (TMS) will be utilized to record neurophysiological changes, specifically assessing alterations in cortical excitability and inhibition.

This study expects to clarify the differences in efficacy between distinct tPBM frequencies in TRD patients, particularly those with somatic symptom-dominant subtypes. Furthermore, it aims to establish a preliminary link among tPBM treatment parameters, neurophysiological markers, and clinical symptom changes, providing a scientific basis and empirical evidence for future precision neuromodulation therapies.

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Taiwan
      • Taipei, Taiwan, 11217
        • Recruiting
        • Taipei Veterans General Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Must have a current diagnosis of Major Depressive Disorder (MDD).

The clinical severity must be evaluated by a psychiatrist as moderate or above, defined as a Clinical Global Impression-Severity (CGI-S) score > 4 and a 17-item Hamilton Depression Rating Scale (HDRS-17) total score ≥ 18.

Must be currently receiving stable antidepressant treatment for at least four weeks but showing inadequate response (treatment-resistant). This study will be conducted as an add-on therapy.

Must have full behavioral capacity, normal intellectual functioning, and the ability to comprehend and sign the informed consent form.

Exclusion Criteria:

Individuals diagnosed with Bipolar Disorder or Schizophrenia.

Individuals with current or recent Substance Use Disorder.

History of organic brain lesions (e.g., neurodegenerative diseases, epilepsy, stroke) or any medical conditions affecting central nervous system function.

Individuals with abnormal intellectual functioning based on clinical judgment (e.g., suspected intellectual disability, severe learning difficulties).

Individuals who are currently pregnant (due to limited evidence regarding the safety of tPBM during pregnancy).

Any other condition that, in the investigator's judgment, would render the participant unable to cooperate, unsuitable for the study, or unwilling to sign the informed consent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 10 Hz tPBM
Device: transcranial photobiomodulation
Participants will receive active transcranial photobiomodulation (tPBM) stimulation at a frequency of 10 Hz. The device delivers near-infrared light targeting the prefrontal cortex. Each treatment session lasts for 20 minutes, administered twice a week for four consecutive weeks (totaling 8 sessions).
Experimental: 40 Hz tPBM
Device: transcranial photobiomodulation
Participants will receive active transcranial photobiomodulation (tPBM) stimulation at a frequency of 10 Hz. The device delivers near-infrared light targeting the prefrontal cortex. Each treatment session lasts for 20 minutes, administered twice a week for four consecutive weeks (totaling 8 sessions).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in the 17-item Hamilton Depression Rating Scale (HDRS-17) Total Score
Time Frame: Baseline, Week 4 (Post-treatment), and Week 8 (1-month follow-up after treatment)

The 17-item Hamilton Depression Rating Scale (HDRS-17 or HAM-D) is a clinician-administered tool used to assess depression severity, with scores typically ranging from 0-52.

Typical HDRS-17 Scoring Interpretation:

0-7: Normal or remission (no depression) 8-13: Mild depression 14-18: Moderate depression 19-22: Severe depression 23: Very severe depression
Baseline, Week 4 (Post-treatment), and Week 8 (1-month follow-up after treatment)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Taipei Veterans General Hospital, Taiwan

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 6, 2026

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

March 31, 2027

Study Registration Dates

First Submitted

April 14, 2026

First Submitted That Met QC Criteria

April 14, 2026

First Posted (Actual)

April 21, 2026

Study Record Updates

Last Update Posted (Actual)

April 30, 2026

Last Update Submitted That Met QC Criteria

April 24, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2025-08-017A
  • V115B-016 (Other Grant/Funding Number: Taipei Veterans General Hospital)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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