Transcranial Photobiomodulation for Bipolar Depression

Photobiomodulation (PBM) refers to the application of low levels of red or near-infrared (NIR) light to either stimulate or inhibit biological cells and tissues involving photochemical mechanisms. Transcranial PBM (tPBM), targeting delivery of light energy to the brain, is associated with increased cerebral blood flow, oxygen availability and consumption, adenoside triphophosphate (ATP) production, and improved mitochondrial activity. More recently, tPBM has demonstrated its value as a treatment for neurological and neurodegenerative conditions. Evidence of mitochondrial dysfunction in patients with BD suggests that PBM may have therapeutic benefits for patients with BD. The primary objective of this study is to confirm the safety and efficacy of using tPBM at 40Hz stimulation in improving symptoms of depression in patients diagnosed with bipolar depression.The study will be a single-blind randomized sham-controlled pilot trial with subjects receiving treatment 5 days/week for 6 weeks.

• Vielight Neuro Rx Gamma (Device): Participants assigned to the intervention will be administered treatment with the Neuro Rx Gamma 5 days/week in clinic
• Sham Device (Device): Participant assigned to the sham device will be administered the sham device in clinic 5 days/week

Primary outcomes

• Montgomery-Asberg Depression Rating Scale (MADRS) [Baseline to week 6]: Change in depression symptoms as measured by the Montgomery-Asberg Depression ( Rating Scale (MADRS). Scale is from 0-60, with higher score indicating high depression severity.

Secondary outcomes

• Clinical Global Impression Scale-Bipolar [Change from baseline to week 6]: Change in Clinical Global Impression Scale-Bipolar (CGI-BP). Scale from 1-7 with a higher means more severe illness.
• Trails Making Test [Baseline to week 6]: Change in score of the Trails Making Test. Scored based on the total time in seconds it takes to complete each part, meaning a lower score is better and a higher score indicates greater cognitive impairment.
• N-Back (2-Back) [Baseline to week 6]: Change in performance in N-Back (2-back)
• World Health Disability Assessment Schedule 2.0 (WHODAS 2.0) [Baseline to week 6]: Change in quality of life as measured by the World Health Disability Assessment Schedule 2.0 (WHODAS 2.0). Scores range from 0 to 100, where higher scores indicate greater disability.
• Pain Visual Analog Scale [Baseline to week 6]: Change in Pain Visual Analog Scale. The scale ranges from 0-100mm, with a higher number indicating more severe pain.
• Rest electroencephalography (5min rest, eyes closed) [Baseline to week 6]: Change in characteristic features of rest electroencephalography. This is not a scale.
• Stanford expectancy scale ratings [Baseline]: Stanford expectancy scale rating. The scale includes six items. Each of the six items is typically rated on an 11-point Likert scale (0-10), ranging from "not at all" to "extremely".
• Young Mania Rating Scale (YMRS) [Baseline to week 6]: Change in Young Mania Rating Scale (YMRS). The Young Mania Rating Scale (YMRS) has a total score range of 0 to 60. A higher value on the YMRS does indicate greater severity of manic symptoms.
• Columbia-Suicide Severity Rating Scale (C-SSRS) [Baseline to week 6]: Change in Columbia-Suicide Severity Rating Scale. The Columbia-Suicide Severity Rating Scale (C-SSRS) is a multi-part tool and does not have a fixed range, but it generally categorizes risk on a scale of 0-6 for the screener version (0=No Risk, 1-6=Increased Risk) or uses a 2-25 range for intensity of ideation. A higher values on the C-SSRS indicate more severe suicide risk/illness.

Other outcomes

• Device-related adverse events [Baseline to week 6]: Mean difference in device related adverse events between active and sham groups

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* • Diagnosis of bipolar depression

  * Montgomery-Asberg Depression Rating Scale (MADRS) of 24 or higher
  * Capable of providing consent
  * Currently inpatient or outpatient
  * Ability to communicate in spoken and written English fluently enough to complete the required study assessments

Exclusion Criteria:

* Currently in manic or mixed episode, as measured by Young Mania Rating Scale (YMRS) more than 8-10

  * Currently psychotic
  * Judged to be at serious and imminent suicidal risk
  * Currently has alcohol or substance use disorder (meeting criteria in the past 1 months)
  * Unstable medical conditions
  * Inability to consent or to complete study procedures
  * Changes in medications or use of augmentative devices and other interventions in the 4 weeks prior to the study
  * Participation in other clinical research trials that may influence primary outcomes or adherence to the proposed study
  * Current pregnancy or intention to become pregnant