Transcranial Photobiomodulation For The Management Of Depression: Current Perspectives

Figures & data

Table 1 All Relevant Basic Research Studies That Utilized Photobiomodulation, With Wavelengths In The Red And/Or Near-Infrared Range, In Experimental Models Of Depression

Paper	Subjects	Device	Number Of Treatments	Area Irradiated	Wavelength	Pulsed Or Continuous	Irradiance	Fluence	Results
Mohammed(2016)^Citation72 Transcranial low-level infrared laser irradiation ameliorates depression induced by reserpine in rats	Rats	Diode (GaAlAs) Laser (Lasotronic Inc., Zug, Switzerland)	Daily for 1 week	Six points arranged symmetrically to ensure irradiation of the entire cortex	804nm	Continuous	0.64, 1.60, and 3.18W/cm^2 for three assigned powers of laser	4.8, 12, and 24 J/point for three powers of laser	Treatment with lower power (80mW) reversed depressive effects of reserpine
Xu et al (2017)^Citation44 Low-level Laser Irradiation Improves Depression-like Behaviors in Mice	Mice	Diode laser quipped with quartz-silica fiber (FU808AD500-BD10, Shenzhen Fuzhe Technology co., Ltd.)	30 min per day for 28 days	Cerebral cortex	808nm	Continuous	23mW/cm^2	Not provided	t-PBM attenuated depression-like behaviors
Salehpour et al (2016)^Citation73 Therapeutic Effects of 10-HzPulsed Wave Lasers in Rat Depression Model: A Comparison Between Near-Infrared and Red Wavelengths	Rats	Red and NIR probes derived by GaAlAs diode laser (Mustang 2000þ, Moscow, Russia)	Four times a week for three weeks	Prefrontal region	630nm (Red), 810nm (NIR)	10-Hz, Pulsed	89mW/cm^2 (Red), 562mW/cm^2 (NIR)	1.18 ± 0.01J/cm^2 per each session, about 14.4J/cm^2 over entire treatments	NIR and citalopram significantly decreased depression-like behaviors, but the red wavelength condition did not
Ando et al (2011)^Citation76 Comparison of Therapeutic Effects between Pulsed and Continuous Wave 810-nm Wavelength Laser Irradiation for Traumatic Brain Injury in Mice	Mice	Diode laser (DioDent Micro 810, HOYA ConBio, Fremont, CA) equipped with quartz-silica fiber	Single 12-min exposure of transcranial t-PBM, 4 hrs post TBI	Left frontal-parietal cortex	810 ± 2nm	Continuous, 10- Hz Pulsed, or 100-Hz Pulsed	Average = 50mW/cm^2, Peak for pulsed modes = 100mW/cm^2	36J/cm^2	t-PBM had an antidepressant effect 4 weeks after treatment
Tanaka et al (2011)^Citation69 Infrared radiation has potential antidepressant and anxiolytic effects in animal model of depression and anxiety	Rats	Infrared emitter	Acute exposure group = one session for 3 mins, Chronic exposure group = 10 sessions for 3 mins daily	Head	Emitter had highest emissivity values within 600–1600nm	Not provided	Calculated maximal irradiation intensity of 1800–2200mW	Not provided	Depressive-like behavior significantly improved in chronically exposed group
Wu et al (2012)^Citation75 Pulsed Light Irradiation Improves Behavioral Outcome in a Rat Model of Chronic Mild Stress	Rats	Diode laser	Three times a week for three weeks, 2-min irradiation time for each treatment	Midline of the dorsal surface of the head, between the eyes and ears	810nm	100-Hz, Pulsed	Average = 15mW/cm^2	120J/cm^2	Depressive-like behavior significantly decreased in the fluoxetine and transcranial light therapy groups
Salehpour et al (2019)^Citation65 Near-infrared photobiomodulation combined with coenzyme Q10 for depression in a mouse model of restraint stress: reduction in oxidative stress, neuroinflammation, and apoptosis	Mice	NIR GaAlAs laser (Thor Photomedicine, Chesham, UK)	Once a day for five consecutive days, 5-s irradiation time for each treatment	Midline of the dorsal surface of the head in the region between the eyes and ears	810nm	10-Hz, Pulsed	6.66W/cm^2	33.3J/cm^2	PBM and CoQ10, alone or in combination, reduced depressive-like behaviors
Salehpour et al (2017)^Citation74 A comparison between antidepressant effects of transcranial near- infrared laser and Citalopram in a rat model of depression	Rats	NIR probe derived by GaAlAs diode laser (Mustang 2000+, Russia)	Four times a week for three weeks	Prefrontal region	810nm	10-Hz, Pulsed	Output power of 39.3 ± 1.1mW	1.2J/cm^2	NILT and Citalopram decreased depressive-like behaviors

Table 2 All Available Clinical Research Studies And Case Reports That Utilized Transcranial Photobiomodulation, With Wavelengths In The Red And/Or Near-Infrared Range, For Treatment Of Depression

Paper	Subjects	Design	Device	Number Of Treatments	Area Irradiated	Wavelength	Pulsed Or Continuous	Irradiance	Fluence	Results
Cassano et al (2018)^Citation84 Transcranial Photobiomodulation for the treatment of Major Depressive Disorder. The ELATED-2 Pilot Trial	13 MDD completers	Randomized, double-blind, sham controlled, pilot trial	Omnilux New U, light emitting diode (LED) by Photomedex, Inc., Montgomeryville, PA	Twice a week for 8 weeks; sessions 25–30 mins	Dorsolateral prefrontal cortex, bilateral	823 nm	Continuous	36.2mW/cm^2	Up to 65.2J/cm^2	NIR increased mean change in Ham-D scores
Cassano et al (2015)^Citation79 Near-Infrared Transcranial Radiation for Major Depressive Disorder: Proof of Concept Study	4 MDD completers	Pilot, open, proof of concept, prospective, double-blind, randomized study, crossover design	NeuroThera, continuously emitting GaAlAs- laser, manufactured by PhotoThera Inc.	Twice a week for three weeks, 4 sites, 2 mins per site	Prefrontal cortex	808 ± 10nm	Continuous	700mW/cm^2	84J/cm^2	50% Remission of MDD at weeks 6–7 (HAMD17 ≤7)
Caldieraro et al (2018)^Citation86 Long-Term Near-Infrared Photobiomodulation for Anxious Depression Complicated by Takotsubo Cardiomyopathy	1 MDD with anxious distress	Case report	i-PBM: Vielight light-emitting diode t-PBM: Omnilux New U light emitting diode device (Photomedex Inc)	i-PBM: titrated up to twice daily, 25 mins per nostril t-PBM (F3/F4): twice per week for 25 mins t-PBM (Fpz): titrated up to 30 mins daily	i-PBM: Proposed systemic effect t-PBM: EEG sites F4, F3, or both on same day; later switched to Fpz	i-PBM: 810 nm t-PBM: 830nm	i-PBM: 10-Hz, Pulsed t-PBM: Continuous	i-PBM: peak 14.2mW/cm^2 t-PBM: 33.2mW/cm^2	i-PBM: average 10.65J/cm^2 t-PBM (F3/F4): 49.8J/cm^2 t-PBM (Fpz): 59.8J/cm^2	Daily t-PBM treatments at Fpz site reduced MDD symptoms
Henderson and Morries (2017)^Citation81 Multi-Watt near-infrared Phototherapy for the Treatment of comorbid Depression: an Open-label single-arm study	39 TBI patients who completed depression questionnaires	Open-label single arm, proof-of-concept study	Class IV Lasers: LT1000 (LiteCure, Newark, DE, USA), Diowave 810 (Diowave, Riviera Beach, FL, USA), or Aspen Laser (Denver, CO, USA)	8–34 treatments, 30 mins per session	Overlying forehead and temporal regions bilaterally	810/980nm	Continuous, sweeping	8–15W	55–81J/cm^2	92% were responders (decrease of QIDS score ≥ 50% from baseline), 82% were remitters (QIDS ≤ 5)
Disner et al (2016)^Citation82 Transcranial laser stimulation as neuroenhancement for attention bias modification in adults with elevated depression symptoms	51 adults with elevated symptoms of depression	Randomized, sham-controlled proof-of-principle study	CG-5000 high density laser (Cell Gen Therapeutics, Dallas, TX, USA)	Two sessions, 8 mins per session	Left or right forehead	1064nm	Continuous	250mW/cm^2	60J/cm^2	Right t-PBM yielded greater improvement in participants whose attention was responsive to attention bias modification
Henderson and Morries (2015)^Citation85 SPECT Perfusion Imaging Demonstrates Improvement of Traumatic Brain Injury With Transcranial Near-infrared Laser Phototherapy	1 TBI	Case Report	Class IV laser (Diowave 810, West Palm Beach, FL, USA)	20 treatments over the course of 4 months	Unknown	810nm	Unknown	Unknown	55 to 81J/cm^2	Improved mood (self-report), SPECT: Significant change in left and right frontal cortices, as well as left and right temporal cortices.
Morries et al (2015)^Citation80 Treatments for traumatic brain injury with emphasis on transcranial near-infrared laser phototherapy	10 TBI who completed depression questionnaires	Retrospective Case Series	Class IV lasers: LT1000 (LiteCure, Newark, DE, USA) or Diowave 810 (Diowave, Riviera Beach, FL, USA)	10–20 treatments, 16–30 mins per session	Bilateral frontal, bilateral frontal + left temporal, bilateral frontal + bilateral temporal	810/980nm, one pt 810nm only	10-Hz Pulsed, scanning	Unknown	55 to 81J/cm^2	BDI and QIDS-SR scores decreased from moderately depressed range to non-depressed range
Schiffer et al (2009)^Citation77 Psychological benefits 2 and 4 weeks after a single treatment with near infrared light to the forehead: a pilot study of 10 patients with major depression and anxiety	10 MDD	Pilot Study	(LED) array (Marubeni America Corp, Santa Clara, CA)	One session consisting of Four 4-min treatments	Left forehead at F3 (over dorsolateral prefrontal cortex), Right forehead at F4	810nm	Unknown	250mW/cm^2	60J/cm^2 per site	At 2-weeks post treatment, 4 out of 10 were responders (>50% reduction in HAM-D), and 4 out of 10 were in remission (HAM-D <8)
Naeser et al (2014)^Citation78 Significant Improvements in Cognitive Performance Post-Transcranial, Red/Near-Infrared Light-Emitting Diode Treatments in Chronic, Mild Traumatic Brain Injury: Open-Protocol Study	11 mild TBI who completed BDI	Pilot, Open-Protocol Study; Case series	LED Console Units (MedX Health, Model 1100, Toronto), three LED cluster heads per unit	18 sessions over 6 weeks, 20 mins per session	11 scalp placements: midline from front-to-back hairline, and bilaterally on frontal, parietal, and temporal regions	633/870nm	Continuous	22.2mW/cm^2 per cluster head	13J/cm^2 per cluster head placement	Trend towards significance for BDI scores 1 week post treatment

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