Transcranial Photobiomodulation for the Treatment of Major Depressive Disorder. The ELATED-2 Pilot Trial.
- 1 Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital , Boston, Massachusetts.
- 2 Center for Anxiety and Traumatic Stress Disorders , Massachusetts General Hospital, Boston, Massachusetts.
- 3 Department of Neurosurgery, Massachusetts General Hospital , Boston, Massachusetts.
- 4 LiteCure LLC , Newark, Delaware.
- 5 Wellman Center for Photomedicine, Massachusetts General Hospital , Boston, Massachusetts.
- 6 Department of Dermatology, Harvard Medical School , Boston, Massachusetts.
- 7 Harvard-MIT Division of Health Sciences and Technology , Cambridge, Massachusetts.
- 8 Adult Psychopharmacology Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai , New York, New York.
Our objective was to test the antidepressant effect of transcranial photobiomodulation (t-PBM) with near-infrared (NIR) light in subjects suffering from major depressive disorder (MDD).
t-PBM with NIR light is a new treatment for MDD. NIR light is absorbed by mitochondria; it boosts cerebral metabolism, promotes neuroplasticity, and modulates endogenous opioids, while decreasing inflammation and oxidative stress.
MATERIALS AND METHODS:
We conducted a double-blind, sham-controlled study on the safety and efficacy (change in Hamilton Depression Rating Scale [HAM-D17] total score at end-point) of adjunct t-PBM NIR [823?nm; continuous wave (CW); 28.7?×?2?cm2; 36.2?mW/cm2; up to 65.2?J/cm2; 20-30?min/session], delivered to dorsolateral prefrontal cortex, bilaterally and simultaneously, twice a week, for 8 weeks, in subjects with MDD. Baseline observation carried forward (BOCF), last observation carried forward (LOCF), and completers analyses were performed.
The effect size for the antidepressant effect of t-PBM, based on change in HAM-D17 total score at end-point, was 0.90, 0.75, and 1.5 (Cohen’s d), respectively for BOCF (n?=?21), LOCF (n?=?19), and completers (n?=?13). Further, t-PBM was fairly well tolerated, with no serious adverse events.
t-PBM with NIR light demonstrated antidepressant properties with a medium to large effect size in patients with MDD. Replication is warranted, especially in consideration of the small sample size.
depression; low-level laser therapy; randomized controlled trial
Low-Level Laser Irradiation Improves Depression-Like Behaviors in Mice.
- Department of Neurology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou City, Jiangsu, 215004, China.
- Institute of Neuroscience, Soochow University, Suzhou City, Jiangsu, 215123, China.
- Department of Psychiatry, Guangji Hospital, Suzhou City, Jiangsu, 215000, China.
- Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, 1120 15th Street, Augusta, GA, 30912, USA.
- Department of Neurology, Suzhou Kowloon Hospital, Suzhou City, 215028, China.
- Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, 1120 15th Street, Augusta, GA, 30912, USA. firstname.lastname@example.org.
- Department of Neurology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou City, Jiangsu, 215004, China. email@example.com.
- Institute of Neuroscience, Soochow University, Suzhou City, Jiangsu, 215123, China. firstname.lastname@example.org.
Major depressive disorder (MDD) is one of the leading forms of psychiatric disorders, characterized by aversion to mobility, neurotransmitter deficiency, and energy metabolic decline. Low-level laser therapy (LLLT) has been investigated in a variety of neurodegenerative disorders associated with mitochondrial dysfunction and functional impairments. The goal of this study was to examine the effect of LLLT on depression-like behaviors and to explore the potential mechanism by detecting mitochondrial function following LLLT. Depression models in space restriction mice and Abelson helper integration site-1 (Ahi1) knockout (KO) mice were employed in this work. Our results revealed that LLLT effectively improved depression-like behaviors, in the two depression mice models, by decreasing immobility duration in behavioral despair tests. In addition, ATP biosynthesis and the level of mitochondrial complex IV expression and activity were significantly elevated in prefrontal cortex (PFC) following LLLT. Intriguingly, LLLT has no effects on ATP content and mitochondrial complex I-IV levels in other tested brain regions, hippocampus and hypothalamus. As a whole, these findings shed light on a novel strategy of transcranial LLLT on depression improvement by ameliorating neurotransmitter abnormalities and promoting mitochondrial function in PFC. The present work provides concrete groundwork for further investigation of LLLT for depression treatment.
Brain Photobiomodulation Therapy: a Narrative Review.
- Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran. email@example.com.
- Department of Medical Physics, Tabriz University of Medical Sciences, Tabriz, Iran. firstname.lastname@example.org.
- Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran.
- Department of Medical Physics, Tabriz University of Medical Sciences, Tabriz, Iran.
- Department of Medical Bioengineering, Tabriz University of Medical Sciences, Tabriz, Iran.
- School of Medical Sciences, University of Aberdeen, Aberdeen, UK.
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, 02114, USA. email@example.com.
- Department of Dermatology, Harvard Medical School, Boston, MA, 02115, USA. firstname.lastname@example.org.
- Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, 02139, USA. email@example.com.
Brain photobiomodulation (PBM) therapy using red to near-infrared (NIR) light is an innovative treatment for a wide range of neurological and psychological conditions. Red/NIR light is able to stimulate complex IV of the mitochondrial respiratory chain (cytochrome c oxidase) and increase ATP synthesis. Moreover, light absorption by ion channels results in release of Ca2+ and leads to activation of transcription factors and gene expression. Brain PBM therapy enhances the metabolic capacity of neurons and stimulates anti-inflammatory, anti-apoptotic, and antioxidant responses, as well as neurogenesis and synaptogenesis. Its therapeutic role in disorders such as dementia and Parkinson’s disease, as well as to treat stroke, brain trauma, and depression has gained increasing interest. In the transcranial PBM approach, delivering a sufficient dose to achieve optimal stimulation is challenging due to exponential attenuation of light penetration in tissue. Alternative approaches such as intracranial and intranasal light delivery methods have been suggested to overcome this limitation. This article reviews the state-of-the-art preclinical and clinical evidence regarding the efficacy of brain PBM therapy.
Brain function; Cortical neurons; Dementia; Depression; Low-level laser therapy; Photobiomodulation therapy; Stroke; Traumatic brain injury
Transcranial low-level infrared laser irradiation ameliorates depression induced by reserpine in rats.
- 1Biophysics Department, Faculty of Science, Cairo University, Giza, Egypt. Haitham@sci.cu.edu.eg.
Transcranial low-level infrared laser is a modality of therapy based on the principle of photons delivered in a non-invasive manner through the skull for the treatment of some neurological conditions such as psychological disorders, traumatic brain injuries, and neurodegenerative diseases among others. In the present study, effects of low-level infrared laser irradiation with different radiation powers (80, 200, and 400 mW, continuous wave) were investigated on normal animals subjected to forced swimming test (FST). Results indicated that there are changes in FST parameters in animals irradiated with laser; the lowest dose provoked a significant increase in animal activity (swimming and climbing) and a significant decrease in animal’s immobility, while the highest laser dose resulted in a complete inverse action by significantly increasing animal immobility and significantly decreasing animal activity with respect to control animals. The lowest dose (80 mW) of transcranial laser irradiation has then utilized on animals injected with a chronic dose of reserpine (0.2 mg/kg i.p. for 14 days) served as an animal model of depression. Laser irradiation has successfully ameliorated depression induced by reserpine as indicated by FST parameters and electrocorticography (ECoG) spectral analysis in irradiated animals. The findings of the present study emphasized the beneficial effects of low-level infrared laser irradiation on normal and healthy animals. Additionally, it indicated the potential antidepressant activity of the low dose of infrared laser irradiation.
Review of transcranial photobiomodulation for major depressive disorder: targeting brain metabolism, inflammation, oxidative stress, and neurogenesis.
- 1Massachusetts General Hospital, Depression Clinical and Research Program, One Bowdoin Square, 6th Floor, Boston, Massachusetts 02114, United States; Harvard Medical School, Department of Psychiatry, 401 Park Drive, Boston, Massachusetts 02215, United States.
- 2Massachusetts General Hospital, Depression Clinical and Research Program, One Bowdoin Square, 6th Floor, Boston, Massachusetts 02114, United States.
- 3Massachusetts General Hospital, Wellman Center for Photomedicine, 50 Blossom Street, Boston, Massachusetts 02114, United States; Harvard Medical School, Department of Dermatology, 55 Fruit Street, Boston, Massachusetts 02114, United States; Harvard-MIT Division of Health Sciences and Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
- 4Synaptic Space, 3979 East Arapahoe Road, Littleton, Colorado 80122, United States; Neuro-Laser Foundation, Suite 420, 215 South Wadsworth, Lakewood, Colorado 80226, United States.
- 5Mount Sinai Medical School, Mood and Anxiety Disorders Program, 1428 Madison Avenue, New York, New York 10029, United States; Mount Sinai Medical School, Department of Psychiatry and Neuroscience, 1 Gustave L. Levy Place, New York, New York 10029, United States.
We examined the use of near-infrared and red radiation (photobiomodulation, PBM) for treating major depressive disorder (MDD). While still experimental, preliminary data on the use of PBM for brain disorders are promising. PBM is low-cost with potential for wide dissemination; further research on PBM is sorely needed. We found clinical and preclinical studies via PubMed search (2015), using the following keywords: “near-infrared radiation,” “NIR,” “low-level light therapy,” “low-level laser therapy,” or “LLLT” plus “depression.” We chose clinically focused studies and excluded studies involving near-infrared spectroscopy. In addition, we used PubMed to find articles that examine the link between PBM and relevant biological processes including metabolism, inflammation, oxidative stress, and neurogenesis. Studies suggest the processes aforementioned are potentially effective targets for PBM to treat depression. There is also clinical preliminary evidence suggesting the efficacy of PBM in treating MDD, and comorbid anxiety disorders, suicidal ideation, and traumatic brain injury. Based on the data collected to date, PBM appears to be a promising treatment for depression that is safe and well-tolerated. However, large randomized controlled trials are still needed to establish the safety and effectiveness of this new treatment for MDD.
Behavioral and Brain Functions 2009, 5:46doi:10.1186/1744-9081-5-46
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
Fredric Schiffer , Andrea L Johnston , Caitlin Ravichandran , Ann Polcari , Martin H Teicher , Robert H Webb and Michael R Hamblin
Published 8 December 2009
Many studies have reported beneficial effects from the application of near-infrared (NIR) light photobiomodulation (PBM) to the body, and one group has reported beneficial effects applying it to the brain in stroke patients. We have reported that the measurement of a patient’s left and right hemispheric emotional valence (HEV) may clarify data and guide lateralized treatments. We sought to test whether a NIR treatment could 1. improve the psychological status of patients, 2. show a relationship between immediate psychological improvements when HEV was taken into account, and 3. show an increase in frontal pole regional cerebral blood flow (rCBF), and 4. be applied without side effects.
We gave 10 patients, (5M/5F) with major depression, including 9 with anxiety, 7 with a past history of substance abuse (6 with an opiate abuse and 1 with an alcohol abuse history), and 3 with post traumatic stress disorder, a baseline standard diagnostic interview, a Hamilton Depression Rating Scale (HAM-D), a Hamilton Anxiety Rating Scale (HAM-A), and a Positive and Negative Affect Scale (PANAS). We then gave four 4-minute treatments in a random order: NIR to left forehead at F3, to right forehead at F4, and placebo treatments (light off) at the same sites. Immediately following each treatment we repeated the PANAS, and at 2-weeks and at 4-weeks post treatment we repeated all 3 rating scales. During all treatments we recorded total hemoglobin (cHb), as a measure of rCBF with a commercial NIR spectroscopy device over the left and the right frontal poles of the brain.
At 2-weeks post treatment 6 of 10 patients had a remission (a score less than or equal to 10) on the HAM-D and 7 of 10 achieved this on the HAM-A. Patients experienced highly significant reductions in both HAM-D and HAM-A scores following treatment, with the greatest reductions occurring at 2 weeks. Mean rCBF across hemispheres increased from 0.011 units in the off condition to 0.043 units in the on condition, for a difference of 0.032 (95% CI: -0.016, 0.080) units, though this result did not reach statistical significance. Immediately after treatment the PANAS improved to a significantly greater extent with NIR “on” relative to NIR “off” when a hemisphere with more positive HEV was treated than when one with more negative HEV was treated. We observed no side effects.
This small feasibility study suggests that NIR-PBM may have utility for the treatment of depression and other psychiatric disorders and that double blind randomized placebo-controlled trials are indicated. Trial registration ClinicalTrials.gov Identifier: NCT00961454
Vopr Kurortol Fizioter Lech Fiz Kult. 2008 Jul-Aug;(4):24-6.
Low-intensity laser irradiation in the combined treatment of depressive disorders in patients with chronic salpingo-oophoritis
[Article in Russian]
This study was designed to evaluate the possibility to use low-intensity laser radiation in combined therapy of somatogenic depressions in patients having gynecological problems, such as inflammatory disease of uterine appendages. It was shown that the combined treatment including administration of antidepressants significantly accelerated the development of beneficial changes and stabilized depressive manifestations. Inclusion of low-intensity laser irradiation in the combined therapy further improved its positive effect. Nevertheless, the complete recovery could not be achieved in the absence of specific antidepressant treatment despite the alleviation of depressive symptoms.
Infrared irradiation has potential antidepressant effect.
Department of Psychiatry, Buddhist Tzu-Chi General Hospital, Hualien, Taiwan. firstname.lastname@example.org
Light therapy was only partially effective in treatment of depression when compared with summer’s sunlight. The antidepressant effect of infrared irradiation was evaluated using an experimental animal model.
Seventeen mice were randomly assigned to the exposure group (n = 9) and the control group (n = 8). The mice in the exposure group received infrared irradiation for 60 min daily during the study period of 4 weeks. The two groups were given forced swim test once a week to evaluate depression with the measurement of the immobility time.
We found that the exposure group showed a tendency of less immobility time by the end of the 3rd week when compared with the control group, and at the end of 4th week the difference reached a statistical significance (t(15) = 2.873; p = 0.012).
The result indicates that the immobility time in forced swim test, the sign of depression, can be reduced after prolonged (4 weeks) exposure to infrared irradiation in the animal model. The result suggests that a continuous application of infrared irradiation has antidepressant effect.
|Acupunct Med. 2005 Sep;23(3):103-11.|
Laser acupuncture for mild to moderate depression in a primary care setting–a randomised controlled trial.
Quah-Smith JI, Tang WM, Russell J.
Monash University, Victoria, Australia. email@example.com
OBJECTIVE: Depression is a major public health problem. There is some evidence supporting the effectiveness of needle acupuncture in its treatment. Laser stimulation, regarded here as a modality of acupuncture, is non-invasive and therefore free of infection risk; and it is acceptable to patients with needle phobia. The technique is relatively easily learned by community-based general practitioners. It is also amenable to sham control and therefore double-blinding in clinical trials. A double-blind randomised controlled trial was conducted to test the efficacy of low level laser acupuncture in mild to moderate depression.
METHODS: Thirty patients with depression were randomised to receive either active or inactive laser treatment. The laser unit could be switched to one of two settings. One switch position delivered active laser acupuncture and the other was inactive (sham). In the active mode, 0.5J was delivered to each of six to eight individually tailored acupuncture sites per visit. All patients were treated twice weekly for four weeks then weekly for a further four weeks. The patients and the acupuncturist were both blinded to conditions. Outcome was assessed using the Beck Depression Inventory at baseline, weeks four and eight during treatment, and at 4 and 12 weeks following the treatment.
RESULTS: At the end of the treatment period, Beck Depression Inventory scores fell from baseline by 16.1 points in the intervention group and by 6.8 points in the sham control group (P<0.001). The difference showed only a trend four weeks later, but was again significant after 12 weeks (P=0.007). Laser acupuncture was well tolerated with transient fatigue as the most common adverse effect.
CONCLUSION: Laser acupuncture may be worth further investigation as a treatment for mild to moderate depression in primary care.
|Lasers Med Sci. 2004;19(2):100-4.|
Use of low-energy laser as adjunct treatment of alcohol addiction.
Zalewska-Kaszubska J, Obzejta D.
Department of Pharmacodynamics, Medical University, Muszynskiego 1, 90-151 Lodz, Poland.firstname.lastname@example.org
Auricular acupuncture is a medical method that has been used in the treatment of alcohol addiction. In our study we decided to intensify this method by additional biostimulation of the whole organism. The aim of this study was the therapy of patients with alcohol dependence syndrome. Fifty-three alcoholics were treated with two types of laser stimulation in four sessions. Each session consisted of 20 consecutive daily helium-neon laser neck biostimulations and 10 auricular acupuncture treatments with argon laser (every 2nd day). The Beck Depression Inventory-Fast Screen (BDI-FS) was used to assess their frame of mind before the session and after 2 months of treatment. Moreover, beta-endorphin plasma concentration was estimated five times using the radioimmunoassay (RIA) method. Improvement in BDI-FS and increase in, beta-endorphin level were observed. These results suggest that laser therapy can be useful as an adjunct treatment for alcoholism.