No abstract

Incompletely treated major depressive disorder (MDD) poses an enormous global health burden. Conventional treatment for MDD consists of pharmacotherapy and psychotherapy, though a significant number of patients do not achieve remission with such treatments. Transcranial photobiomodulation (t-PBM) is a promising novel therapy that uses extracranial light, especially in the near-infrared (NIR) and red spectra, for biological and therapeutic effects. The aims of this Review are to evaluate the current clinical and preclinical literature on t-PBM in MDD and to discuss candidate mechanisms for effects of t-PBM in MDD, with specific attention to biophotons and oxidative stress. A search on PubMed and ClinicalTrials.gov identified clinical and preclinical studies using t-PBM for the treatment of MDD as a primary focus. After a systematic screening, only 19 studies containing original data were included in this review (9 clinical and 10 preclinical trials). Study results demonstrate consensus that t-PBM is a safe and potentially effective treatment; however, varying treatment parameters among studies complicate definitive conclusions about efficacy. Among other mechanisms of action, t-PBM stimulates the complex IV of the mitochondrial respiratory chain and induces an increase in cellular energy metabolism. We suggest that future trials include biological measures to better understand the mechanisms of action of t-PBM and to optimize treatment efficiency. Of particular interest going forward will be studying potential effects of t-PBM—an external light source on the NIR spectra—on neural circuitry implicated in depression.