Transcranial and systemic photobiomodulation for major depressive disorder: A systematic review of efficacy, tolerability and biological mechanisms

J Affect Disord. 2019 Jan 15:243:262-273. doi: 10.1016/j.jad.2018.09.048. Epub 2018 Sep 17.


Background: Photobiomodulation (PBM) with red and near-infrared light (NIR) -also known as Low-Level Light Therapy-is a low risk, inexpensive treatment-based on non-retinal exposure-under study for several neuropsychiatric conditions. The aim of this paper is to discuss the proposed mechanism of action and to perform a systematic review of pre-clinical and clinical studies on PBM for major depressive disorder (MDD).

Methods: A search on MEDLINE and EMBASE databases was performed in July 2017. No time or language restrictions were used. Studies with a primary focus on MDD and presenting original data were included (n = 17). References on the mechanisms of action of PBM also included review articles and studies not focused on MDD.

Results: Red and NIR light penetrate the skull and modulate brain cortex; an indirect effect of red and NIR light, when delivered non-transcranially, is also postulated. The main proposed mechanism for PBM is the enhancement of mitochondrial metabolism after absorption of NIR energy by the cytochrome C oxidase; however, actions on other pathways relevant to MDD are also reported. Studies on animal models indicate a benefit from PBM that is comparable to antidepressant medications. Clinical studies also indicate a significant antidepressant effect and good tolerability.

Limitations: Clinical studies are heterogeneous for population and treatment parameters, and most lack an appropriate control.

Conclusions: Preliminary evidence supports the potential of non-retinal PBM as a novel treatment for MDD. Future studies should clarify the ideal stimulation parameters as well as the overall efficacy, effectiveness and safety profile of this treatment.

Keywords: Depression; Low-level laser therapy; Low-level light therapy; Mitochondria; Near-infrared; Photobiomodulation; Treatment.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Animals
  • Depressive Disorder, Major / physiopathology
  • Depressive Disorder, Major / therapy*
  • Humans
  • Infrared Rays / therapeutic use*
  • Low-Level Light Therapy / methods*
  • Mitochondria / metabolism