Transcranial Photobiomodulation for the Treatment of Major Depressive Disorder. The ELATED-2 Pilot Trial

<b><i>Objective:</i></b> 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). <b><i>Background:</i></b> 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. <b><i>Materials and methods:</i></b> 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. <b><i>Results:</i></b> 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 <i>d</i>), respectively for BOCF (<i>n</i> = 21), LOCF (<i>n</i> = 19), and completers (<i>n</i> = 13). Further, t-PBM was fairly well tolerated, with no serious adverse events. <b><i>Conclusions:</i></b> 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.