Iosifescu, Dan V.Norton, Richard J.Tural, UmitMischoulon, DavidCollins, KatherineMcDonald, ErinTaboada, Luis DeFoster, SimmieCusin, CristinaYeung, AlbertClain, AlisabetSchoenfeld, DavidHamblin, Michael R.Cassano, Paolo2023-08-222022-08-08Iosifescu, Dan V., Richard J. Norton, Umit Tural, David Mischoulon, Katherine Collins, Erin McDonald, Luis De Taboada et al. "Very Low-Level Transcranial Photobiomodulation for Major Depressive Disorder." J. Clin. Psychiatry 83, no. 5 (2022). DOI: 10.4088/jcp.21m142261555-2101https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37376886Background: Transcranial photobiomodulation (t-PBM) with near-infrared (NIR) light might represent a treatment for major depressive disorder (MDD). However, the dosimetry of administered t-PBM varies widely. We tested the efficacy of t-PBM with low irradiance, low energy per session and low number of sessions in individuals with MDD. Methods: We conducted a two site, double-blind, sham-controlled study of adjunct t-PBM NIR [830 nm; continuous wave; 35.8 cm2 treatment area; 54.8 mW/cm2 irradiance; 65.8 J/cm2 fluence, 20 min/session; ~2W total power; 2.3 kJ total energy per session], delivered to the prefrontal cortex, bilaterally, twice a week for 6-weeks, in subjects diagnosed with MDD per the DSM-IV criteria. Subjects were recruited between August 2016 and May 2018. We used a sequential parallel comparison design: 18 non-responders to sham in phase 1 (6 weeks) were re-randomized in phase 2. The primary outcome was reduction in depression severity (HAM-D17 and QIDS-C scores) from baseline. Statistical analyses used R package SPCDAnalyze2, including all subjects with ≥1 post-randomization evaluation. Results: Of the 54 subjects recruited, we included 49 MDD subjects in the analysis (71% female, age 40.8±16.1 years). There were no significant differences between t-PBM and sham with respect to the change in HAM-D17 (t=-0.319, p=0.751) or QIDS-C scores (t=-0.499, p=0.620). The sham effect was reasonably low. Conclusion: Mostly uncontrolled studies suggest the efficacy of t-PBM for MDD; however, its optimal dose is still to be defined. A minimal dose threshold is likely necessary, similarly to other neuromodulation techniques in MDD (ECT, TMS). We established a threshold of inefficacy of t-PBM for MDD, based on combined low irradiance, low energy per session and low number of sessions.en-USPsychiatry and Mental healthJournal Article2023-08-2210.4088/jcp.21m14226