Dose-dependent tolerability and safety of transcranial photobiomodulation: a randomized controlled trial

Transcranial photobiomodulation (t-PBM) with near-infrared (NIR) light has emerged as a promising therapy for major depressive disorder (MDD). However, the dose-dependent tolerability of t-PBM has not been adequately explored. This secondary analysis of a sham-controlled clinical trial evaluated the safety and tolerability of t-PBM across varying doses in 31 subjects with MDD. Participants were randomly assigned to receive four sessions of NIR (808 nm) t-PBM (sham, low, medium, and high doses) approximately one week apart. The outcome was the emergence of side effects, assessed by the Systematic Assessment for Treatment-Emergent Effects-Specific Inquiry (SAFTEE-SI) scale. The frequency of side effects, compared to baseline or the prior week, was analyzed using Cochran’s Q test. Additionally, body weight and systolic and diastolic blood pressures (SBP and DBP, respectively) were recorded and assessed with repeated measures ANOVA. The results showed no statistically significant changes in rates of any adverse events compared to baseline or prior week. The most notable rate increases were in “delayed or absent orgasm” for the medium dose compared to baseline among 10% of participants (Cochran’s Q = 6.231; p = 0.101), and in “ringing in ears or trouble hearing” for the high dose compared to the prior week among 13% of participants (Cochran’s Q = 6.231; p = 0.101). There were no significant changes in weight or SBP and DBP (F_{(4, 85)} = 0.277, p = 0.892; F_{(4, 87.45)} = 1.722, p = 0.152; F_{(4, 87.10)} = 1.672, p = 0.164, respectively). In conclusion, this study did not find a significant association between the dose of t-PBM sessions and rates of adverse events or changes in vital signs. The side-effect profile of t-PBM appears benign, regardless of dosimetry.