Efficacy and acceptability of blue-wavelength light therapy for post-TBI behavioral symptoms: A systematic review and meta-analysis of randomized controlled trials

Abstract

Objective: Behavioral symptoms are common after traumatic brain injury (TBI), but their treatments remain unsatisfactory. This systematic review and meta-analysis compared the efficacy and acceptability between blue-wavelength light therapy (BWLT) and long-wavelength/no light therapy (LW/NLT) for post-TBI sleepiness, sleep disturbance, depressive symptoms, and fatigue.

Methods: This study included randomized controlled trials comparing the effects of BWLT and LW/NLT on post-TBI sleepiness, sleep disturbance, depression, or fatigue. We searched Pubmed, Embase, CINAHL, and Cochrane Central Register of Controlled of Trials on April 13, 2022. The revised tool for assessing the risk of bias in randomized trials was applied. We performed a frequentist pairwise meta-analysis using a random-effects model.

Results: Of 233 retrieved records, six trials (N = 278) were included in this meta-analysis. TBIs ranged from mild to severe, and the interventions were administered for a median of 35 days. Most trials delivered light therapy via lightboxes. Three trials had a high risk of bias. BWLT was significantly superior to LW/NLT in reducing sleep disturbance (5 trials; SMD = -0.63; 95% CI = -1.21 to -0.05; p = 0.03; I2 = 61%) and depressive symptoms (4 trials; SMD = -1.00; 95% CI = -1.62 to -0.38; p < 0.01; I2 = 56%). There were trends that BWLT was superior to LW/NLT in reducing sleepiness (6 trials; SMD = -0.92; 95% CI = -1.84 to 0.00; p = 0.05; I2 = 88%) and fatigue (4 trials; SMD = -1.44; 95% CI = -2.95 to 0.08; p = 0.06; I2 = 91%). All-cause dropout rates were not significantly different between groups.

Conclusion: Limited and heterogenous evidence suggests that short-term BWLT is well accepted, has a large treatment effect on post-TBI depressive symptoms, and may have a moderate treatment effect on post-TBI sleep disturbance.

Fig 1. PRISMA diagram showing the process of trial selection.

The systematic review and meta-analysis searched four databases, removed the duplicated records, and screened the titles and abstracts of records. After examining 14 full-text reports of relevant records, six trials were quantitatively synthesized.

Fig 2. Risk of bias in the included trials.

A) Risk of bias in each domain of individual trials and B) Risk of bias across all included trials. Risk of bias were assessed using version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2).

Fig 3. Forest plots comparing the efficacy between blue-wavelength light therapy (BWLT) and control interventions in reducing behavioral symptoms.

Behavioral symptoms included sleepiness (A), sleep disturbance (B), depressive symptoms (C), and fatigue (D). Standardized mean differences (SMDs) expressed the differences in depressive symptom reduction between groups. The diamonds indicate the treatment estimates of the total sample. Control interventions included amber, red, or no light therapy.

Fig 4. Funnel plot showing the relationships between behavioral symptoms reduced by BWLT and their precision.

Standardized mean differences (SMDs) of behavioral symptom reduction indicate the effect estimates of Blue-Wavelength Light Therapy (BWLT) compared with control interventions. The standard errors of those SMDs express the precision. The outer dashed lines indicate the triangular region within which 95% of studies are expected to lie in the absence of both biases and heterogeneity. The bold dash line corresponds to no intervention effect. Control interventions included amber, red, or no light therapy.