Development of a Home-Based Light Therapy for Fatigue Following Traumatic Brain Injury: Two Case Studies.

Background and Objectives: Fatigue and sleep disturbance negatively impact quality of life following brain injury and there are no established treatments. Building on research showing efficacy of blue light therapy delivered via a lightbox in reducing fatigue and daytime sleepiness after traumatic brain injury (TBI), this paper describes the development and implementation of a novel in-home light therapy to alleviate fatigue and sleep disturbance in two case studies. Methods: During the 8-week lighting intervention, participants' home lighting was adjusted to provide high intensity, blue-enriched (high melanopic) light all day as a stimulant and dimmer, blue-depleted (low melanopic) light for 3 h before sleep as a soporific. The sham 8-week control condition resembled participants' usual (baseline) lighting conditions (3,000-4,000 K all day). Lighting conditions were crossed-over. Outcomes were measures of fatigue, subjective daytime sleepiness, sleep quality, insomnia symptoms, psychomotor vigilance and mood. Case study participants were a 35-year old male (5 years post-TBI), and a 46-year-old female (22 years post-TBI). Results: The relative proportion of melanopic lux was greater in Treatment lighting than Control during daytime, and lower during evenings. Participants found treatment to be feasible to implement, and was well-tolerated with no serious side effects noted. Self-reported compliance was >70%. Both cases demonstrated reduced fatigue, sleep disturbance and insomnia symptoms during the treatment lighting intervention. Case 2 additionally showed reductions in daytime sleepiness and depressive symptoms. As expected, symptoms trended toward baseline levels during the control condition. Discussion: Treatment was positively received and compliance rates were high, with no problematic side-effects. Participants expressed interest in continuing the ambient light therapy in their daily lives. Conclusions: These cases studies demonstrate the acceptability and feasibility of implementing a personalized in-home dynamic light treatment for TBI patients, with evidence for efficacy in reducing fatigue and sleep disturbance. Clinical Trial Registration:www.anzctr.org.au, identifier: ACTRN12617000866303.

Factors Associated With Response to Pilot Home-Based Light Therapy for Fatigue Following Traumatic Brain Injury and Stroke.

Background: Fatigue and sleep disturbance are common and debilitating problems after brain injury. Light therapy shows promise as a potential treatment. We conducted a trial of in-home light therapy to alleviate fatigue and sleep disturbance. The aim of the current study was to identify factors moderating treatment response. Methods: Participants were 24 individuals with traumatic brain injury (TBI) (n = 19) or stroke (n = 5) reporting clinically significant fatigue. Outcomes included fatigue on Brief Fatigue Inventory (primary outcome), sleep disturbance on Pittsburgh Sleep Quality Index, reaction time (RT) on Psychomotor Vigilance Task and time spent in productive activity. Interactions of demographic and clinical variables with these outcomes were examined in linear mixed-model analyses. Results: Whilst there were no variables found to be significantly associated with change in our primary outcome of fatigue, some variables revealed medium or large effect sizes, including chronotype, eye color, injury severity as measured by PTA, and baseline depressive symptoms. Chronotype significantly moderated sleep quality, with evening chronotype being associated with greater improvement during treatment. Injury type significantly predicted mean RT, with stroke participants exhibiting greater post-treatment reduction than TBI. Age significantly predicted productive activity during Treatment, with younger participants showing stronger Treatment effect. Conclusion: Light therapy may have a greater impact on sleep in younger individuals and those with an evening chronotype. Older individuals may need higher treatment dose to achieve benefit. Clinical Trial Registration: www.anzctr.org.au, identifier: ACTRN12617000866303.

Home-based light therapy for fatigue following acquired brain injury: a pilot randomized controlled trial.

BACKGROUND AND OBJECTIVES: Fatigue and sleep disturbance are debilitating problems following brain injury and there are no established treatments. Building on demonstrated efficacy of blue light delivered via a lightbox in reducing fatigue and daytime sleepiness after TBI, this study evaluated the efficacy of a novel in-home light intervention in alleviating fatigue, sleep disturbance, daytime sleepiness and depressive symptoms, and in improving psychomotor vigilance and participation in daily productive activity, following injury METHODS: The impact of exposure to a dynamic light intervention (Treatment) was compared to usual lighting (Control) in a randomized within-subject, crossover trial. Outcomes were fatigue (primary outcome), daytime sleepiness, sleep disturbance, insomnia symptoms, psychomotor vigilance, mood and activity levels. Participants (N = 24, M ± SDage = 44.3 ± 11.4) had mild-severe TBI or stroke > 3 months previously, and self-reported fatigue (Fatigue Severity Scale ≥ 4). Following 2-week baseline, participants completed each condition for 2 months in counter-balanced order, with 1-month follow-up. Treatment comprised daytime blue-enriched white light (CCT > 5000 K) and blue-depleted light (< 3000 K) 3 h prior to sleep. RESULTS: Random-effects mixed-model analysis showed no significantly greater change in fatigue on the Brief Fatigue Inventory during Treatment, but a medium effect size of improvement (p = .33, d = -0.42). There were significantly greater decreases in sleep disturbance (p = .004), insomnia symptoms (p = .036), reaction time (p = .004) and improvements in productive activity (p = .005) at end of Treatment relative to Control, with large effect sizes (d > 0.80). Changes in other outcomes were non-significant. CONCLUSIONS: This pilot study provides preliminary support for in-home dynamic light therapy to address sleep-related symptoms in acquired brain injury. TRIAL REGISTRATION: This trial was registered with the Australian and New Zealand Clinical Trials Registry on 13 June 2017, www.anzctr.org.au , ACTRN12617000866303.

Cognitive Behavioural Therapy and Light Dark Therapy for Maternal Postpartum Insomnia Symptoms: Protocol of a Parallel-Group Randomised Controlled Efficacy Trial.

Background: Symptoms of insomnia are common in new mothers and have been associated with a range of negative maternal and child outcomes. Despite this, interventions to improve maternal postpartum sleep remain scarce. Cognitive Behavioural Therapy (CBT) and Light Dark Therapy (LDT) represent two promising interventions for insomnia symptoms and associated daytime consequences such as fatigue. This randomised controlled trial examines whether CBT and LDT improve maternal insomnia symptoms as the primary outcome and maternal sleep disturbance, mood, fatigue, and sleepiness as secondary outcomes. This protocol paper outlines the development, design, and implementation of the trial. Methods: Participants are an Australian community-sample of 90 first-time mothers who are 4-12 months postpartum with self-reported symptoms of insomnia (Insomnia Severity Index scores ≥ 8). Exclusion criteria include current severe sleep/psychiatric disorders, unsettled infant sleep behaviour, sleep-affecting medication use, and photosensitivity. Eligible women are randomised into a CBT (strategies targeting sleep, worries, fatigue, and relaxation), LDT, or a treatment-as-usual control condition. Interventions are therapist-assisted and personalised through two telephone calls and include a series of automated intervention emails delivered over 6 weeks. Primary and secondary outcomes are assessed at four time points: baseline, intervention mid-point, post-intervention, and 1-month post-intervention. Discussion: If found effective, these interventions could represent efficacious, safe, and inexpensive treatments for improving postpartum insomnia and mitigate its negative impact on maternal well-being. Interventions tested are highly scalable and can be integrated into postpartum care and made available to the broader community. ANZCTR trial registration: Accessible at: https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12618000842268.

Temporal dynamics of circadian phase shifting response to consecutive night shifts in healthcare workers: role of light-dark exposure.

KEY POINTS: Shift work is highly prevalent and is associated with significant adverse health impacts. There is substantial inter-individual variability in the way the circadian clock responds to changing shift cycles. The mechanisms underlying this variability are not well understood. We tested the hypothesis that light-dark exposure is a significant contributor to this variability; when combined with diurnal preference, the relative timing of light exposure accounted for 71% of individual variability in circadian phase response to night shift work. These results will drive development of personalised approaches to manage circadian disruption among shift workers and other vulnerable populations to potentially reduce the increased risk of disease in these populations. ABSTRACT: Night shift workers show highly variable rates of circadian adaptation. This study examined the relationship between light exposure patterns and the magnitude of circadian phase resetting in response to night shift work. In 21 participants (nursing and medical staff in an intensive care unit) circadian phase was measured using 6-sulphatoxymelatonin at baseline (day/evening shifts or days off) and after 3-4 consecutive night shifts. Daily light exposure was examined relative to individual circadian phase to quantify light intensity in the phase delay and phase advance portions of the light phase response curve (PRC). There was substantial inter-individual variability in the direction and magnitude of phase shift after three or four consecutive night shifts (mean phase delay -1:08 ± 1:31 h; range -3:43 h delay to +3:07 h phase advance). The relative difference in the distribution of light relative to the PRC combined with diurnal preference accounted for 71% of the variability in phase shift. Regression analysis incorporating these factors estimated phase shift to within ±60 min in 85% of participants. No participants met criteria for partial adaptation to night work after three or four consecutive night shifts. Our findings provide evidence that the phase resetting that does occur is based on individual light exposure patterns relative to an individual's baseline circadian phase. Thus, a 'one size fits all' approach to promoting adaptation to shift work using light therapy, implemented without knowledge of circadian phase, may not be efficacious for all individuals.

Efficacy of melatonin for sleep disturbance following traumatic brain injury: a randomised controlled trial.

BACKGROUND: The study aimed to determine the efficacy of melatonin supplementation for sleep disturbances in patients with traumatic brain injury (TBI). METHODS: This is a randomised double-blind placebo-controlled two-period two-treatment (melatonin and placebo) crossover study. Outpatients were recruited from Epworth and Austin Hospitals Melbourne, Australia. They had mild to severe TBI (n = 33) reporting sleep disturbances post-injury (mean age 37 years, standard deviation 11 years; 67% men). They were given prolonged-release melatonin formulation (2 mg; Circadin®) and placebo capsules for 4 weeks each in a counterbalanced fashion separated by a 48-hour washout period. Treatment was taken nightly 2 hours before bedtime. Serious adverse events and side-effects were monitored. RESULTS: Melatonin supplementation significantly reduced global Pittsburgh Sleep Quality Index scores relative to placebo, indicating improved sleep quality [melatonin 7.68 vs. placebo 9.47, original score units; difference -1.79; 95% confidence interval (CI), -2.70 to -0.88; p ≤ 0.0001]. Melatonin had no effect on sleep onset latency (melatonin 1.37 vs. placebo 1.42, log units; difference -0.05; 95% CI, -0.14 to 0.03; p = 0.23). With respect to the secondary outcomes, melatonin supplementation increased sleep efficiency on actigraphy, and vitality and mental health on the SF-36 v1 questionnaire (p ≤ 0.05 for each). Melatonin decreased anxiety on the Hospital Anxiety Depression Scale and fatigue on the Fatigue Severity Scale (p ≤ 0.05 for both), but had no significant effect on daytime sleepiness on the Epworth Sleepiness Scale (p = 0.15). No serious adverse events were reported. CONCLUSIONS: Melatonin supplementation over a 4-week period is effective and safe in improving subjective sleep quality as well as some aspects of objective sleep quality in patients with TBI. TRIAL REGISTRATION: Identifier: 12611000734965; Prospectively registered on 13 July 2011.

Diagnosis, Cause, and Treatment Approaches for Delayed Sleep-Wake Phase Disorder.

Delayed sleep-wake phase disorder (DSWPD) is commonly defined as an inability to fall asleep and wake at societal times resulting in excessive daytime sleepiness. Although the cause is multifaceted, delays in sleep time are largely driven by misalignment between the circadian pacemaker and the desired sleep-wake timing schedule. Current treatment approaches focus on correcting the circadian delay; however, there is a lack of data investigating combined therapies for treatment of DSWPD.

Cognitive Behavioral Therapy for Chronic Insomnia: A Systematic Review and Meta-analysis.

BACKGROUND: Because psychological approaches are likely to produce sustained benefits without the risk for tolerance or adverse effects associated with pharmacologic approaches, cognitive behavioral therapy for insomnia (CBT-i) is now commonly recommended as first-line treatment for chronic insomnia. PURPOSE: To determine the efficacy of CBT-i on diary measures of overnight sleep in adults with chronic insomnia. DATA SOURCES: Searches of MEDLINE, EMBASE, PsycINFO, CINAHL, the Cochrane Library, and PubMed Clinical Queries from inception to 31 March 2015, supplemented with manual screening. STUDY SELECTION: Randomized, controlled trials assessing the efficacy of face-to-face, multimodal CBT-i compared with inactive comparators on overnight sleep in adults with chronic insomnia. Studies of insomnia comorbid with medical, sleep, or psychiatric disorders were excluded. DATA EXTRACTION: Study characteristics, quality, and data were assessed independently by 2 reviewers. Main outcome measures were sleep onset latency (SOL), wake after sleep onset (WASO), total sleep time (TST), and sleep efficiency (SE%). DATA SYNTHESIS: Among 292 citations and 91 full-text articles reviewed, 20 studies (1162 participants [64% female; mean age, 56 years]) were included. Approaches to CBT-i incorporated at least 3 of the following: cognitive therapy, stimulus control, sleep restriction, sleep hygiene, and relaxation. At the posttreatment time point, SOL improved by 19.03 (95% CI, 14.12 to 23.93) minutes, WASO improved by 26.00 (CI, 15.48 to 36.52) minutes, TST improved by 7.61 (CI, -0.51 to 15.74) minutes, and SE% improved by 9.91% (CI, 8.09% to 11.73%). Changes seemed to be sustained at later time points. No adverse outcomes were reported. LIMITATION: Narrow inclusion criteria limited applicability to patients with comorbid insomnia and other sleep problems, and accuracy of estimates at later time points was less clear. CONCLUSION: CBT-i is an effective treatment for adults with chronic insomnia, with clinically meaningful effect sizes. PRIMARY FUNDING SOURCE: None. (PROSPERO registration number: CRD42012002863).

Randomized controlled trial of light therapy for fatigue following traumatic brain injury.

BACKGROUND: Fatigue is a common, persistent complaint following traumatic brain injury (TBI). Effective treatment is not well established. OBJECTIVE: .The current study aimed to investigate the efficacy of 4 weeks of light therapy for fatigue in patients with TBI. METHODS: We undertook a randomized, placebo-controlled study of 4-week, 45 min/morning, home-based treatment with short wavelength (blue) light therapy (λmax = 465 nm, 84.8 µW/cm(2), 39.5 lux, 1.74 × 10(14) photons/cm(2)/s) compared with yellow light therapy (λmax = 574 nm, 18.5 µW/cm(2), 68 lux, 1.21 × 10(12) photons/cm(2)/s) containing less photons in the short wavelength range and a no treatment control group (n = 10 per group) in patients with TBI who self-reported fatigue and/or sleep disturbance. Assessments of fatigue and secondary outcomes (self-reported daytime sleepiness, depression, sleep quality, and sustained attention) were conducted over 10 weeks at baseline (week -2), midway through and at the end of light therapy (weeks 2 and 4), and 4 weeks following cessation of light therapy (week 8). RESULTS: After controlling age, gender, and baseline depression, treatment with high-intensity blue light therapy resulted in reduced fatigue and daytime sleepiness during the treatment phase, with evidence of a trend toward baseline levels 4 weeks after treatment cessation. These changes were not observed with lower-intensity yellow light therapy or no treatment control conditions. There was also no significant treatment effect observed for self-reported depression or psychomotor vigilance performance. CONCLUSIONS: Blue light therapy appears to be effective in alleviating fatigue and daytime sleepiness following TBI and may offer a noninvasive, safe, and nonpharmacological alternative to current treatments.

Sustained attention following traumatic brain injury: use of the Psychomotor Vigilance Task.

OBJECTIVE: Deficits in sustained attention are common following traumatic brain injury (TBI), as a result of primary (i.e., neuropathology) and/or secondary factors (i.e., fatigue, sleep disturbance, depressed mood). The extent to which secondary factors play a role in attention deficits is relatively unexamined. Moreover, the Psychomotor Vigilance Task (PVT) is seldom used in TBI assessment despite its sensitivity to secondary factors observed following injury. The primary aim of the current study was to examine the usefulness of the auditory PVT in identifying attentional difficulties in patients with TBI compared with noninjured controls, and also to explore the impact of fatigue, sleep quality, and daytime sleepiness on sustained attention performances. METHOD: Participants (n = 20 per group) completed the auditory PVT and self-report measures of fatigue, sleep quality, daytime sleepiness, and depression. RESULTS: Compared to controls, patients with TBI had widespread PVT deficits including slower response times, increased response variability and attention lapses, and delayed responding in the slowest 10% of responses. Distribution analyses suggested this was likely due to generalized cognitive slowing. Self-reported secondary factors had varying impacts on aspects of PVT performance, with self-reported fatigue exhibiting a more global impact on attention performance. CONCLUSIONS: The auditory PVT is a sensitive measure of sustained attention deficits in patients with TBI, with aspects of performance influenced by fatigue, sleep disturbance, and depression.

Fatigue and sleep disturbance following traumatic brain injury--their nature, causes, and potential treatments.

BACKGROUND: Although fatigue and sleep disturbance are commonly reported following traumatic brain injury (TBI), understanding of their nature and treatment remains limited. OBJECTIVES: This article reviews a series of investigations of the nature and causes of fatigue and sleep disturbance following TBI. METHODS: A large cohort of community-based patients with TBI, recruited from a TBI rehabilitation program, completed measures of subjective fatigue and sleep disturbances, as well as attentional measures. A subgroup of participants completed polysomnography and assessment of dim light melatonin onset. RESULTS: Fatigue and sleep disturbance are common. Both are associated with anxiety, depression, and pain. However, fatigue is also associated with slowed information processing and the need for increased effort in performing tasks. Sleep disturbances contribute to fatigue. Objective sleep studies show reduced sleep efficiency, increased sleep onset latency, and increased time awake after sleep onset. Depression and pain exacerbate but cannot entirely account for these problems. There is increased slow-wave sleep. Individuals with TBI show lower levels of evening melatonin production, associated with less rapid-eye movement sleep. CONCLUSIONS: These findings suggest potential treatments including cognitive behavior therapy supporting lifestyle modifications, pharmacologic treatments with modafinil and melatonin, and light therapy to enhance alertness, vigilance, and mood. Controlled trials of these interventions are needed.

Spectral responses of the human circadian system depend on the irradiance and duration of exposure to light.

In humans, modulation of circadian rhythms by light is thought to be mediated primarily by melanopsin-containing retinal ganglion cells, not rods or cones. Melanopsin cells are intrinsically blue light-sensitive but also receive input from visual photoreceptors. We therefore tested in humans whether cone photoreceptors contribute to the regulation of circadian and neuroendocrine light responses. Dose-response curves for melatonin suppression and circadian phase resetting were constructed in subjects exposed to blue (460 nm) or green (555 nm) light near the onset of nocturnal melatonin secretion. At the beginning of the intervention, 555-nm light was equally effective as 460-nm light at suppressing melatonin, suggesting a significant contribution from the three-cone visual system (lambda(max) = 555 nm). During the light exposure, however, the spectral sensitivity to 555-nm light decayed exponentially relative to 460-nm light. For phase-resetting responses, the effects of exposure to low-irradiance 555-nm light were too large relative to 460-nm light to be explained solely by the activation of melanopsin. Our findings suggest that cone photoreceptors contribute substantially to nonvisual responses at the beginning of a light exposure and at low irradiances, whereas melanopsin appears to be the primary circadian photopigment in response to long-duration light exposure and at high irradiances. These results suggest that light therapy for sleep disorders and other indications might be optimized by stimulating both photoreceptor systems.