Seasonal affective disorder (SAD) is a seasonal form of major depression with features similar to major depressive disorder but occurring on a cyclical basis related to ambient light deprivation during winter months. Both phototherapy and medications are frequently used (University of Michigan, 2005). Current evidence-based guidelines on treatment of depression state that use of bright light therapy for the treatment of major depression with a

specifier is well-established (ICSI, 2006; American Psychiatric Association, 2000).

Westrin and Lam (2007) stated that clinical studies show equal effectiveness with light and anti-depressants, so patient preference should be considered in the selection of initial treatment. Dawn stimulation, negative air ions, exercise as well as cognitive behavioral therapy are under investigation and may also be helpful treatments for SAD.

There is a lack of evidence for bright light therapy for indications other than SAD. Systematic evidence reviews have failed to identify reliable evidence of LT for post-natal depression (Corral et al, 2000; Craig and Howard, 2008), pre-menstrual syndrome (Krasnik, 2005; Kwan and Onwude, 2006), non-seasonal depression (Arja et al, 2004), sleep disorders in children (Montgomery and Dunne, 2006), sleep disorders in the elderly (Montgomery and Dennis, 2002), and sleep or behavioral disorders in dementia (Cohen-Mansfield, 2001; Forbes et al, 2004).

In a review on bright-light therapy (BLT) for the treatment of mood disorders, Pail and colleagues (2011) stated that BLT is established as the treatment of choice for SAD/winter type. In the last 2 decades, the use of BLT has expanded beyond SAD: there is preliminary evidence for its effectiveness in chronic depression, antepartum depression, pre-menstrual depression, bipolar depression and disturbances of the sleep-wake cycle. However, the authors noted that data on the usefulness of BLT in non-seasonal depression are promising; further systematic studies are still needed.

Khan et al (2011) evaluated the current therapeutic options in the management of sleep disorders in visually impaired children to identify knowledge gaps and guide future research. A search of primary literature was conducted using the bibliographic databases PubMed (1980 to August 2010), EMBASE (1990 to August 2010), Science Citation Index Expanded (1990 to August 2010), and CINHAL (1992 to August 2010) and the Cochrane Central Register of Controlled Trials (CENTRAL). Additional studies were identified through snowballing search techniques (manually by searching retrieved references and electronically by using citation-tracking software). Search terms included behavioral treatment, children, circadian rhythm, hypnosedatives, intellectual disability, light therapy, melatonin, phototherapy, random allocation, randomized controlled trial (RCT), sleep disorder, and visual impairment. Randomized and quasi-randomized clinical trials of therapeutic options (behavioral treatment, LT, melatonin, or hypnosedatives) used in participants aged 3 months to 18 years who had both a visual impairment and a sleep disorder were included. Independent extraction of articles was performed by 2 authors using pre-defined data fields, including quality of the therapeutic options, based on the Strength of Recommendation Taxonomy evidence-rating system. Two RCTs were retrieved for melatonin, with improved effect on sleep latency (p = 0.019 and p < 0.05, respectively). However, separate analysis for visual impairment was not conducted. No RCTs were retrieved for behavioral intervention, LT, or hypnosedatives. Three studies using behavioral therapy (2 case reports and 1 case series) anecdotally showed improvement in sleep habit. No improvement in sleep rhythm was observed with a case series applying LT as an intervention. The authors concluded that children with visual impairment and sleep disorders are a heterogeneous patient group, making diagnosis and treatment difficult. Randomized controlled trials on treatment options remain in their infancy, with a lack of evidence for appropriate therapeutic strategies. Trials across a range of selected diagnoses need to be conducted with adequate sample populations to differentiate the effectiveness of 4 different treatment modalities (namely, behavioral therapy, LT, melatonin, and hypnosedatives) as agents for improving sleep.

Poon and colleagues (2012) stated that many patients diagnosed with bipolar disorder (BD) respond incompletely or unsatisfactorily to available treatments. Given the potentially devastating nature of this prevalent disorder, there is a pressing need to improve clinical care of such patients. These researchers performed a literature review of the research findings related to treatment-resistant BD reported through February 2012. Therapeutic trials for treatment-resistant bipolar mania are uncommon, and provided few promising leads other than the use of clozapine. Far more pressing challenges are the depressive-dysthymic-dysphoric-mixed phases of BD and long-term prophylaxis. Therapeutic trials for treatment-resistant bipolar depression have assessed anti-convulsants, modern anti-psychotics, glutamate [N-methyl-D-aspartate (NMDA)] antagonists, dopamine agonists, calcium-channel blockers, and thyroid hormones, as well as behavioral therapy, sleep deprivation, light therapy, electroconvulsive therapy (ECT), transcranial magnetic stimulation, and deep brain stimulation – all of which are promising but limited in effectiveness. Several innovative pharmacological treatments (an anti-cholinesterase, a glutamine antagonist, a calcium-channel blocker, triiodothyronine, olanzapine and topiramate), ECT, and cognitive-behavior therapy have some support for long-term treatment of resistant BD patients, but most of trials of these treatments have been methodologically limited. The authors concluded that most studies identified were small, involved supplementation of typically complex ongoing treatments, varied in controls, randomization, and blinding, usually involved brief follow-up, and lacked replication. Moreover, they stated that clearer criteria for defining and predicting treatment resistance in BD are needed, as well as improved trial design with better controls, assessment of specific clinical subgroups, and longer follow-up.

Dauphinais et al (2012) stated that treatment of BD often results in patients taking several drugs in an attempt to alleviate residual depressive symptoms, which can lead to an accumulation of side effects. New treatments for bipolar depression that do not increase the side effect burden are needed. One non-pharmacological treatment with few side effects, BLT, has been shown to be an effective therapy for seasonal affective disorder, yet has not been extensively studied for other forms of depression. In this study, a total of 44 adults with BD (depressed phase) were randomized to treatment with BLT, low-density or high-density negative ion generator for 8 weeks. The primary measure of effectiveness was the Structured Interview Guide for the Hamilton Depression Rating Scale with Atypical Depression Supplement (SIGH-ADS). Adverse events were assessed using the Young Mania Rating Scale (YMRS) and Systematic Assessment for Treatment Emergent effects (SAFTEE). All outcome variables were statistically analyzed using a mixed model repeated measure analysis of variance (ANOVA). The results showed no statistically significant differences between groups in any outcome measures at study end-point; adverse events, including switches into hypomania, were rare. The authors concluded that further research is needed to determine the effectiveness of BLT in this population.

In a Cochrane review, Forbes and colleagues (2014) examined the effectiveness of light therapy in improving cognition, activities of daily living (ADLs), sleep, challenging behavior, and psychiatric symptoms associated with dementia. ALOIS, the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (CDCIG), The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS were searched on January 20, 2014 using the terms: "bright light*", "light box*", "light visor*", "dawn-dusk*", phototherapy, "photo therapy", "light therapy" "light treatment", light*. The CDCIG Specialized Register contains records from all major healthcare databases (The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS) as well as from many trials databases and grey literature sources. All relevant RCTs were included in which light therapy, at any intensity and duration, was compared with a control group for the effect of improving cognition, ADLs, sleep, challenging behavior, and psychiatric symptoms associated with dementia (as well as institutionalization rates or cost of care). Included were people with dementia of any type and degree of severity. Two review authors independently assessed the retrieved articles for relevance, and 4 review authors independently assessed the selected studies for risk of bias and extracted the data. Statistically significant differences in outcomes between the treatment and control groups at the end of treatment and follow-up were examined. Each study was summarized using a measure of effect (e.g., mean difference). A total of 11 trials (13 articles) met the inclusion criteria. However, 3 of the studies could not be included in the analyses either because the reported data could not be used in the meta-analysis or these researchers were unable to retrieve the required data from the authors. This updated review found no effect of light therapy on cognitive function, sleep, challenging behavior (e.g., agitation), or psychiatric symptoms associated with dementia. Reduction in the development of ADL limitations was reported in 1 study, at 3 of 5 time points, and light therapy was found to have an effect after 6 weeks and 2 years but not after 1 year. The authors concluded that there is insufficient evidence to justify the use of bright light therapy in dementia. Moreover, they stated that further research should concentrate on replicating the suggested effect on ADLs, and establishing the biological mechanism for how light therapy improves these important outcomes.

Knapen et al (2014) examined retrospectively whether a single week of LT is as effective as 2 weeks, whether males and females respond differently, and whether there is an effect of expectations as assessed before treatment. A total of 83 women, and 25 men received either 1-week (n = 42) or 2 weeks (n = 66) of LT were included in 3 studies. Before LT, patients׳ expectations on therapy response were assessed. Depression severity was similar in both groups before treatment (F(1,106) = 0.19, non-significant) and decreased significantly during treatment (main effect "time" F(2,105) = 176.7, p < 0.001). The speed of therapy response differs significantly in treatment duration, in favor of 1 week (F(2,105) = 3.2, p = 0.046). A significant positive correlation between expectations and therapy response was found in women (ρ = 0.243, p = 0.027) and not in men (ρ = -0.154, non-significant). When expectation was added as a co-variate in the repeated-measures analysis it showed a positive effect of the level of expectation on the speed of therapy response (F(2,104) = 4.1, p = 0.018). The authors concluded that there is no difference between 1 and 2 weeks of LT in overall therapy outcome, but the speed of therapy response differed between 1 week LT and 2 weeks LT. Together with the significant correlation between expectations and therapy response in women, these investigators hypothesized that expectations play a role in the speed of therapy response.

Martensson et al (2015) stated that light therapy is an accepted treatment option, at least for SAD. These investigators evaluated treatment effects of bright white light (BWL) on the depressive symptoms in both SAD and non-seasonal depression. The systematic review was performed according to the PRISMA guidelines. PubMed, Embase, and PsycINFO were searched (December 1974 through June 2014) for RCTs published in peer-reviewed journals. Study quality was assessed with a check-list developed by the Swedish Council on Technology Assessment in Health Care. Only studies with high or medium quality were used in the meta-analyses. A total of 8 studies of SAD and 2 studies of non-seasonal depression met inclusion and quality criteria. Effects on SAD were estimated in 2 meta-analyses. In the first, week-by-week, BWL reached statistical significance only at 2 and 3 weeks of treatment (Standardized Mean Difference, SMD: -0.50 (confidence interval [CI]: 0.94 to -0.05); -0.31 (-0.59 to -0.03) respectively). The second meta-analysis, of end-point data only, showed a SMD of -0.54 (CI: -0.95 to -0.13), which indicated an advantage for BWL. No meta-analysis was performed for non-seasonal depression due to heterogeneity between studies. The authors concluded that most studies of BWL had considerable methodological problems, and the results of published meta-analyses were highly dependent on the study selection. They stated that even though quality criteria were introduced in the selection procedures of studies, when the results were carefully scrutinized, the evidence was not unequivocal.

Danilenko and Ivanova (2015) noted that studies comparing the effectiveness of dawn simulation to conventional bright light for the treatment of SAD (in parallel groups) have yielded conflicting results. This cross-over study investigated treatment outcomes and long-term treatment preference. A total of 40 winter depressives were treated for 1 week with bright light (4.300 lx for 30 to 45 mins shortly after awakening) or dawn simulation (gradually increasing light during the last 30 mins of sleep achieving 100 lx before alarm beep, with the dawn simulator placed closer to the open eyes for a further 15 mins: 250 lx). The depression level was self-rated using SIGH-SAD-SR. Depression scores reduced similarly following bright light and dawn simulation: for 43.8 % and 42.2 % (medians), respectively; effectiveness ratio was 23:17. The preference was also similar (21:19). Among those who preferred bright light, the most common reason was that they perceived the bright light to be more effective (19/21; it was more effective, p = 0.0096; this subgroup tended to have more severe depression) and ease of use (6/21). Among those who preferred the dawn simulator, the reasons were a more "natural" action (9/19), device compactness and/or time-saving (10/19) and in 4 cases where bright light caused eye-strain. The authors concluded that dawn simulation was similarly effective to bright light in the treatment of winter depression. They stated that patients with more severe depression tended to report greater improvement with bright light; in such cases, this would out-weigh the non-clinical advantages of dawn simulation.

Light Therapy for Patients with Depression and Type 2 Diabetes

Brouwer et al (2015) stated that major depression and type 2 diabetes often co-occur. Novel treatment strategies for depression in type 2 diabetes patients are needed, as depression in type 2 diabetes patients is associated with poor prognosis and treatment results. Major depression and concurrent sleep disorders have been related to disturbances of the biological clock. The biological clock is also involved in regulation of glucose metabolism by modulating peripheral insulin sensitivity. Light therapy has been shown to be an effective anti-depressant that “re-sets” the biological clock. These researchers described the protocol of a study that evaluates the hypothesis that light therapy improves mood as well as insulin sensitivity in patients with a major depressive episode and type 2 diabetes. This study is a randomized, double-blind, parallel-arm trial in 98 participants with type 2 diabetes and a major depressive episode, according to DSM-IV criteria. These investigators will examine if light therapy improves depressive symptoms and insulin sensitivity, the primary outcome measures. They also investigate whether these effects are mediated by restoration of the circadian rhythmicity, as measured by sleep and hypothalamic-pituitary-adrenal axis activity. Participants will be randomly allocated to a bright white-yellowish light condition or dim green light condition. Participants will undergo light therapy for 30 mins every morning for 4 weeks at home. At several time-points, namely before the start of light therapy, during light therapy, after completion of 4 weeks of light therapy and after 4 weeks follow-up, several psychometrical, psychophysiological and glucometabolic measures will be performed. The authors concluded that if light therapy effectively improves mood and insulin sensitivity in type 2 diabetes patients with a major depressive episode, light therapy may be a valuable patient-friendly addition to the currently available treatment strategies. Additionally, if the data support the role of restoration of circadian rhythmicity, such an observation may guide further development of chrono-biological treatment strategies in this patient population.

Light Therapy for Patients with Depression and Cystic Fibrosis

In a pilot study, Kopp and colleagues (2016) noted that depression is common in cystic fibrosis (CF) and linked with worse outcomes during hospitalization. Bright-light therapy during hospitalizations augments anti-depressant regimens and reduces length of stay (LOS) in depressed non-CF patients, but has not been examined in patients with CF. a total of 30 CF patients used a light box emitting 10,000lx for 30 minutes each day for 7 straight days following hospital admission for pulmonary exacerbation. Depressive symptom severity (QIDS-C) and quality of life factors (CFQ-R) were recorded pre-/post-light therapy; 80 % of subjects had at least mild depressive symptoms upon admission. Hospitalized CF patients had a significantly lower mean LOS of 11.0 ± 3.6 days compared to a historical cohort from the year prior (13.3 ± 4.4 days, p = 0.038). There was a significant decrease in depressive symptoms for all subjects receiving light therapy (p < 0.0001). There was no relation between depressive symptoms and lung function or vitamin D; 6 out of 12 quality of life indicators improved with light therapy including the domains of vitality, emotion, and health perceptions. There were no adverse events (AEs) reported. The authors concluded that light therapy was well-tolerated by hospitalized CF patients and resulted in improved depressive symptoms and quality of life. They stated that light therapy was associated with a reduced length of stay; however, large, randomized trials of light therapy may be indicated for hospitalized CF patients. The main drawbacks of this study were the lack of a control group and possible confounding effects of hospitalization treatment on systemic symptoms.

Light Therapy for Patients with Insomnia

Riemann and colleagues (2017) stated that the European guideline for the diagnosis and treatment of insomnia was developed by a task force of the European Sleep Research Society, with the aim of providing clinical recommendations for the management of adult patients with insomnia. The guideline was based on a systematic review of relevant meta-analyses published till June 2016. The target audience for this guideline includes all clinicians involved in the management of insomnia, and the target patient population includes adults with chronic insomnia disorder. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) system was used to grade the evidence and guide recommendations. The diagnostic procedure for insomnia, and its co-morbidities, should include a clinical interview consisting of a sleep history (sleep habits, sleep environment, work schedules, circadian factors), the use of sleep questionnaires and sleep diaries, questions about somatic and mental health, a physical examination and additional measures if indicated (i.e., blood tests, electrocardiogram, electroencephalogram; strong recommendation, moderate- to high-quality evidence). Polysomnography can be used to evaluate other sleep disorders if suspected (i.e., periodic limb movement disorder, sleep-related breathing disorders), in treatment-resistant insomnia, for professional at-risk populations and when substantial sleep state misperception is suspected (strong recommendation, high-quality evidence). Cognitive behavioral therapy for insomnia is recommended as the 1st-line treatment for chronic insomnia in adults of any age (strong recommendation, high-quality evidence). A pharmacological intervention can be offered if cognitive behavioral therapy for insomnia is not sufficiently effective or not available. Benzodiazepines, benzodiazepine receptor agonists and some anti-depressants are effective in the short-term treatment of insomnia (less than or equal to 4 weeks; weak recommendation, moderate-quality evidence). Anti-histamines, anti-psychotics, melatonin and phyto-therapeutics are not recommended for insomnia treatment (strong to weak recommendations, low- to very-low-quality evidence). Light therapy and exercise need to be further evaluated to judge their usefulness in the treatment of insomnia (weak recommendation, low-quality evidence). Complementary and alternative treatments (e.g., homeopathy, acupuncture) are not recommended for insomnia treatment (weak recommendation, very-low-quality evidence).

Photo-Biomodulation for Depressive Disorder / Dementia

In a pilot study, Cassano and colleagues (2018) examined the anti-depressant effect of transcranial photo-biomodulation (t-PBM) with near-infrared (NIR) light in subjects suffering from major depressive disorder (MDD). 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. These researchers performed 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 to 30 mins/session], delivered to dorsolateral prefrontal cortex, bilaterally and simultaneously, twice-weekly, for 8 weeks, in subjects with MDD. Baseline observation carried forward (BOCF), last observation carried forward (LOCF), and completers analyses were performed. The effect size for the anti-depressant 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 d), respectively for BOCF (n = 21), LOCF (n = 19), and completers (n = 13). Further, t-PBM was fairly well-tolerated, with no serious AEs. The authors concluded that t-PBM with NIR light demonstrated anti-depressant properties with a medium to large effect size in patients with MDD. These researchers stated that replication is needed, especially in consideration of the small sample size.

Scope of Policy

This Clinical Policy Bulletin addresses phototherapy for psychiatric disorders.

Medical Necessity

Aetna considers a high-intensity light unit for light box therapy medically necessary durable medical equipment (DME) for members who have seasonal affective disorder (SAD) and meet

of the following criteria.

Experimental and Investigational

The following procedures are considered experimental and investigational because the effectiveness of these approaches has not been established (not an all-inclusive list):

Notes