Effectiveness of visible light for seasonal affective disorder: A systematic review and network meta-analysis

Abstract

Background:

To determine the efficacy of different visible light therapies in treating seasonal affective disorder (SAD) through both direct and indirect comparisons.

Methods:

We conducted a search of the PubMed, Embase, Cochrane Library, Scopus, Web of Science, China National Knowledge Infrastructure, Wanfang, VIP, and China Biomedical Literature databases for randomized controlled trials up to November 12, 2024. The using search terms were: white light, blue light, green light, and SAD/winter depression. Two independent researchers reviewed and extracted the data.

Results:

After screening, a total of 17 studies were obtained, involving 773 patients. These studies included 14 on white light, 6 on blue light, 2 on green light, and 5 on red light. The results indicated that, in terms of alleviating seasonal mood dysregulation or typical depressive symptoms, white light therapy was most effective, followed by green light, blue light and red light. Furthermore, usual care of SAD was found to be more effective than green light therapy in improving seasonal mood dysregulation.

Conclusion:

The existing evidence suggests that white light may be the best visible light therapy for patients with SAD, with usual care being more effective than green light. However, larger-scale studies are still needed to verify the potential differences among green light and blue light, further comprehensively evaluate the effectiveness of visible light at different wavelengths for SAD.

1. Introduction

Seasonal affective disorder (SAD) is a subtype of depression that typically occurs during specific seasons, with the most common onset being in the winter.^[1] According to the latest diagnosis and statistical manual of mental disorders, SAD is now distinctly differentiated from major depressive disorder, bipolar disorder, and other related concepts, and has its own independent diagnostic criteria.^[2] The characteristic symptoms of SAD include depressed mood, lack of energy, sleep disturbances, and appetite changes.^[3] These symptoms represent a group of behavioral manifestations influenced by environmental fluctuations, and they are regulated by the rest-activity rhythm (RAR).^[4] A phase-delayed RAR is associated with specific depressive symptoms such as late sleep onset and feeling low during the daytime. SAD is believed to be related to disruptions in circadian rhythms,^[5] alterations in the conversion of melatonin, serotonin, and other neurotransmitter systems,^[6] as well as reduced exposure to natural sunlight.^[7] Among these factors, natural sunlight plays a key role in regulating mood and sleep patterns. Furthermore, SAD is typically observed during colder months and in geographical regions characterized by limited daylight exposure. The prevalence of SAD exhibits significant geographical variation, with its incidence increasing as 1 moves farther from the equator, high-latitude regions signifies that a notable reduction in sunlight during the winter months.^[8] And this trend is observed in both the Southern and Northern hemispheres.^[9] Given the seasonal nature of this disorder, treatment often focuses on counteracting the lack of sunlight. One of the most widely studied and used therapeutic methods is light therapy, particularly the use of bright light that mimics natural sunlight to enhance environmental lighting.^[10]

Although there exist various forms of light therapy available, the color of visible light has received limited attention. The prior research has proven the validity of phototherapy in alleviating symptoms of SAD,^[11] has conducted the comparative analysis of the efficacy between light therapy and primary treatment (antipsychotic drugs, psychological treatments, etc).^[12] However, there is a lack of evidence regarding phototherapy of specific color in alleviating SAD conditions. This article is the first to use a network meta-analysis to investigate the efficacy differences of light with different wavelengths in treating SAD, with the aim of identifying the optimal color for clinical light therapy. Based on substantial literature evidence, red light has been confirmed to have a strong placebo effect for SAD. Therefore, red light should not be regarded as an intervention, and its comparative effect with other visible lights is still considered. White light has been extensively utilized in the treatment of SAD to simulate natural sunlight exposure, and its efficacy has been well-documented. Research has shown that blue light can regulate brain regions associated with SAD, such as the amygdala, hippocampus, and hypothalamus, promoting the activation of positive emotions and modulating the brain’s emotional responses.^[13] Since the intrinsically photosensitive retinal ganglion cells (ipRGCs) are more sensitive to blue light wavelengths, the melatonin-suppressing effect of blue light at lower intensities is even stronger than that of brighter white light,^[14] in this regard, blue light has shown a more significant improvement in depressive symptoms compared to white light. Blue light has the characteristic of short wavelength and high energy, which gives it a distinct advantage over other wavelengths of light in the treatment of depression.^[15] Nevertheless, an increasing body of research suggests that exposure to blue light at night may increase the risk of developing depression, presenting a completely opposite conclusion.^[16–18] While green light may have effects similar to those of white light, such as inhibiting melatonin, altering circadian rhythms, and improving depression, it may be more effective.^[19] Hence, we incorporated white light, blue light, and green light as interventions for network meta-analysis, in order to determine the key parameters of superior light wavelengths. This can help improve therapeutic devices and treatment strategies, providing guidance for clinical treatment.

2. Materials and methods

2.1. Search strategy

This review and network meta-analysis were registered in PROSPERO under the number CRD42025637686. Subsequently, we conducted a systematic review following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. We searched of databases including PubMed, Embase, Cochrane Library, Scopus, Web of Science, China National Knowledge Infrastructure, Wanfang, VIP, and China Biomedical Literature up to November 12, 2024. The language was limited to studies published in English and Chinese, and the study type was restricted to randomized controlled trials (RCTs). The search was conducted by flexibly combining medical subject headings and free headings, with the following words used: SAD, winter depression, white light, blue light, green light. A complete list of detailed search strategies for each database is available in Table 1. In addition, through the examination of relevant reviews and references, additional literature was obtained, ensuring a thorough and comprehensive search process. Given the significance of gray literature in policy and practice,^[20] we screened it alongside journal articles. Relevant gray literature meeting this study’s scope were documented with details such as trial registry databases, recorders, and timelines. For instances of incomplete data or inaccessible original datasets, we contacted authors for accessing. If unreachable, such literature would be excluded.

Table 1.

Search strategies on databases.

Database	#	Searches
PubMed	1	(“Seasonal Affective Disorder”[Title/Abstract] OR “Winter Depression”[Title/Abstract]) AND (“White light”[Title/Abstract])
	2	(“Seasonal Affective Disorder”[Title/Abstract] OR “Winter Depression”[Title/Abstract]) AND (“Blue light”[Title/Abstract])
	3	(“Seasonal Affective Disorder”[Title/Abstract] OR “Winter Depression”[Title/Abstract]) AND (“Green light”[Title/Abstract])
Embase	1	(“Seasonal Affective Disorder”:ti,ab,kw OR “Winter Depression”:ti,ab,kw) AND (“White light”:ti,ab,kw)
	2	(“Seasonal Affective Disorder”:ti,ab,kw OR “Winter Depression”:ti,ab,kw) AND (“Blue light”:ti,ab,kw)
	3	(“Seasonal Affective Disorder”:ti,ab,kw OR “Winter Depression”:ti,ab,kw) AND (“Green light”:ti,ab,kw)
Cochrane Library	1	(“Seasonal Affective Disorder”:ti,ab,kw OR “Winter Depression”:ti,ab,kw) AND (“White light”:ti,ab,kw)
	2	(“Seasonal Affective Disorder”:ti,ab,kw OR “Winter Depression”:ti,ab,kw) AND (“Blue light”:ti,ab,kw)
	3	(“Seasonal Affective Disorder”:ti,ab,kw OR “Winter Depression”:ti,ab,kw) AND (“Green light”:ti,ab,kw)
Scopus	1	(TITLE-ABS-KEY “Seasonal affective diorder” OR TITLE-ABS-KEY “Winter depression”) AND (TITLE-ABS-KEY “White light”)
	2	(TITLE-ABS-KEY “Seasonal affective diorder” OR TITLE-ABS-KEY “Winter depression”) AND (TITLE-ABS-KEY “Blue light”)
	3	(TITLE-ABS-KEY “Seasonal affective diorder” OR TITLE-ABS-KEY “Winter depression”) AND (TITLE-ABS-KEY “Green light”)
Web of Science	1	(TS=“Seasonal Affective Disorder” OR TS=“Winter”)
	2	(TS=“Seasonal Affective Disorder” OR TS=“Winter Depression”) AND (“Blue light”)
	3	(TS=“Seasonal Affective Disorder” OR TS=“Winter Depression”) AND (“Green light”)
CNKI	1	(Subject: “Seasonal Affective Disorder” OR Subject:“Winter Depression”) AND (Subject:“White light”)
	2	(Subject: “Seasonal Affective Disorder” OR Subject:“Winter Depression”) AND (Subject:“Blue light”)
	3	(Subject: “Seasonal Affective Disorder” OR Subject:“Winter Depression”) AND (Subject:“Green light”)
Wangfang	1	(Subject: “Seasonal Affective Disorder” OR Subject:“Winter Depression”) AND (Subject:“White light”)
	2	(Subject: “Seasonal Affective Disorder” OR Subject:“Winter Depression”) AND (Subject:“Blue light”)
	3	(Subject: “Seasonal Affective Disorder” OR Subject:“Winter Depression”) AND (Subject:“Green light”)
VIP	1	(Subject: “Seasonal Affective Disorder” OR Subject:“Winter Depression”) AND (Subject:“White light”)
	2	(Subject: “Seasonal Affective Disorder” OR Subject:“Winter Depression”) AND (Subject:“Blue light”)
	3	(Subject: “Seasonal Affective Disorder” OR Subject:“Winter Depression”) AND (Subject:“Green light”)
China Biomedical Literature	1	(Subject: “Seasonal Affective Disorder” OR Subject:“Winter Depression”) AND (Subject:“White light”)
	2	(Subject: “Seasonal Affective Disorder” OR Subject:“Winter Depression”) AND (Subject:“Blue light”)
	3	(Subject: “Seasonal Affective Disorder” OR Subject:“Winter Depression”) AND (Subject:“Green light”)

2.2. Inclusion and exclusion criteria

Inclusion criteria:

1. Research subjects: patients diagnosed with SAD.

2. Research design: RCTs.

3. Interventions: the intervention group included those visible lights from white light, blue light, and green light.

4. Control group: the control group was divided into 3 subgroups: the usual care group (including dawn simulation, pharmacological treatment, psychological treatment, etc); the placebo group (including negative ions, negative control, etc); red light group. we aimed to add red light into the comparative analysis with other visible lights in therapeutic effects, so red light group was excluded from the placebo group.

5. Outcome: using an effective depression assessment scale.

Exclusion criteria:

1. Nonhuman experiments and non-RCTs

2. The full text could not be accessed, and the literature did not report the change scores of baseline after intervention, nor provide data such as standard errors or 95% confidence intervals (CI) from which the standard deviation could be calculated; the data were incomplete and the original data could not be obtained even after contacting authors.

3. There was no report of spectrum range, wavelength, or color of the light used in the phototherapy during the experiment.

4. The standardized depression assessment scale was not implemented.

5. Articles that reused the same experimental data.

6. The overall quality of the literature was evaluated as high-risk articles.

2.3. Literature selection and data extraction

Two independent researchers imported the retrieved literature into the EndNote reference management software and removed any duplicate articles. Then, they read the title and abstract to perform the first round of literature screening, followed by a full-text review to determine the final included studies, and cross-check the results. If any disagreements arised, we discussed and addressed the research findings with a third researcher. The extracted data included demographic information (sample size, average age, gender ratio), study baseline characteristics (authors, publication year, country), and detailed study data (intervention measures, control measures, duration of light therapy, assessment methods).

2.4. Risk of bias and quality assessment

Two researchers assessed the following categories of bias according to the Cochrane Handbook for Systematic Reviews of Interventions (version 5.1.0): selection bias (randomization); performance bias (blinding of both subjects and investigators); detection bias; attrition bias (completeness of result data); reporting bias; other biases. The bias for each category was evaluated as 1 of 3 outcomes: “low risk,” “some concerns,” or “high risk,” and presented in graphical form. Additionally, the grading of recommendations assessment, development and evaluation (GRADE) system was applied to evalute the quality of evidence of each paired comparison as high, moderate, low and very low.

2.5. Statistical analysis

During the analysis process, we used the endpoint score differences of the Structured interview guide for the Hamilton depression rating scale (HDRS)-SAD (SIGH-SAD)^[21] as the primary outcome indicator. This approach was based on the fact that this scale is composed of not only the 17-item version of the HDRS but also includes atypical symptoms such as increased appetite and cravings for carbohydrates, as well as related weight gain, hypersomnia, fatigue, and social withdrawal. And these atypical symptoms often manifest more prominently in individuals with SAD, they are representative symptoms in SAD condition. In 2003, the SIGH-SAD was updated to the Structured Interview Guide for the HDRS with atypical depression supplement (SIGH-ADS). The SIGH-ADS was expanded to 29 items, composed of 21 items of the HDRS and 8 items atypical supplementary symptoms. One additional atypical symptom, namely diurnal mood variation, was added to the original set of atypical symptoms. SIGH-ADS allows for a more accurate and specific assessment of patients with SAD. As for the HDRS, which has long been regarded as one of the gold standards for quantifying depressive symptoms. It is considered the most reliable measure of the severity of depression in patients. Some studies have also utilized the HDRS as an evaluation tool for patients with SAD.^[22,23] Therefore, we had adopted the endpoint score difference in Hamilton Scale scores as a secondary indicator in this study. HDRS has several versions, including those with 17, 21, and 24 items.

The network meta-analysis was conducted using R software to compare the effects of various visible light conditions. The assumption of common heterogeneity between studies is unreliable when involve each comparison in numerous studies, so we employed a random effects model to calculate the results.^[24] Additionally, to select an appropriate model to describe the variability of the data, we implemented both global and local inconsistency tests. Due to the many variations in versions of the SIGH-SAD and HDRS scales mentioned above, we calculated the standardized mean difference (SMD) of the endpoint score differences for each study’s depression scale, along with the corresponding 95% CI, rather than opting for the MD. For multi-arm experiments, we reasonably disregard the data from arm trials that were unrelated to the subject of this study, such as the differences between high-density and low-density negative ions. To intuitively present the results and combined effects, we displayed the effect estimates and CI of each study in the league table ordered by Surface under the cumulative ranking curve (SUCRA) values. Moreover, we constructed a network relationship diagram to observe the results of direct and indirect comparisons in multi-arm trials, providing an intuitive representation of the relationships between different interventions. Ultimately, sensitivity analysis was performed to assess the robustness of the results and identify sensitive studies or data set.

3. Results

3.1. Retrieval results of literature

Through the searching of multiple databases and the reviewing of relevant literature, a total of 650 articles were obtained. After removing duplicate articles, 365 studies remained. Two researchers read the article titles and abstracts, articles that do not meet the inclusion and exclusion criteria were excluded, and 40 articles were selected. A total of 17 studies were ultimately included in this meta-analysis after a full-text review of 40 articles. Figure 1 shows the PRISMA flowchart for the literature selection process.

Figure 1.

Flowchart of literature screening.

3.2. Baseline characteristics of study

Table 2 presents the basic characteristics of the 17 included RCTs,^[23,25–40] encompassing a total of 773 participants. And the sample sizes across the studies vary considerably, ranging from 10 to 177 participants. The gender distribution of patients shows a clear predominance of females, as women tend to be more emotional and are more susceptible to the influence of negative moods. In the 17 visible light RCTs, 14 involved white light data,^{[23,25,27–36,39,40]} 6 involved blue light data,^{[25,26,29,31,32,38]} 2 involved green light data,^[35,37] and 5 involved red light data.^{[28,30,37–39]} Most experimental studies that explored the efficacy of white light therapy had used extremely high illuminance levels. There were 9 studies employed 10,000 illuminances (lux) of white light,^{[23,28,30–34,36,39]} which corresponded to Bright Light Therapy. Except for 1 study,^[31] the light intensity used in blue light therapy did not exceed 200 lux.

Table 2.

Baseline characteristics of included studies.

Study	Sample size	Mean age (SD)	Sex distribution (%)	Intervention	Control	Light treatment duration	Outcome measure
Anderson, 2009, USA[25]	18	49.1 (9.5)	Female 66.7	White LED; 711 lux; 400–700 nm	Blue LED; 98 lux; 464 ± 27 nm	45-min daily after normally awakened between 6 and 9 am; 21 d	SIGH-ADS
Anderson, 2016, USA[26]	35	44.6 (12.4)	Female 74.3	Blue LED; 149.2 ± 12.1 lux; 465 nm	Placebo (blue-free LED); 119.6 ± 21.3 lux; 595 nm	30 min daily in morning; 42 d	SIGH-ADS
Desan, 2007, USA/Canada/Netherlands[27]	23	45.9 (11.6)	Female 73.9	White LED; 1350 lux; 400–700 nm	Placebo (negative ions)	30 min daily immediately upon arising before 8 am; 28 d	SIGH-SAD
Flory, 2010, USA[28]	55	–	–	White light box; 10,000 lux	Red light box; 300 lux	30 min daily between 7:30 and 11:00 am; 12 d	SIGH-SAD-SR, HDRS-21
					Placebo (negative ions)
Gordijn, 2012, Netherlands[29]	35	38.5 (12.4)	Female 80.0	White light; 400–750 nm	Blue light; 400–625 nm	30 min on workdays between 7:45 and 8:45 am; 10 d	SIGH-SAD, HDRS-17
Lam, 2006, Canada[23]	96	43.5 (10.3)	Female 66.7	White light box; 10,000 lux	Usual care (fluoxetine)	30 min daily immediately after awakened between 7 and 8 am; 56 d	HDRS-24
Magnusson, 1991, Iceland[30]	10	36 (7.5)	–	White light box; 10,000 lux	Red light box; 400 lux	40 min daily in morning or afternoon; 8 d	SIGH-SAD, HDRS-17
Meesters, 2011, Netherlands[31]	22	40.8 (12.6)	Female 77.3	White light; 10,000 lux	Blue light; 750 lux	30 min on workdays between 7:45 and 8:45 am; 10 d	SIGH-SAD, HDRS-17
Meesters, 2018, Netherlands[32]	45	37.9 (13.2)	Female 75.6	White light; 10,000 lux	Blue LED; 100 lux; 470 ± 25 nm	30 min on workdays between 7:30 and 8:30 am; 10 d	SIGH-SAD, HDRS-17
Rohan, 2015, USA[33]	177	45.6 (12.7)	Female 83.6	White light box; 10,000 lux	Usual care (CBT)	30 min daily immediately upon awakening for 1 wk at first, in the case of insufficient response, increasing the daily duration incrementally by 15 min per wk up to a maximum of 120 min daily, in the case of significant side effects, duration was decreased in 15 min decrements to a minimum of 30 min daily; 42 d	SIGH-SAD, HDRS-21
Rohan, 2007, USA[34]	46	45.6 (11.3)	Female 89.1	White light box; 10,000 lux	Usual care (CBT)	90 min daily in morning and evening during wk 1, 2 45-min daily doses to be completed between 6 am and 9 am and 6 am and 9 pm, respectively. For wk 2–6, consultant recommended individually tailored adjustments to treatment duration; 42 d	SIGH-SAD, HDRS-21
					Placebo (negative control)
Stewart, 1991, USA[35]	12	35.5 (5.6)	Female 58.3	White light box; 1103 lux; 350–800 nm	Green light box; 1103 lux; 475–650 nm	120 min daily between 5 and 9 am; 7 d	SIGH-SAD, HDRS-21
Terman, 2006, USA[36]	58	-	-	White light box; 10,000 lux	Usual care (dawn simulation)	30 min daily within 10 min of arising; 21 d	SIGH-SAD, HDRS
					Placebo (negative ions)
Oren, 1991, USA[37]	14	-	Female 71.4	Green light 2500 lux; 505–555 nm	Red light; 2500 lux; 615–685 nm	120 min daily between 5:30 and 9:00 am; 7 d	HDRS-21
Strong, 2009, USA[38]	30	45.3 (12.5)	Female 76.7	Blue LED; 176 lux; 470 nm	Red LED; 201 lux; 650 nm	45-min daily between 6 and 8 am; 21 d	SIGH-SAD, HDRS-17
Wileman, 2001, UK[39]	57	41.5 (10.0)	Female 91.2	White light box; 10,000 lux	Red light box; 500 lux	30 min daily for the 1st wk, 45-min daily for the 2nd wk and up to 60 min daily for the remaining 2 wk of treatment; 28 d	SIGH-SAD-SR
Ruhrmann, 1998, German[40]	40	40.7 (10.6)	Female 77.5	White light box; 3000 lux	Usual care (fluoxetine)	120 min daily in morning or evening; 35 d	HDRS-21

HDRS = hamilton depression rating scale, lux = illuminance, SD = standard deviation, SIGH-ADS = structured interview guide for the hamilton depression rating scale with atypical depression supplement, SIGH-SAD = structured interview guide for the hamilton depression rating scale-seasonal affective disorder, SIGH-SAD-SR = structured interview guide for the hamilton depression rating scale-seasonal affective disorder-self rating.

3.3. Quality of included studies

The risk of bias assessment is presented in Figures 2 and 3. All 17 included studies^[23,25–40] generally exhibited high quality, with no studies were categorized as high risk for overall quality. Therefore, none of the 17 studies were excluded. Except for 1 study that existed nonrandomized subjects,^[39] all other studies completed the randomization process. Eleven studies accomplished the double-blind procedure for both patients and raters, effectively avoiding performance bias and detection bias.^{[23,25–27,29,32,35,36,38–40]} And the data included in studies was nearly complete, with no reporting bias or other deviation.

Figure 2.

Risk of bias map.

Figure 3.

Risk of bias summary map.

The quality of included studies assessment is shown in Figure 4. In comparisons of white light versus blue light, evidence quality was relative high, reaching the level of moderate. For white light versus green light, evidence quality was rated as low across both SIGH-SAD and HDRS outcome measures, while white light versus red light comparisons were assessed as very low. Overall, studies involving white light and red light comparisons suggest substantial discrepancies between observed and true effects, warranting cautious interpretation of results due to weak recommendation strength.

Figure 4.

GRADE evidence summary chart. GRADE = grading of recommendations assessment, development and evaluation.

3.4. Network meta-analysis

The overall inconsistency test for the SIGH-SAD and HDRS outcome measures yielded results of (Q = 3.72, P = .7145) and (Q = 4.75, P = .4476), respectively. Since the P-values were >.05, no inconsistency between direct and indirect evidence was observed. The test of local inconsistency (Tables 3 and 4) shows that the P-values for all interventions were >.05, also indicating that the differences between direct and indirect comparisons were not statistically significant. Therefore, this study used the consistency model for analysis, and at the same time, it met the conditions for network meta-analysis and network geometry.

Table 3.

Node-splitting inconsistency analysis of visible lights on structured interview guide for the hamilton depression rating scale – seasonal affective disorder.

Name	Direct effect	Indirect effect	Overall	P-value
Blue light, placebo	2.5 (−2.9 to 7.9)	3.2 (−1.7 to 8.6)	2.8 (−0.52 to 6.4)	.83
Blue light, red light	5.5 (−2.4 to 14.0)	1.4 (−3.2 to 6.2)	2.4 (−1.5 to 6.6)	.36
Blue light, white light	−3.6 (−6.9 to −0.10)	−2.3 (−8.0 to 3.1)	−3.2 (−6.0 to −0.39)	.70
Placebo, red light	1.7 (−4.3 to 7.8)	−2.7 (−8.6 to 3.5)	−0.43 (−4.5 to 3.7)	.29
Placebo, usual care	−8.8 (−17.0 to −1.0)	−4.4 (−11.0 to 2.0)	−5.6 (−10.0 to −1.4)	.38
Placebo, white light	−7.0 (−12.0 to −2.5)	−5.3 (−13.0 to 2.0)	−6.0 (−9.4 to −2.9)	.67
Red light, white light	−4.0 (−8.5 to −0.10)	−9.4 (−18.0 to −0.79)	−5.6 (−9.3 to −2.1)	.26

Table 4.

Node-splitting inconsistency analysis of visible lights on hamilton depression rating scale.

Name	Direct effect	Indirect effect	Overall	P-value
Blue light, red light	4.1 (−0.06 to 8.2)	5.2 (−0.49 to 11.0)	4.4 (1.2–7.7)	.76
Blue light, white light	−1.2 (−3.6 to 1.4)	−2.2 (−8.6 to 4.4)	−1.3 (−3.6 to 0.98)	.77
Green light, red light	3.3 (−6.4 to 14.0)	8.4 (−2.6 to 20.0)	5.6 (−1.8 to 13.0)	.50
Green light, white light	2.3 (−8.4 to 13.0)	−2.4 (−13.0 to 7.7)	−0.18 (−7.6 to 7.2)	.53
Placebo, red light	2.1 (−5.9 to 9.9)	0.15 (−5.6 to 6.3)	0.98 (−3.5 to 5.7)	.71
Placebo, usual care	−5.7 (−11.0 to −0.98)	−1.8 (−8.8 to 5.0)	−4.3 (−8.2 to −0.59)	.34
Red light, white light	−6.4 (−12.0 to −1.1)	−4.9 (−9.4 to −0.14)	−5.8 (−9.3 to −2.4)	.65

3.4.1. Structured interview guide for the hamilton depression rating scale-seasonal affective disorder

Fourteen articles^{[25–36,38,39]} reported the effects of various visible light interventions on SIGH-SAD of patients with SAD. And the light included in that study concerning 4 types of visible light colors,12 on white light, 6 on blue light, 1 on green light, and 4 on red light. The network geometry shows the impact of different visible lights on SIGH-SAD (Fig. 5). In the figure, the lines connecting the nodes indicated the existence of direct comparison RCTs between 2 interventions, the thickness of lines was weighted according to the number of studies. If there was no line between 2 nodes, it indicated that there was no direct comparison RCT available; however, indirect comparisons could be made to rank the probability.

Figure 5.

Network geometry of treatment comparisons of different visible lights on SIGH-SAD. SIGH-SAD = structured interview guide for the Hamilton depression rating scale-seasonal affective disorder.

The estimated effects of the SIGH-SAD scores were shown in the league table as SMD [95% CI], and ranked them in descending order according to the values of SUCRA (Table 5). Relative to the placebo group, the estimated effects ranking were as follows: green light (SMD = −6.92, 95% CI = [−35.91, 21.78]) > white light (SMD = −5.96, 95% CI = [−9.41, −2.90]) > blue light (SMD = −2.81, 95% CI = [−6.39, 0.45]) > red light (SMD = −0.38, 95% CI = [−4.53, 3.73]). However, the level of evidence is often downgraded due to inaccuracies and internal biases within studies.^[41] The SUCRA value is used to rank the effectiveness and probability of interventions. Specifically, white light (SUCRA: 80.7%) was superior to green light (SUCRA: 60.4%), which in turn was superior to blue light (SUCRA: 46.6%) and red light (SUCRA: 21.0%). So white light may be the optimal visible light on SIGH-SAD in patients with SAD, with the highest probability of reducing SIGH-SAD scores. It is noteworthy that our research found that usual care of SAD (SUCRA: 75.5%) was superior to green light therapy (SUCRA: 60.4%). The sensitivity analysis demonstrated robust and reliable outcomes. Sequential exclusion of each study revealed that white light therapy remained the most effective intervention among all visible lights, consistent with SUCRA rankings, and no sensitive studies were identified (Fig. 6). There is no significant publication bias observed in the funnel plot (Fig. 7).

Table 5.

League table of the relative effect estimates of different visible lights on structured interview guide for the hamilton depression rating scale – seasonal affective disorder.

White light	0.35 (−3.21 to 3.78)	−0.89 (−29.69 to 27.41)	3.16 (0.39–5.96)	5.55 (2.13–9.34)	5.96 (2.90–9.41)
−0.35 (−3.78 to 3.21)	Usual care	−1.25 (−30.43 to 27.42)	2.80 (−1.48 to 7.27)	5.20 (0.60 to 10.41)	5.59 (1.34 to 10.39)
0.89 (−27.41 to 29.69)	1.25 (−27.42 to 30.43)	Green light	4.05 (−24.46 to 32.90)	6.55 (−22.1 to 35.50)	6.92 (−21.78 to 35.91)
−3.16 (−5.96 to −0.39)	−2.80 (−7.27 to 1.48)	−4.05 (−32.90 to 24.46)	Blue light	2.38 (−1.53 to 6.59)	2.81 (−0.45 to 6.39)
−5.55 (−9.34 tom −2.13)	−5.20 (−10.41 to −0.60)	−6.55 (−35.5 to 22.10)	−2.38 (−6.59 to 1.53)	Red light	0.38 (−3.73 to 4.53)
−5.96 (−9.41 to −2.90)	−5.59 (−10.39 to −1.34)	−6.92 (−35.91 to 21.78)	−2.81 (−6.39 to 0.45)	−0.38 (−4.53 to 3.73)	Placebo

Figure 6.

Sensitivity analysis of white light on SIGH-SAD in patients with SAD. SAD = seasonal affective disorder, SIGH-SAD = structured interview guide for the Hamilton depression rating scale-seasonal affective disorder.

Figure 7.

Funnel plot of visible lights on SIGH-SAD. SIGH-SAD = structured interview guide for the Hamilton depression rating scale-seasonal affective disorder.

3.4.2. Hamilton depression rating scale

Thirteen articles^{[23,28–38,40]} reported the effects of different visible light interventions on HDRS of patients with SAD, of which 11 data in white light, 4 data in blue light, 2 data in green light, and 4 data in red light. The network geometric diagram illustrates the relationship of different visible lights on HDRS, as shown in Figure 8. The estimated effect of the HDRS scores were also ranked according to the SUCRA values and presented in the league table in Table 6. Relative to the placebo group, white light (SMD = −5.76, 95%CI = [−9.12, −2.50]), green light (SMD = −5.51, 95%CI = [−13.00 to 2.30]) and blue light (SMD = −4.43, 95% CI = [−7.67 to −1.34]) had significant efficacy, red light (SMD = 0.99, 95% CI = [−3.58 to 5.41]), however, was less effective than placebo group.

Figure 8.

Network geometry of treatment comparisons of different visible lights on HDRS. HDRS = Hamilton depression rating scale.

Table 6.

League table of the relative effect estimates of different visible lights on hamilton depression rating scale in patients with seasonal affective disorder.

White light	0.40 (−1.47 to 2.22)	0.33 (−7.32 to 8.01)	1.33 (−0.96 to 3.58)	4.82 (1.26–8.34)	5.76 (2.50–9.12)
−0.40 (−2.22 to 1.47)	Usual care	−0.07 (−7.79 to 7.81)	0.92 (−2.01 to 3.88)	4.42 (0.68–8.18)	5.36 (1.63–9.21)
−0.33 (−8.01 to 7.32)	0.07 (−7.81 to 7.79)	Green light	1.02 (−6.90 to 8.83)	4.43 (−3.97 to 13.08)	5.51 (−2.30 to 13.00)
−1.33 (−6.00 to −0.40)	−0.92 (−3.88 to 2.01)	−1.02 (−8.83 to 6.90)	Blue light	3.47 (−0.58 to 7.53)	4.43 (1.34–7.67)
−4.82 (−8.34 to −1.26)	−4.42 (−8.18 to −0.68)	−4.43 (−13.08 to 3.97)	−3.47 (−7.53 to 0.58)	Placebo	0.99 (−3.58 to 5.41)
−5.76 (−9.12 to −2.50)	−5.36 (−9.21 to −1.63)	−5.51 (−13.00 to 2.30)	−4.43 (−7.67 to −1.34)	−0.99 (−5.41 to 3.58)	Red light

The SUCRA values indicated that white light was also the most effective intervention, with the highest probability of reducing HDRS scores. Specifically, white light (SUCRA: 81.7%) was superior to green light (SUCRA: 67.4%), which in turn was superior to blue light (SUCRA: 54.6%), and red light (SUCRA: 8.4%) was the least effective. Our network meta-analysis results demonstrated that usual care of SAD (SUCRA: 70.9%) perform slightly better than green light therapy (SUCRA: 67.4%), while the placebo group (SUCRA: 17.2%) outperformed red light therapy (SUCRA: 8.4%). Consistent with the above result of sensitivity analysis, this sensitivity analysis revealed invariant conclusion, white light maintained maximum efficacy probability under all exclusion scenarios (Fig. 9). Funnel plot indicates that all the studies exhibited a symmetrical distribution, suggesting minimal publication bias and a reliable result, as shown in Figure 10.

Figure 9.

Sensitivity analysis of white light on HDRS in patients with SAD. HDRS = Hamilton depression rating scale, SAD = seasonal affective disorder.

Figure 10.

Funnel plot of visible lights on HDRS. HDRS = Hamilton depression rating scale.

4. Discussion

Our study found that, both in alleviating seasonal mood dysregulation or typical depressive symptoms, white light may be the best visible light therapy, followed by green light, blue light, and red light. Patients with SAD exhibit elevated levels of peripheral blood cytokines Tumor necrosis factor α (TNF-α) and Interleukin 6 (IL-6), indicating the presence of a neuroinflammatory state. This neuroinflammatory response further reduces neuroplasticity and alters neuroplasticity markers such as brain-derived neurotrophic factor and Tropomyosin receptor kinase B (TrkB), exerting cytotoxic effects.^[42] However, Martin research indicates that green light can reduce neuroinflammation and neuroplasticity in patients,^[43] therefore, green light may simultaneously alleviate symptoms of SAD while also increasing depressive expression. It may led to green light exhibited the highest estimated effect (SMD = −6.92, 95% CI = [−35.91 to 21.78]) on SIGH-SAD of patients with SAD but demonstrated low stability, with minor probability of ranking as the optimal intervention (SUCRA = 60.4%). The primary role of green light is to alleviate chronic pain by increasing the levels of endogenous opioids.^[44,45] Based on our study findings, the efficacy of conventional rehabilitation treatments excluding light therapy, is superior to that of green light therapy. As a result, we recommend using other conventional rehabilitation methods for the treatment of SAD rather than green light therapy.

Although there is substantial evidence showing that blue light has significant therapeutic effects on SAD,^[32,38,46] recent reviews suggest that the efficacy of blue light in treating both seasonal and nonseasonal depression is not significant,^[47] which is consistent with our findings. The observed discrepancies between prior studies and our findings may stem from differences in blue light parameters, notably higher illuminance, extended daily exposure durations, and prolonged total treatment periods. For instance, Strong et al^[38] demonstrated enhanced therapeutic efficacy with intensified blue light regimens; however, this coincided with a marked increase in adverse effects, including headaches reported by one-third of participants in the blue light group. To balance efficacy and safety, we recommend adhering to blue light therapy at ≤ 100 lux for ≤ 30 minutes daily to minimize such risks while retaining clinical benefits. The biological effects of light on the human body are influenced by various factors, such as light exposure timing, duration of light, intensity of illumination, and wavelength of light. Exposure to blue light in the morning can improve the RAR and enhance sleep quality. In contrast, blue light exposure in the evening can delay biological rhythms, thereby negatively affecting mood and sleep quality.^[48] Blue light is located at the high wavelength end of the visible light spectrum, containing a higher photon density and energy, which may represent a potential high risk for retinal damage.^[49] Furthermore, studies have confirmed that high-intensity blue light causes more significant damage to the retina and photoreceptors.^[50] Maybe for this reason, all the trials included in this study employed low-intensity blue light therapy. Sunlight is rich in white and blue light. Typically, the illuminance of natural light during the day ranges from 32,000 to 100,000 lux.^[51] Furthermore, many global guidelines and recommendations for the treatment of depression advocate the use of high-intensity light therapy as an effective treatment approach.^[52–54] Consequently, many of the included studies in this research employed bright white light therapy, with light intensities reaching up to 10,000 lux. It suggests that light intensity is an important factor influencing the biological effects of light therapy and may be the main reason for the differences in effects between white light and blue light.

Compared to light with other wavelengths, red light has a stronger ability to penetrate the skin, more affects the skin layers rather than the retina of eye. The treatment of SAD typically relies on the reception of light signals through the eyes, thereby regulating the circadian rhythm in the brain. Due to the weaker effect of long-wavelength red light on the photoreceptors in eyes, particularly the cone cells in retina,^[55] it is unable to regulate biological rhythms as effectively as white light and blue light. In summary, white light is highly suitable for individuals with SAD, as it offers many advantages. White light is a composite light with a broad spectral range, encompassing the characteristics of light with other wavelengths; white light is soft and can safely increase the illuminance of white light therapy, thereby strengthening its effectiveness in treating SAD. White light can also simulate natural sunlight, compensating for the trait of lack of abundant environmental light in patients with SAD.

Moreover, this study itself has certain limitations. Firstly, the number of RCTs assessing the effect of different visible light therapies for SAD are limited, and the sample sizes are relatively small. Secondly, some studies exist potential biases, with some articles lacking clear randomization methods, allocation concealment procedures, or blinding. The studies also vary in terms of light exposure timing, intensity, duration, and wavelength. Even there is a lack of direct comparative results between some visible lights. There are only 2 studies on the use of green light for SAD, and these are quite outdated. Thus, there is a need to strengthen modern evidence and conduct more rigorous visible light trials to validate the findings of this study. Thirdly, the outcomes of observation lack indicators of sleep quality. Sleep disturbance is a significant feature of SAD and can also reflect the symptomatic presentation of SAD patients. Finally, the included studies were predominantly conducted in mid-to-high-latitude regions (e.g., North America and Northern Europe), whereas data from low-latitude populations remain scarce. Given the seasonal light deprivation characteristic of high-latitude areas, individuals in these regions may exhibit heightened therapeutic responsiveness to visible light therapy. Future research could further explore the impact of different visible lights on sleep quality of SAD patients and the differences between various regions, providing a comprehensive evaluation of the effect differences among various visible light treatments.

5. Conclusion

In sum, our study provides evidence for the treatment of SAD, demonstrating that white light is more effective than green light and blue light in improving depressive performance. Furthermore, usual care was more effective than green light in treating SAD. To gain a more comprehensive understanding of the effects of various visible light treatments on patients with SAD and their underlying mechanisms, further large-scale, multicenter, double-blind, and well-designed high quality RCTs are needed. This will enhance the understanding of treating SAD among scholars, clinicians, and medical students.

Acknowledgments

We would like to acknowledge all participants involved in this study.

Author contributions

Conceptualization: Yujie Wan, Hailiang Huang.

Data curation: Jiali Ding, Mengmeng Fan.

Methodology: Yujie Wan.

Supervision: Hailiang Huang.

Visualization: Jiali Ding, Mengmeng Fan.

Writing – original draft: Yujie Wan.

Writing – review & editing: Hailiang Huang.