Effects of red and blue light therapy combined with paroxetine on anxiety, depression and inflammatory factors in papulopustular rosacea

Abstract

Introduction

Papulopustular rosacea (PPR) remains a significant clinical and psychosomatic challenge in dermatological practice.

Aim

To examine the clinical utility and interventional impact of red and blue light therapy in conjunction with paroxetine on serum inflammatory markers, anxiety, and depression in PPR patients.

Material and methods

120 PPR patients who were treated at our institution between May 2021 and March 2025 were the subject of a retrospective research. Patients were assigned to an observation group (n = 60) receiving red–blue light therapy with paroxetine, or to a control group (n = 60) receiving red–blue light therapy alone. The clinical efficacy before and after 7 weeks of treatment was compared between the two groups. Depression status (HAMA/HAMD), clinical symptom score (IGA), TNF-α, IL-6, and IL-8 levels in the serum, and adverse reactions were assessed.

Results

In contrast to the control group, participants in the observation group exhibited markedly attenuated HAMA, HAMD, and IGA scores (p < 0.05). In parallel, levels of the pro-inflammatory mediators TNF-α, IL-6, and IL-8 in the blood underwent substantially greater suppression in the observation group (p < 0.05). The incidence of adverse responses/reactions did not differ statistically significantly between the two groups (p > 0.05).

Conclusions

Combining paroxetine with red and blue light therapy can more effectively alleviate anxiety and depression, improve skin lesions, and reduce systemic inflammation levels, with a good safety profile. It is a promising treatment regimen.

Introduction

Rosacea is a chronic inflammatory disorder primarily affecting facial skin [1]. A Brazilian study in 2023 reported a 12.7% prevalence of rosacea among its outpatients [2]. Recent molecular studies have increasingly highlighted the role of genomics and transcriptomics in elucidating inflammatory skin disease mechanisms [3]. Among them, papulopustular rosacea (PPR) has a burden on patients’ appearance and psychosocial function due to the presence of significant erythema, inflammatory papules and pustules [4]. Recent studies have shown that the pathological process of PPR involves not only abnormal immune activation, neurovascular dysregulation and microbial colonization, but is also closely related to chronic inflammatory state. Pro-inflammatory variables like interleukin-8 (IL-8) levels in serum are often significantly elevated [5]. It is worth noting that such skin lesions often induce or aggravate patients’ anxiety and depression, and mood disorders can further exacerbate immune disorders and skin inflammation through neuroendocrine pathways, becoming a key factor affecting efficacy and prognosis [6]. At present, the clinical management of PPR still faces challenges. Conventional therapies, including topical antibacterial agents, systemic antibiotics, and retinoids, can partially control skin lesions; however, their long-term use may be limited by tolerability and safety concerns [7]. Phototherapy, as an important physical therapy method, especially narrow-spectrum red and blue light therapy, can inhibit microorganisms such as Propionibacterium acnes, reduce perifollicular inflammation, and regulate local cytokine expression through photomodulation [8], but its effects on systemic inflammatory factors and mood state have not yet been clarified. In the meantime, recent basic research has demonstrated that selective serotonin reuptake inhibitors (SSRIs) like paroxetine, in addition to being first-line anti-anxiety and antidepressant medications, also have anti-inflammatory effects by blocking signalling pathways like nuclear factor κB (NF-κB) of B cells, NOD-like receptor thermoprotein domain-associated protein 3 (NLRP3) inflammasome, and glutamatergic system [9]. However, there are few clinical studies that combine phototherapy with SSRIs for PPR, and it is unknown whether the two have a synergistic effect in regulating systemic inflammation and emotional state.

Aim

This study aimed to evaluate the impact of red and blue light therapy coupled with paroxetine on patients’ serum inflammatory factor levels and mental state in order to give new data for the overall treatment of papulopustular rosacea. After that, it will look into its overall clinical effectiveness.

Material and methods

Research subjects

This retrospective study reviewed 120 patients diagnosed with papulopustular rosacea who received treatment at our hospital from May 2021 to March 2025. After the study protocol was approved by the Institutional Medical Ethics Committee (Approval No. 2026-1-02) in 2026, clinical data from previously treated cases were retrospectively extracted and analysed. Based on treatment modality, participants were split into two groups: an observation group and a control group, each consisting of 60 participants. The two groups’ overall characteristics did not differ statistically significantly (p > 0.05).

Inclusion criteria: (1) fulfilling the requirements for papulopustular rosacea diagnosis [10]; (2) not having received any rosacea-related treatment in the past 3 months; (3) being ≥ 18 years old; and (4) being able to communicate independently and giving informed consent.

Exclusion criteria: (1) those who are allergic to drugs or lasers; (2) those who have other skin diseases such as contact dermatitis or seborrheic dermatitis on their face; (3) women who are nursing or pregnant, or who want to get pregnant within a year; (4) patients with moderate to severe systemic diseases such as liver, kidney, lung or blood diseases; (5) patients presenting with severe mental disorders, including schizophrenia and bipolar disorder, as well as those at elevated risk of suicide in the recent period.

Treatment methods

Control group

Patients assigned to the control group were treated using an 87C-type red and blue light therapy device (Shenzhen Pumen Technology Co., Ltd.). Each treatment session lasted 10 min and involved concurrent exposure to blue light (415 nm) and red light (633 nm). The treatment frequency is 4 times per week, with no more than 1 time/once per day. The interval between two treatments is no less than 24 h, and the total course of treatment is 7 weeks [10, 11]. Before treatment, the patient were instructed to clean their face and wear specialised goggles. During treatment, it was ensured that the equipment is in close contact with the skin. Treatment parameters were individually adjusted based on patient tolerance, and the use of photosensitising topical agents was avoided throughout the treatment period.

Observation group

In addition to the same red–blue light therapy protocol as the control group, patients in the observation group received adjunctive paroxetine treatment. Oral paroxetine hydrochloride tablets (National Medical Standard H20031106, specification: 20 mg/tablet), with an initial dose of 10 mg/day, taken orally in the morning; after 1 week of treatment, the dose could be increased to 20–40 mg/day based on tolerability and clinical response, not exceeding 40 mg/day [12]. During the treatment period, adverse reactions were closely monitored and individualised dose adjustments were made.

Both groups maintained a light diet, avoided direct sunlight, and avoided scratching the acne-affected areas during the treatment period, and the treatment lasted for 7 weeks.

Observation indicators

Degree of anxiety and depression

Anxiety and depression levels in individuals were measured both before and after therapy using the Hamilton Anxiety/Depression Rating Scale (HAMA/HAMD) [13, 14]. The HAMA scale has 14 items totalling 56 points. Anxiety is more intense when the score is greater. The HAMD scale has 17 elements totalling 52 points. The severity of the depression increases with the score.

Clinical symptom score (Investigator’s Global Assessment, IGA)

The amount of inflammatory skin lesions on the patient’s face, including papules, pustules, and nodules, is evaluated using the IGA score [15]. The IGA is a five-point scale ranging from 0 to 4 that reflects increasing disease severity, with a score of 0 indicating completely clear skin without inflammatory or noninflammatory lesions, a score of 1 representing an almost clear state characterised by rare noninflammatory lesions and the presence of more than one small inflammatory lesion, a score of 2 corresponding to mild disease with findings exceeding grade 1 and consisting of some noninflammatory lesions accompanied by only a limited number of inflammatory lesions limited to papules or pustules and without nodular involvement, a score of 3 denoting moderate severity beyond grade 2 with numerous noninflammatory lesions and potential inflammatory lesions, but just one little nodule, and a score of 4 indicating severe disease characterised by extensive noninflammatory and inflammatory lesions with the presence of up to several nodular lesions.

Inflammatory factor levels

Prior to and following the therapy, 5 ml of blood were extracted from the patient’s elbow vein. After centrifuging the blood at 800×g for 15 min, enzyme-linked immunosorbent assay (ELISA) was employed to ascertain the concentrations of IL-8, TNF-α, and IL-6 in serum.

Adverse reactions

Adverse reactions in both groups of patients during treatment and follow-up were observed and recorded, including dizziness, dry skin, facial itching and stinging, and pigmentation. Patients were advised to seek medical attention promptly if adverse reactions occurred.

Statistical analysis

The statistical program SPSS 21.0 was used to analyse the data in this study. The expression for quantitative data is mean ± standard deviation ($\overline{\text{x}}$ ± s). Within-group differences were evaluated using paired t-tests, while independent t-tests were applied for comparisons between groups. Categorical data are presented as counts and percentages [n (%)], and group differences were assessed with the χ² test. A two-sided p-value below 0.05 was considered statistically significant.

Results

Comparison of general data between the two groups

The baseline characteristics of the 2 patient groups showed no significant differences (p > 0.05) (Table 1).

Table 1.

Baseline characteristics of patients in both groups [n (%), $\overline{x}$ ± s]

Characteristic	Category	Control group (n = 60)	Observation group (n = 60)	t/χ2 value	P-value
Age [years]		26.43 ±8.82	27.75 ±8.58	–0.829	0.409
Gender	Male	23 (38.33)	21 (35.00)	0.144	0.705
	Female	37 (61.67)	39 (65.00)
Disease duration [year]		2.85 ±1.27	2.68 ±1.27	0.718	0.474

Comparing the two patient groups’ levels of anxiety and depression before and after the therapy

Both groups’ HAMA and HAMD ratings dropped after treatment, but the observation group’s decline was noticeably larger than that of the control group (all p < 0.05) (Table 2).

Table 2.

HAMA and HAMD scores before and after treatment in both groups (n = 60, $\overline{x}$ ± s)

Group	HAMA		HAMD
	Before	After	Before	After
Control	23.98 ±4.64	9.18 ±3.64a	22.72 ±5.82	12.45 ±3.27a
Observation	24.75 ±4.88	7.52 ±3.19a	23.38 ±4.61	10.25 ±3.62a
t value	–0.882	2.667	–0.696	3.498
P-value	0.380	0.009	0.488	0.001

^aCompared with the pre-treatment level in the same group, p < 0.05.

IGA scores before and after treatment in observation and control groups

Both groups’ IGA scores dropped after treatment, but the observation group’s decline was noticeably greater than that of the control group (p < 0.05) (Table 3).

Table 3.

IGA scores before and after treatment in both groups (n = 60, $\overline{x}$ ± s)

Group	Before	After	t value	P-value
Control	2.55 ±0.81	1.18 ±0.75a	10.872	< 0.001
Observation	2.48 ±0.89	0.78 ±0.45a	12.784	< 0.001
t value	0.428	3.541
P-value	0.669	0.001

Comparison of inflammatory factors before and after treatment in both groups

Both groups showed reductions in serum TNF-α, IL-6, and IL-8 levels following treatment, with the control group showing a far smaller decline than the observation group (all p < 0.05) (Table 4).

Table 4.

TNF-α, IL-6, and IL-8 levels pre- and post-treatment in observation and control groups (n = 60, $\overline{x}$ ± s)

Group	TNF-α [pg/ml]		IL-6 [pg/ml]		IL-8 [pg/ml]
	Before	After	Before	After	Before	After
Control	52.66 ±6.32	43.56 ±5.41a	70.71 ±8.24	42.31 ±5.95a	82.54 ±9.73	68.27 ±7.68a
Observation	50.71 ±6.34	32.53 ±4.20a	71.35 ±9.13	32.68 ±5.64a	80.66 ±10.06	54.18 ±6.51a
t value	1.684	12.472	–0.406	9.100	1.045	10.839
P-value	0.095	< 0.001	0.685	< 0.001	0.298	< 0.001

^aCompared with the pre-treatment level in the same group, p < 0.05.

Incidence of adverse effects/reactions in observation and control groups

The rate of adverse responses/reactions did not significantly differ between the observation and control groups (p > 0.05) (Table 5).

Table 5.

Adverse reactions in observation and control groups [n (%)]

Group	Dizziness	Dry skin	Facial itching and stinging	Pigmentation
Control	2 (3.33)	2 (3.33)	1 (1.67)	1 (1.67)
Observation	0 (0.00)	1 (1.67)	2 (3.33)	2 (3.33)
χ2 value				2.872
P-value				0.782

Discussion

PPR is a chronic, relapsing facial inflammatory disease. The challenge in treating it lies not only in the skin lesions such as erythema, papules, and pustules, but also in the frequent presence of significant anxiety and depressive mood disorders, severely impacting patients’ quality of life The mechanisms and sites of action of red and blue light therapy and paroxetine are mutually complementary. Red and blue light therapy is an important non-invasive physical therapy for treating PPR. Its blue light mainly acts on the epidermis and has an antimicrobial effect, which may inhibit microorganisms such as Demodex folliculorum associated with the pathogenesis of rosacea [16]. Red light can penetrate into the dermis and reduce inflammation around the hair follicles through photomodulation and promote tissue repair [17]. Red and blue light radiation therapy has been shown in earlier research to be one of the most successful treatments for sunburn relief and inflammatory acne. For instance, Zhao et al.’s findings demonstrated that collagen and alternating red and blue light irradiation might enhance the therapeutic outcome for acne vulgaris patients. Patients’ blood levels of IL-1β and IL-6 were considerably reduced following the therapy [18]. However, its effect is mainly limited to the local skin. Paroxetine is a psychotropic medication used for mood regulation, primarily aimed at alleviating symptoms of anxiety and depression. It can help mitigate persistent low mood, recurrent negative thoughts, and excessive tension in social situations, and has become a first-line treatment for anxiety and depressive disorders [19]. At the same time, the study by Park et al. showed that paroxetine can reduce inflammation by preventing monocytes from activating immunosterols [20]. This study compared the efficacy of red-blue light treatment alone versus red-blue light therapy combined with paroxetine. The study demonstrated that the combined approach effectively alleviated anxiety and depression, strengthened anti-inflammatory activity, and promoted lesion healing in patients with PPR, with good tolerability. These findings offer a promising clinical strategy for the diversified and comprehensive management of PPR.

In this study, both treatment regimens showed a certain emotional improvement effect. After the therapy, both groups exhibited reductions in HAMA and HAMD scores, with a noticeably greater decline in the observation group compared to the control group. The reason for this may be that for the control group, although red blue light therapy mainly targets local anti-inflammatory, bactericidal, and skin barrier repair, it directly improves skin lesions. As a chronic inflammatory skin disease affecting the face, papulopustular rosacea has a close connection between the intensity of skin lesions and the psychological burden of patients. Red and blue light therapy can effectively alleviate facial inflammatory skin lesions, improve visible signs such as erythema and pustules. By enhancing skin appearance, this treatment may reduce patients’ social anxiety and improve their self-image perception, thereby contributing to the improvement in emotional scores at the psychological level. Moreover, it can improve sleep quality and circadian rhythm, indirectly enhancing emotional regulation [21]. Mean-while, studies have shown that red blue light therapy can reduce the levels of some pro-inflammatory cytokines in peripheral blood by inhibiting local and systemic inflammatory responses [22]. Although its anti-inflammatory strength may be limited compared to systemic drugs, it also indicates that this therapy has a certain contribution to reducing skin and potential inflammation, which may indirectly reduce the adverse effects of inflammatory signals on emotional regulation by the central nervous system. Additionally, more pronounced reductions in anxiety and depression were observed in the observation group, potentially reflecting the combined effect of red and blue light therapy with paroxetine, a highly effective selective serotonin reuptake inhibitor. This drug has a dual mechanism in regulating the central nervous system and peripheral immune inflammation. Firstly, paroxetine is a selective serotonin reuptake inhibitor that specifically blocks the presynaptic membrane serotonin transporter, effectively reducing serotonin reuptake, raising the synaptic cleft’s serotonin concentration, enhancing serotonin neurotransmission, improving the regulation of the brain neurotransmitter system, and thus improving anxiety symptoms [23]. Secondly, in addition to regulating central neurotransmitters, paroxetine also has peripheral anti-inflammatory properties. It may improve gut microbiota imbalance by regulating gut microbiota composition, increasing beneficial bacteria and reducing pathogenic bacteria. This regulatory effect, as suggested by preliminary studies, may suppress key pro-inflammatory mediators’ expression, including IL-6, IL-1β, TNF-α, S100A9, and S100A8, while concurrently attenuating inflammation-related signalling pathways such as TNF-α, IL-17, and NF-κB [24]. Mean-while, studies have shown that it has anti-inflammatory properties as well by inhibiting the activation of immune sterols by monocytes [20]. Moreover, a study by Dionisie et al. reported that selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors exert anti-inflammatory effects in depressive disorders, partly by suppressing the generation of pro-inflammatory cytokines such as IFN-γ [25]. These effects were associated with reduced Toll-like receptor expression, disruption of T-cell proliferative responses, and additional immunomodulatory mechanisms. Neuroimmunological studies have shown that elevated pro-inflammatory factors such as IL-6 and TNF-α in peripheral blood can affect central neurotransmitter metabolism and hypothalamic pituitary adrenal axis function through pathways such as the blood-brain barrier or vagus nerve transmission, directly inducing or exacerbating anxiety and depression symptoms [26]. In summary, paroxetine can indirectly improve patients’ anxiety and depression via lowering pro-inflammatory cytokine levels. Therefore, red and blue light contribute to local anti-inflammatory effects and skin barrier repair, while paroxetine participates in central emotional regulation and peripheral anti-inflammatory effects. The combination of the two forms a multidimensional intervention from local to systemic, from skin to mind, which may be the mechanism basis for synergistic effects.

At the level of lesion improvement and anti-inflammatory mechanisms, the combined treatment significantly ameliorated the patients’ facial skin lesions, demonstrating stronger systemic anti-inflammatory effects. Post-treatment reductions in IGA scores were more pronounced in the observation group than in the control group, demonstrating that the combined regimen had greater advantages in rapidly eliminating inflammatory papules and pustules and reducing facial erythema. The reason lies in the fact that the local anti-inflammatory and antibacterial effects of red and blue light therapy directly target the origin of the skin lesions, while paroxetine may, through its systemic anti-inflammatory properties, create a more favourable microenvironment for local inflammation resolution. The two approaches complement each other synergistically. The study demonstrated that reductions in serum TNF-α, IL-6, and IL-8 concentrations were significantly greater in the observation group compared with the control group. TNF-α and IL-6 serve as central pro-inflammatory cytokines [26, 27] that drive and sustain chronic inflammatory states, while IL-8 is a potent chemokine that directly mediates neutrophil recruitment to the lesions [28]. The significant downregulation of these factors correlates with the clinically observed rapid resolution of papules and pustules. The underlying mechanism may involve red and blue light irradiation modulating local cytokine levels in the skin, indirectly influencing systemic inflammation, while paroxetine directly acts on immune cells to limit the engagement of core molecular pathways driving inflammatory response. The combination of the two achieves multi-level anti-inflammatory intervention, which may represent one of the core mechanisms underlying its superior clinical efficacy compared to monotherapy.

Regarding safety, in both groups, the frequency of adverse reactions was comparable, mainly manifesting as mild, tolerable skin dryness and transient tingling, with no serious adverse events occurring. In other words, under standard operating procedures, the combination of red and blue light therapy with paroxetine did not increase additional safety risks and demonstrated good clinical tolerability.

Additionally, this study has a number of limitations. First, selection bias is inevitable in a retrospective study. Second, the 7-week treatment observation time was insufficient to evaluate the long-term effectiveness, relapse rate of the combination therapy, and the ideal paroxetine maintenance medication length. To strengthen the clinical evidence as a foundation for this combination therapy, future prospective, large-sample, long-term randomised controlled trials should be carried out and further investigate optimum combinations of various paroxetine dosages with red and blue light therapy with various parameters.

Conclusions

For the treatment of PPR, red and blue light therapy combined with paroxetine maximises the benefits of both systemic medication therapy and local phototherapy. It significantly improves facial skin lesions while effectively alleviating anxiety and depressive symptoms, reducing serum levels of pro-inflammatory cytokines, with a favourable safety profile. This combined strategy provides a new and effective approach for the comprehensive management of both physical symptoms and psychological distress in PPR patients, aligning with the principle of holistic physical and psychological treatment and a high clinical application value.

Funding Statement

Funding No external funding.

Ethical approval

The study protocol was approved by the Institutional Medical Ethics Committee of the First People’s Hospital of Shuangliu District, Chengdu (Sichuan University West China Airport Hospital) (Approval No. 2026-1-02) and was conducted in accordance with the Declaration of Helsinki.

Conflict of interest

The authors declare no conflict of interest.