TOPLINE:

In a secondary analysis of a randomized clinical trial, 12 weeks of treatment with the selective serotonin reuptake inhibitor paroxetine was associated with significant improvements in erythema and flushing among patients with refractory rosacea, with proteomic changes involving neuro-vascular-immune pathways.

METHODOLOGY:

• To investigate the mechanism behind paroxetine’s effects in rosacea, researchers conducted a prospective plasma proteomic analysis nested within a multicenter, randomized, double-blind, placebo-controlled clinical trial (PRRERCT) in China, with data analyzed between September 2025 and November 2025.
• A total of 24 women (mean age, 35 years) with refractory erythematous rosacea (Clinician’s Erythema Assessment [CEA] score ≥ 3) received oral paroxetine (25 mg/d) for 12 weeks.
• Plasma samples were collected at baseline and after 12 weeks of treatment.
• Clinical response was assessed using CEA and Flushing Assessment Tool scores, and predictive biomarkers were evaluated using receiver operating characteristic curve analysis.

TAKEAWAY:

• Among the women treated with paroxetine, mean CEA scores dropped from 3.1 to 2.3 (P < .001) and mean Flushing Assessment Tool scores dropped from 3.1 to 2.0 (P < .001). Significant mean reductions in symptom scores were also reported for burning (from 2.5 to 1.0; P < .0001), edema (from 1.4 to 0.5; P < .001), and dryness (from 2.0 to 0.7; P < .001).
• Proteomic analysis identified 497 differentially expressed proteins after paroxetine treatment, with downregulated proteins showing preliminary enrichment in pathways related to immune response activation, insulin receptor signaling, metabolic pathways, and neuronal remodeling.
• A subset of 98 reversed-response proteins was observed, primarily linked to synaptic vesicle cycles and vascular smooth muscle contraction, representing proteins both downregulated after treatment and elevated in neurogenic rosacea at baseline.
• Two biomarkers emerged as candidate biomarkers with a high predictive value for a clinical response.

IN PRACTICE:

This plasma proteomic analysis “provides initial insights into the multidimensional mechanisms through which paroxetine may alleviate rosacea via coordinated modulation of the neuro-vascular-immune network and identifies potentially translatable predictive biomarkers,” the authors wrote. They added, “These findings contribute to a deeper understanding of neuromodulator therapy in inflammatory skin diseases” and “may inform future directions for advancing precision medicine in rosacea management.”

SOURCE:

The study was led by Ben Wang, MD; Xinyi Deng, MS; and Yifan Zhang, MS, Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China, and was published online on June 17 in JAMA Dermatology.

LIMITATIONS: 

The study had a small sample size, was conducted at a single center, and had a treatment duration of only 12 weeks. Proteomic analyses were performed only in the paroxetine group without placebo group proteomic comparisons. Additionally, the biomarker analyses were exploratory.

DISCLOSURES:

This research received support from the National Natural Science Funds for Distinguished Young Scholars, National Natural Science Foundation of China, National Key Research and Development Program of China, Program of Youth Talent Support for Changsha City, Natural Science Foundation of Hunan Province in China, Science Fund for Creative Research Groups of the National Natural Science Foundation of China, Educational Science Planning Project of Hunan Province, and The Scientific Research Program of FuRong Laboratory. The authors reported no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.