Paroxetine Linked to Neurovascular and Immune Proteomic Changes in Refractory Rosacea: Analysis

A secondary analysis of a randomized clinical trial in JAMA Dermatology identified systemic proteomic changes associated with paroxetine treatment in patients with refractory erythematous rosacea, offering new insight into the drug’s potential mechanism of action and highlighting candidate biomarkers that may predict therapeutic response.

The prospective proteomic study was nested within the multicenter, randomized, double-blind, placebo-controlled Prospective Rosacea Refractory Erythema Randomized Clinical Trial (PRRERCT). Investigators analyzed plasma samples collected before and after 12 weeks of oral paroxetine 25 mg daily in 24 women with refractory rosacea (mean age, 35 years).

Proteomics Analysis Reveals Potential Rosacea Biomarkers

Treatment was associated with significant clinical improvement. Mean Clinician’s Erythema Assessment (CEA) scores decreased from 3.1 to 2.3, while Flushing Assessment Tool scores declined from 3.1 to 2.0 (both P < 0.001).

Proteomic profiling identified 497 differentially expressed proteins following treatment. Downregulated proteins showed enrichment in pathways related to immune activation, insulin receptor signaling, and neuronal remodeling. Investigators also identified 98 “reversed-response” proteins—proteins elevated in rosacea that were reduced after treatment—primarily associated with synaptic vesicle cycling, vascular smooth muscle contraction, chemokine signaling, and neuroimmune pathways.

Changes in protein expression correlated with clinical improvement, with 65 proteins associated with erythema reduction and 73 linked to flushing improvement. Among potential predictive biomarkers, OLFML3 demonstrated an area under the curve (AUC) of 0.87, while IGFBP2 achieved an AUC of 0.80 for predicting treatment response.

“Paroxetine treatment was associated with modulation of systemic neuro-vascular-immune networks in patients with rosacea,” the authors wrote. “These exploratory findings provide preliminary mechanistic clues regarding the possible disease-modifying potential of paroxetine and point to circulating protein signatures that may facilitate personalized therapeutic strategies for rosacea management.”

Source

Wang B, Deng X, Zhang Y, et al. Systemic proteomic alterations and predictive biomarkers of paroxetine response in refractory rosacea: a secondary analysis of a randomized clinical trial. JAMA Dermatol. Published online June 17, 2026. doi:10.1001/jamadermatol.2026.1437.