Paroxetine May Modulate Neurovascular-Immune Pathways in Rosacea: Study
A secondary analysis published in the Journal of the American Medical Association found that paroxetine treatment was associated with modulation of systemic neurovascular-immune networks in patients with rosacea. The exploratory findings provide preliminary mechanistic evidence for a possible disease-modifying effect of paroxetine and identified circulating protein signatures that could potentially support patient stratification and personalized treatment strategies.
This research analyzed plasma samples from 24 women with refractory erythematous rosacea who received oral paroxetine at a daily dose of 25 mg for 12 weeks as part of the Prospective Rosacea Refractory Erythema Randomized Clinical Trial (PRRERCT). Participants, aged between 18 and 65 years, underwent detailed proteomic profiling before and after treatment to investigate systemic molecular changes associated with clinical improvement.
The treatment significantly improved symptoms, with average Clinician’s Erythema Assessment (CEA) scores declining from 3.1 to 2.3 and Flushing Assessment Tool scores falling from 3.1 to 2.0. Both improvements were statistically significant, reinforcing previous evidence that paroxetine can effectively reduce persistent facial redness and flushing in difficult-to-treat rosacea.
Proteomic analysis identified 497 differentially expressed proteins following treatment, with many downregulated proteins involved in immune activation, insulin receptor signaling, and neuronal remodeling. Also, this study identified a subset of 98 "reversed-response" proteins that appeared to normalize after therapy. These proteins were enriched in biological pathways related to synaptic vesicle cycling and vascular smooth muscle contraction, suggesting that paroxetine may act by simultaneously modulating nervous system signaling, vascular function, and inflammatory responses.
Changes in protein expression closely tracked improvements in patients' symptoms. 65 proteins were associated with reductions in persistent erythema, while 73 correlated with improvements in flushing, indicating that systemic protein signatures may reflect therapeutic response.
Among the most promising discoveries were two circulating proteins (OLFML3 and IGFBP2) which demonstrated preliminary ability to predict treatment outcomes. OLFML3 achieved an area under the receiver operating characteristic curve (AUC) of 0.87, while IGFBP2 recorded an AUC of 0.80, suggesting these biomarkers could eventually help identify patients most likely to respond to paroxetine before treatment begins. Overall, the results provide compelling evidence that paroxetine's therapeutic effects may extend beyond symptom control to broader modulation of systemic neuro-vascular-immune networks.
Source:
Wang, B., Deng, X., Zhang, Y., Xiao, X., Jian, D., Shi, W., Liu, F., Zhao, Z., Tang, Y., Chen, M., Deng, Z., Li, J., Huang, Y., Huang, J., & Zhang, Y. (2026). Systemic proteomic alterations and predictive biomarkers of paroxetine response in refractory Rosacea: A secondary analysis of a randomized clinical trial: A secondary analysis of a randomized clinical trial. JAMA Dermatology (Chicago, Ill.), 162(8), 804–812. https://doi.org/10.1001/jamadermatol.2026.1437
