Topical imipramine and amitriptyline: Potential treatments for UVB-triggered redness in rosacea

Summary: Rosacea is a chronic inflammatory condition with limited therapeutic options. It is typically exacerbated by stimuli such as sunlight and alcohol use. Functional inhibitors of acid sphingomyelinase (FIASMs) such as amitriptyline and imipramine have been shown to inhibit the production of microvesicle particles (MVPs) which are membrane-bound mediators of cell signaling and biological activity. It is hypothesized that FIASMs, through their ability to inhibit the release of MVPs, may reduce the erythema response associated with ultraviolet B light exposure in rosacea patients. This study was conducted as a single-center, double-blinded, placebo-controlled randomized clinical trial. Patients with rosacea and non-rosacea controls were recruited, de-identified, and then randomized to receive 4% amitriptyline or 4% imipramine on either the left or right side of their face and a placebo medication on the other. Baseline erythema, photography, pain, and itch measurements were taken. Respective topical medications were applied, then 300Joules/m² of artificial UVB light was administered and subsequent measurements were taken after UVB administration at 10 min, 60 min, 120 min, and 24 hours. UVB-induced erythema in patients with rosacea had a statistically significant reduction from baseline in 4% topical amitriptyline and 4% imipramine compared to vehicle (one-tailed t-test, p= 0.043). In conclusion, topical FIASMs such as amitriptyline and imipramine work by blocking the release of microvesicle particles and thus reducing the erythema associated with rosacea. These medications may serve as an adjunct treatment to UVB exposure in rosacea patients without adverse events or safety concerns. Jade Bryant^{1, 3}, Winston Owens¹, Garrett Fisher¹, Madison Owens¹, Craig A. Rohan^{1, 2}, Jeffrey B. Travers^{1, 2} 1. Pharmacology and Toxicology, Wright State University Boonshoft School of Medicine, Dayton, OH, United States. 2. Dermatology, Dayton VA Medical Center, Dayton, OH, United States. 3. Florida State University College of Medicine, Tallahassee, FL, United States. UV Biology/Injury and Non-melanoma Cancers