Background: Pressure ulcers remain a significant burden in healthcare, particularly among elderly, immobile, and depressed patients. Established risk assessment scales (Braden, Norton, Waterlow) consider factors such as mobility, nutrition, and moisture but do not account for pharmacological influences on wound healing. Selective serotonin reuptake inhibitors (SSRIs) are among the most widely prescribed medications in the pressure ulcer risk population. Despite converging mechanistic evidence linking SERT inhibition to impaired platelet-mediated wound healing, no study has directly investigated the association between SSRI use and pressure ulcer risk. Methods: A systematic literature search was conducted across PubMed/MEDLINE to identify publications directly linking SSRIs to pressure ulcer risk. Major systematic reviews and clinical practice guidelines that searched additional databases (CINAHL, Embase, Cochrane Library) were consulted to confirm the absence of relevant findings. A pharmacovigilance disproportionality analysis was performed using the FDA Adverse Event Reporting System (FAERS, approximately 20 million reports) to detect and characterize statistical signals. Reporting Odds Ratios (ROR) with 95% confidence intervals were calculated. Negative controls (metformin, amlodipine) and mechanistic controls (sumatriptan, buspirone) were included to assess specificity. Results: The literature search yielded zero publications directly investigating the association between SSRIs and pressure ulcers. FAERS analysis revealed a statistically significant signal for sertraline and decubitus ulcer (ROR 2.08; 95% CI 1.91-2.27; n = 546 reports). Fluoxetine showed a significant signal for wound dehiscence (ROR 1.63; 95% CI 1.38-1.92). Paroxetine showed a significant signal for decubitus ulcer (ROR 2.05; 95% CI 1.76-2.39). Negative controls showed no significant signal (metformin: ROR 1.13, not significant; amlodipine: ROR 1.09, not significant). Serotonin receptor agonists (sumatriptan, buspirone) showed no wound healing or electrolyte signals, suggesting the effect is mediated by serotonin reuptake transporter (SERT) inhibition rather than serotonin receptor activation. Adjacent evidence from related wound types further supports the finding: antidepressant use has been associated with increased diabetic foot ulcer incidence, and sertraline has been shown to inhibit bone wound healing in preclinical models. Conclusions: This pharmacovigilance analysis identifies a novel, statistically significant association between SSRI use and pressure ulcer occurrence in the FAERS database. Three independently published mechanistic pathways converge to support a SERT-mediated mechanism. The SERT-specific differential pattern, in which reuptake inhibitors show consistent signals while receptor agonists do not, argues against confounding as the sole explanation. Retrospective cohort analyses using electronic health records could further characterize this association after controlling for age, immobility, and comorbidities. These findings suggest that SSRI status may represent a clinically relevant, modifiable risk factor for pressure ulcer risk assessment. Keywords: SSRI, pressure ulcer, decubitus, serotonin, wound healing, pharmacovigilance, FAERS, disproportionality analysis, risk assessment, Braden scale, drug safety signal
Daniele Dirienzo (Thu,) studied this question.